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["Retinoids and reproduction (female)",null,null,null,null,null,"PubMed query used:  (retinoid OR retinoic OR Vitamin A) AND ((reproduction AND female) OR breast OR Genitalia, Female[mh] OR uterus or Genital Diseases, Female[mh]) AND (review[pt] OR review[tiab])"]
[null,"Your search terms"]
["PMID","retin","pregnancy","uteru","Total","Pub Yr","Title","Fauthor","LinkPMID","tiab"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I4,I4)","v":16433796},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(B$3),\"\")))/LEN(B$3)","v":22},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B4:D4)","v":24},2006,"Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years experience on 23 patients.","Katugampola",16433796,"Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years experience on 23 patients.    Abstract:    BACKGROUND : Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children.  OBJECTIVES : The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago.  METHODS : Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes.  RESULTS : Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit +/- side-effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate.  CONCLUSIONS : This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life-long treatment with retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I5,I5)","v":10874003},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(B$3),\"\")))/LEN(B$3)","v":23},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B5:D5)","v":23},2000,"Retinoids in chemoprevention and differentiation therapy.","Hansen",10874003,"Retinoids in chemoprevention and differentiation therapy.    Abstract:   Retinoids are essential for the maintenance of epithelial differentiation. As such, they play a fundamental role in chemoprevention of epithelial carcinogenesis and in differentiation therapy. Physiological retinoic acid is obtained through two oxidation steps from dietary retinol, i.e. retinol--gt;retinal--gt;retinoic acid. The latter retinal--gt;retinoic acid step is irreversible and eventually marks disposal of this essential nutrient, through cytochrome P450-dependent oxidative steps. Mutant mice deficient in aryl hydrocarbon receptor (AHR) accumulate retinyl palmitate, retinol and retinoic acid. This suggests a direct connection between the AHR and retinoid homeostasis. Retinoids control gene expression through the nuclear retinoic acid receptors (RARs) alpha, beta and gamma and 9-cis-retinoic acid receptors alpha, beta and gamma, which bind with high affinity the natural ligands all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Retinoids are effective chemopreventive agents against skin, head and neck, breast, liver and other forms of cancer. Differentiation therapy of acute promyelocytic leukemia (APL) is based on the ability of retinoic acid to induce differentiation of leukemic promyelocytes. Patients with relapsed, retinoid-resistant APL are now being treated with arsenic oxide, which results in apoptosis of the leukemic cells. Interestingly, induction of differentiation in promyelocytes and consequent remission of APL following retinoid therapy depends on expression of a chimeric PML-RAR alpha fusion protein resulting from a t(15;17) chromosomal translocation. This protein functions as a dominant negative against the function of both PML and RARs and its overexpression is able to recreate the phenotypes of the disease in transgenic mice. The development of new, more effective and less toxic retinoids, alone or in combination with other drugs, may provide additional avenues for cancer chemoprevention and differentiation therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I6,I6)","v":23740788},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(B$3),\"\")))/LEN(B$3)","v":21},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B6:D6)","v":21},2013,"Retinoids for preventing the progression of cervical intra-epithelial neoplasia.","Helm",23740788,"Retinoids for preventing the progression of cervical intra-epithelial neoplasia.    Abstract:    BACKGROUND : Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe cases of intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing the regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation that may have potential for the treatment of CIN.  OBJECTIVES : To ascertain whether retinoids can cause regression or prevent progression of CIN.  SEARCH METHODS : We searched the Cochrane Gynaecological Cancer Review Groups Specialised Register and Non-Trials Database, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), and MEDLINE and EMBASE (July 2010).For the 2013 update, the searches were re-run as follows: CENTRAL, Issue 3, 2013; MEDLINE, April, Week 2, 2013; and EMBASE, Week 16, 2013.  SELECTION CRITERIA : Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women.  DATA COLLECTION AND ANALYSIS : Two review authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials.  MAIN RESULTS : Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effects on CIN2 and CIN3 of the retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally. Two examined the effect of all-trans-retinoic acid administered topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally to human immunodeficiency virus (HIV)-positive participants with CIN1 and condyloma.Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, and the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over that seen with placebo, which was of borderline statistical significance (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.25 to 1.02). The other study reported a nonsignificant dose-related trend toward increased rates of complete and partial regression compared with placebo. One study reported significantly worse outcomes in women receiving retinoid (OR for regression 6.00, 95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated.In the 2010 review and in this update, no new studies were identified for inclusion.  AUTHORS CONCLUSIONS : The retinoids studied are not effective in causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 are inadequate. Retinoids are not effective in preventing progression of CIN of any grade. At the doses given for the duration of treatment studied, the retinoids were reasonably well tolerated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I7,I7)","v":17943787},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(B$3),\"\")))/LEN(B$3)","v":21},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B7:D7)","v":21},2007,"Retinoids for preventing the progression of cervical intra-epithelial neoplasia.","Helm",17943787,"Retinoids for preventing the progression of cervical intra-epithelial neoplasia.    Abstract:    BACKGROUND : Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation and may have potential for the treatment of CIN.  OBJECTIVES : To ascertain whether retinoids can cause regression or prevent progression of CIN.  SEARCH STRATEGY : Cochrane Gynaecological Cancer Review Groups Specialised Register and Non-Trials Database, Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2,2007),MEDLINE and EMBASE (June 2007).  SELECTION CRITERIA : Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women.  DATA COLLECTION AND ANALYSIS : Two authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials.  MAIN RESULTS : Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effect on CIN2 and CIN3 of retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) (Follen 2001) and 9-cis-retinoic acid (aliretinoin) (Alvarez 2003) given orally and two examined the effect of all-trans-retinoic acid given topically to the cervix (Meyskens 1994; Ruffin 2004). The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally in HIV positive patients with CIN1 and condyloma (Robinson 2002).Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, whilst the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over placebo, which was of borderline statistical significance, odds ratio(OR) = 0.5 (95% confidence interval (CI) 0.25 to 1.02). The other study reported a non-significant dose-related trend towards increased rates of complete and partial regression compared with placebo. One study reported a significantly worse outcome in women receiving retinoid, OR for regression = 6.00 (95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated.  AUTHORS CONCLUSIONS : The retinoids studied are not effective at causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 is inadequate. Retinoids are not effective at preventing progression of CIN of any grade. At the doses given and duration of treatment studied, the retinoids were reasonably well-tolerated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I8,I8)","v":11306068},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(B$3),\"\")))/LEN(B$3)","v":19},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B8:D8)","v":19},2001,"Genetic dissection of retinoid dehydrogenases.","Duester",11306068,"Genetic dissection of retinoid dehydrogenases.    Abstract:   Biochemical studies indicate that alcohol dehydrogenase (ADH) metabolizes retinol to retinal, and that aldehyde dehydrogenase (ALDH) metabolizes retinal to retinoic acid, a molecule essential for growth and development. Summarized herein are several genetic studies supporting in vivo functions for ADH and ALDH in retinoic acid synthesis. Gene targeting was used to create knockout mice for either Adh1 or Adh4. Both knockout mice were viable and fertile without obvious defects. However, when wild-type and Adh4 knockout mice were subjected to vitamin A deficiency during gestation, the survival rate at birth was 3.3-fold lower for Adh4 knockout mice. When adult mice were examined for production of retinoic acid following retinol administration, Adh1 knockout mice exhibited 10-fold lower retinoic acid levels in liver compared with wild-type, whereas Adh4 knockout mice differed from wild-type by less than 2-fold. Thus, Adh1 plays a major role in the metabolism of a large dose of retinol to retinoic acid in adults, whereas Adh4 plays a role in maintaining sufficient retinol metabolism for development during retinol deficiency. ALDHs were examined by overexpression studies in frog embryos. Injection of mRNAs for either mouse Raldh1 or Raldh2 stimulated retinoic acid synthesis in frog embryos at the blastula stage when retinoic acid is normally undetectable. Overexpression of human ALDH2, human ALDH3, and mouse Aldh-pb did not stimulate retinoic acid production. In addition, Raldh2 knockout mice exhibit embryonic lethality with defects in retinoid-dependent tissues. Overall, these studies provide genetic evidence that Adh1, Adh4, Raldh1, and Raldh2 encode retinoid dehydrogenases involved in retinoic acid synthesis in vivo."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I9,I9)","v":8647698},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(B$3),\"\")))/LEN(B$3)","v":18},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B9:D9)","v":19},1996,"[Trans-acitretin is metabolized back to etretinate. Importance for oral retinoid therapy].","Almond-Roesler",8647698,"[Trans-acitretin is metabolized back to etretinate. Importance for oral retinoid therapy].    Abstract:   The oral retinoid etretinate (Tigason) has recently been replaced by trans-acitretin (Neotigason) in the treatment of severe psoriasis, primarily because of its short half-life and the assumption that a shorter period of subsequent contraception would be required. After introduction of the new drug, however, circulating quantities of etretinate were detected in patients treated with trans-acitretin. Thus far, re-esterification has been detected in at least 83 cases. The 2-month period of strict contraception initially recommended after oral intake of trans-acitretin has been extended to 2 years, as with etretinate. We review some aspects of trans-acitretin metabolism, with special emphasis on etretinate formation. Re-esterification of trans-acitretin into etretinate takes place under varying conditions in volunteers and patients, as well as in animal models. Ethanol is a co-factor for the enzymatic re-esterification of trans-acitretin. It is unclear whether the introduction of trans-acitretin has been of any significant benefit to patients. Monitoring of plasma retinoid levels during and after retinoid therapy remains of decisive importance in managing difficult cases and or in approving decisions for pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I10,I10)","v":8744592},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(B$3),\"\")))/LEN(B$3)","v":18},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B10:D10)","v":18},1996,"Receptor-selective retinoid agonists and teratogenic activity.","Willhite",8744592,"Receptor-selective retinoid agonists and teratogenic activity.    Abstract:   Retinoid mechanism of action is dependent upon interaction with the retinoid nuclear RAR and RXR subfamilies of receptors. Study of ligands selective for the different receptors or which modify that interaction may provide insight into which receptors play roles in or contribute to retinoid teratogenesis. The retinoids considered here include in the RAR alpha-selective arylcarboxamidobenzoic acid CD 336 (Am580), the RAR beta/gamma-selective naphthalenecarboxylic acid CD 135 and the adamantyl-phenylcarboxamidobenzoic acid CD 394, the RAR-selective tetrahydrotetra-methylanthracenylbenzoic acid (TTAB) SRI 3961, the carboxyphenylretinamide SRI 7167-67, and the RXR-selective diarylisopropylidene SR 11217. CD 135 has a 3-fold higher affinity for RAR beta when compared with RAR gamma, whereas CD 394 has a 3-fold higher affinity for RAR gamma when compared with RAR beta. A separate investigation into potential amelioration of retinoid teratogenesis by concomitant administration of the cyclohexanetrione (Ro 31-0521) was also conducted. When pregnant hamsters were given an oral bolus of CD 336 or CD 135 during the early primitive streak stage of gestation, these retinoids proved 60-100 times more potent teratogens than all-trans-retinoic acid. Intubation of CD 394 resulted in production of terata similar to that seen after an equivalent dose of all-trans-retinoic acid. Administration of SRI 3961 found this compound 8000 times more potent than all-trans-retinoic acid, while SRI 7167-67 failed to show any evidence for developmental toxicity even after exposure to 105 mg/kg. Studies with the RXR-selective SR 11217 found it to be far less potent than all-trans-retinoic acid. These data point to the conclusion that those retinoids which have no affinity for retinoid nuclear receptors also have little potential for induction of developmental toxicity at doses which do not also provoke maternal intoxication. Comparing in vitro transcriptional activation of wild-type human RAR for the supertoxic TTNBP (Ro 13-7410) and TTAB (SRI 3961) with their relative teratogenic potency in hamster found that the more toxic congener also had the lower in vitro EC50 transactivation value (at ratios approximating their differential toxicities measured as administered dose). The RAR beta/gamma-selective CD 135 (TTNN) was not as efficient as TTNBP (Ro 13-7410) or TTAB (SRI 3961) in hRAR transactivation and CD 135 was less toxic than either Ro 13-7410 or SRI 3961. Although the RXR-selective SR 11217 failed to elicit terata after moderate doses, malformations consistent with those induced by high doses of retinoic acid could be produced following a single large bolus of SR 11217. Under the conditions here, simultaneous administration of Ro 31-0521 with all-trans-retinoic acid appeared to reduce the total percentage of abnormal fetuses seen after exposure to retinoic acid alone, but fetal body weights remained depressed and the numbers of dead embryos remained elevated, suggesting only limited influence of the cyclohexanetrione on retinoid developmental toxicity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I11,I11)","v":2052162},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(B$3),\"\")))/LEN(B$3)","v":17},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B11:D11)","v":18},1991,"The intracellular vitamin A-binding proteins: an overview of their functions.","Wolf",2052162,"The intracellular vitamin A-binding proteins: an overview of their functions.    Abstract:   The intracellular retinoid-binding proteins bind retinol, retinaldehyde, and retinoic acid for purposes of protection against decomposition, solubilize them in aqueous medium, render them nontoxic, and transport them within cells to their site of action. These binding proteins also function by presenting the retinoids to the appropriate enzymes for metabolism. The cytosolic retinol and retinoic acid-binding proteins--CRBP, CRABP, CRBP (II)--function in transport and metabolism of retinoids within parenchymal, intestinal, reproductive, and fetal cells and across blood-organ barriers. A different group of retinoid-binding proteins, more related to serum retinol-binding protein, functions in epididymis and uterus. Retinaldehyde-binding protein aids in the oxidation-reduction reaction of 11-cis-retinol-11-cis-retinaldehyde in the retina, where the interphotoreceptor retinol-binding protein transports retinol between pigment epithelium and photoreceptors. Finally, a group of retinoic acid-binding proteins termed quot;receptorsquot; functions in the nucleus by attaching to promoter regions of a number of specific genes to stimulate their transcription and thus affect growth, development, and differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I12,I12)","v":17368313},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(B$3),\"\")))/LEN(B$3)","v":17},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B12:D12)","v":17},2007,"Metabolism of retinol during mammalian placental and embryonic development.","Marceau",17368313,"Metabolism of retinol during mammalian placental and embryonic development.    Abstract:   Retinol (vitamin A) is a fat-soluble nutrient indispensable for a harmonious mammalian gestation. The absence or excess of retinol and its active derivatives [i.e., the retinoic acids (RAs)] can lead to abnormal development of embryonic and extraembryonic (placental) structures. The embryo is unable to synthesize the retinol and is strongly dependent on the maternal delivery of retinol itself or precursors: retinyl esters or carotenoids. Before reaching the embryonic tissue, the retinol or the precursors have to pass through the placental structures. During this placental step, a simple diffusion of retinol can occur between maternal and fetal compartments; but retinol can also be used in situ after its activation into RA(1) or stored as retinyl esters. Using retinol-binding protein knockout model, an alternative way of embryonic retinol supply was described using retinyl esters incorporated into maternal chylomicrons. In the embryo, the principal metabolic event occurring for retinol is its conversion into RAs, the active molecules implicated on the molecular control of embryonic morphogenesis and organogenesis. All these placental and embryonic events of retinol transport and metabolism are highly regulated. Nevertheless, some genetic and/or environmental abnormalities in the transport and/or metabolism of retinol can be related to developmental pathologies during mammalian development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I13,I13)","v":16054987},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(B$3),\"\")))/LEN(B$3)","v":17},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B13:D13)","v":17},2005,"Alcohol, vitamin A, and cancer.","Wang",16054987,"Alcohol, vitamin A, and cancer.    Abstract:   Chronic and excessive alcohol intake is associated with an increased risk of a variety of cancers (e.g., oral cavity, larynx, esophagus, liver, lung, colorectal, and breast). Retinoids (vitamin A and its derivatives) are known to exert profound effects on cellular growth, cellular differentiation, and apoptosis, thereby controlling carcinogenesis. Lower hepatic vitamin A levels have been well documented in alcoholics. Substantial research has been done, investigating the mechanisms by which excessive alcohol interferes with retinoid metabolism. More specifically, (1) alcohol acts as a competitive inhibitor of vitamin A oxidation to retinoic acid involving alcohol dehydrogenases and acetaldehyde dehydrogenases; (2) alcohol-induced cytochrome P450 enzymes (CYP), particularly CYP2E1, enhance catabolism of vitamin A and retinoic acid; and (3) alcohol alters retinoid homeostasis by increasing vitamin A mobilization from liver to extrahepatic tissues. As a consequence, long-term and excessive alcohol intake results in impaired status of retinoic acid, the most active derivative of vitamin A and a ligand for both retinoic acid receptors and retinoid X receptors. Moreover, this alcohol-impaired retinoic acid homeostasis interferes with (1) retinoic acid signaling (e.g., down-regulates retinoid target gene expression) and (2) retinoic acid quot;cross-talkquot; with the mitogen-activated protein kinase [(MAPK), including Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 kinase] signaling pathway. In addition, restoration of retinoic acid homeostasis by retinoic acid supplementation restored the normal status of both retinoid and MAPK signaling, thereby maintaining normal cell proliferation and apoptosis in alcohol-fed animals. These observations would have implications for the prevention of alcohol-promoted liver (and peripheral tissue) carcinogenesis. However, a better understanding of the alcohol-retinoid interaction and the molecular mechanisms involved is needed before retinoids can be pursued in the prevention of alcohol-related carcinogenesis in human beings, particularly regarding the detrimental effects of polar metabolites of vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I14,I14)","v":11606951},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(B$3),\"\")))/LEN(B$3)","v":17},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B14:D14)","v":17},2001,"Teratogenicity of isotretinoin revisited: species variation and the role of all-trans-retinoic acid.","Nau",11606951,"Teratogenicity of isotretinoin revisited: species variation and the role of all-trans-retinoic acid.    Abstract:   This paper reviews the teratogenicity of isotretinoin in regard to aspects of species variation, toxicokinetics, and metabolism. Particular emphasis is given to the hypothesis that most effects of isotretinoin (13-cis-retinoic acid) are mediated by isomerization to the all-trans-retinoic acid. This mechanism of action would provide a basis for the understanding of species differences and the extrapolation of experimental results to the human situation and thus improve drug development. The insensitive species (rat, mouse) eliminate the drug rapidly through detoxification to the beta-glucuronide; also, placental transfer is limited in these species. On the other hand, in sensitive species (primates), the drug is predominantly metabolized to the active 13-cis-4-oxo-retinoic acid; placental transfer is more extensive here. The beta-glucuronides showed limited placental transfer in all species examined; these metabolites exhibited very low, if any, measurable concentrations in the human. The 13-cis-retinoic acid is not appreciably bound to cellular retinoid-binding proteins or nuclear receptors and exhibits low tissue distribution and placental transfer. Its access to the nucleus may be extensive. Because of the long half life of 13-cis-retinoic acid, continuous isomerization results in significant area under the concentration-time curve levels of all-trans-retinoic acid in the mouse, monkey and the human; the all-trans-retinoic acid formed is extensively distributed across the placenta and may be an important factor that contributes to the teratogenic potency of 13-cis-retinoic acid. Isomerization cannot explain the teratogenic effects of 13-cis-retinoic acid in the rat and rabbit. It is concluded that the high teratogenic activity of isotretinoin in sensitive species (human, monkey) is related to slow elimination of the 13-cis-isomer, to metabolism to the 4-oxo-derivative, to increased placental transfer, to continuous isomerization and significant exposure of the target tissue to all-trans-retinoic acid; and to lack of binding to cytoplasmic retinoid binding proteins that could possibly result in ready access to the nucleus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I15,I15)","v":8142110},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(B$3),\"\")))/LEN(B$3)","v":17},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B15:D15)","v":17},1993,"Embryotoxicity and teratogenicity of topical retinoic acid.","Nau",8142110,"Embryotoxicity and teratogenicity of topical retinoic acid.    Abstract:   All-trans-retinoic acid is a potent developmental toxicant in all species examined. The teratogenic risk of topical all-trans-retinoic acid is reviewed. Experimental studies are limited because of the high maternal toxicity, including skin irritation, with doses below those resulting in significant teratogenic response with other application routes, such as oral application. The maximal systemic availability reported for transdermal exposure of all-trans-retinoic acid was 5-6% in the rat, 9.6% in the monkey (48% with dermatitic skin) and 5-7% in the human. Oral administration of threshold teratogenic doses of all-trans-retinoic acid (6 mg/kg/day) to Wistar rats and Swiss hare rabbits resulted in embryonic area under the concentration time curve levels (approximately 1,000 ng.h/g) which were 2- to 4-fold higher than the endogenous all-trans-retinoic acid levels; corresponding maternal plasma area under the concentration time curve values were 98 and 321 ng.h/ml in rat and rabbit, respectively. The 4-oxo-metabolite was also found in maternal plasma and embryo. Large, controlled studies on the possible developmental toxicity of topical all-trans-retinoic acid in the human are not available. Isolated case reports appeared in the literature claiming teratogenic outcome resembling effects after oral isotretinoin use or those observed in experimental studies with oral or parenteral all-trans-retinoic acid administration. The dose absorbed from daily cosmetic or therapeutic application of all-trans-retinoic acid is expected to be below 0.015 mg/kg, which is at least 30-fold lower than the lowest teratogenic dose of isotretinoin in the human. Topical all-trans-retinoic acid application did not appreciably alter endogenous plasma retinoid levels. The influence of nutrition, diurnal variation and in particular oral vitamin A supplements are more important determinants of plasma retinoic acid compounds than topical all-trans-retinoic acid. These results imply a low risk of therapeutic or cosmetic application of topical all-trans-retinoic acid. However, the highly specific spatial and temporal distribution of binding proteins and nuclear receptors in the embryo suggests that even small alterations in endogenous levels of all-trans-retinoic acid in the embryo may alter crucial developmental processes such as morphogenes; this aspect should be further investigated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I16,I16)","v":21073338},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(B$3),\"\")))/LEN(B$3)","v":15},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B16:D16)","v":15},2011,"Retinoids, retinoic acid receptors, and cancer.","Tang",21073338,"Retinoids, retinoic acid receptors, and cancer.    Abstract:   Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the differentiation of various types of stem cells. Nuclear retinoic acid receptors mediate most but not all of the effects of retinoids. Retinoid signaling is often compromised early in carcinogenesis, which suggests that a reduction in retinoid signaling may be required for tumor development. Retinoids interact with other signaling pathways, including estrogen signaling in breast cancer. Retinoids are used to treat cancer, in part because of their ability to induce differentiation and arrest proliferation. Delivery of retinoids to patients is challenging because of the rapid metabolism of some retinoids and because epigenetic changes can render cells retinoid resistant. Successful cancer therapy with retinoids is likely to require combination therapy with drugs that regulate the epigenome, such as DNA methyltransferase and histone deacetylase inhibitors, as well as classical chemotherapeutic agents. Thus, retinoid research benefits both cancer prevention and cancer treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I17,I17)","v":20716214},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B17:D17)","v":15},2011,"Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review.","Crijns",20716214,"Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review.    Abstract:   Most of the publications on isotretinoin, pregnancy and compliance with the pregnancy prevention programme (PPP) originate from North America. Information specific for the European situation is very limited. The aim of this study was to identify publications describing the use of isotretinoin in humans and the compliance with the PPP in Europe, a systematic search in Medline and Embase was conducted using the terms isotretinoin, pregnancy (and Europe). Furthermore, a manual search in publications was performed. A total of 17 publications were identified. Publications consisted of case reports of exposed pregnancies, surveys among dermatologists or pharmacists and database studies evaluating compliance with the PPP. The studies and surveys dealt with groups of patients exposed to isotretinoin before or during pregnancy and/or compliance with the isotretinoin PPP. Where the information was provided, in 6-26% of cases isotretinoin was prescribed in full accordance with the PPP. Pregnancy incidence was seen in 0·2-1·0 per 1000 women of childbearing age using isotretinoin. Between 65% and 87% of these pregnancies were terminated. This review of studies in Europe performed to date shows failures in the implementation of the PPP. Therefore, the isotretinoin PPP must be scrutinized to identify whether new measures should be taken or whether the failures in the implementation need to be corrected. New measures should take into account the definition of the ultimate goal of a PPP and the acceptable burden. In the meantime, stakeholders could make a start with adjustments in the implementation of the PPP by taking responsibility and enhancing the performance by explicit instructions, monitoring the performance and adjusting, if necessary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I18,I18)","v":19678713},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(B$3),\"\")))/LEN(B$3)","v":15},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B18:D18)","v":15},2009,"Alitretinoin: in severe chronic hand eczema.","Garnock-Jones",19678713,"Alitretinoin: in severe chronic hand eczema.    Abstract:   Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors (RXR). Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. In a large (n = 1032), randomized, double-blind, placebo-controlled, multicentre study (BACH) of up to 24 weeks duration in adults with severe chronic hand eczema, significantly more patients in the alitretinoin 10 or 30 mg/day groups than in the placebo group responded to treatment with clear/almost clear hands, as assessed by the Physician Global Assessment (PGA) [primary endpoint]. In an extension phase of the BACH study, alitretinoin was effective in patients who relapsed after responding to initial treatment with the drug. Of patients who had responded to initial treatment with alitretinoin 30 mg/day, significantly more alitretinoin 30 mg/day than placebo recipients responded on the PGA with clear/almost clear hands during the extension phase (primary endpoint; 80% vs 8%). Of those who had responded to initial treatment with alitretinoin 10 mg/day, 48% of alitretinoin 10 mg/day and 10% of placebo recipients responded during the extension phase. Alitretinoin was generally well tolerated in clinical trials excluding pregnant women. The most common treatment-emergent adverse events and abnormal laboratory test results were consistent with those previously observed with other oral retinoids and RXR agonists."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I19,I19)","v":16129372},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(B$3),\"\")))/LEN(B$3)","v":15},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B19:D19)","v":15},2005,"Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer.","Abu",16129372,"Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer.    Abstract:   Retinoids are natural and synthetic derivatives of vitamin A, which can be obtained from animal products (milk, liver, beef, fish oils, and eggs) and vegetables (carrots, mangos, sweet potatoes, and spinach). Retinoids regulate various important cellular functions in the body through specific nuclear retinoic-acid receptors and retinoid-X receptors, which are encoded by separate genes. Retinoic-acid receptors specifically bind tretinoin and alitretinoin, whereas retinoid-X receptors bind only alitretinoin. Retinoids have long been established as crucial for several essential life processes-healthy growth, vision, maintenance of tissues, reproduction, metabolism, tissue differentiation (normal, premalignant cells, and malignant cells), haemopoiesis, bone development, spermatogenesis, embryogenesis, and overall survival. Therefore, deficiency of vitamin A can lead to various unwanted biological effects. Several experimental and epidemiological studies have shown the antiproliferative activity of retinoids and their potential use in cancer treatment and chemoprevention. Emerging clinical trials have shown the chemotherapeutic and chemopreventive potential of retinoids in cancerous and precancerous conditions of the uterine cervix. In this review, we explore the potential chemopreventive and therapeutic roles of retinoids in preinvasive and invasive cervical neoplasia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I20,I20)","v":6192964},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(B$3),\"\")))/LEN(B$3)","v":15},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B20:D20)","v":15},1983,"Isotretinoin: new therapy for severe acne.","Perry",6192964,"Isotretinoin: new therapy for severe acne.    Abstract:   The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and FDA-approved indications of isotretinoin, a new agent used for treating acne, are reviewed. Isotretinoin is a synthetic retinoid compound with pharmacologic actions similar to those of other retinoids. Isotretinoins effects on nodulocystic acne lesions apparently result from its reduction of the size of sebaceous glands, inhibition of sebum production, and inhibition of follicular keratinization. Isotretinoin is administered orally; peak serum drug concentrations occur approximately three hours after ingestion. The drug is widely distributed throughout body tissues and metabolized by the liver by oxidation and glucuronidation; both parent drug and metabolites are excreted in the urine and feces. Clinical trials of isotretinoin have shown the drug to be effective in treating cystic or conglobate acne that is unresponsive to therapy with oral or topical antibiotics, topical tretinoin, or topical benzoyl peroxide. Isotretinoin is unique in that acne remission continues after discontinuance of therapy. The most frequent adverse effects involve mucocutaneous tissues and include cheilitis, xerosis, xerostomia, dry nose, epistaxis, and pruritus. Other adverse effects--including some serious ones--have been found rarely in humans or animals receiving isotretinoin. The usual oral dosage of isotretinoin for patients with cystic acne is 1-2 mg/kg/day in two divided doses; administration should continue for 15-20 weeks. Isotretinoin is currently more expensive than other acne treatments. Isotretinoin is an effective agent for treating cystic acne; pending accumulation of further data, its use should be limited to patients with severe conditions that do not respond to older therapies because of isotretinoins cost and sometimes serious adverse effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I21,I21)","v":15134535},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B21:D21)","v":14},2004,"Retinoids in cancer chemoprevention.","Okuno",15134535,"Retinoids in cancer chemoprevention.    Abstract:   We review the therapeutic and preventive applications of a retinoid analog (vitamin A and its derivatives) for human cancers. Chemoprevention of cancer is an intervention in the carcinogenic process by chemical agents that block or reverse the malignant transformation of cells. Retinoids are prime candidates for cancer chemoprevention since cancer is characterized by abnormal growth with a lack of differentiation, which could be modified by retinoids. Retinoids exert their biological functions through nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR). A number of experimental and clinical studies have been performed in the past two decades with retinoids showing that they inhibit or reverse the carcinogenic process in some organs, including hematological malignancy as well as premalignant and malignant lesions in the oral cavity, head and neck, breast, skin and liver. We particularly focus upon the therapeutic application of all-trans RA (atRA) to acute promyelocytic leukemia (APL) and on the preventive approach to hepatocellular carcinoma (HCC) by a synthetic retinoid analog, acyclic retinoid. In both malignancies, malfunction of retinoid nuclear receptors is closely related to their carcinogenic process. In APL, a chromosomal translocation produces a chimeric protein between RAR alpha and a protein called promyelocyte leukemia protein (PML). PML-RAR alpha works as a dominant negative receptor in the leukemic cells, interfering with the normal function of RAR alpha and/or PML, which in turn results in the arrest of cell maturation at the stage of promyelocytes. Oral administration of atRA induces differentiation of promyelocytic leukemic cells to mature neutrophils, and leads to a high rates (over 90%) of complete remission. AtRA therapy has become standard in the treatment of APL. In the case of HCC, post-translational modification of RXR by phosphorylation impairs its function, which leads to uncontrolled cell growth. Acyclic retinoid suppresses the phosphorylation of RXR alpha, restores its function in the presence of its endogenous ligand, 9-cis RA, and thereby induces apoptosis of the cancer cells. Acyclic retinoid given orally successfully suppresses the development of second primary tumors in cirrhotic patients who undergo curative removal of preceding HCC. Eradication of (pre)malignant clones (clonal deletion) from the liver is suggested as a mechanism of the chemopreventive effect. Further development of more effective retinoids as well as their use in combination with other classes of anticancer agents including immunopreventive drugs like interferons may provide strategies for cancer prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I22,I22)","v":10721933},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B22:D22)","v":14},2000,"Advances in the development of retinoids as chemopreventive agents.","Lippman",10721933,"Advances in the development of retinoids as chemopreventive agents.    Abstract:   With the inclusion of brief discussions of retinoid drug development in animal carcinogenesis models (e.g., skin, breast, oral cavity, lung, prostate or bladder) and clinical trials (e.g., head and neck or cervix), this review will focus on recent advances in retinoid molecular targeting studies designed primarily to develop retinoids with reduced toxicity, while maintaining or enhancing activity in the context of chemoprevention. Major current retinoid molecular targets include the six known nuclear retinoid receptors (RAR and RXR). Receptor numbers, distinct functions, tissue-expression patterns, ligand specificities, functional redundancy and regulation of multiple pathways make retinoid signaling highly complex. Development of receptor-selective synthetic retinoids is a major focus of molecular retinoid development. RAR heterodimerize with RXR and mediate classic retinoid activity/toxicity. RXR are more promiscuous, heterodimerizing with several other members of the steroid receptor superfamily [e.g., peroxisome proliferator-activated receptors (PPAR) or vitamin D receptors]. RXR-selective ligands are less toxic and more active in animal breast cancer prevention studies and less toxic than RAR ligands in clinical trials. Other new avenues of retinoid molecular drug development include newly identified retinoid-regulated genes, orphan-receptor ligands/functions, novel retinoid mechanisms involving potent receptor-independent apoptosis-inducing activity (e.g., 4-HPR or anhydroretinol), synergistic combinations [e.g., RXR agonists plus selective estrogen receptor modulators (SERM)], activity in other diseases and novel delivery systems."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I23,I23)","v":10705921},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B23:D23)","v":14},1999,"Role of retinoid receptors in the prevention and treatment of breast cancer.","Yang",10705921,"Role of retinoid receptors in the prevention and treatment of breast cancer.    Abstract:   Retinoids are vitamin A-related compounds that have been found to prevent cancer in animals and humans. In this review, we discuss the role of retinoids and their receptors in the treatment and prevention of breast cancer. The retinoid receptors are expressed in normal and malignant breast cells, and are critical for normal development. In breast cells, when bound by retinoid hormones, these proteins regulate proliferation, apoptosis, and differentiation. The mechanism by which retinoids inhibit breast cell growth has not been completely elucidated, however, retinoids have been shown to affect multiple signal transduction pathways, including IGF-, TGFbeta-, and AP-1-dependent pathways. Retinoids have also been shown to suppress the growth and prevent the development of breast cancer in animals. These agents suppress tumorigenesis in carcinogen-treated rats and in transgenic mice, and inhibit the growth of transplanted breast tumors. These promising preclinical results have provided the rationale to test retinoids in clinical trials for the treatment and prevention of breast cancer. Several retinoids, including all trans retinoic acid and 9-cis retinoic acid, have been shown to have modest activity in the treatment of breast cancer, and these agents are now in clinical trials in combination with cytotoxic agents and anti-estrogens. Another retinoid, 4-HPR, is currently being tested in a human cancer prevention trial. Preliminary results suggest that 4-HPR may suppress breast cancer development in premenopausal women. Future clinical trials will focus on testing new synthetic retinoids that have reduced toxicity and enhanced therapeutic and preventive efficacy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I24,I24)","v":8923019},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B24:D24)","v":14},1996,"Retinoids as cancer-preventive agents.","Sankaranarayanan",8923019,"Retinoids as cancer-preventive agents.    Abstract:   Vitamin A and its metabolites play a crucial role in regulating the differentiation and proliferation of epithelial cells, and are potent inducers of apoptosis. The effects of retinoids are thought to be mediated through the metabolite retinoic acid, which binds to nuclear retinoic acid receptors that then interact with specific retinoic acid response elements. The development of cancers involves alterations in growth and differentiation of cells as a result of carcinogen-induced damage to DNA of regulatory genes. Most of the results from experimental animal studies indicate that retinoids are effective in preventing or suppressing cancers. Although the relationship between preformed vitamin A in the diet and epithelial cancers remains to be further clarified, a high intake of vegetables and fruits has been consistently associated with a lower risk of these cancers. This interesting biological activity profile of retinoids has prompted investigators to study them in the chemoprevention of epithelial cancers and in the treatment of advanced cancers. Although the therapeutic response of retinoids against advanced cancers is disappointing, they have emerged as promising chemopreventive agents, particularly in head and neck sites. Both natural and synthetic analogues of vitamin A have been shown to be effective in suppressing micronucleated cells, reversing oral leukoplakia, and preventing new and recurrent lesions in subjects with oral leukoplakia, as well as in reducing the occurrence of second primaries in treated head and neck cancer patients. They have not been consistently effective in suppressing either bronchial atypia or metaplasia, nor have they been proven effective in reducing the occurrence of recurrent lesions in treated skin cancer patients, although some activity has been demonstrated in reducing lesion counts in actinic keratoses. Vitamin A in combination with other micronutrients has not reduced incidence and mortality from oesophageal and stomach cancers. A synthetic retinoid, fenretinide, is currently being evaluated in preventing contralateral breast cancer in treated breast cancer patients. Toxicity has been a major concern with retinoids, as prolonged administration is required in chemoprevention studies. Available evidence indicates that natural analogues of retinoids are less toxic than synthetic compounds such as isotretinoin. Large studies are currently evaluating retinoids in the prevention of head and neck cancers and lung cancers. The outcome of these studies will be important in directing future research initiatives and in forming policies regarding the use of vitamin A compounds in the prevention of cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I25,I25)","v":7832047},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B25:D25)","v":14},1994,"The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation.","Ross",7832047,"The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation.    Abstract:   Recent advances in the molecular biology of the retinoids have provided a mechanistic explanation for the observations, first made several decades ago, that vitamin A profoundly influences the differentiation of tissues throughout the body. A central concept has recently emerged, namely that retinoids seldom exist quot;freequot; in solution but, rather, are nearly always associated with specific retinoid-binding proteins. In plasma, these include RBP and the chylomicron whereas, in cells two distinct classes of retinoid-binding proteins exist: the cellular (cytoplasmic) proteins (CRBPs and CRABPs) and the nuclear receptors proteins (RARs and RXRs). Whereas the cellular retinoid-binding proteins serve as buffers and as chaperones during metabolism (Ross, 1993b), the nuclear receptors are now recognized to be the direct mediators of retinoid actions on the genome. Both the cytoplasmic and nuclear classes of retinoid-binding proteins are expressed early in development and are proposed to control the concentration of retinoic acid and the transcription of retinoid-responsive genes, respectively. Given the profound effects of retinoic deficiency or excess on the developing fetus, it is not surprising that mechanisms have evolved to control the placental transfer of vitamin A. Transfer is nearly uniform over a rather wide range of maternal dietary vitamin A intake. The importance of RBP in transporting retinol to tissues is suggested by the observations that the visceral yolk sac and the liver of the fetus transcribe and translate RBP. In comparison to pregnancy, vitamin A transport during lactation is much more responsive to variations in maternal vitamin A intake. The young of mothers with good vitamin A nutriture may thus accumulate significant retinol reserves during the suckling period. Conversely, young nursed by mothers with poor vitamin A status and low intake during lactation may fail to develop adequate stores and be vulnerable to vitamin A deficiency if the post-weaning diet is also poor in vitamin A. In populations with low vitamin A status, the lactation period provides an excellent window of opportunity for supplementing mothers and, indirectly, their offspring, with vitamin A to replenish the mothers vitamin A reserves and assure that the infants growth and development are not limited by an inadequate quantity of this essential nutrient."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I26,I26)","v":25879031},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(B$3),\"\")))/LEN(B$3)","v":13},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B26:D26)","v":13},2015,"Vitamin A, cancer treatment and prevention: the new role of cellular retinol binding proteins.","Doldo",25879031,"Vitamin A, cancer treatment and prevention: the new role of cellular retinol binding proteins.    Abstract:   Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cells in vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients screening for a more personalized and efficacy retinoid therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I27,I27)","v":11118831},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(B$3),\"\")))/LEN(B$3)","v":13},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B27:D27)","v":13},2000,"Recent advances in the use of vitamin A (retinoids) in the prevention and treatment of cancer.","Niles",11118831,"Recent advances in the use of vitamin A (retinoids) in the prevention and treatment of cancer.    Abstract:   Vitamin A, its physiologic metabolites, and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. In addition, pharmacologic amounts of retinoids have been used with some success in the treatment of a few human tumors. The chemoprevention effect of retinoids is most likely exerted at the tumor-promotion phase of carcinogenesis. Retinoids block tumor promotion by inhibiting proliferation, inducing apoptosis, inducing differentiation, or a combination of these actions. Clinically, isotretinoin (13-cis-retinoic acid) significantly decreases the incidence of second primary tumors in patients with head-and-neck cancer and reduces appearance of non-melanoma skin cancer in patients with xeroderma pigmentosum. Retinoic acid has proved to be an effective treatment for promyelocytic leukemia. However, retinoid resistance limits its use as a single agent. Clinical trials are in progress to determine the efficacy of retinoids in treating other types of cancer such as neuroblastoma and breast carcinoma. The development of receptor-selective retinoids and selective inhibitors of retinoid metabolism may lead to further use of retinoids in both chemoprevention and treatment of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I28,I28)","v":9345570},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B28:D28)","v":13},1997,"[Teratogenic effects of vitamin A and its derivates].","Guillonneau",9345570,"[Teratogenic effects of vitamin A and its derivates].    Abstract:   Retinoids, the synthetic derivates of vitamin A, have a key role on cellular differentiation and developmental tissue specificity. Their effects are mediated by nuclear receptors which transactivate homeobox genes. They are teratogenic to animals and they all induce similar malformations dependent on the dose and the duration of exposure. This is a review of the teratogenic effects of vitamin A and its synthetic derivates--isotretinoin, acitretine and topical retinoids--in humans. High dose vitamin A have a potent teratogenic effect and are therefore contra-indicated during pregnancy. Isotretinoin is responsible for a syndrome including malformations of the central nervous system, heart and thymus, together with craniofacial defects. The incidence rate is high and comparable to thalidomide (ie, 25%). This high teratogenic potency justifies a strict limitation of such a prescription in women susceptible to become pregnant. Acitretine, which replaces etretinate because of its long half life of 120 days, might also be teratogenic in humans. In addition, it may be back transformed into etretinate, thus contraindicating pregnancy for 2 years after withdrawal. Finally, despite a low percutaneous resorption, available data on the use of retinoids as topicals are limited and their use during pregnancy is therefore not recommended. Although they are efficient in skin diseases, the use of retinoids in women of the child bearing age is very limited because of their potent teratogenic effect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I29,I29)","v":21198520},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B29:D29)","v":12},2010,"Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin.","Rademaker",21198520,"Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin.    Abstract:    BACKGROUND/OBJECTIVES : Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist.  METHODS : Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6-year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded.  RESULTS : One-fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose-dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide.  CONCLUSIONS : Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse-effect profile when used at lower doses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I30,I30)","v":17491551},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B30:D30)","v":12},2007,"Role of retinoids and their cognate nuclear receptors in breast cancer chemoprevention.","Brtko",17491551,"Role of retinoids and their cognate nuclear receptors in breast cancer chemoprevention.    Abstract:   Retinoids are natural and synthetic compounds related to retinoic acid that act through interaction with two basic types of nuclear receptors: retinoic acid receptors (RARalpha, RARbeta and RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) as ligand-activated, DNA-binding, transacting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Function of retinoids in organisms affecting broad spectrum of various biochemical and molecular biology reactions is unimaginable without fully functional nuclear receptors--retinoid inducible transcription factors. Retinoic acids exert tumour-suppressive activity due to their antiproliferative and apoptosis-inducing effects. A number of novel retinoids and rexinoids acting through cognate nuclear receptors have been tested both in vitro and in vivo, using cell culture or animal models for breast cancer. This article briefly summarizes the role and properties of nuclear retinoid/rexinoid receptors as well as selected effects of retinoic acids or selected synthetic retinoids and rexinoids with respect to their potential use in chemoprevention of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I31,I31)","v":16601279},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B31:D31)","v":12},2006,"Clinical trials with retinoids for breast cancer chemoprevention.","Zanardi",16601279,"Clinical trials with retinoids for breast cancer chemoprevention.    Abstract:   Retinoids have been studied as chemopreventive agents in clinical trials due to their established role in regulating cell growth, differentiation and apoptosis in preclinical models. Experimental evidence suggests that retinoids affect gene expression both directly, by activating and/or repressing specific genes, and indirectly, by interfering with different signal transduction pathways. Induction of apoptosis is a unique feature of fenretinide, the most widely studied retinoid in clinical trials on breast cancer chemoprevention due to its selective accumulation in breast tissue and to its favourable toxicological profile. In a phase III breast cancer prevention trial, fenretinide showed a durable trend to a reduction of second breast malignancies in premenopausal women. This pattern was associated with a favourable modulation of circulating IGF-I and its main binding protein (IGF-binding protein-3, IGFBP-3), which have been associated with breast cancer risk in premenopausal women in different prospective studies. In a subsequent biomarker study on premenopausal women who had participated in the phase III trial, high IGF-I and low IGFBP-3 baseline levels were found to predict second breast cancer risk, although the magnitude of their changes during treatment did not fulfil the requirements for suitable surrogate end-point biomarkers. In postmenopausal women, fenretinide did not reduce second breast cancer incidence, nor did it induce significant modulation of the IGF system. Similarly, fenretinide was not found to affect risk biomarkers significantly in early postmenopausal women on hormone replacement therapy, who are at increased risk of developing breast cancer. Biomarker studies of fenretinide alone or in combination with different nuclear receptor ligands are being conducted. In particular, clinical trials of fenretinide and tamoxifen have proved to be feasible, and this combination appears to be safe and well tolerated in high-risk women, especially when low-dose tamoxifen is employed. Novel retinoid X receptor-selective retinoids, or rexinoids, have been shown to suppress the development of breast cancer in several animal models with minimal toxicity, and are being intensively studied either alone or in combination with selective oestrogen receptor modulators, both in vitro and in vivo. The rexinoid, bexarotene, has recently been approved for the treatment of patients with cutaneous T-cell lymphoma, and a biomarker trial with bexarotene in women with high breast cancer risk is currently underway."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I32,I32)","v":14704336},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B32:D32)","v":12},2004,"Assessing vitamin A status: past, present and future.","Tanumihardjo",14704336,"Assessing vitamin A status: past, present and future.    Abstract:   Xerophthalmia classification was traditionally used to identify populations with vitamin A deficiency. Currently, night blindness and dark adaptometry have been proposed as population assessment methods. While eye signs and function tests are still used in areas where vitamin A deficiency is severe, a subclinical vitamin A deficiency is more prevalent. Serum and breast milk retinol concentrations are used to identify vitamin A deficiency risk. However, in healthy individuals, serum retinol concentrations are homeostatically controlled and do not begin to decline until liver reserves of vitamin A are dangerously low. Moreover, serum retinol and retinol binding protein (RBP) concentrations fall during times of infection. The RBP:transthyretin ratio may help to determine if serum retinol concentrations are depressed by infection. Other methods better reflect liver reserves of vitamin A, the quot;goldquot; standard. The relative dose response and modified relative dose response tests involve giving a small dose of retinyl or dehydroretinyl ester, respectively, and determining a response in the serum at about 5 h. A new response test where retinoyl beta-glucuronide is administered and the degree of hydrolysis to retinoic acid is measured has been investigated. Unlike isotope dilution tests, the dose response tests lack utility in defining the total body reserve of vitamin A. The deuterated retinol isotope dilution test has been used in several different groups. Recently, a new isotope assay was developed using 13C-retinyl acetate and gas chromatography-combustion-isotope ratio mass spectrometry for analysis. Thus, having many choices of vitamin A assessment methods, laboratory sophistication and resources available will usually dictate which methods are chosen."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I33,I33)","v":11255826},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(C$3),\"\")))/LEN(C$3)","v":8},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B33:D33)","v":12},2001,"quot;Be smart, be safe, be surequot;. The revised Pregnancy Prevention Program for women on isotretinoin.","Perlman",11255826,"quot;Be smart, be safe, be surequot;. The revised Pregnancy Prevention Program for women on isotretinoin.    Abstract:    OBJECTIVES : After studying the information in this article, the reader should be able to: 1. Describe the purpose of the pregnancy prevention program. 2. Discuss the five most common reasons for unintended pregnancy. 3. List the components of the expanded pregnancy prevention program. Preventing unintended pregnancy is currently an unsolved problem in the United States, especially among teens. However, successful programs to minimize unintended pregnancy do exist and can serve as a model for other efforts. One such program is the Pregnancy Prevention Program, for use when prescribing isotretinoin to women with childbearing potential. Isotretinoin is a known teratogen and is prescribed disproportionately to teens, who are at higher risk of unintended pregnancy. The program has shown impressive effectiveness despite these handicaps, but since exposure to isotretinoin is so harmful to the fetus and some women still become pregnant while taking the drug, the program has been revised to reduce the failure rate further."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I34,I34)","v":10942515},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B34:D34)","v":12},2000,"Retinoids and ovarian cancer.","Zhang",10942515,"Retinoids and ovarian cancer.    Abstract:   Each year, an estimated 26,000 women in the United States are diagnosed with ovarian cancer. During any given year, approximately 14,500 women die from this disease. Ovarian cancer is the seventh most common cancer in women worldwide, after breast, cervix, colon/rectum, stomach, corpus uteri, and lung cancers. In the U.S., ovarian cancer is the second most common gynecologic cancer, and is the fourth leading cause of solid tumor cancer deaths among women. Currently, postoperative chemotherapy of ovarian cancer is still suboptimal. Drug resistance is a common problem resulting in only 20 approximately 30% overall 5-year survival rates. Clearly, continued development of alternative therapeutic strategies is essential for the management of this fatal disease. A number of recent studies have suggested that retinoids may play a potential role as an ovarian cancer chemotherapeutic agent. Retinoids, the natural and synthetic derivatives of vitamin A, have been shown to inhibit the growth of human ovarian cancer cells both in vivo and in culture. This review will initially summarize what is known about the pathological and molecular characteristics of ovarian carcinoma. It will then describe retinoid metabolism and the role of the cellular and nuclear retinoid binding proteins in mediating retinoid action. Following this general review of retinoids and their function, data supporting the role of retinoic acid as a suppresser of ovarian carcinoma cell growth will be presented. Particular attention will be paid to studies suggesting that members of the RB family of proteins and RB2/p130, in particular, are the molecular targets responsible for retinoid mediated inhibition of ovarian carcinoma cell growth. This review will then conclude with a brief discussion of two synthetic retinoids, 4 HPR R(fenretinide) and AHPN/CD437, which have been shown to induce apoptosis in ovarian tumor cells. It will be clear from the studies summarized in this review that retinoids represent a potentially powerful alternative to present chemotherapeutic approaches to the treatment of late stage ovarian cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I35,I35)","v":1460123},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B35:D35)","v":12},1992,"Retinoids for the future: oncology.","DiGiovanna",1460123,"Retinoids for the future: oncology.    Abstract:   A major incentive for the development of the synthetic retinoids has been their potential for the treatment and prevention of cancer. Early studies demonstrated that treatment with isotretinoin or etretinate alone could result in the regression of some existing skin cancers. However, even at high doses the response rates were poor. Greater efficacy has been observed with retinoids used in the prevention of cancer of the skin and oral cavity in high-risk patients. The potential for retinoids as chemopreventive agents is being further explored as selected retinoids are being targeted to specific malignancies, such as fenretinide for breast cancer chemoprevention. The effectiveness of tretinoin as a treatment for promyelocytic leukemia has raised enthusiasm for retinoids as cancer therapeutic agents. Furthermore, evidence of synergy between the retinoids and a variety of cytokines as enhances of differentiation chart a bright future for retinoids in oncology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I36,I36)","v":1447394},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B36:D36)","v":12},1992,"Retinoids in cancer treatment.","Tallman",1447394,"Retinoids in cancer treatment.    Abstract:   Since initial studies identifying the important role of vitamin A and its derivatives (retinoids) in maintaining the integrity of epithelial tissues, these compounds have served as paradigms for experimental studies exploring the pharmacologic modification of carcinogenesis. Retinoids have clearly been shown to inhibit chemically induced mammary and urothelial carcinogenesis in experimental animals. Prohibitive toxicity of the parent compound, vitamin A, led to a systematic search for synthetic derivatives with an improved therapeutic index. More than 1500 such compounds have been synthesized, many retaining chemopreventive potential, but with less toxicity. Although several anecdotal reports confirming therapeutic benefits of cis-retinoic acid in patients with acute promyelocytic leukemia and myelodysplastic syndromes appeared in the late 1970s and early 1980s, the remarkable studies of Huang and his colleagues in China in 1988 reporting complete remissions in patients with this uncommon variety of acute myelogenous leukemia with the transisomer of retinoic acid (all-trans-retinoic acid) led to a resurgence of interest in the retinoids as differentiating agents for the prevention and therapy of cancer. Furthermore, molecular studies showing DNA rearrangements of the alpha nuclear receptor for retinoic acid located on chromosome 17 in patients with acute promyelocytic leukemia, a disease invariably associated with a translocation between chromosomes 15 and 17, provided a direct connection between an altered nuclear receptor and the development of a human malignancy. The retinoids also may have important beneficial effects in prevention of recurrent malignancies once the primary tumor has been treated, such as in squamous cell carcinoma of the head and neck. Because retinoids appear to be less effective in inducing differentiation in nonpromyelocytic leukemia cells, investigators have conducted a number of studies to exploit potential synergism between retinoids and other differentiating agents or biologic effectors. Differentiation therapy and chemoprevention are attractive alternative approaches to intensive cytotoxic chemotherapy. It is now clear that retinoids represent one class of compounds with which it may be possible to reverse the progression of malignant disease and prevent carcinogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I37,I37)","v":26215715},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B37:D37)","v":11},2015,"Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis.","Kaplan",26215715,"Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis.    Abstract:   Evaluation of human data regarding the outcomes of topical-retinoid-exposed pregnancies is important in terms of counselling pregnant women with inadvertent exposure. The objective of this study was thus to determine whether exposure to topical retinoids leads to an increase in the risk of adverse pregnancy outcomes. We carried out a search using the Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases from inception to 4 December 2014. The selection, review and quality assessment of the studies were carried out by two independent reviewers according to predetermined inclusion criteria. Odds ratios (ORs) were calculated by the random effects method. This meta-analysis, including a total of 654 pregnant women who were exposed to topical retinoids, and 1375 unexposed control pregnant women, did not detect significant increases in rates of major congenital malformations [OR 1·22, 95% confidence interval (CI) 0·65-2·29], spontaneous abortions (OR 1·02, 95% CI 0·64-1·63), stillbirth (OR 2·06, 95% CI 0·43-9·86), elective termination of pregnancy (OR 1·89, 95% CI 0·52-6·80), low birthweight (OR 1·01, 95% CI, 0·31-3·27) or prematurity (OR 0·69, 95% CI 0·39-1·23). No significant heterogeneity was detected among the studies for the evaluated outcomes. The present meta-analysis ruled out a major increase in the rates of major congenital malformations, spontaneous abortions, low birthweight and prematurity. This result may be used primarily in reassuring women who were inadvertently exposed to topical retinoids during their pregnancy. However, the statistical power is not adequate to justify the use of topical retinoids during pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I38,I38)","v":25520935},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B38:D38)","v":11},2014,"Retinoic acid and cancer treatment.","Chen",25520935,"Retinoic acid and cancer treatment.    Abstract:    NlmCategory=UNASSIGNEDRetinoic acid which belongs to the retinoid class of chemical compounds is an important metabolite of vitamin A in diets. It is currently understood that retinoic acid plays important roles in cell development and differentiation as well as cancer treatment. Lung, prostate, breast, ovarian, bladder, oral, and skin cancers have been demonstrated to be suppressed by retinoic acid. Our results also show that low doses and high doses of retinoic acid may respectively cause cell cycle arrest and apoptosis of cancer cells. Also, the common cell cycle inhibiting protein, p27, and the new cell cycle regulator, Cdk5, are involved in retinoic acids effects. These results provide new evidence indicating that the molecular mechanisms of/in retinoic acid may control cancer cells fates. Since high doses of retinoic acid may lead to cytotoxicity, it is probably best utilized as a potential supplement in ones daily diet to prevent or suppress cancer progression. In this review, we have collected numerous references demonstrating the findings of retinoic acid in melanoma, hepatoma, lung cancer, breast cancer, and prostate cancer. We hope these observations will shed light on the future investigation of retinoic acid in cancer prevention and therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I39,I39)","v":23322901},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B39:D39)","v":11},2013,"Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.","Connolly",23322901,"Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.    Abstract:   Retinoids and their naturally metabolized and synthetic products (e.g., all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (α, β, γ), which are transcriptional and homeostatic regulators with functions that are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their use in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high risk for breast cancer. Ongoing phase III randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARβ. Robust evaluation of RARβ and downstream genes may permit optimized use of retinoids in the solid tumor arena."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I40,I40)","v":15897377},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B40:D40)","v":11},2005,"Trends in adherence to a revised risk management program designed to decrease or eliminate isotretinoin-exposed pregnancies: evaluation of the accutane SMART program.","Brinker",15897377,"Trends in adherence to a revised risk management program designed to decrease or eliminate isotretinoin-exposed pregnancies: evaluation of the accutane SMART program.    Abstract:    OBJECTIVE : To review adherence to selected procedures outlined in the System to Manage Accutane-Related Teratogenicity (SMART) program during the first year of implementation vs the procedures in effect in the year prior to initiation of the SMART program.  DESIGN : Observational.  SETTING : A novel pharmacy compliance survey and an ongoing, voluntary survey.  PATIENTS : Female recipients of isotretinoin.  INTERVENTION : In April 2002, Hoffmann-La Roche Inc, Nutley, NJ, manufacturer of Accutane brand isotretinoin and at that time the sole source of isotretinoin, revised earlier guidelines and instituted the SMART risk management program, which included the use of qualification stickers to affix to all prescriptions for Accutane to indicate, among other things, a negative pregnancy test just before the prescription was written. The goal of the SMART program was to decrease or eliminate isotretinoin-exposed pregnancies.  MAIN OUTCOME MEASURES : Use and completion of prescription qualification stickers; changes in pretherapy pregnancy testing and birth control use.  RESULTS : The results of the pharmacy compliance survey indicated high (gt;90%) use of prescription qualification stickers. Results of the patient survey suggested that 9% of prescription qualification stickers within the observed user cohort were issued without a pregnancy test. Furthermore, the pregnancy rate for patients participating in the survey was similar to that reported for cohorts recruited before the SMART program.  CONCLUSIONS : The usefulness of the results derived from 2 surveys designed to evaluate the SMART program is limited by the lack of reliability and validity of the survey instruments and by questionable generalizability to all female recipients of isotretinoin. The presence of a qualification sticker may not have an impact on pregnancy testing or compliance with effective birth control behavior as outlined in the SMART program."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I41,I41)","v":12452454},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B41:D41)","v":11},2002,"Retinoid, retinoic acid receptor beta and breast cancer.","Yang",12452454,"Retinoid, retinoic acid receptor beta and breast cancer.    Abstract:   Retinoids have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoic acid (RA) can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. The regulation of cell growth and differentiation of normal, premalignant, and malignant cells by retinoids is mediated by the RA receptors (RARs) and retinoid X receptor. One of the target genes of retinoid receptors is RARbeta2. A growing body of evidence supports the hypotheses that the RARbeta2 gene is a tumor suppressor gene and the chemopreventive effects of retinoids are due to induction of RARbeta2. RARbeta2 expression is reduced in many malignant tumors including breast carcinoma. This paper will briefly discuss basic aspects of retinoids and retinoid acid receptor. In particular, we review what is now known for inactivation mechanism of RARbeta2 and its role in tumor cell growth inhibition."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I42,I42)","v":10489539},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B42:D42)","v":11},1999,"Synthesis and biological evaluation of butanoate, retinoate, and bis(2,2,2-trichloroethyl)phosphate derivatives of 5-fluoro-2-deoxyuridine and 2,5-difluoro-2-deoxyuridine as potential dual action anticancer prodrugs.","Xia",10489539,"Synthesis and biological evaluation of butanoate, retinoate, and bis(2,2,2-trichloroethyl)phosphate derivatives of 5-fluoro-2-deoxyuridine and 2,5-difluoro-2-deoxyuridine as potential dual action anticancer prodrugs.    Abstract:   A group of 3-O-butanoyl, 5-O-butanoyl, and 3,5-di-O-butanoyl esters of 5-fluoro-2-deoxyuridine (FDU), and 2,5-difluoro-2-deoxyuridine (DFDU), 3-O-retinoyl, and 3,5-di-O-retinoyl esters of FDU, and 5-O-bis(2,2,2-trichloroethyl)phosphoryl-FDU and its 3-O-butanoyl ester, was synthesized. These compounds were designed to act as double prodrugs that would serve as a depot to release two active drugs that act through different mechanisms. Thus, a nucleotide derivative of FDU or DFDU could act as a competitive inhibitor for thymidylate synthase, whereas retinoic acid and butyric acid would be expected to induce cell differentiation. The in vitro anticancer activities for these prodrugs were determined against a panel of nine tumor types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, breast) that encompassed about 60 human tumor cell lines. Structure-activity relationships indicate that O-butanoyl esters of FDU are approximately equipotent to FDU, the O-butanoyl esters of DFDU are less active than FDU, and the retinoyl and bis(2,2,2-trichloroethyl)phosphate derivatives of FDU exhibit comparable activity to FDU. In addition to their cytotoxic effect, 3-O-retinoyl-FDU (12) and 3-O-butanoyl-5-O-bis(2,2,2-trichloroethyl)phosphoryl-FD U (16) also induced in vitro cell differentiation of promyelocytic leukemia HL60 cells. These combined cytotoxic and cell differentiation effects exhibited by 12 and 16 produced greater morphological drug-induced granulation and neutrophil vacuolation, and more cell apoptosis, than observed upon exposure to either retinoic acid or sodium butanoate. Dose-escalation studies in mice showed that 12 or 16 did not induce any acute or chronic toxicity, change in plasma clinical chemistry parameters, or gross histapathological changes at 60 days following an initial dosage regimen of 0.013 mmol/kg i.p. for 7-consecutive days. The in vivo growth delay response of murine mammary EMT6 solid tumors suggests that 3-O-retinoyl-FDU (12) delays tumor growth relative to the other prodrugs investigated, sodium butyrate, retinoic acid, FDU, or a combination of retinoic acid and FDU. These preliminary results suggest that 3-O-retinoyl-FDU (12) warrants further in vivo investigation to determine its tissue biodistribution and pharmacokinetic parameters that would be of value in assessing its potential usefulness as an anticancer prodrug."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I43,I43)","v":9478050},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B43:D43)","v":11},1998,"Retinoids and their receptors in vertebrate embryogenesis.","Smith",9478050,"Retinoids and their receptors in vertebrate embryogenesis.    Abstract:   Vitamin A and its derivatives, the retinoids, participate in formation of diverse embryonic structures, including face, heart, eye, limb and nervous system. Studies of retinoid-deficient and -treated embryos, and of receptor null mutants, provide evidence that this participation involves interactions between retinoids and their receptors. Targeted retinoid application and retinoid deficiency, using in ovo avian embryos, has identified early cardiogenic contributions, including cardiocyte gene expression and differentiation, heart tube fusion and laterality, and segmental identity. Also useful is a mammalian model, which targets retinoid deficiency to distinct gestational windows, circumventing limitations of traditional deficiency studies and current null mutant technologies. Rat embryos made deficient in retinoids during gestational d 11.5-13.5 exhibit specific cardiac, limb, ocular and nervous system deficits. That many of the anomalies previously reported in retinoid receptor null mutants are observed in deficiency confirms that ligand-receptor interactions are essential for embryonic development. Other defects are novel, reemphasizing the functional redundancy of retinoid receptors and that retinoid receptors have multiple and overlapping contributions to morphogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I44,I44)","v":8075435},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B44:D44)","v":11},1994,"Teratogenic risk with etretinate and acitretin treatment.","Geiger",8075435,"Teratogenic risk with etretinate and acitretin treatment.    Abstract:   Etretinate (Tigason, Tegison) and its active metabolite acitretin (Neotigason, Soriatane) are known teratogens. Pregnancy should be avoided during treatment and until 2 years after treatment discontinuation. The question is discussed whether a dose or a blood concentration of the drug below which there is no teratogenic risk can be determined. Animal experimental and human pharmacokinetic data are reviewed. An evaluation of the outcomes of pregnancies which occurred in mothers exposed to etretinate or acitretin was performed. A threshold dose in human therapy below which there is no risk of congenital malformation cannot be determined based on animal experimental data. With regard to pharmacokinetics, there are currently no data suggesting that blood levels of the drug below the detection limit of 2 ng/ml are associated with a teratogenic risk. The most useful information is given by reports in women who were exposed to either retinoid before or during pregnancy. The data indicate that the risk of spontaneous abortion or congenital malformation is high when the drug is administered during the first trimester of pregnancy. After treatment discontinuation, the risk is low since the number of abnormalities seems not to exceed those observed in a general population. There are currently no available data which suggest that the pregnancy warnings are inappropriate in terms of duration of contraception."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I45,I45)","v":23559397},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B45:D45)","v":10},2013,"Important controversies associated with isotretinoin therapy for acne.","Wolverton",23559397,"Important controversies associated with isotretinoin therapy for acne.    Abstract:   Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drugs release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I46,I46)","v":12461777},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B46:D46)","v":10},2003,"Induction of senescence-associated growth inhibitors in the tumor-suppressive function of retinoids.","Roninson",12461777,"Induction of senescence-associated growth inhibitors in the tumor-suppressive function of retinoids.    Abstract:   Retinoids, physiological regulators of cell growth and differentiation, are used in the treatment or chemoprevention of several malignant diseases. This class of compounds can induce growth arrest or apoptosis in tumor cells. Permanent growth arrest of retinoid-treated cells is often assumed to result from retinoid-induced differentiation. Recent studies in breast carcinoma and neuroblastoma cells demonstrated that retinoids can stop tumor cell growth through the program of senescence rather than differentiation. Retinoid-induced tumor suppression is associated with the induction of multiple intracellular and secreted growth-inhibitory proteins. Most of these proteins were also found to be upregulated in senescent cells. The induction of senescence-associated growth inhibitors appears to be an indirect effect of retinoids. Elucidation of the mechanisms responsible for the induction of growth-inhibitory genes in retinoid-treated cells should help in developing agents that would mimic the antiproliferative effect of retinoids in retinoid-insensitive cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I47,I47)","v":9478273},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B47:D47)","v":10},1997,"Dietary retinoids and carotenoids in rodent models of mammary tumorigenesis.","Moon",9478273,"Dietary retinoids and carotenoids in rodent models of mammary tumorigenesis.    Abstract:   In this review of the scientific literature the relationship between retinoids, carotenoids, and mammary carcinogenesis is examined. Several retinoids have shown promise as chemopreventive agents against chemically induced mammary carcinogenesis in mice and especially in rats. The most promising retinoids are retinyl acetate (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide). In rats, dietary administration of these retinoids reduced tumor incidence and multiplicity, and increased the latency of DMBA or MNU-induced mammary cancers. In mice, 4-HPR reduced the number of hyperplastic alveolar nodules and the number of tumors in MTV- and MTV+ mice, respectively. Among retinoids, 4-HPR is at present the most promising analogue, due to its ability to concentrate in the mammary gland. The combination of 4-HPR with tamoxifen not only is more effective in suppressing breast cancer than either agent alone, but also inhibits the appearance of subsequent cancers following the surgical removal of the first tumor. These studies suggest that retinoids, like tamoxifen, may be applicable to the prevention of contralateral breast cancer in women who underwent breast cancer surgery. It is also becoming evident that differentiation therapy and chemoprevention can become attractive alternative approaches to intensive cytotoxic chemotherapy. The role of carotenoids in the prevention of mammary carcinogenesis, however, is ambiguous. Poor absorption and low levels of carotenoids that reach the target tissues complicate interpretation of data in rodent models of mammary carcinogenesis. Very few animal studies are presently available in which purified carotenoids were found effective against mammary carcinogenesis. These results do not justify undertaking clinical evaluation of individual carotenoids against breast cancer at this time."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I48,I48)","v":9201819},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B48:D48)","v":10},1997,"Vitamin A and its congeners.","Monga",9201819,"Vitamin A and its congeners.    Abstract:   Vitamin A (retinol) is a fat-soluble vitamin that is necessary for cell growth and differentiation. Excess vitamin A has been associated with teratogenic effects in animals and humans. Because vitamin A deficiency is very uncommon in the industrialized world, the current recommendation is that routine vitamin A supplementation is not necessary. If vitamin A supplements are used, they should be limited to less than 5,000 IU per day. Systemic administration of the naturally occurring retinoid tretinoin has been associated with birth defects, fetal resorption, and stillbirths in animals; however, topical use is not associated with increased birth defects and is classified as a category B drug during pregnancy. The synthetic retinoids isotretinoin, etretinate, and etretin are strictly contraindicated during pregnancy (category X) as they have been associated with teratogenic syndromes in humans. In addition, owing to the prolonged elimination half-life of aromatic retinoids, effective contraception should be used for at least 2 years following discontinuation of treatment with these drugs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I49,I49)","v":8137334},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B49:D49)","v":10},1994,"Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide.","Costa",8137334,"Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide.    Abstract:   Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s. This retinoid shows a preferential accumulation in breast instead of liver, is effective in the inhibition of chemically induced mammary carcinoma in rats, and has proved to be less toxic than many other vitamin A analogues. The Milan Cancer Institute has put a particular effort in this molecule in both the experimental and clinical fields. We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast. To date, 2969 stage I breast cancer patients have been randomized to evaluate the efficacy of this retinoid to prevent contralateral new primaries, 709 subjects have been accrued in a prevention trial of basal cell carcinoma of the head and neck, and 153 patients entered a study the preliminary results of which already show the capability of fenretinide to prevent recurrences and new localizations of oral leukoplakia. Further studies on fenretinide will be aimed at evaluating its preventive efficacy in superficial bladder and prostate cancers and at exploring possible synergism with tamoxifen and interferons in breast cancer and skin cancer, respectively."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I50,I50)","v":7808027},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B50:D50)","v":10},1994,"Breast cancer and fenretinide, an analogue of vitamin A.","Cobleigh",7808027,"Breast cancer and fenretinide, an analogue of vitamin A.    Abstract:   Preclinical studies make fenretinide attractive for prevention and treatment of breast cancer. It inhibits mammary gland end bud formation in developing animals. Carcinogen-induced mammary cancer is suppressed by fenretinide, both at early and late stages of carcinogenesis, in young and mature rats. Fenretinide causes regression of invasive rat mammary cancer. Cytostatic activity has been demonstrated against human breast cancer cell lines. Autocrine stimulation of human breast cancer cell lines by tgf-alpha, insulin-like growth factors I and II is significantly abrogated by fenretinide. The human half-life is 24 hours. Absorption is markedly affected by meal content. Serum levels of 1 mM are achieved at doses of 200 mg/day. This dose significantly suppresses serum IGF-I levels in women. This concentration is capable of suppressing human breast cancer growth in vitro. A 3-day drug holiday is given each month in order to restore serum retinol levels. Under these circumstances, fenretinide is well tolerated. A phase III trial evaluating the efficacy of fenretinide for breast cancer prevention in high-risk women has been completed. Tamoxifen enhances the effectiveness of fenretinide in carcinogenesis models. The combination can be safely administered to women. A phase III adjuvant trial of tamoxifen, with or without fenretinide will be conducted in the United States."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I51,I51)","v":1551141},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B51:D51)","v":10},1992,"Retinoids as chemopreventive agents for breast cancer.","Moon",1551141,"Retinoids as chemopreventive agents for breast cancer.    Abstract:   Although several retinoids have been evaluated for prevention of mammary carcinogenesis in rats and mice, retinyl acetate (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) proved most effective. In rats, dietary administration of the retinoids reduced the incidence and number, and increased the latency of N-methyl-N-nitrosourea (MNU)-induced mammary cancers. 4-HPR reduced the number of hyperplastic alveolar nodules (HAN) in MTV- mice and the number of tumors in MTV+ mice. Other studies indicate that the synergistic effect of retinoid administration and hormonal deprivation is more efficacious in prevention of MNU-induced mammary cancer than either modality alone. Furthermore, retinoids alone and the combination of retinoid and tamoxifen inhibit the appearance of mammary cancers following the surgical removal of the first cancer as well as inhibit the growth of established cancers. Again, the combined modality was the most effective. Retinoids also exert an antiproliferative effect upon the mammary epithelium in vivo, which is represented morphologically by a bare duct system with little branching, end buds, and few, if any, alveoli. In organ culture, retinoids inhibit mammary end bud differentiation and proliferation induced by insulin and prolactin or carcinogens."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I52,I52)","v":2672772},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B52:D52)","v":10},1989,"Retinol (vitamin A) and the neonate: special problems of the human premature infant.","Zachman",2672772,"Retinol (vitamin A) and the neonate: special problems of the human premature infant.    Abstract:   Retinol stores accumulate in fetal tissue during gestation. Hence, the premature infant faces extrauterine adaptation with less total reserves of retinol than does the term infant. Retinol-binding protein in serum is also lower in the premature infant population. The parenteral retinol supplementation frequently required for these infants has only recently become adequate by the finding of methods to avoid large losses of retinol onto intravenous tubing. Retinol is an essential vitamin for epithelial cell function; nearly 40% of lung cells are of epithelial origin. The premature infants lung often is the initial site of difficulties during extrauterine adaptation, and respiratory system epithelial-cell damage and chronic lung disease frequently develop. Because these infants have associated low retinol reserves, retinol supplementation to help repair pulmonary injury is being considered. Some of these relationships are beginning to be clarified by basic research on the metabolism and function of retinol in lung."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I53,I53)","v":770206},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B53:D53)","v":10},1976,"Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids).","Sporn",770206,"Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids).    Abstract:   An approach to chemoprevention of common forms of epithelial cancer, during the period of preneoplasia, is described. Vitamin A and its synthetic analogs (retinoids) are potent agents for control of cell differentiation in many epithelial tissues. Direct effects of retinoids on normal and preneoplastic cell differentiation can be measured in organ culture. In experimental animals, deficiency of dietary retinoids enhances susceptibility to chemical carcinogenesis. Natural retinoids, fed at high dietary levels, have some ability to prevent chemical carcinogenesis in epithelial tissues of bronchi, trachea, stomach, uterus, and skin of experimental animals. However, natural retinoids have limited usefulness for chemoprevention of cancer because of inadequate tissue distribution and excessive toxicity. Synthetic retinoids have been made and shown to be more potent and less toxic for prevention of cancer in animals. Several structural modifications of the ring and terminal portions of the retinoid molecule have significant biological activity; modification of the side chain has been more difficult. The potential future usefulness of this approach to cancer prevention in man will depend on further synthetic modification of the retinoid molecule."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I54,I54)","v":24480385},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B54:D54)","v":9},2014,"Retinoids and breast cancer: from basic studies to the clinic and back again.","Garattini",24480385,"Retinoids and breast cancer: from basic studies to the clinic and back again.    Abstract:   All-trans retinoic acid (ATRA) is the most important active metabolite of vitamin A controlling segmentation in the developing organism and the homeostasis of various tissues in the adult. ATRA as well as natural and synthetic derivatives, collectively known as retinoids, are also promising agents in the treatment and chemoprevention of different types of neoplasia including breast cancer. The major aim of the present article is to review the basic knowledge acquired on the anti-tumor activity of classic retinoids, like ATRA, in mammary tumors, focusing on the underlying cellular and molecular mechanisms and the determinants of retinoid sensitivity/resistance. In the first part, an analysis of the large number of pre-clinical studies available is provided, stressing the point that this has resulted in a limited number of clinical trials. This is followed by an overview of the knowledge acquired on the role played by the retinoid nuclear receptors in the anti-tumor responses triggered by retinoids. The body of the article emphasizes the potential of ATRA and derivatives in modulating and in being influenced by some of the most relevant cellular pathways involved in the growth and progression of breast cancer. We review the studies centering on the cross-talk between retinoids and some of the growth-factor pathways which control the homeostasis of the mammary tumor cell. In addition, we consider the cross-talk with relevant intra-cellular second messenger pathways. The information provided lays the foundation for the development of rational and retinoid-based therapeutic strategies to be used for the management of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I55,I55)","v":22742601},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(C$3),\"\")))/LEN(C$3)","v":9},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B55:D55)","v":9},2012,"Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis.","Thorne-Lyman",22742601,"Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis.    Abstract:   Vitamin A (VA) deficiency during pregnancy is common in low-income countries and a growing number of intervention trials have examined the effects of supplementation during pregnancy on maternal, perinatal and infant health outcomes. We systematically reviewed the literature to identify trials isolating the effects of VA or carotenoid supplementation during pregnancy on maternal, fetal, neonatal and early infant health outcomes. Meta-analysis was used to pool effect estimates for outcomes with more than one comparable study. We used GRADE criteria to assess the quality of individual studies and the level of evidence available for each outcome. We identified 23 eligible trials of which 17 had suitable quality for inclusion in meta-analyses. VA or beta-carotene (βC) supplementation during pregnancy did not have a significant overall effect on birthweight indicators, preterm birth, stillbirth, miscarriage or fetal loss. Among HIV-positive women, supplementation was protective against low birthweight (lt;2.5 kg) [risk ratio (RR) = 0.79 [95% confidence interval (CI) 0.64, 0.99]], but no significant effects on preterm delivery or small-for-gestational age were observed. Pooled analysis of the results of three large randomised trials found no effects of VA supplementation on neonatal/infant mortality, or pregnancy-related maternal mortality (random-effects RR = 0.86 [0.60, 1.24]) although high heterogeneity was observed in the maternal mortality estimate (I(2) = 74%, P = 0.02). VA supplementation during pregnancy was found to improve haemoglobin levels and reduce anaemia risk (lt;11.0 g/dL) during pregnancy (random-effects RR = 0.81 [0.69, 0.94]), also with high heterogeneity (I(2) = 52%, P = 0.04). We found no effect of VA/βC supplementation on mother-to-child HIV transmission in pooled analysis, although some evidence suggests that it may increase transmission. There is little consistent evidence of benefit of maternal supplementation with VA or βC during pregnancy on maternal or infant mortality. While there may be beneficial effects for certain outcomes, there may also be potential for harm through increased HIV transmission in some populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I56,I56)","v":22050373},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B56:D56)","v":9},2012,"Implementation of the harmonized EU isotretinoin Pregnancy Prevention Programme: a questionnaire survey among European regulatory agencies.","Crijns",22050373,"Implementation of the harmonized EU isotretinoin Pregnancy Prevention Programme: a questionnaire survey among European regulatory agencies.    Abstract:    BACKGROUND : There is little information on the status of the implementation of the isotretinoin Pregnancy Prevention Programme (PPP) in the EU, and on compliance with this programme by the regulatory agencies.  OBJECTIVE : The aim of the study was to obtain information on implementation of the harmonized PPP of isotretinoin in the EU member states plus Norway and Iceland.  MATERIALS AND METHODS : In January 2009, a questionnaire (request for non-urgent information [NUI]) was sent to all 25 EU member states, plus Norway and Iceland, to collect information on the implementation status of the PPP and its effectiveness.  RESULTS : The response rate was 82% (22 of the 27 countries). In 21 of the 27 member states, isotretinoin is marketed and the PPP is in force, and in 18 of the 22 responding countries, the total required elements (seven) following a formal EU review are incorporated in the PPP. Seven member states had additional measures in place. In spite of implementation of the PPP and additional measures, a total of 143 isotretinoin-exposed pregnancies have been reported in 16 of the 22 responding member states since implementation of the harmonized PPP.  CONCLUSIONS : Despite implementation of the isotretinoin PPP in most member states, isotretinoin-exposed pregnancies were reported. This has led some member states to implement additional measures to the PPP, resulting in inconsistency with the approach agreed in 2003 following the European-wide review. It has been further suggested that common elements should be developed for PPPs for all medicines that are known to carry a high teratogenic risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I57,I57)","v":21621637},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B57:D57)","v":9},2012,"Maternal-fetal transfer and metabolism of vitamin A and its precursor β-carotene in the developing tissues.","Spiegler",21621637,"Maternal-fetal transfer and metabolism of vitamin A and its precursor β-carotene in the developing tissues.    Abstract:   The requirement of the developing mammalian embryo for retinoic acid is well established. Retinoic acid, the active form of vitamin A, can be generated from retinol and retinyl ester obtained from food of animal origin, and from carotenoids, mainly β-carotene, from vegetables and fruits. The mammalian embryo relies on retinol, retinyl ester and β-carotene circulating in the maternal bloodstream for its supply of vitamin A. The maternal-fetal transfer of retinoids and carotenoids, as well as the metabolism of these compounds in the developing tissues are still poorly understood. The existing knowledge in this field has been summarized in this review in reference to our basic understanding of the transport and metabolism of retinoids and carotenoids in adult tissues. The need for future research on the metabolism of these essential lipophilic nutrients during development is highlighted. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I58,I58)","v":14585058},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B58:D58)","v":9},2003,"Fenretinide: a prototype cancer prevention drug.","Malone",14585058,"Fenretinide: a prototype cancer prevention drug.    Abstract:   Fenretinide (N-4-hydroxyphenylretinamide [4-HPR]) is a synthetic retinoid that has been examined in in vitro assays, preclinical animal models and clinical trials as a cancer chemopreventive agent. Its pharmacology, toxicity and mechanisms of action initially suggested an increased therapeutic index relative to native retinoids for the control of tumours of the breast, prostate, bladder, colon, cervix and head and neck. Although fenretinide at the doses and schedules used in several pivotal Phase II and III clinical trials has not been proven to be efficacious in reducing the incidence of cancer or in retarding the development of preneoplastic lesions, encouraging observations regarding unanticipated preventative activity, such as for ovarian cancer control, have arisen from these studies. Research in cancer therapy and the elucidation of molecular pathways activated by fenretinide have also yielded clues about how this agent might be better used in a prevention setting. Current trials are underway to re-examine both dose and schedule of fenretinide administration as well as the target tissues of interest. Investigations of potential synergism between fenretinide and other candidate chemopreventative molecules with complementary mechanisms of action may support future assessments of this prototype cancer prevention drug or its newer analogues."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I59,I59)","v":11434448},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B59:D59)","v":9},2001,"Chemoprevention of breast cancer with fenretinide.","Torrisi",11434448,"Chemoprevention of breast cancer with fenretinide.    Abstract:   Chemoprevention of cancer represents a challenge for oncology during this new millennium. Substantial advances have been accomplished in the last decade, especially for primary and secondary prevention of breast cancer. In addition to tamoxifen, raloxifene and other selective estrogen receptor modulators, retinoids are among the most promising agents, given their ability to inhibit mammary carcinogenesis in preclinical models. Fenretinide, the synthetic amide of retinoic acid, inhibits cell growth mostly through the induction of apoptosis with mechanisms which may partly involve the retinoid receptors. Because it has a favourable toxicological profile, fenretinide has been extensively investigated in clinical trials. A large randomised phase III trial for secondary breast cancer prevention has been recently carried out in Italy. Results showed a reduction of second breast malignancies in premenopausal women. In addition, a significant decrease of circulating insulin-like growth factor (IGF)-1, a known risk factor for premenopausal breast cancer, was observed after 1 year of fenretinide administration in premenopausal women with breast cancer. Ongoing studies on the validation of the circulating IGF-1 as a surrogate endpoint biomarker of fenretinide activity and on the effectiveness of the combination with low dose tamoxifen may provide further insight into the future clinical application of fenretinide."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I60,I60)","v":9891904},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B60:D60)","v":9},1998,"Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data.","van Hoogdalem",9891904,"Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data.    Abstract:    BACKGROUND : Apart from oral drug treatment, drug therapy in acne vulgaris comprises topical treatment with agents with a primarily keratolytic action (e.g. tretinoin and benzoylperoxide), and with antibiotics (clindamycin, erythromycin, and erythromycin-zinc complex). The acne grade in the particular patient usually determines the selection of the preferred route of administration, viz. topical or oral, or a combination of both, and topical treatment is usually preferred in mild to moderate acne. The fact that a topically applied compound may also become systemically available to a quantifiable extent, is not generally considered.  AIM : The present paper reviews the clinical data on transdermal uptake of anti-acne agents in man, also with respect to their relevance for daily clinical practice.  OUTCOME : The majority of published data on transdermal penetration of topical anti-acne agents focuses on the retinoid tretinoin, and on the antimicrobial agent clindamycin. This interest emerges from the fact that these agents have been associated with embryotoxicity/teratogenicity, and pseudomembranous colitis, respectively. For both compounds the extent of systemic availability after topical application is low, viz. 5-7% and 8%, respectively, at its highest. The height and variability in endogenous retinoid levels is very likely to outweigh any contribution of exogenously applied tretinoin, but a full consensus on the safe use of topical tretinoin in pregnancy is still lacking. With respect to clindamycin, the suggested association between its topical use and the occurrence of pseudomembranous colitis appears not to be of clinical relevance. In order to reduce systemic exposure to clindamycin as much as possible, topical application of clindamycin phosphate is to be preferred over clindamycin hydrochloride salt. Regarding other topical anti-acne agents, it has been suggested that topical zinc-erythromycin is to be preferred over erythromycin, both from clinical efficacy and safety viewpoints. With respect to the currently used compounds like benzoylperoxide, azelaic acid, and adapalene, available clinical pharmacokinetic data are scarce, and significant safety concerns did not emerge as yet.  CONCLUSION : The limited transdermal uptake of topical anti-acne agents underpins their safe use in daily clinical practice. With respect to topical retinoids, formal consensus is lacking regarding their use in pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I61,I61)","v":9279062},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B61:D61)","v":9},1997,"Retinoyl beta-glucuronide: a biologically active form of vitamin A.","Barua",9279062,"Retinoyl beta-glucuronide: a biologically active form of vitamin A.    Abstract:   Retinoyl beta-glucuronide is a naturally occurring, biologically active metabolite of vitamin A. Although retinoyl beta-glucuronide is regarded as a detoxification product of retinoic acid, it plays several roles in the functions of vitamin A. It can serve as a source of retinoic acid, and it may be a vehicle for transport of retinoic acid to target tissues. Topically applied retinoyl beta-glucuronide is comparable in efficacy to retinoic acid in the treatment of acne in humans, without the same side effects. Retinoyl beta-glucuronide may or may not be teratogenic, depending on the mode of administration and the species in which it is used. It may be a valuable therapeutic compound for the treatment of skin disorders and certain types of cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I62,I62)","v":8538183},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B62:D62)","v":9},1995,"Retinoids and chemoprevention: clinical and basic studies.","Lippman",8538183,"Retinoids and chemoprevention: clinical and basic studies.    Abstract:   Retinoids, which include natural vitamin A (retinol) and its esters and synthetic analogues, are the best-studied class of agents in chemoprevention. There are more than 4,000 different retinoids which have a wide spectrum of preclinical activities, structures, pharmacological profiles, tissue distributions, receptor specificities, and toxicities. A number of retinoids have significant activity in many in vivo experimental systems including skin, bladder, lung, breast and oral carcinogenesis. In clinical trials, several retinoids have achieved significant activity in the reversal of head and neck, skin, and cervical premalignancy, and in the prevention of second primary tumors associated with head and neck, skin, and non-small cell lung cancer. Since 1984, our group has conducted a series of clinical trials to explore the chemopreventive potential of 13-cis-retinoic acid (13cRA) in the aerodigestive tract. We have conducted two consecutive randomized studies in subjects with premalignant lesions of the oral cavity. These studies showed that high-dose 13cRA alone can achieve significant short-term reversal of oral premalignancy, and that high-dose followed by low-dose 13cRA can maintain suppression of oral carcinogenesis. Three other randomized trials have confirmed significant retinoid activity in this human carcinogenic system. We also developed a randomized, placebo-controlled trial of adjuvant high-dose 13cRA in patients with head and neck cancer. Second primary tumor development was significantly decreased in the 13cRA group, but 13cRA had no impact on primary disease recurrence or survival. This presentation will update the current status of clinical trials and correlative laboratory studies of potential intermediate endpoint biomarkers in retinoid chemoprevention of aerodigestive tract carcinogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I63,I63)","v":7544060},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B63:D63)","v":9},1995,"Human cervical cancer. Retinoids, interferon and human papillomavirus.","Eckert",7544060,"Human cervical cancer. Retinoids, interferon and human papillomavirus.    Abstract:   Our studies highlight the importance of dietary vitamin A (retinol) and other retinoids in maintaining normal cervical cell function and in inhibiting the growth of cervical tumors. Based on our results we conclude that 1) HPV 16-immortalization enhances cervical cell sensitivity to retinoids, 2) cytokeratin expression may be useful as a marker for evaluating the success of retinoid therapy in vivo, 3) retinoids do not necessarily act to inhibit proliferation of HPV-immortalized cervical cells via effects on HPV E6 and E7 RNA levels and 4) retinoids may act to inhibit cervical proliferation by quot;suppressingquot; the activity of the EGF and IGF signalling pathways. Based on these and other results, it is worth considering the possibility that vitamin A or related retinoids could be administered therapeutically, early in the neoplastic process (either systemically or locally), to inhibit the progress of the disease. These results also suggest that combined interferon/retinoid therapy may provide an enhanced beneficial effect to reduce cervical tumor size due to the fact that each agent is inhibiting cervical cell proliferation via distinct, but reinforcing, pathways (i.e., IFN gamma reduces E6/E7 expression, RA inhibits the function of the EGF and IGF1 signalling pathways)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I64,I64)","v":7934176},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B64:D64)","v":9},1994,"Solid tumours--chemoprevention with retinoids.","Man",7934176,"Solid tumours--chemoprevention with retinoids.    Abstract:   There is a clear change in the treatment strategies for solid tumours towards the treatment of early rather than advanced disease. Retinoids represent a potentially useful class of drugs in chemoprevention. Preclinical data and clinical experience suggests that different retinoids may have different spectra of antitumour activity and synergistic interactions between retinoids and cytokines have also been reported. 13-cis retinoic acid has shown some promising activity in preventing the onset of second primary tumours in head and neck cancer and fenretinide is being tested in the prevention of second primary breast cancers. An understanding fo the role of the different retinoid receptors could lead to the design of compounds with a better therapeutic index. Despite these early indications that retinoids could be useful in this area, the development of such drugs is far from easy. Appropriate study designs for screening differentiating agents in the clinic, and the relevance of preclinical models of chemoprevention are challenges to be addressed. Unresolved issues include optimal patient selection, long clinical trial times, optimal dose, schedule and treatment duration. The use of biological surrogate markers for longer time-dependent trial endpoints could significantly contribute to more rapid development. Ongoing clinical studies, particularly in tobacco-related diseases, will better define the role of retinoids in this clinical setting. Clinicians should be encouraged to enter patients into large well organized clinical studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I65,I65)","v":1877746},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B65:D65)","v":9},1991,"A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step.","Duester",1877746,"A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step.    Abstract:   Ethanol acts as a teratogen causing brain, craniofacial, and limb abnormalities in those suffering from fetal alcohol syndrome. Normal embryonic development of the vertebrate nervous system and limbs has recently been shown to be governed by retinoic acid, the active form of vitamin A. Retinol dehydrogenase is an enzyme needed to convert vitamin A (retinol) to retinoic acid, a molecule that specifies embryonic pattern formation by controlling gene expression. Ethanol acts as a competitive inhibitor of the retinol dehydrogenase activity attributed to mammalian alcohol dehydrogenase (ADH), an enzyme that uses both retinol and ethanol as substrates. An hypothesis is presented in which many of the abnormalities observed in fetal alcohol syndrome may be caused by high levels of ethanol acting as a competitive inhibitor of ADH-catalyzed retinol oxidation in the embryo or fetus. This would presumably result in a reduction of retinoic acid synthesis in embryonic tissues such as the nervous system and limbs that require critical levels of this molecule to specify spatial patterns."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I66,I66)","v":6101134},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B66:D66)","v":9},1982,"The roles of vitamin E and unsaturated fatty acids in the visual process.","Robison",6101134,"The roles of vitamin E and unsaturated fatty acids in the visual process.    Abstract:   Relatively high proportions of long-chain, polyunsaturated fatty acids seem to be required in rod photoreceptor membranes in order to provide the precise microenvironment for the proper function of the visual pigment rhodopsin. At the same time, such high levels of lipid unsaturation put the photoreceptor membranes at a high risk for autoxidation. The antioxidant vitamin E which can minimize autoxidation of polyunsaturated fatty acids is found in rather high concentrations in the outer segment membranes. Dietary deficiency in vitamin E induces disintegration of rod outer segment membranes, probably by increasing autoxidation. Also, it greatly accelerates the accumulation of aging pigments in the retinal pigment epithelium, probably because these lipofuscin granules do indeed represent the end products of lipid peroxidation. Vitamin E supplements, up to threefold normal levels, appear to provide no significant protection of the retina from light damage produced either by short but acute or by long-term, low level exposures to light. This is not consistent with current theories which implicate lipid peroxidation in the destruction of rod outer segments in light damaged retinas; more work is needed before any relation between retinal light damage and vitamin E levels can be assessed. Surprisingly, the amount of lipofuscin granule accumulation in the retinal pigment epithelium is influenced dramatically by dietary levels of vitamin A. Even retinas lacking a source of polyunsaturated fatty acids from rod outer segments still may accumulate massive lipofuscin if dietary vitamin A is provided. Perhaps vitamin A, which has such a dynamic relationship with the retinal pigment epithelium, becomes oxidized, and then contributes to the formation of a lipofuscin-like pigment. Centrophenoxine, a drug claimed to be effective in reversing the accumulation of age-related lipofuscin in the central nervous system, has no obvious effect in the eye or uterus in removing the lipofuscin granules induced by vitamin E deficiency. Microperoxisomes are abundant in the retinal pigment epithelium, and may be associated with rapid lipid turnover and/or utilization of lipid soluble vitamins. Their potential roles, however, need further documentation and clarification. Recently developed techniques and new discoveries in lipid research open the way for many fruitful studies on the interactions and precise roles of lipids and lipid-soluble vitamins in vision."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I67,I67)","v":27336223},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B67:D67)","v":8},2016,"Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.","Marchwicka",27336223,"Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.    Abstract:    INTRODUCTION : Differentiation therapy using all-trans retinoic acid (ATRA) revolutionised the treatment of acute promyelocytic leukaemia to such an extent that it is now one of the most curable types of leukaemia, with ATRA and anthracycline-based chemotherapy providing cure rates above 80%. Isotretinoin is used to treat chronic acne. Here, we examine the information described in recent patents and the extent to which new findings are influencing extending retinoid-based differentiation therapy to other cancers, as well as the development of new therapies for other disorders.  AREAS COVERED : A search has been performed on the literature and worldwide patents filed during 2014 to the present time, focusing on synthetic agonists and antagonists of retinoic acid receptors and novel compositions for the delivery of these agents.  EXPERT OPINION : New potential therapeutic applications have been described, including lung, breast and head and neck cancers, T cell lymphoma and neurodegenerative, metabolic, ophthalmic, muscle, and inflammatory disorders. Recent patents have described the means to maximise retinoid activity. Two decades of efforts to extend retinoid-based therapies have been disappointing and new synthetic retinoids, target diseases and modes of delivery may well resolve this long standing issue."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I68,I68)","v":21249660},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(C$3),\"\")))/LEN(C$3)","v":8},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B68:D68)","v":8},2011,"Vitamin supplementation for preventing miscarriage.","Rumbold",21249660,"Vitamin supplementation for preventing miscarriage.    Abstract:    BACKGROUND : Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage.  OBJECTIVES : The objectives of this review are to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage, maternal adverse outcomes and fetal and infant adverse outcomes.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 June 2010).  SELECTION CRITERIA : All randomised and quasi-randomised trials comparing one or more vitamins with either placebo, other vitamins, no vitamins or other interventions, prior to conception, periconceptionally or in early pregnancy (less than 20 weeks gestation).  DATA COLLECTION AND ANALYSIS : At least two review authors independently assessed trials for inclusion, extracted data and assessed trial quality.  MAIN RESULTS : We identified 28 trials assessing supplementation with any vitamin(s) starting prior to 20 weeks gestation and reporting at least one primary outcome that was eligible for the review. Overall, the included trials involved 96,674 women and 98,267 pregnancies. Three trials were cluster randomised and combined contributed data for 62,669 women and 64,210 pregnancies in total. No significant differences were seen between women taking any vitamins compared with controls for total fetal loss (relative risk (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.14), early or late miscarriage (RR 1.09, 95% CI 0.95 to 1.25) or stillbirth (RR 0.86, 95% CI 0.65 to 1.13) and most of the other primary outcomes, using fixed-effect models. Compared with controls, women given any type of vitamin(s) pre or peri-conception were more likely to have a multiple pregnancy (RR 1.38, 95% CI 1.12 to 1.70, three trials, 20,986 women).  AUTHORS CONCLUSIONS : Taking any vitamin supplements prior to pregnancy or in early pregnancy does not prevent women experiencing miscarriage or stillbirth. However, women taking vitamin supplements may be more likely to have a multiple pregnancy. There is insufficient evidence to examine the effects of different combinations of vitamins on miscarriage, stillbirth or other maternal and infant outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I69,I69)","v":17428163},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B69:D69)","v":8},2007,"Synthetic retinoid fenretinide in breast cancer chemoprevention.","Bonanni",17428163,"Synthetic retinoid fenretinide in breast cancer chemoprevention.    Abstract:   Preclinical models suggest that retinoids inhibit mammary carcinogenesis. The induction of apoptosis is a unique feature of fenretinide, the most-studied retinoid in clinical trials of breast cancer chemoprevention, owing to its selective accumulation in breast tissue and its favorable toxicological profile. In a Phase III breast cancer prevention trial, fenretinide showed a strong trend of reduction of incidence of second breast malignancies in premenopausal women, which was confirmed by 15 years of follow-up. This warrants further research on the mechanisms of action and potential efficacy of fenretinide and provides the rationale for a Phase III primary prevention trial in young women at high risk for breast cancer. This review will highlight the role of fenretinide in breast cancer chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I70,I70)","v":15846697},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(C$3),\"\")))/LEN(C$3)","v":8},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B70:D70)","v":8},2005,"Vitamin supplementation for preventing miscarriage.","Rumbold",15846697,"Vitamin supplementation for preventing miscarriage.    Abstract:    BACKGROUND : Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage.  OBJECTIVES : The objectives of this review are to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage, maternal adverse outcomes and fetal and infant adverse outcomes.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Group Trials Register (8 September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) and MEDLINE (1966 to May 2003), Current Contents (1998 to May 2003) and EMBASE (1980 to May 2003).  SELECTION CRITERIA : All randomised and quasi-randomised trials comparing one or more vitamins with either placebo, other vitamins, no vitamins or other interventions, prior to conception, periconceptionally or in early pregnancy (less than 20 weeks gestation).  DATA COLLECTION AND ANALYSIS : Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality.  MAIN RESULTS : We identified seventeen trials assessing supplementation with any vitamin(s) starting prior to 20 weeks gestation and reporting at least one primary outcome that were eligible for the review. Overall, the included trials involved 35,812 women and 37,353 pregnancies. Two trials were cluster randomised and contributed data for 20,758 women and 22,299 pregnancies in total. No difference was seen between women taking any vitamins compared with controls for total fetal loss (relative risk (RR) 1.05, 95% confidence interval (CI) 0.95 to 1.15), early or late miscarriage (RR 1.08, 95% CI 0.95 to 1.24) or stillbirth (RR 0.85, 95% CI 0.63 to 1.14) and most of the other primary outcomes, using fixed-effect models. For the other primary outcomes, women given any type of vitamin(s) compared with controls were less likely to develop pre-eclampsia (RR 0.68, 95% CI 0.54 to 0.85, four trials, 5580 women) and more likely to have a multiple pregnancy (RR 1.38, 95% CI 1.12 to 1.70, three trials, 20,986 women).  AUTHORS CONCLUSIONS : Taking vitamin supplements, alone or in combination with other vitamins, prior to pregnancy or in early pregnancy, does not prevent women experiencing miscarriage or stillbirth. However, women taking vitamin supplements may be less likely to develop pre-eclampsia and more likely to have a multiple pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I71,I71)","v":15569396},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B71:D71)","v":8},2004,"Retinoids: potential in cancer prevention and therapy.","Clarke",15569396,"Retinoids: potential in cancer prevention and therapy.    Abstract:   Retinoids (derivatives of vitamin A) are signalling molecules that play important roles in cell growth, differentiation and death. Retinoids act through two types of receptors - retinoic acid receptors (RAR alpha, RAR beta and RAR gamma) and retinoid X receptors (RXR alpha, RXR beta and RXR gamma) - which themselves act as ligand-dependent transcription factors. Retinoids are of special interest in cancer research owing to their antiproliferative and cancer-preventative properties. They have been used successfully to cure acute promyelocytic leukaemia (APL) and can suppress carcinogenesis in a variety of tissue types (e.g. skin, lung, breast and oral cancers). Extensive research efforts have been dedicated to elucidating the molecular and cellular networks that are induced by retinoids, and this has recently yielded novel insights into how retinoids can both prevent and combat cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I72,I72)","v":15197471},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B72:D72)","v":8},2004,"How retinoids regulate breast cancer cell proliferation and apoptosis.","Simeone",15197471,"How retinoids regulate breast cancer cell proliferation and apoptosis.    Abstract:   Breast cancer still remains a major problem in its incidence, morbidity and mortality; therefore, more effective strategies for its prevention are urgently needed. Retinoids, natural and synthetic derivatives of vitamin A, possess antiproliferative and proapoptotic properties, making them a promising class of chemopreventive agents against breast cancer. The efficacy of all-trans retinoic acid, 9-cis-retinoic acid, LGD1069 (Targretin, bexarotene), and N-(4-hydroxyphenyl)retinamide (fenretinide) as breast cancer chemopreventive agents is being studied. A better understanding of the molecular mechanisms of action of these agents should lead to improvements in their clinical application. In this review, we discuss the mechanisms by which retinoids exert their antiproliferative and apoptotic effects in breast cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I73,I73)","v":12852263},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B73:D73)","v":8},2003,"Vitamin A and infancy. Biochemical, functional, and clinical aspects.","Perrotta",12852263,"Vitamin A and infancy. Biochemical, functional, and clinical aspects.    Abstract:   Vitamin A is a very intriguing natural compound. The molecule not only has a complex array of physiological functions, but also represents the precursor of promising and powerful new pharmacological agents. Although several aspects of human retinol metabolism, including absorption and tissue delivery, have been clarified, the type and amounts of vitamin A derivatives that are intracellularly produced remain quite elusive. In addition, their precise function and targets still need to be identified. Retinoic acids, undoubtedly, play a major role in explaining activities of retinol, but, recently, a large number of physiological functions have been attributed to different retinoids and to vitamin A itself. One of the primary roles this vitamin plays is in embryogenesis. Almost all steps in organogenesis are controlled by retinoic acids, thus suggesting that retinol is necessary for proper development of embryonic tissues. These considerations point to the dramatic importance of a sufficient intake of vitamin A and explain the consequences if intake of retinol is deficient. However, hypervitaminosis A also has a number of remarkable negative consequences, which, in same cases, could be fatal. Thus, the use of large doses of retinol in the treatment of some human diseases and the use of megavitamin therapy for certain chronic disorders as well as the growing tendency toward vitamin faddism should alert physicians to the possibility of vitamin overdose."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I74,I74)","v":12757024},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B74:D74)","v":8},2003,"Clinical applications of retinoids in cancer medicine.","Camacho",12757024,"Clinical applications of retinoids in cancer medicine.    Abstract:   The retinoids are compounds structurally related to vitamin A. The most extensively studied agents in cancer medicine include all-trans-retinoic acid, 9-cis-retinoic acid, and 13-cis-retinoic acid. In addition to several described immune regulatory functions, these agents may exert their antineoplastic effects through the regulation of tumor suppressor genes such as RAR-beta2. The survival benefit provided to patients with acute promyelocytic leukemia (APL) after induction therapy with all-trans RA and the responses experienced by patients with cutaneous lesions from Kaposis sarcoma and cutaneous T cell lymphoma treated with 9-cis RA and a selective rexinoid--bexarotene--respectively, led to their approval by the Food and Drug Administration during the last decade. As chemopreventive agents, retinoids have proven to effectively regress laryngeal papillomatosis and oral leukoplakia lesions. The ability of 13-cis-RA to prevent second primary malignancies in patients with carcinoma of the head and neck has also been demonstrated. Unfortunately, this intervention did not affect the primary tumor recurrence rates. The toxicity and efficacy of retinoids administered in combination with other biological and cytotoxic agents have also been explored in patients with renal cell carcinoma, breast cancer, myelodysplasia, prostate, cervix, and other malignancies with a broad range of reported responses. Further characterization of the molecular processes modulated by these agents will serve to better define their role in the prevention and treatment of human cancer and to tailor specific targeted therapies in combination with other compounds. Newer and more selective retinoids and rexinoids are completing phase I and phase II studies and hold promising."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I75,I75)","v":11375780},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B75:D75)","v":8},2001,"The role of metabolism and toxicokinetics in retinoid teratogenesis.","Tzimas",11375780,"The role of metabolism and toxicokinetics in retinoid teratogenesis.    Abstract:   Retinoids (vitamin A and its analogs) exert profound effects on a wide variety of life processes, including morphogenesis and embryonic development. Several retinoids are also effective drugs for therapy of skin diseases and some types of cancer. However, the applicability of this class of compounds is limited by their teratogenic activity. A major question in retinoid toxicology has been the marked interspecies differences in the lowest teratogenic doses of 13-cis-retinoic acid and retinol. In addition, great attention has been drawn to the risk assessment of embryotoxicity resulting from excessive intake of vitamin A by pregnant women. The present review first gives an overview of the biochemistry, metabolism and mode of action of retinoids as well as their role in embryonic development. It then summarizes the results of recent studies on retinoid metabolism, toxicokinetics, and embryonic exposure and discusses how the available information provides explanation of the aforementioned interspecies variations. Finally, it presents some approaches for risk assessment of high vitamin A intake by humans based on various animal models and epidemiological studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I76,I76)","v":10549233},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(C$3),\"\")))/LEN(C$3)","v":7},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B76:D76)","v":8},1999,"[Pharmacotherapy in pregnancy].","Paulus",10549233,"[Pharmacotherapy in pregnancy].    Abstract:   Between 1958 and 1961 approximately 10,000 children with severe limb defects were born, whose mothers had taken the somnifacient thalidomid. Since then, pharmaceutical agents in pregnancy are applied with legitimate caution by the pharmaceutical industry, physicians and patients, although often accompanied by irrational panic. According to statistical inquests, 15 to 50 percent of expectant mothers take pharmaceutical agents in the first trimester of pregnancy, often being not aware of their pregnancy. Considering the sensitive phase of organogenesis, the consequences may be particularly fatal in the first three months of pregnancy. After thalidomid more teratogenic pharmaceutical agents were discovered, i.e. coumarin derivates (e.g. warfarin), vitamin A and its derivates (e.g. isotretinoin), antifolates or anticonvulsants such as hydantoin or valproic acid. A number of other drugs are supposed to be potentially embryotoxic/fetotoxic, the effect of those pharmaceutical agents above all depending on dose and time of exposure. Case reports on malformations are available for numerous drugs, but studies with statistical validity are often missing. The pharmaceutical industry takes a legally safe position noting quot;contraindicationquot; or at least quot;strict indicationquot; in the consumer information. Concerning expectant mothers with chronic diseases like epilepsy, hypertension or bronchial asthma a therapeutic nihilism may lead to a dramatic deterioration of the disease, thereby causing high risks in fetal development. On the other hand numerous abortions without profound indications are carried out due to insufficient information of patients and medical staff on the real risks of a medication during early pregnancy. On principle reliable drugs should be preferred to new agents during fertile age of women. Special information centres for reproductive toxicology with corresponding data banks should be established and consulted, if an exposure with an insufficiently tested substance has taken place in ignorance of pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I77,I77)","v":10331090},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B77:D77)","v":8},1999,"Teratology of retinoids.","Collins",10331090,"Teratology of retinoids.    Abstract:   Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is important. This review first gives an overview of the principles of teratology as they apply to retinoid-induced malformations. It then describes relevant aspects of the biochemical pathway and signal transduction of retinoids. The teratogenic activity of various retinoid compounds, the role of the retinoid receptors, and important toxicokinetic parameters in teratogenesis are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I78,I78)","v":8634987},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B78:D78)","v":8},1995,"Chemoprevention trials and surrogate end point biomarkers in the cervix.","Mitchell",8634987,"Chemoprevention trials and surrogate end point biomarkers in the cervix.    Abstract:   Cervical cancer is the second most common malignancy in women worldwide and remains a significant health problem for women, especially minority and underserved women. Despite an understanding of the epidemiologic risks, the screening Papanicolaou smear, and morbid and costly treatment, overall survival remains 40%. New strategies, based on the clinical and molecular aspects of cervical carcinogenesis, are desperately needed. Chemoprevention refers to the use of chemical agents to prevent or delay the development of cancer in healthy populations. Chemoprevention studies have several unique features that distinguish them from classic chemotherapeutic trials; these features touch on several disciplines and weave knowledge of the biology of carcinogenesis into the trial design. In the design of chemoprevention trials, four factors are important: high risk cohorts must be identified; suitable medications must be selected; study designs should include Phases I, II, and III; and studies should include the use of surrogate end point biomarkers. Surrogate end point biomarkers are sought because the cancer develops over a long period of time, and studies of chemopreventives would require a huge number of subjects followed for many years. Surrogate end point biomarkers serve as alternative end points for examination of the efficacy of chemopreventives in tissue. High risk cohorts include women with cervical intraepithelial neoplasia (CIN) or squamous intraepithelial lesions (SIL). Nutritional studies have helped define micronutrients of interest (folate, carotenoids, vitamin C, vitamin E). Other medications of interest include retinoids (4-hydroxyphenylretinamide [4-HPR], retinyl acetate gel, topical all-trans-retinoic acid), polyamine synthesis inhibitors (alpha-difluoromethylornithine [DFMO]), and nonsteroidal anti-inflammatory drugs (ibuprofen). Phase I chemoprevention studies of the cervix have tested retinyl acetate gel and all-trans-retinoic acid. Phase II trials of all-trans-retinoic acid, beta-carotene, and folic acid have been and are being carried out, whereas Phase III trials of all-trans-retinoic acid have been completed and have shown significant regression of CIN 2 but not CIN 3. Phase I studies of DFMO and Phase II studies of DFMO and 4-HPR are underway. Surrogate end point biomarkers under study include (1) quantitative cytology and histopathology; (2) human papillomavirus type testing; (3) biologic measures of proliferation, regulation, differentiation, and genomic instability; and 4) fluorescence spectroscopic emission. Clinical trials with biologic end points will contribute to our understanding of the neoplastic process and hence aid us in developing new preventive and therapeutic strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I79,I79)","v":1392106},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B79:D79)","v":8},1992,"Retinoids and contraception.","Ceyrac",1392106,"Retinoids and contraception.    Abstract:   The main side effect of the retinoids is teratogenicity. Every dermatologist has a moral obligation to ensure that this effect is avoided, and the present publication is aimed at helping prescribe these drugs. After a review of the key properties of each of the retinoids on the market, the different forms of contraception available and their indication in young patients undergoing retinoid treatment are discussed. Unless otherwise contraindicated, oral contraception with an estrogen-progestogen formulation is the contraceptive method of choice for women undergoing retinoid treatment. The intrauterine device (IUD) is of little or almost no relevance for young women undergoing treatment with a retinoid. IUDs are indicated in older multiparae who have practised this form of contraception before starting retinoid treatment and who refuse to take the pill. Natural and local methods of contraception are totally unsuitable for women undergoing treatment with retinoids. However, they may be used as an additional precautionary measure by IUD users."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I80,I80)","v":2643696},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B80:D80)","v":8},1989,"Comparative aspects of carotenoids and retinoids as chemopreventive agents for cancer.","Moon",2643696,"Comparative aspects of carotenoids and retinoids as chemopreventive agents for cancer.    Abstract:   Retinoids are well established chemopreventive agents for experimental carcinogenesis of many target organs including mammary gland, urinary bladder, lung, skin, liver, pancreas, colon and esophagus. Modification of the basic retinoid structure has produced analogs with enhanced target organ specificity, increased inhibitory activity and reduced toxicity. N-(4-hydroxyphenyl) retinamide (4-HPR) currently appears to be the most efficaceous retinoid against carcinogen-induced breast, urinary bladder, and lung cancer in rodents. Retinoids are most effective when administered shortly after the carcinogen treatment; however, the treatment can be delayed significantly while maintaining its chemopreventive effect. Under various experimental conditions, combining retinoid treatment with other modifiers of growth enhances its chemopreventive activity; for example, retinoid plus hormonal modulation can provide better protection against mammary cancer than either treatment alone. The role of carotenoids in cancer chemoprevention is less well defined. Studies have been complicated by the poor absorption and low tissue levels of carotenoids in the rodent models used for such studies. Aside from experimental skin carcinogenesis, little information is available relative to the effect of carotenoids on the chemoprevention of cancer at other organ sites."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I81,I81)","v":7040511},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B81:D81)","v":8},1982,"Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids.","Kamm",7040511,"Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids.    Abstract:   This paper is a review of the acute, subchronic, and chronic toxicity, mutagenicity, carcinogenicity, and teratogenicity of vitamin A, tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), and etretinate. The results of in vitro mutagenicity testing of the retinoids are also presented. In addition to teratogenesis studies, experiments designed to evaluate the effects of the retinoids on fertility and reproductive performance and on perinatal and postnatal development are also described."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I82,I82)","v":27150280},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(C$3),\"\")))/LEN(C$3)","v":7},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B82:D82)","v":7},2016,"Vitamin supplementation for preventing miscarriage.","Balogun",27150280,"Vitamin supplementation for preventing miscarriage.    Abstract:    BACKGROUND : Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage.  OBJECTIVES : The objectives of this review were to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage.  SEARCH METHODS : We searched the Cochrane Pregnancy and Childbirth Group Trials Register (6 November 2015) and reference lists of retrieved studies.  SELECTION CRITERIA : All randomised and quasi-randomised trials comparing supplementation during pregnancy with one or more vitamins with either placebo, other vitamins, no vitamins or other interventions. We have included supplementation that started prior to conception, periconceptionally or in early pregnancy (less than 20 weeks gestation).  DATA COLLECTION AND ANALYSIS : Three review authors independently assessed trials for inclusion, extracted data and assessed trial quality. We assessed the quality of the evidence using the GRADE approach. The quality of evidence is included for numerical results of outcomes included in the Summary of findings tables.  MAIN RESULTS : We included a total of 40 trials (involving 276,820 women and 278,413 pregnancies) assessing supplementation with any vitamin(s) starting prior to 20 weeks gestation and reporting at least one primary outcome that was eligible for the review. Eight trials were cluster-randomised and contributed data for 217,726 women and 219,267 pregnancies in total.Approximately half of the included trials were assessed to have a low risk of bias for both random sequence generation and adequate concealment of participants to treatment and control groups. Vitamin C supplementation There was no difference in the risk of total fetal loss (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.92 to 1.40, seven trials, 18,949 women; high-quality evidence); early or late miscarriage (RR 0.90, 95% CI 0.65 to 1.26, four trials, 13,346 women; moderate-quality evidence); stillbirth (RR 1.31, 95% CI 0.97 to 1.76, seven trials, 21,442 women; moderate-quality evidence) or adverse effects of vitamin supplementation (RR 1.16, 95% CI 0.39 to 3.41, one trial, 739 women; moderate-quality evidence) between women receiving vitamin C with vitamin E compared with placebo or no vitamin C groups. No clear differences were seen in the risk of total fetal loss or miscarriage between women receiving any other combination of vitamin C compared with placebo or no vitamin C groups. Vitamin A supplementation No difference was found in the risk of total fetal loss (RR 1.01, 95% CI 0.61 to 1.66, three trials, 1640 women; low-quality evidence); early or late miscarriage (RR 0.86, 95% CI 0.46 to 1.62, two trials, 1397 women; low-quality evidence) or stillbirth (RR 1.29, 95% CI 0.57 to 2.91, three trials, 1640 women; low-quality evidence) between women receiving vitamin A plus iron and folate compared with placebo or no vitamin A groups. There was no evidence of differences in the risk of total fetal loss or miscarriage between women receiving any other combination of vitamin A compared with placebo or no vitamin A groups. Multivitamin supplementation There was evidence of a decrease in the risk for stillbirth among women receiving multivitamins plus iron and folic acid compared iron and folate only groups (RR 0.92, 95% CI 0.85 to 0.99, 10 trials, 79,851 women; high-quality evidence). Although total fetal loss was lower in women who were given multivitamins without folic acid (RR 0.49, 95% CI 0.34 to 0.70, one trial, 907 women); and multivitamins with or without vitamin A (RR 0.60, 95% CI 0.39 to 0.92, one trial, 1074 women), these findings included one trial each with small numbers of women involved. Also, they include studies where the comparison groups included women receiving either vitamin A or placebo, and thus require caution in interpretation.We found no difference in the risk of total fetal loss (RR 0.96, 95% CI 0.93 to 1.00, 10 trials, 94,948 women; high-quality evidence) or early or late miscarriage (RR 0.98, 95% CI 0.94 to 1.03, 10 trials, 94,948 women; moderate-quality evidence) between women receiving multivitamins plus iron and folic acid compared with iron and folate only groups.There was no evidence of differences in the risk of total fetal loss or miscarriage between women receiving any other combination of multivitamins compared with placebo, folic acid or vitamin A groups. Folic acid supplementation There was no evidence of any difference in the risk of total fetal loss, early or late miscarriage, stillbirth or congenital malformations between women supplemented with folic acid with or without multivitamins and/or iron compared with no folic acid groups. Antioxidant vitamins supplementation There was no evidence of differences in early or late miscarriage between women given antioxidant compared with the low antioxidant group (RR 1.12, 95% CI 0.24 to 5.29, one trial, 110 women).  AUTHORS CONCLUSIONS : Taking any vitamin supplements prior to pregnancy or in early pregnancy does not prevent women experiencing miscarriage. However, evidence showed that women receiving multivitamins plus iron and folic acid had reduced risk for stillbirth. There is insufficient evidence to examine the effects of different combinations of vitamins on miscarriage and miscarriage-related outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I83,I83)","v":27012320},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B83:D83)","v":7},2016,"Vitamin A supplementation for postpartum women.","Oliveira",27012320,"Vitamin A supplementation for postpartum women.    Abstract:    BACKGROUND : In areas where vitamin A deficiency (VAD) is a public health concern, the maternal dietary intake of vitamin A may be not sufficient to meet either the maternal nutritional requirements, or those of the breastfed infant, due the low retinol concentrations in breast milk.  OBJECTIVES : To evaluate the effects of vitamin A supplementation for postpartum women on maternal and infant health.  SEARCH METHODS : We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (8 February 2016), LILACS (1982 to December 2015), Web of Science (1945 to December 2015), and the reference lists of retrieved studies.  SELECTION CRITERIA : Randomised controlled trials (RCTs) or cluster-randomised trials that assessed the effects of vitamin A supplementation for postpartum women on maternal and infant health (morbidity, mortality and vitamin A nutritional status).  DATA COLLECTION AND ANALYSIS : Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias and checked for accuracy. We assessed the quality of the evidence using the GRADE approach.  MAIN RESULTS : Fourteen trials of mainly low or unclear risk of bias, enrolling 25,758 women and infant pairs were included. The supplementation schemes included high, single or double doses of vitamin A (200,000 to 400,000 internation units (IU)), or 7.8 mg daily beta-carotene compared with placebo, no treatment, other (iron); or higher (400,000 IU) versus lower dose (200,000 IU). In all trials, a considerable proportion of infants were at least partially breastfed until six months. Supplement (vitamin A as retinyl, water-miscible or beta-carotene) 200,000 to 400,000 IU versus control (placebo or no treatment) Maternal: We did not find evidence that vitamin A supplementation reduced maternal mortality at 12 months (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.44 to 2.21; 8577 participants; 1 RCT, moderate-quality evidence). Effects were less certain at six months (risk ratio (RR) 0.50, 95% CI 0.09 to 2.71; 564 participants; 1 RCT; low-quality evidence). The effect on maternal morbidity (diarrhoea, respiratory infections, fever) was uncertain because the quality of evidence was very low (50 participants, 1 RCT). We found insufficient evidence that vitamin A increases abdominal pain (RR 1.28, 95% CI 0.95 to 1.73; 786 participants; 1 RCT; low-quality evidence). We found low-quality evidence that vitamin A supplementation increased breast milk retinol concentrations by 0.20 µmol/L at three to three and a half months (mean difference (MD) 0.20 µmol/L, 95% CI 0.08 to 0.31; 837 participants; 6 RCTs). Infant: We did not find evidence that vitamin A supplementation reduced infant mortality at two to 12 months (RR 1.08, 95% CI 0.77 to 1.52; 6090 participants; 5 RCTs; low-quality evidence). Effects on morbidity (gastroenteritis at three months) was uncertain (RR 6.03, 95% CI 0.30 to 121.82; 84 participants; 1 RCT; very low-quality evidence). There was low-quality evidence for the effect on infant adverse outcomes (bulging fontanelle at 24 to 48 hours) (RR 2.00, 95% CI 0.61 to 6.55; 444 participants; 1 RCT). Supplement (vitamin A as retinyl) 400,000 IU versus 200,000 IUThree studies (1312 participants) were included in this comparison. None of the studies assessed maternal mortality, maternal morbidity or infant mortality. Findings from one study showed that there may be little or no difference in infant morbidity between the doses (diarrhoea, respiratory illnesses, and febrile illnesses) (312 participants, data not pooled). No firm conclusion could be drawn on the impact on maternal and infant adverse outcomes (limited data available).The effect on breast milk retinol was also uncertain due to the small amount of information available.  AUTHORS CONCLUSIONS : There was no evidence of benefit from different doses of vitamin A supplementation for postpartum women on maternal and infant mortality and morbidity, compared with other doses or placebo. Although maternal breast milk retinol concentrations improved with supplementation, this did not translate to health benefits for either women or infants. Few studies reported on maternal and infant mortality and morbidity. Future studies should include these important outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I84,I84)","v":24239628},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B84:D84)","v":7},2014,"Retinoids and their biological effects against cancer.","Alizadeh",24239628,"Retinoids and their biological effects against cancer.    Abstract:   There are more than 4000 natural and synthetic molecules structurally and/or functionally related to vitamin A. Retinoids are a class of these compounds that are structurally associated to vitamin A. The retinoids have a wide spectrum of functions. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation and apoptosis. It suppresses carcinogenesis in tumorigenic animal models for the skin, oral, lung, breast, bladder, ovarian and prostate. It is important how major retinoids may act in cancer treatment or prevention. The reports have indicated that lower levels of vitamin A in humans may be associated with relative type 1 cytokine dominance and a higher proportion of NK cells. In addition, very low vitamin A levels would be undesirable explaining the essential role of vitamin A in epithelial and general cell maturation and function. However, the cytokine shifts associated with moderately low levels of vitamin A may be in some ways beneficial in an environment where HIV infection, M. tuberculosis infection, or other type 1 infections are highly prevalent and/or when acquired immunity is cooperated. In this review, we intend to describe the biochemical and immunological functions of retinoids against cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I85,I85)","v":23996075},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B85:D85)","v":7},2013,"The management of acne vulgaris in pregnancy.","Meredith",23996075,"The management of acne vulgaris in pregnancy.    Abstract:   Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy. This review seeks to clarify what management options are available to treat acne during pregnancy and what data are available to guide decision making. Topical treatments are considered the safest option during pregnancy. They have the best safety profile and minimize the levels of systemic absorption, and therefore the least risk of fetal exposure. If these are applied properly with a strong emphasis on adherence, excellent results can be achieved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I86,I86)","v":23891453},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B86:D86)","v":7},2013,"Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.","Carretero",23891453,"Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.    Abstract:   Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I87,I87)","v":22771225},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B87:D87)","v":7},2012,"Influence of mineral and vitamin supplements on pregnancy outcome.","Hovdenak",22771225,"Influence of mineral and vitamin supplements on pregnancy outcome.    Abstract:   The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) absorption. Zn deficiency in pregnant animals may limit fetal growth. Supplemental Zn may be prudent for women with poor gastrointestinal function, and in Zn deficient women, increasing birth weight and head circumference, but no evidence was found for beneficial effects of general Zn supplementation during pregnancy. Selenium (Se) is an antioxidant supporting humoral and cell-mediated immunity. Low Se status is associated with recurrent abortion, pre-eclampsia and IUGR, and although beneficial effects are suggested there is no evidence-based recommendation for supplementation. An average of 20-30% of pregnant women suffer from any vitamin deficiency, and without prophylaxis, about 75% of these would show a deficit of at least one vitamin. Vitamin B6 deficiency is associated with pre-eclampsia, gestational carbohydrate intolerance, hyperemesis gravidarum, and neurologic disease of infants. About 25% of pregnant women in India are folate deficient. Folate deficiency may lead to congenital malformations (neural tube damage, orofacial clefts, cardiac anomalies), anaemia and spontaneous abortions, and pre-eclampsia, IUGR and abruption placentae. Pregestational supplementation of folate prevents neural tube defects. A daily supplemental dose of 400 μg/day of folate is recommended when planning pregnancy. In developing countries diets are generally low in animal products and consequently in vitamin B12 content. An insufficient supply may cause reduced fetal growth. In vegetarian women, supplementation of vitamin B12 may be needed. Vitamin A deficiency is prevalent in the developing world, impairing Fe status and resistance to infections. The recommended upper limit for retinol supplements is 3000 IU/day. Vitamin A supplementation enhances birth weight and growth in infants born to HIV-infected women. Overdosing should be avoided. Low concentrations of vitamin C seem to increase the development of pre-eclampsia, and supplementation may be beneficial. Supplementation with vitamin D in the third trimester in vitamin D deficient women seems to be beneficial. The use of vitamins E, although generally considered quot;healthyquot;, may be harmful to the pregnancy outcome by disrupting a physiologic oxidative gestational state and is consequently not recommended to prevent pre-eclampsia. Further studies on specific substances are needed as the basis for stratified, placebo-controlled analyses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I88,I88)","v":22205187},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(C$3),\"\")))/LEN(C$3)","v":7},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B88:D88)","v":7},2012,"Pregnancy after bariatric surgery: a current view of maternal, obstetrical and perinatal challenges.","Magdaleno",22205187,"Pregnancy after bariatric surgery: a current view of maternal, obstetrical and perinatal challenges.    Abstract:    UNLABELLEDWith the increase in the number of bariatric surgeries being performed in women of childbearing age, physicians must have concerns regarding the safety of pregnancy after bariatric surgery. The aim of this review is to summarize the literature reporting on maternal, obstetrical and perinatal implications of pregnancy following BS.  METHODS : English, Spanish and Portuguese-language articles were identified in a PUBMED search from 2005 to February 2011 using the keywords for pregnancy and bariatric surgery or gastric bypass or gastric banding.  RESULTS : The studies show improved fertility and a reduced risk of gestational diabetes, pregnancy-induced hypertension and pre-eclampsia, macrosomia in pregnant women after bariatric surgery. The incidence of intrauterine growth restriction and small for gestational age are increased. No conclusions can be drawn concerning the risk for cesarean delivery and the best surgery-to-conception interval. Deficiencies in iron, vitamin A, vitamin B12, vitamin K, folate and calcium can result in maternal and fetal complications.  CONCLUSIONS : Pregnancy outcome of women who delivered after BS, as compared to obese populations, is better and safer and comparable to the general population. Close supervision before, during and after pregnancy following bariatric surgery and nutrient supplementation adapted to the patients individual requirements can prevent nutrition-related complications and improve maternal and fetal health."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I89,I89)","v":20961299},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B89:D89)","v":7},2010,"Tissue-specific increases in endogenous all-trans retinoic acid: possible contributing factor in ethanol toxicity.","Wolf",20961299,"Tissue-specific increases in endogenous all-trans retinoic acid: possible contributing factor in ethanol toxicity.    Abstract:   All-trans retinoic acid (atRA) is required for neurogenesis and dendritic growth in the hippocampus. The toxic effects of ethanol include developmental defects, cognitive dysfunction, and increased risk of cancer and have some similarities to the detrimental effects of excess atRA, the active form of vitamin A. It is therefore possible that disruption of atRA homeostasis would contribute to the deleterious effects of ethanol. However, previous work, using very high exogenous doses of retinol, found that ethanol toxicity led to decreased formation of atRA, apparently due to competitive inhibition of alcohol dehydrogenase, which is purportedly involved in the conversion of retinol to retinal. A new study, using assays that are highly sensitive for endogenous atRA, has reported that ethanol toxicity in mice actually increased atRA concentration in certain tissues, including brain hippocampus, apparently due to a mobilization of hepatic retinyl esters that led to increased retinol and atRA in specific tissues."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I90,I90)","v":20034809},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B90:D90)","v":7},2010,"Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies.","Sogno",20034809,"Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies.    Abstract:   Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic quot;angiopreventivequot; properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I91,I91)","v":19476422},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B91:D91)","v":7},2009,"Treatment of acute promyelocytic leukemia during pregnancy.","Yang",19476422,"Treatment of acute promyelocytic leukemia during pregnancy.    Abstract:   Management of the pregnant patient with acute promyelocytic leukemia (APL) is a challenge. Immediate treatment of APL is critical, as it is an oncologic emergency, with a high risk of morbidity and mortality associated with disseminated intravascular coagulation. However, administration of chemotherapy and differentiating agents in pregnancy is controversial because of potential teratogenic effects. In addition, complications associated with APL, including retinoic acid syndrome, add to the complexity of management. To better understand how to manage this complex patient care situation, we searched the PubMed database (January 1972-May 2008) for English-language articles about maternal and fetal outcomes resulting from APL treatment during pregnancy. A total of 42 cases from 35 articles were identified: 12 first-trimester, 21 second-trimester, and 9 third-trimester cases. The most commonly administered agents were all-trans-retinoic acid (ATRA), anthracyclines, and antimetabolites. Complete remission was reported in 35 (83%) of 42 patients. Administration of ATRA or chemotherapy in the first trimester was associated with an increased risk of fetal malformations and spontaneous abortion, whereas administration in the second and third trimesters was associated with relatively favorable fetal outcomes. The overall treatment of the pregnant patient with APL should include a discussion about pregnancy termination, especially if APL is diagnosed in the first trimester. If the pregnancy is to continue, then the appropriate chemotherapy regimen needs to be determined. Frequent fetal monitoring, along with aggressive management of potential APL-related complications, is necessary to allow for optimal maternal and fetal outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I92,I92)","v":17852449},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B92:D92)","v":7},2007,"Outcome of pregnancy in women treated with all-trans retinoic acid; a case report and review of literature.","Valappil",17852449,"Outcome of pregnancy in women treated with all-trans retinoic acid; a case report and review of literature.    Abstract:   All-trans-retinoic acid (ATRA) has been proved to be an effective treatment for acute promyelocytic leukemia (APL), inducing remission in more than 90% of cases. Treatment of APL in pregnancy is controversial as the use of ATRA has been questioned due to the teratogenic effect of retinoids. We report a case of pregnancy in a woman exposed to ATRA during the first trimester. The baby was born healthy, without any anomalies. Review of all reported cases of the use of ATRA in pregnancy revealed no serious adverse outcomes or congenital anomalies although only very few cases had exposure in the first trimester."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I93,I93)","v":17539885},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(C$3),\"\")))/LEN(C$3)","v":7},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B93:D93)","v":7},2007,"Does birth spacing affect maternal or child nutritional status? A systematic literature review.","Dewey",17539885,"Does birth spacing affect maternal or child nutritional status? A systematic literature review.    Abstract:   This review addresses the question of whether a short birth interval is associated with adverse nutritional outcomes for the mother or the child. Indices of anthropometric status (maternal weight or body mass index; child growth) and micronutrient status (e.g. iron or vitamin A) were included as outcomes. A computerized search of all relevant papers published since 1966 was completed, and the snowball method was used to identify additional relevant published or unpublished papers. In total, 57 papers were found to contain data regarding the relationship between birth spacing and nutritional outcomes (35 for child nutrition, 11 for maternal anthropometric status, and 11 for maternal anaemia or micronutrient status). Of these, 23 papers were excluded from further consideration because they did not include any multivariate analysis, leaving 34 papers that met the criteria for the review (22 for child nutrition, eight for maternal anthropometric status, and four for maternal anaemia or micronutrient status). The studies on child nutrition outcomes indicate that a longer birth interval is associated with a lower risk of malnutrition in some populations, but not all. In those countries in which the relationship was significant, the reduction in stunting associated with a previous birth interval gt;or=36 months ranged from approximately 10% to 50%. Some of this reduction may be due to residual confounding, i.e. to factors not included in the analysis (such as breastfeeding and maternal height). The studies on maternal anthropometric outcomes yielded mixed results. Because the nutritional burden on the mother between pregnancies depends on the extent of breastfeeding, the interpregnancy interval is not the best measure of whether the mother has had a chance to recover from the pregnancy, in terms of repleting her nutritional status. Therefore, some studies examined the recuperative interval (duration of the non-pregnant, non-lactating interval) instead. Taken as a whole, the studies do not provide clear evidence of a link between interpregnancy or recuperative interval and maternal anthropometric status. This may be due, in part, to changes in the hormonal regulation of nutrient partitioning between the mother and the fetus when a mother is malnourished. Only four papers were identified that related to micronutrient status, three of which examined maternal anaemia. One study showed an increased risk for maternal anaemia when the interpregnancy interval was lt;6 months, but the analysis did not control for iron supplementation during pregnancy. The other two studies did not show a significant association between interpregnancy interval and maternal anaemia. One study of micronutrient status indicated no significant relationship between interpregnancy interval and maternal serum zinc, copper, magnesium, ferritin, folate or thyroid-stimulating hormone. Important methodological limitations were apparent in most of the studies. Thus, further research with more comprehensive control of potentially confounding variables is needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I94,I94)","v":15639998},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B94:D94)","v":7},2004,"[Molecular biology of the retinol-binding proteins and their genes].","Guo",15639998,"[Molecular biology of the retinol-binding proteins and their genes].    Abstract:   Retinol-binding proteins (RBPs) are a kind of circulating carrier proteins for serum and cellular retinol and retinol acid, which are lipid-soluble vitamins, and are members of hydrophobic binding protein family. Serum RBPs were synthesized primarily in liver, then was released into blood streams, and then to various tissues. Under the interaction with substances such as retinol, pre-albumin and the receptors of cellular surface, they play important roles in storage, metabolism of VitA and transport of VitA to the target cells. Cellular RBPs play the similar function as serum RBPs in intracell. This review introduces action mechanism, tissue localization and developmental expression of retinol-binding proteins. This review also introduces the structure, chromosome mapping and their relationships with reproductive performance of retinol-binding protein genes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I95,I95)","v":15095280},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B95:D95)","v":7},2004,"Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines.","Holmes",15095280,"Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines.    Abstract:   Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I96,I96)","v":12218221},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B96:D96)","v":7},2002,"Is there a reproductive safety risk in male patients treated with acitretin (neotigason/soriatane?","Geiger",12218221,"Is there a reproductive safety risk in male patients treated with acitretin (neotigason/soriatane?    Abstract:   Review of preclinical data including genotoxicity assays and a male rat reproduction toxicology study demonstrates that acitretin (Neotigason)/Soriatane) does not affect the reproductive outcome in naive females mated with treated males. Prospective studies of teratogenic risk or impairment of fertility cannot be ethically conducted in humans. However, it is highly unlikely that any fetal malformation could be induced by an ejaculate containing traces of acitretin. Indeed, worldwide postmarketing surveillance has not revealed any cases of retinoid embryopathy associated with paternal treatment with acitretin. Birth defects seen in pregnancies fathered by male acitretin patients were all events expected to occur in the general population at known frequencies. In conclusion, therefore, available data do not appear to indicate any reproductive safety risk due to paternal treatment with acitretin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I97,I97)","v":12055350},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B97:D97)","v":7},2002,"The role of vitamin A in mammalian reproduction and embryonic development.","Clagett-Dame",12055350,"The role of vitamin A in mammalian reproduction and embryonic development.    Abstract:   Since the late 1980s, there has been an explosion of information on the molecular mechanisms and functions of vitamin A. This review focuses on the essential role of vitamin A in female reproduction and embryonic development and the metabolism of vitamin A (retinol) that results in these functions. Evidence strongly supports that in situ-generated all-trans retinoic acid (atRA) is the functional form of vitamin A in female reproduction and embryonic development. This is supported by the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency with atRA, the block in embryonic development that occurs in retinaldehyde dehydrogenase type 2 null mutant mice, and the essential roles of the retinoic acid receptors, at least in embryogenesis. Early studies of embryos from marginally vitamin A-deficient (VAD) pregnant rats revealed a collection of defects called the vitamin A-deficiency syndrome. The manipulation of all-trans retinoic acid (atRA) levels in the diet of VAD female rats undergoing a reproduction cycle has proved to be an important new tool in deciphering the points of atRA function in early embryos and has provided a means to generate large numbers of embryos at later stages of development with the vitamin A-deficiency syndrome. The essentiality of the retinoid receptors in mediating the activity of atRA is exemplified by the many compound null mutant embryos that now recapitulate both the original vitamin A-deficiency syndrome and exhibit a host of new defects, many of which can also be observed in the VAD-atRA-supported rat embryo model and in retinaldehyde dehydrogenase type 2 (RALDH2) mutant mice. A major task for the future is to elucidate the atRA-dependent pathways that are normally operational in vitamin A-sufficient animals and that are perturbed in deficiency, thus leading to the characteristic VAD phenotypes described above."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I98,I98)","v":11796231},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B98:D98)","v":7},2002,"Retinoids and their receptors in cancer development and chemoprevention.","Sun",11796231,"Retinoids and their receptors in cancer development and chemoprevention.    Abstract:   Retinoids play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially epithelial cells, mainly through interaction with two types of nuclear receptors: retinoic acid receptors (RARalpha, beta and gamma) and retinoid X receptors (RXRalpha, beta and gamma). Vitamin A deficiency in experimental animals has been associated with a higher incidence of cancer and with increased susceptibility to chemical carcinogens. This is in agreement with the epidemiological studies indicating that individuals with a lower dietary vitamin A intake are at a higher risk to develop cancer. At the molecular level, aberrant expression and function of nuclear retinoid receptors have been found in various types of cancer including premalignant lesions. Thus, aberrations in retinoid signaling are early events in carcinogenesis. Retinoids at pharmacological doses exhibit a variety of effects associated with cancer prevention. They suppress transformation of cells in vitro, inhibit carcinogenesis in various organs in animal models, reduce premalignant human epithelial lesions and prevent second primary tumors following curative therapy for epithelial malignancies such as head and neck, lung, liver, and breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I99,I99)","v":11509110},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B99:D99)","v":7},2001,"Micronutrients in pregnancy.","Black",11509110,"Micronutrients in pregnancy.    Abstract:   Vitamins and minerals, referred to collectively as micronutrients, have important influences on the health of pregnant women and the growing fetus. Iron deficiency results in anemia which may increase the risk of death from hemorrhage during delivery, but its effects on fetal development and birth outcomes is still unclear. Folic acid deficiency can lead to hematological consequences, pregnancy complications and congenital malformations, but again the association with other birth outcomes is equivocal. Zinc deficiency has been associated in some, but not all studies with complications of pregnancy and delivery, as well as with growth retardation, congenital abnormalities and retarded neurobehavioral and immunological development in the fetus. Iodine deficiency during pregnancy results in cretinism and possible fetal wastage and preterm delivery. Deficiency of other minerals such as magnesium, selenium, copper, and calcium have also been associated with complications of pregnancy, childbirth or fetal development. Deficiencies of vitamins other than folate may likewise be related to such complications; and vitamin A or beta-carotene supplements in pregnancy reduced maternal mortality by 50 % in a controlled trial in Nepal. Additional research is need on the prevalence of such deficiencies and their consequences and on cost-effective public health interventions for their control."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I100,I100)","v":10828175},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B100:D100)","v":7},2000,"The role of retinoic acid in embryonic and post-embryonic development.","Maden",10828175,"The role of retinoic acid in embryonic and post-embryonic development.    Abstract:   Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes. Thus, in addition to the well-established experimental paradigm of depriving animals of vitamin A to determine the role of RA in embryonic and post-embryonic development, molecular biology has provided us with two additional methodologies: knockout the enzymes or the RAR and RXR in the mouse embryo. The distribution of the enzymes and receptors, and recent experiments to determine the endogenous distribution of RA in the embryo are described here, as well as the effects on the embryo of knocking out the enzymes and receptors. In addition, recent studies using the classical vitamin A-deprivation technique are described, as they have provided novel insights into the regions of the embryo which crucially require RA, and the gene pathways involved in their development. Finally, the post-embryonic or regenerating systems in which RA plays a part are described, i.e. the regenerating limb, lung regeneration, hair cell regeneration in the ear and spinal cord regeneration in the adult."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I101,I101)","v":8709884},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B101:D101)","v":7},1996,"Oral retinoids and pregnancy.","Chan",8709884,"Oral retinoids and pregnancy.    Abstract:   The oral retinoids isotretinoin and etretinate are uniquely effective in the treatment of severe cystic acne and keratinisation disorders. Because of their known teratogenicity, there are strict prescription guidelines, but exposure during pregnancy still occurs. A dedicated effort by women and their clinicians is required, involving patient selection, education and informed consent, detailed contraceptive counselling, and careful monitoring and management, including pregnancy testing before commencement of therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I102,I102)","v":8801162},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B102:D102)","v":7},1996,"Bioactivities of N-(4-hydroxyphenyl) retinamide and retinoyl beta-glucuronide.","Formelli",8801162,"Bioactivities of N-(4-hydroxyphenyl) retinamide and retinoyl beta-glucuronide.    Abstract:   N-(4-Hydroxyphenyl) retinamide (4HPR) and retinoyl beta-glucuronide (RAG) are two derivatives of all-trans retinoic acid (RA) that show properties both similar to as well as different from their parent compound, RA. Both retinoids possess the important property of showing much-reduced toxicity relative to RA while maintaining significant biological activity. 4HPR, a synthetic derivative, is active in the prevention and treatment of a variety of neoplasms in animals, and by inducing apoptosis, shows growth inhibitory activity against many human tumor cell types in vitro. In humans, 4HPR reduces the incidence of new occurrences of leukoplakia and is currently being tested as a preventive agent for breast cancer. RAG, a naturally occurring metabolite of RA, effectively stimulates the growth of vitamin A-deficient animals, induces the differentiation of epithelial cells in vivo and in vitro, and is effective in the topical treatment of acne in humans. Unlike RA, RAG is nontoxic when applied to the skin and is nonteratogenic when given orally to rats. Possible mechanisms of action of both compounds are discussed. These two derivatives of retinoids show interesting physiologic effects and potentially beneficial pharmacologic actions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I103,I103)","v":8657191},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B103:D103)","v":7},1996,"Retinoid receptors in human lung cancer and breast cancer.","Zhang",8657191,"Retinoid receptors in human lung cancer and breast cancer.    Abstract:   Retinoids, the natural and synthetic vitamin A derivatives, are known to inhibit the proliferation of lung cancer and breast cancer cells and the growth of carcinogen-induced bronchogenic squamous cell carcinoma and mammary tumors, and have been used as chemoprevention agents against both types of cancer. However, clinical trials of retinoids in patients with advanced lung cancer and breast cancer have not been successful. In studying how retinoid sensitivity is lost in cancer cells, we have found that lack of the retinoic acid receptor beta (RAR beta) gene expression and its abnormal regulation by retinoic acid (RA) are common features in human lung cancer and breast cancer cells. The absence and abnormal RA regulation of RAR beta correlates with the loss of anti-proliferation effect of RA in hormone-independent breast cancer cells, and is due to different abnormalities found in cancer cells. Furthermore, expression of RAR beta gene in hormone-independent breast cancer cells restores their RA sensitivity. These data demonstrate that RAR beta can mediate the growth inhibitory effect of RA and suggest that the lack of RAR beta may contribute to retinoid resistance in certain cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I104,I104)","v":8635026},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B104:D104)","v":7},1995,"Acute promyelocytic leukemia and pregnancy. A case report.","Hoffman",8635026,"Acute promyelocytic leukemia and pregnancy. A case report.    Abstract:    BACKGROUND : Acute promyelocytic leukemia (APL) is an uncommon form of acute myeloid leukemia usually associated with disseminated intravascular coagulation (DIC). Pregnancy in patients with APL requires special consideration to maximize the probability of survival of both mother and fetus.  METHODS : A patient with APL diagnosed during pregnancy who developed DIC is described. Obstetric and oncologic management of this difficult patient is discussed, and a pertinent literature review of pregnancy in APL is presented.  RESULTS : Of 23 pregnancies in patients with APL reported in the literature (including the present patient), 19 yielded live births, including 8 of 12 who received chemotherapy during late pregnancy and all 3 patients who received all-trans-retinoic acid (ATRA) during late pregnancy. Chemotherapy or ATRA induced complete remission in 72% of treated patients.  CONCLUSIONS : Proper management of pregnant patients with APL usually results in a live birth and complete remission of the mothers leukemia, despite the potentially devastating consequences of DIC, which is present at diagnosis in most patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I105,I105)","v":21607448},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B105:D105)","v":7},1994,"Fenretinide in breast-cancer chemoprevention (review).","Decensi",21607448,"Fenretinide in breast-cancer chemoprevention (review).    Abstract:   Fenretinide (4-HPR), a synthetic amide derivative of retinoic acid, has proven effective in preventing chemically induced mammary carcinoma in rodents. During the past years, our group has made a particular effort with regard to this molecule in clinical studies aimed at evaluating its pharmacology, toxicity and efficacy in breast cancer prevention. We have demonstrated that 4-HPR blood levels remain constant during administration for as long as 5 years, that the drug accumulates in the human breast, and that it induces a significant decline of plasma retinol and insulinlike growth factor-I (IGF-I) levels. Accrual of the phase III study was closed on July 31, 1993 including 2,972 Stage I breast cancer patients. The aim is to evaluate the efficacy of a 5-year administration of 4-HPR to prevent new contralateral primary breast cancers. Compliance to protocol and treatment is high and tolerability of the drug is good; only 51 women out of 1,397 (3.6%) have interrupted drug intake due to toxicity. The only remarkable adverse effect of 4-HPR administration is diminished dark adaptation, which occurs in about one-fourth of the patients and is dependent on the decline of plasma retinol below the threshold level of 100 ng/ml. However, about 50% of the patients with altered dark-adaptometry are asymptomatic and the alterations of dark adaptation are promptly reversible upon drug discontinuation. Plasma level of N-(4-methoxyphenyl) retinamide (4-MPR), the principal metabolite of 4-HPR, which tends to be higher in women over 55 years with a high percentage of adipose tissue, is the major determinant of both retinol and IGF-I decrease. Since the combination of 4-HPR with the antioestrogen tamoxifen has shown a synergistic activity in preclinical models, it is currently an important avenue of clinical investigation in an attempt to prevent breast cancer. Moreover, a dose reduction of one or both agents in an effort to minimise toxicity while maintaining activity, would represent a major improvement in cancer chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I106,I106)","v":8463566},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B106:D106)","v":7},1993,"[Teratogenicity of retinoids. A case and review of the literature].","Heckel",8463566,"[Teratogenicity of retinoids. A case and review of the literature].    Abstract:   Retinoids are vitamin A derivatives used in dermatology. One of them, isotretinoin, is frequently prescribed for refractory juvenile acne. The teratogenetic power of this drug is substantial, being estimated at 15 to 45% of exposures in utero. The risk is maximum in the first trimester of pregnancy and persists up to one month after treatment has been discontinued. The most frequently described multiple malformation syndrome involves the face, the central nervous system and the heart. There is also a 20 to 30% rate of spontaneous abortion. The authors report a case where exposure during the first trimester did not result in foetal malformation. From a full review of the literature the various malformations observed, the presumed mechanisms of teratogenesis and the strict rules of prescription and surveillance in women child-bearing age are presented. The problem of the measures to be taken in case of retinoid treatment during pregnancy is discussed. The teratogenic risk from other retinoids is dealt with."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I107,I107)","v":1514108},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B107:D107)","v":7},1992,"Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants.","Porcelli",1514108,"Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants.    Abstract:   The combination of marginal hepatic retinol stores at delivery and the reduction of daily retinol dose due to complications with the delivery system places the VLBW infant receiving parenteral nutrition at high risk for retinol deficiency during the first month of life. This has serious health implications because retinol is essential during this period for normal growth and repair of the pulmonary tissue in VLBW infants. Enterally fed VLBW infants, on the other hand, receive relatively higher doses of retinol from vitamin-supplemented premature infant formula and fortified breast milk. Equally serious is the problem of monitoring vitamin A status in infants receiving supplemental doses of vitamin A. It seems clear that while plasma vitamin A levels are the most easily available method of monitoring vitamin A status, further studies are necessary to determine if these levels correlate with hepatic content. This is of particular concern since liver disease is common in VLBW infants and vitamin A hepatotoxicity has been described in a cohort of 41 patients receiving therapeutic doses of the vitamin. While further research of daily enteral and parenteral retinol requirements of VLBW infants should continue, formulation of a specific VLBW parenteral vitamin supplement should also be developed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I108,I108)","v":1667403},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B108:D108)","v":7},1991,"Retinoid-binding proteins in craniofacial development.","Dencker",1667403,"Retinoid-binding proteins in craniofacial development.    Abstract:   Cephalic neural crest cells are known to form the frontonasal mesenchyme and contribute to the mesenchyme of the visceral arches. Retinoids affect neural crest cells and their derivatives during development, and thus cause craniofacial, thymus, and conotruncal heart malformations. In addition, retinoids induce malformations of the central nervous system (CNS). Retinoic acid (RA) and its congeners accumulate in a saturable manner in neural crest and neural crest-derived cells, in the hindbrain, and the spinal cord of mouse embryos. Cellular retinoic acid-binding protein (CRABP) was localized by immunohistochemistry in the same areas as were the labelled RA congeners. Thus, CRABP and RA congeners were found in the transitional zone between surface ectoderm and neuropeithelium, from where neural crest cells are known to emanate (day 8 1/2). Later, specific labelling was found in the frontonasal mesenchyme and in the visceral arches. Also in the trunk, neural crest cells were labelled. In CNS, strong staining was seen in the rhombomeres (especially numbers 4-6) of the hindbrain and in the spinal cord. Retinol and cellular retinol-binding protein (CRBP) were more evenly distributed, with exception of surface ectoderm, epithelium of gut, and myocardium, where CRBP was specifically expressed. These findings are discussed in relation to the differential expression of nuclear RA receptors and homeobox genes in the craniofacial region and in the hindbrain. It is possible that RA is important for the normal pattern formation in these regions and acts as a morphogen as previously proposed in limb development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I109,I109)","v":2694156},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B109:D109)","v":7},1989,"Chemoprevention of experimental carcinogenesis in animals.","Moon",2694156,"Chemoprevention of experimental carcinogenesis in animals.    Abstract:   Retinoids are well-established chemopreventive agents for experimental carcinogenesis of many target organs including mammary glands, urinary bladder, lung, skin, liver, pancreas, colon, and esophagus. Modification of the basic retinoid structure has produced analogs with enhanced target organ specificity, increased inhibitory activity, and reduced toxicity. N-(4-hydroxyphenyl)retinamide (4-HPR) currently appears to be the most efficacious retinoid against carcinogen-induced breast, urinary bladder, and lung cancer in rodents. Retinoids are most effective when administered shortly after the carcinogen treatment; however, the treatment can be delayed significantly while maintaining its chemopreventive effect. Under various experimental conditions combining retinoid treatment with other modifiers of growth enhances its chemopreventive activity; for example retinoid plus hormonal modulation can provide better protection against mammary cancer than either treatment alone. More recently chemopreventive activity of various other classes of agents, such as thiols, phenols, antioxidants, inhibitors of prostaglandin synthesis, etc., have been investigated in experimental mammary, urinary bladder, and lung cancer models."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I110,I110)","v":2974796},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B110:D110)","v":7},1988,"Isotretinoin revisited.","Shalita",2974796,"Isotretinoin revisited.    Abstract:   Isotretinoin (13-cis-retinoic acid) remains the drug of choice for treatment of severe, recalcitrant nodulocystic acne that is unresponsive to conventional therapy, including oral antibiotics. The drug has been shown to produce dramatic clearing of lesions and prolonged remissions. The length of remission may be dependent on both the dosage used and the duration of therapy. Since fetal malformations have been observed in infants born of mothers taking isotretinoin during pregnancy, it is mandatory to prevent women who are pregnant or may become pregnant during treatment from taking isotretinoin. Because the half-life of isotretinoin is ten to twenty hours, and because it is eliminated from the body rapidly enough, women may become pregnant one month after discontinuation of therapy without an increased risk of birth defects. Common side effects of the drug include mucocutaneous reactions, serum lipid alterations, eye irritation, and myalgias. Less commonly observed are hyperostoses and exuberant granulation tissue, and rarely, pseudotumor cerebri. Recommendations for substantially reducing or eliminating these effects are made."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I111,I111)","v":3015289},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B111:D111)","v":7},1986,"[Metabolism of vitamin A and retinoids].","Jardillier",3015289,"[Metabolism of vitamin A and retinoids].    Abstract:   Dietary vitamin A is stored in the liver as ester derivatives; after hydrolysis it is transported through the organism bound to a Retinol Binding Protein-Prealbumin complex. Intracellular metabolism is complex and involves the binding to specific receptors for retinol (CRBP) and retinoic acid (CRABP) followed by a nuclear translocation. In addition, retinol can be phosphorylated and implicated in glycosylation processes. Retinoids are characterized by their action on cellular growth and differentiation. Such properties result in anticancer activities which have been clearly put in evidence in vitro and begin to be applied in human oncology. Nevertheless there is always a need for a better comprehension on fundamental mechanisms of natural or synthetic retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I112,I112)","v":6233342},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B112:D112)","v":7},1984,"Isotretinoin and pregnancy.","Stern",6233342,"Isotretinoin and pregnancy.    Abstract:   Approximately 120,000 women of childbearing age used isotretinoin in the first 16 months after its release for the treatment of cystic acne. In September, 1983, the American Academy of Dermatology requested its members to relate the outcome of pregnancies of women inadvertently exposed to isotretinoin ( Accutane ) during pregnancy to its Adverse Drug Reaction Reporting System ( ADRRS ). Of nine pregnancies reported, seven ended in spontaneous abortion or the birth of an infant with birth defects. Of thirty-five pregnancies with isotretinoin exposure reported to the ADRRS or the U.S. Food and Drug Administration, twenty-nine (83%) resulted in spontaneous abortion or infants with birth defects. The most frequently reported severe birth defects involved the central nervous system (microcephaly or hydrocephalus) and the cardiovascular system (anomalies of the great vessels). Microtia or absence of external ears were also noted in a majority of cases. These findings illustrate the usefulness of specialty-based reporting of adverse drug effects and emphasize the teratogenic risk of isotretinoin in humans. Physicians need to fully and carefully inform women of childbearing age of these risks."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I113,I113)","v":27511929},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B113:D113)","v":6},2016,"Biomarkers of Nutrition for Development (BOND)-Vitamin A Review.","Tanumihardjo",27511929,"Biomarkers of Nutrition for Development (BOND)-Vitamin A Review.    Abstract:   The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-informed advice to anyone with an interest in the role of nutrition in health. The BOND program provides information with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect, which will be especially useful for readers who want to assess nutrient status. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutritional status at the individual and population levels. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, folate, zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current article in this series. Although the vitamin was discovered gt;100 y ago, vitamin A status assessment is not trivial. Serum retinol concentrations are under homeostatic control due in part to vitamin As use in the body for growth and cellular differentiation and because of its toxic properties at high concentrations. Furthermore, serum retinol concentrations are depressed during infection and inflammation because retinol-binding protein (RBP) is a negative acute-phase reactant, which makes status assessment challenging. Thus, this review describes the clinical and functional indicators related to eye health and biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk retinol, dose-response tests, isotope dilution methodology, and serum retinyl esters). These biomarkers are then related to liver vitamin A concentrations, which are usually considered the gold standard for vitamin A status. With regard to biomarkers, future research questions and gaps in our current understanding as well as limitations of the methods are described."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I114,I114)","v":25997921},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B114:D114)","v":6},2015,"Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications (Review).","Shilkaitis",25997921,"Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications (Review).    Abstract:   Most studies on cellular senescence (CS) have been performed in vitro by employing cytotoxic agents, irradiation, chromatin and telomerase modulators or by activating certain oncogenes. All these approaches usually lead to DNA damage, gene instability and/or chromatin alterations that primarily affect p53-p21 signaling. Little is known on whether retinoids and rexinoids, which are cell differentiation agents, can also induce CS in vitro and in vivo, and which molecular mechanisms are involved in promoting the senescent phenotype. We reviewed the recent publications on CS induced by retinoids and rexinoids in ER+ and ER- breast cancer cell lines and in corresponding animal models of mammary carcinogenesis which simulate those of human breast cancer. The role of retinoic acid receptors β2 and 5 (RARβ2 and RARβ5) and of receptor independent genes involved in mediating the senescence program of retinoids and rexinoids in ER+ and ER- breast cancer cells is discussed. Potential strategists for clinical implication of CS as biomarker of prognosis and of response to treatment with retinoids, rexinoids and with other cell differentiation and antitumor agents are outlined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I115,I115)","v":25904072},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B115:D115)","v":6},2015,"Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.","Zaragozá",25904072,"Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.    Abstract:   Early pregnancy is associated with a reduction in a womans lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an quot;ideal nichequot; for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcription (STAT3), nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGFβ), and retinoid acid receptors (RARs)/retinoid X receptors (RXRs), are reviewed as part of the complex network of signaling pathways that crosstalk in a contextual-dependent manner. These factors, also involved in breast cancer development, are important regulatory nodes for signaling amplification after weaning. Indeed, during involution, p65/p300 target genes such as MMP9, Capn1, and Capn2 are upregulated. Elevated expression and activities of these proteases in breast cancer have been extensively documented. The role of these proteases during mammary gland involution is further discussed. MMPs, calpains, and cathepsins exert their effect by modification of the extracellular matrix and intracellular proteins. Calpains, activated in the mammary gland during involution, cleave several proteins located in cell membrane, lysosomes, mitochondria, and nuclei favoring cell death. Besides, during this period, Capn1 is most probably involved in the modulation of preadipocyte differentiation through chromatin remodeling. Calpains can be implicated in cell anchoring loss, providing a proper microenvironment for tumor growth. A better understanding of the role of any of these proteases in tumorigenesis may yield novel therapeutic targets or prognostic markers for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I116,I116)","v":25255817},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B116:D116)","v":6},2015,"Stretch marks during pregnancy: a review of topical prevention.","Korgavkar",25255817,"Stretch marks during pregnancy: a review of topical prevention.    Abstract:   Striae gravidarum (SG), or stretch marks developing during pregnancy, affect up to 90% of women. While not medically dangerous, SG can be disfiguring, causing emotional and psychological distress. However, studies specifically addressing the prevention of SG, especially during pregnancy, are sparse. Furthermore, the molecular pathogenesis of SG is unclear and may differ from that of striae from other causes. Considering these factors, we review topical modalities that have been used specifically for preventing SG during pregnancy. We identify two major strategies (end points) addressed by these modalities, namely (i) preventing the de novo development of SG and (ii) reducing the severity of SG that have recently developed. We also identify risk factors for the development of SG and suggest that pregnant women with these risk factors are an appropriate target population for prevention. In reviewing the literature, we find that there is limited evidence that centella, and possibly massage with bitter almond oil, may prevent SG and/or reduce their severity. There is weak evidence that hyaluronic acid prevents SG. Tretinoin holds promise for reducing the severity of new-onset SG, but its use is limited by its pregnancy category. Finally, cocoa butter and olive oil are not effective for preventing SG or reducing the severity of lesions. We conclude that reliable methods for preventing SG are scarce. Furthermore, available topical modalities generally lack strong evidence from rigorous, well-designed, randomized controlled trials with ample numbers of subjects. Thus, further research is necessary to elucidate SG pathogenesis, which may lead to effective prevention modalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I117,I117)","v":24147278},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B117:D117)","v":6},2013,"Isotretinoin: update on controversial issues.","Prevost",24147278,"Isotretinoin: update on controversial issues.    Abstract:   Acne vulgaris is a commonly seen dermatologic condition that plagues millions and can be very psychosocially disabling. Severe and recalcitrant acne is typically treated with isotretinoin. Isotretinoin is a synthetic vitamin A derivative that has been available since 1982.This therapeutic option has been the most effective at putting severe and recalcitrant acne vulgaris into remission. Despite its effectiveness,it has been associated with inflammatory bowel disease, depression, suicidality, and teratogenicity. We review the current literature on isotretinoins role in inflammatory bowel disease, depression, and suicidality. In addition, we review whether or not the iPledge program has been successful at reducing pregnancy rates while on isotretinoin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I118,I118)","v":22419909},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B118:D118)","v":6},2012,"Enzymes of the AKR1B and AKR1C Subfamilies and Uterine Diseases.","Rižner",22419909,"Enzymes of the AKR1B and AKR1C Subfamilies and Uterine Diseases.    Abstract:   Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas and 10-15% suffer from endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG). They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen, and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B) and 1C (AKR1C) superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2, and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2α, which stimulates cell proliferation. AKR1C3 converts PGD2 to 9α,11β-PGF2, and thus counteracts the formation of 15-deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor γ. AKR1B10 catalyzes the reduction of retinal to retinol, and thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises an introduction to uterine diseases and AKR1B and AKR1C enzymes, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes in the pathophysiologies are then discussed, followed by conclusions and future perspectives."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I119,I119)","v":20865785},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B119:D119)","v":6},2010,"The neurobehavioral teratology of retinoids: a 50-year history.","Adams",20865785,"The neurobehavioral teratology of retinoids: a 50-year history.    Abstract:   This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I120,I120)","v":20456381},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B120:D120)","v":6},2010,"Differing obstetric outcomes of rosacea fulminans in pregnancy: report of three cases with review of pathogenesis and management.","Jarrett",20456381,"Differing obstetric outcomes of rosacea fulminans in pregnancy: report of three cases with review of pathogenesis and management.    Abstract:   Rosacea fulminans (RF) is a rare facial dermatosis characterized by the sudden onset of severe facial inflammation consisting of numerous pustules, cystic swellings and coalescing sinuses. The standard treatment is the retinoid drug isotretinoin in combination with systemic corticosteroids or with high-dose oral tetracycline antibiotics. We report three recent cases of RF in pregnancy with differing obstetric outcomes: an intrauterine death, a termination of pregnancy, and a normal vaginal delivery. The pathogenesis of RF is considered and therapeutic options in pregnancy are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I121,I121)","v":19305958},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B121:D121)","v":6},2009,"[Drug therapy during pregnancy].","Schaefer",19305958,"[Drug therapy during pregnancy].    Abstract:   Most acute and chronic diseases do not require termination of a pregnancy nor is a pregnancy a reason to withhold necessary drug therapy. As many pregnancies are unplanned, any drug treatment during reproductive age should consider the occurrence of a pregnancy. Wherever possible, only medicinal drugs with sufficient documentation in pregnant women not indicating developmental toxicity should be chosen. There are acceptable drugs for the majority of diseases, although many of them are labeled as contraindicated during pregnancy. This article provides an overview on prenatal risks of ACE-inhibitors, AT II-receptor antagonists, antiepileptics, SSRI, atypical neuroleptics, lithium, coumarin anticoagulants, retinoids, selected antibiotics, immunomodulatory drugs and provides treatment recommendations for the most common diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I122,I122)","v":19213560},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B122:D122)","v":6},2009,"Retinoids and breast cancer prevention.","Bonanni",19213560,"Retinoids and breast cancer prevention.    Abstract:   Preclinical models suggest that retinoids inhibit mammary carcinogenesis. Induction of apoptosis is a unique feature of fenretinide, the most studied retinoid in clinical trials of breast cancer chemoprevention due to its selective accumulation in breast tissue and its favorable toxicological profile. In a phase III breast cancer prevention trial, fenretinide showed a very strong trend of reduction of incidence of second breast malignancies in premenopausal women, which was confirmed by the 15-year follow-up. Interestingly, ovarian cancer incidence appeared reduced during treatment in the same trial. This warrants further research on fenretinide mechanisms of action and potential efficacy and provides the rationale for a phase III primary prevention trial in young women at high risk for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I123,I123)","v":17326003},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B123:D123)","v":6},2007,"Vitamins as hormones.","Reichrath",17326003,"Vitamins as hormones.    Abstract:   Vitamins A and D are the first group of substances that have been reported to exhibit properties of skin hormones, such as organized metabolism, activation, inactivation, and elimination in specialized cells of the tissue, exertion of biological activity, and release in the circulation. Vitamin A and its two important metabolites, retinaldehyde and retinoic acids, are fat-soluble unsaturated isoprenoids necessary for growth, differentiation and maintenance of epithelial tissues, and also for reproduction. In a reversible process, vitamin A is oxidized IN VIVO to give retinaldehyde, which is important for vision. The dramatic effects of vitamin A analogues on embryogenesis have been studied by animal experiments; the clinical malformation pattern in humans is known. Retinoic acids are major oxidative metabolites of vitamin A and can substitute for it in vitamin A-deficient animals in growth promotion and epithelial differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is not synthesized in the body and must be derived from carotenoids in the diet. On the other hand, retinoids are also hormones - with intracrine activity - because retinol is transformed in the cells into molecules that bind to and activate specific nuclear receptors, exhibit their function, and are subsequently inactivated. The mechanisms of action of natural vitamin A metabolites on human skin are based on the time- and dose-dependent influence of morphogenesis, epithelial cell proliferation and differentiation, epithelial and mesenchymal synthetic performance, immune modulation, stimulation of angiogenesis and inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites have been approved for the topical and systemic treatment of mild to moderate and severe, recalcitrant acne, photoaging and biologic skin aging, acute promyelocytic leukaemia and Kaposis sarcoma. On the other hand, the critical importance of the skin for the human bodys vitamin D endocrine system is documented by the fact that the skin is both the site of vitamin D (3)- and 1,25-dihydroxyvitamin D (3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for 1,25(OH) (2)D (3). 1,25(OH) (2)D (3) is not only essential for mineral homeostasis and bone integrity, but also for numerous further physiologic functions including regulation of growth and differentiation in a broad variety of normal and malignant tissues, including cells derived from prostate, breast and bone. In keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Other newly detected functions of vitamin D analogues include profound effects on the immune system as well as protection against cancer and other diseases, including autoimmune and infectious diseases, in various tissues. Current investigation of the biological effects of vitamin D analogues are likely to lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. This review summarizes existing knowledge on vitamins A and D, the major vitamin-hormones of the skin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I124,I124)","v":15981190},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B124:D124)","v":6},2005,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?","Gallot",15981190,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?    Abstract:   Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis remains poor, with a 50% perinatal mortality rate. Most deaths result from hypoxemia due to lung hypoplasia and abnormal development of pulmonary vasculature that results in persistent pulmonary hypertension. Our current understanding of the pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. Pulmonary hypoplasia, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia precedes the diaphragmatic defect, leading to a quot;dual-hit hypothesis.quot; Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the clinical and epidemiological aspects of human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway, and the implications of retinoids in the development of the diaphragm and the lung. Finally, we highlight the existing links between CDH and disruption of the retinoid-signaling pathway, which may suggest an eventual use of retinoids in the treatment of CDH."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I125,I125)","v":14587861},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B125:D125)","v":6},2003,"Breast cancer prevention trials using retinoids.","Decensi",14587861,"Breast cancer prevention trials using retinoids.    Abstract:   Retinoids have been studied as chemopreventive agents in clinical trials. Given their ability to inhibit mammary carcinogenesis in preclinical models. Fenretinide has extensively been investigated because of its favorable toxicological profile in humans. In a phase III secondary prevention trial, fenretinide showed a trend to a reduction of second breast malignancies in premenopausal women but not in postmenopausal women. This pattern was associated with a similar modulation of circulating IGF-I. A trend towards a reduction of ovarian cancer was also noted. Biomarker studies of fenretinide or novel selective retinoids alone and in combination with different nuclear receptor ligands are being conducted. These studies provide a model for testing the safety and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation in high-risk women, and offer clues as to both the pathophysiology of carcinogenesis and the drug mechanisms of action, and help select new compounds and doses for testing in large randomized studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I126,I126)","v":12743994},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B126:D126)","v":6},2003,"Retinoids, retinoic acid receptors, and breast cancer.","Paik",12743994,"Retinoids, retinoic acid receptors, and breast cancer.    Abstract:   Retinoids comprise both naturally and synthetically occurring compounds that have been proven to be differentiation agents for a variety of neoplasias, including breast cancer and promyelocytic leukemia in animal models and humans. They offer a unique panoply of therapeutics for the prevention or treatment of breast cancer. Nonetheless, considerable controversy remains as to the efficacy and potential toxic side-effects and as to which group of patients may most benefit. In this article, we review evidence of retinoid efficacy in breast cancer in humans and in animal models and provide possible mechanisms of retinoid action in breast cancer treatment, focusing on the roles of the different retinoic acid receptors and the metabolic pathways necessary for gene activation and cellular homeostasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I127,I127)","v":12195157},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B127:D127)","v":6},2002,"Linkage between retinoid and fatty acid receptors: implications for breast cancer prevention.","Stoll",12195157,"Linkage between retinoid and fatty acid receptors: implications for breast cancer prevention.    Abstract:   Certain dietary retinoids and polyunsaturated fatty acids (PUFAs) consistently inhibit progression of mammary carcinogenesis both in animal studies and cell culture, but clinically, their effect is inconsistent. New evidence of synergistic interaction between the nuclear receptors for the two groups of nutritional agents suggests that appropriate selective ligands from each group might be combined in breast cancer chemoprevention studies. Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor that is activated by PUFAs, eicosanoids and antidiabetic agents such as troglitazone. Such activation can cause growth inhibition in human mammary cancer cells in culture and the effect is enhanced by ligands of retinoic acid receptor (RAR) and retinoid X receptor (RXR). In mouse mammary tissue in organ culture, an RXR-selective ligand has been shown to enhance the effect of troglitazone in suppressing carcinogen-induced pre-neoplastic changes. A PPAR/RXR heterodimer is involved in tumour growth inhibition and has been shown to bind directly to nuclear oestrogen response elements (ERE) independently of oestrogen receptor (ER) activity. A combination of an RXR-selective retinoid with either troglitazone or else a long-chain n-3 PUFA, is proposed for a short-term study in postmenopausal women after primary surgery for intraductal breast cancer. The resulting activation of PPAR/RXR expression may increase response to retinoid administration, especially in the presence of obesity and insulin resistance, because of the ability of PPAR gamma ligands to reduce insulin-like growth factor I (IGF-I) concentrations. Serial core biopsies of breast tissue over a short term are proposed to identify changes in phenotype, which may influence progression to invasiveness. In addition to cytomorphological criteria, expression of ER alpha and beta, RAR alpha and beta, and IGF-I receptor in the nucleus should be examined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I128,I128)","v":11921197},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B128:D128)","v":6},2002,"Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention.","Zujewski",11921197,"Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention.    Abstract:   Tamoxifen has been shown to decrease the risk of invasive breast cancer by 49% and noninvasive breast cancer by 50%. Tamoxifen is also associated with a threefold increased risk of endometrial cancer. Raloxifene, a second-generation selective estrogen receptor modulator (SERM), has not been associated with endometrial cancer risk, and is currently under study in a large, multi-institutional, randomized Study of Tamoxifen and Raloxifene (STAR) for breast cancer prevention in postmenopausal women. A pilot trial of raloxifene in premenopausal women to assess the safety, tolerability, effects on bone mineral density, mammographic density, and other biological endpoints is ongoing. The retinoids have been shown to decrease mammary tumors in rodent carcinogenesis models. The Italian trial of fenretinide (4-HPR) in women with stage I breast cancer randomized women to fenretinide or no intervention. This study did not show an overall effect of decreasing the risk of contralateral breast cancer. However, a protective effect was suggested in premenopausal women. It has been suggested that this effect may be related to insulin-like growth factor 1 (IGF-1), which has been shown to be modulated by fenretinide in premenopausal but not postmenopausal women. Pilot studies of SERMs alone and in combination with retinoids or other agents provide a model for testing the safety and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation in high-risk women. These studies can provide information as to both the pathophysiology of carcinogenesis and the mechanism of action of chemopreventive agents, and help select agents and doses for testing in large randomized studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I129,I129)","v":11501579},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B129:D129)","v":6},2001,"Epigenetic downregulation of the retinoic acid receptor-beta2 gene in breast cancer.","Widschwendter",11501579,"Epigenetic downregulation of the retinoic acid receptor-beta2 gene in breast cancer.    Abstract:   A growing body of evidence supports the hypothesis that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene which induces apoptosis and that the chemopreventive and therapeutic effects of retinoids are due to induction of RAR-beta2. During breast cancer progression, RAR-beta2 is reduced or even lost. It is known from studies of other tumor-suppressor genes that methylation of the 5-region is the cause of loss of expression. Several groups demonstrated that this is also true for the RAR-beta2 in breast cancer by treating breast cancer cell lines with a demethylating agent and examining expression of the RAR-beta2 gene in response to a challenge with retinoic acid. Studies using sodium bisulfite genomic sequencing as well as methylation specific PCR showed that a number of breast cancer cell lines as well as breast cancer tissue showed signs of methylation. The RAR-beta2 gene was unmethylated in non-neoplastic breast tissue as well as in other normal tissues. A combination of retinoic acid with demethylating agents as well as with histone deacetylase inhibitors acts synergistically to inhibit growth. This review presents data that suggest that treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality. Both the time of commencement of chemoprevention and the choice of substances that are able either to prevent de novo methylation or to reverse methylation-caused gene silencing may be important considerations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I130,I130)","v":11140907},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B130:D130)","v":6},2000,"The oxidation of 9-cis-retinol: a possible synthesis pathway for 9-cis-retinoic acid.","Wolf",11140907,"The oxidation of 9-cis-retinol: a possible synthesis pathway for 9-cis-retinoic acid.    Abstract:   A short-chain alcohol dehydrogenase has been discovered that oxidizes 9-cis- and 11-cis-retinol to their corresponding aldehydes. The gene for this enzyme was sequenced and appears to be expressed with highest efficiency in the retinal pigment epithelium of the eye, as well as in human liver and mammary gland and in mouse liver and kidney. Because 9-cis-retinol occurs in liver, it may be a precursor of 9-cis-retinoic acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I131,I131)","v":10776699},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B131:D131)","v":6},2000,"Acute promyelocytic leukemia and pregnancy.","Giagounidis",10776699,"Acute promyelocytic leukemia and pregnancy.    Abstract:   In acute promyelocytic leukemia (APL), the use of all-trans-retinoic acid (ATRA) as a differentiating agent induces complete remission in a high percentage of patients. In pregnancy, however, this drug bears the risk of severe teratogenicity to the child. We report the case of a 23-yr-old woman at 21 weeks gestation suffering from APL. She was treated with ATRA (45 mg/m2) for 40 d and two courses of standard chemotherapy. The mother achieved complete remission within 22 d of treatment. Fetal development was normal, and a healthy premature girl was born in the 35th week of pregnancy. In a review of the literature we have identified 14 cases of APL in pregnancy treated with ATRA alone or in combination with chemotherapy. ATRA has been used as early as in the 3rd week of gestation and in no case have malformations or other teratogenic effects occurred. Side-effects, however, ranged from fetal cardiac arrhythmias to induction of labour. Although known to exhibit severe teratogenic effects during the first trimester of pregnancy, ATRA seems to be reasonably safe during the second and third trimesters in the treatment of APL. However, careful obstetric follow-up is mandatory regarding fetal cardiac complications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I132,I132)","v":9431575},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B132:D132)","v":6},1998,"Periconceptional vitamin A use: how much is teratogenic?","Miller",9431575,"Periconceptional vitamin A use: how much is teratogenic?    Abstract:   The objective of the review is to determine whether preformed vitamin A (retinol and retinyl esters) is teratogenic at dosages commonly used by women living in industrialized countries. Published human and animal data and research developed by the authors are reviewed. It is well known that vitamin A is essential for normal reproduction and development. Although doses of 10,000 IU/d or less of preformed vitamin A (retinyl esters and retinol) are considered safe, doses gt; 10,000 IU/d as supplements have been reported to cause malformations in a single epidemiologic study. Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 IU/d of preformed vitamin A have not been sufficiently studied to establish specific risk. Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the Recommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who otherwise have nutritionally adequate diets may not need to ingest more than the Recommended Dietary Allowance of preformed vitamin A as supplements. If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 micrograms RE/d) do occur unintentionally, multiple animal studies do support only very low risk. Human epidemiologic studies do not establish at what level vitamin A becomes teratogenic; however, pharmacokinetic data presented in this paper indicate that blood levels of retinoids from women taking 30,000 IU/d of preformed vitamin A are not greater than retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. Interestingly, neither teratogenicity nor vitamin A toxicity has been observed in multiple species exposed to high doses of beta-carotene."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I133,I133)","v":9219460},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B133:D133)","v":6},1997,"Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome.","Tamura",9219460,"Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome.    Abstract:    OBJECTIVE : To review the relationships between various laboratory measures relating to nutrition and pregnancy outcome. The data were obtained during the investigation entitled quot;Successive small-for-gestational-age births studyquot;.  METHODS : A total of 289 pregnant women of the 1545 who participated in the study between 1986 and 1988 in Birmingham, Alabama, USA. The following determinations were done using the serum samples obtained at 18 and 30 weeks of gestation: zinc, folate, vitamins A and E, and proteins (alpha-2-macroglobulin, retinol-binding protein, prealbumin, and albumin). These laboratory values were correlated with various measures of pregnancy outcome including the incidence of fetal-growth retardation and maternal infections during the perinatal period and birth weight and Apgar score of infants.  RESULTS : Serum folate concentrations showed positive relationships with the incidence of fetal-growth retardation as well as birth weight of infants, and alpha-2-macroglobulin was negatively correlated with birth weight. These relationships were significant after adjusting for factors previously known to affect the birth weight of infants. The concentrations of serum zinc, vitamins A and E, and proteins did not show significant correlation with measures of pregnancy outcome.  CONCLUSION : Among the laboratory measures evaluated in this study, serum folate and alpha-2-macroglobulin concentrations correlated with pregnancy outcome. Further research is warranted to investigate the mechanism(s) of the relationship between serum alpha-2-macroglobulin and birth weight of infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I134,I134)","v":9077255},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B134:D134)","v":6},1996,"Fish and healthy pregnancy: more than just a red herring!","Rice",9077255,"Fish and healthy pregnancy: more than just a red herring!    Abstract:   In modern Western diets we eat predominantly omega-6 essential fatty acids from vegetable oils, and too little omega-3. The Department of Health recommends doubling the amount of omega-3s we eat. Omega-3 essential fatty acids (EFAs) are derived mainly from fish oils. Omega-3s are believed to help reduce the risks of cardiovascular disease. Among the main materials required for fetal brain and CNS growth in late pregnancy are omega-3s (mainly docosahexaenoic acid [DHA]) and omega-6 EFAs (mainly arachidonic acid [AA]). These come from the mothers diet. Several formulae for preterm infants now contain DHA and AA to aid optimum brain, nerve and retinal development. One manufacturer has begun to include DHA and AA in formulae for term babies. Breast milk contains DHA and AA, derived from the mothers diet. Eating oily fish in pregnancy has been found to have a slight beneficial effect on birthweight and length of gestation. Eating fresh or canned oil-rich fish (e.g. kippers, herring, mackerel, salmon, sardine, pilchards, tuna) twice or three times a week can be encouraged as part of a healthy balanced diet, in pregnancy and for all the family. As well as containing omega-3 polyunsaturates, oily fish is a good source of protein and vitamins A and D. Alternatively, a fish-oil supplement may be taken. Cod liver oil is best avoided during pregnancy, because of concerns over the possible teratogenicity of vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I135,I135)","v":8825126},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B135:D135)","v":6},1996,"The efficacy of 9-cis retinoic acid in experimental models of cancer.","Gottardis",8825126,"The efficacy of 9-cis retinoic acid in experimental models of cancer.    Abstract:   9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemotherapeutic agent. Treatment of the human promyelocytic leukemia cell line HL-60 with 9-cis RA decreases cell proliferation, increases cell differentiation, and increases apoptosis. Induction of apoptosis correlates with an increase in tissue transglutaminase (type II) activity. In vivo, 9-cis RA induces complete tumor regression of an early passage human lip squamous cell carcinoma xenograft. Finally, 9-cis RA inhibits the anchorage-independent growth of the human breast cancer cell lines MCF-7 and LY2 (an antiestrogen-resistant MCF-7 variant). Transient co-transfection assays indicate that 9-cis RA inhibits estrogen receptor transcription of an ERE-tk-LUC reporter through RAR or RXR receptors. These data suggest that retinoid receptors can antagonize estrogen-dependent transcription and provides one possible mechanism for the inhibition of cell growth by 9-cis RA in breast cancer cell lines. In summary, these findings present evidence that 9-cis RA has a wide range of activities in human cancer models."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I136,I136)","v":8573297},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B136:D136)","v":6},1995,"Risks and benefits of retinoids in the chemoprevention of cancer.","de Palo",8573297,"Risks and benefits of retinoids in the chemoprevention of cancer.    Abstract:   Chemoprevention of cancer is a new branch of clinical research; it may be defined as the reduction of cancer incidence by pharmacological means through the suppression of established malignant cell clones or through alteration in growth and progression of premalignant cell populations. In the last few years, this area of research has progressed dramatically from preclinical studies to phase I, II and III clinical trials. Among the various chemical or natural compounds used as chemopreventive agents, retinoids appear to be one of the most promising groups of agents. Analyses of preclinical and clinical studies have shown retinoids to be active in reversing skin and oral precancer, in preventing primary skin cancer, superficial bladder cancer, and second primary tumours associated with head and neck and lung cancers. Preclinical studies have shown evidence of the activity of fenretinide in breast cancer. Preliminary clinical data seem to show a protective effect of fenretinide against ovarian cancer. Current evidence therefore suggests that chemoprevention of cancer with retinoids is a promising path."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I137,I137)","v":8527214},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B137:D137)","v":6},1995,"Retinoids as teratogens.","Soprano",8527214,"Retinoids as teratogens.    Abstract:   Vitamin A is a necessary nutrient in the diet. However, excessive doses of retinoids by pregnant women result in teratogenesis. In this chapter, we initially discuss the occurrence and characteristics of fetal malformations associated with maternal ingestion of natural and synthetic retinoids in both experimental animals and humans. We then turn to an examination of the pharmacology of teratogenic retinoids, focusing on structure-function relationships and pharmacokinetics. Finally, we review the current literature on the molecular mechanism of action of teratogenic doses of retinoids and the role of the retinoic acid receptors and other target genes in this process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I138,I138)","v":7499738},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B138:D138)","v":6},1995,"[Isotretinoin (RoAccutane) embryopathy. A case report].","Pilorget",7499738,"[Isotretinoin (RoAccutane) embryopathy. A case report].    Abstract:   Retinoids are synthetic vitamin A derivatives, particularly used in dermatology. Their prescription in women of childbearing age can cause, if pregnancy occurs, a serious malformative embryopathy, mainly involving external ear, brain and heart. A neonatal case caused by isotretinoin (RoAccutane) emphasizes the clinical and epidemiological data concerning this embryopathy. The aetiopathological hypothesis of an interaction between isotretinoin and Hox genes is advanced. Prophylactic measures are difficult since neonatal reported cases are uncommon, but antenatal exposition to this strong teratogenic agent results in multiple spontaneous abortions or pregnancy interruptions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I139,I139)","v":8058294},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B139:D139)","v":6},1994,"[Retinoids in the therapy of diseases of the hematopoietic system and malignant tumors].","Bán",8058294,"[Retinoids in the therapy of diseases of the hematopoietic system and malignant tumors].    Abstract:   The antitumor effect of different retinoids focused attention in the treatment of malignant disorders on different pathways. The therapeutic effect was proved in acute promyelocytic leukaemia, but was limited in juvenile form of chronic myeloid leukaemia and in acute myelomonocytic and monoblastic leukaemia. Combined with different leukostatics, long remission could be achieved. The most important therapeutic pathway is direct growth inhibition with and without cell differentiation. Clinically, retinoids are effective in tumours, like: cutan T-cell lymphoma, mycosis fungoides, Sézary syndrome, oral leukoplakia (prevention of head and neck cancer metastases), variant form of small lung cell carcinoma, oestrogen dependent breast-carcinoma and cervix-carcinoma. The most serious complication of the retinoids administration is the retinoic acid syndrome which is followed sometimes with thromboembolic events. Retinoids are teratogenic and hepatotoxic."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I140,I140)","v":7725952},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B140:D140)","v":6},1994,"Vitamin A, retinoids and breast cancer.","Moon",7725952,"Vitamin A, retinoids and breast cancer.    Abstract:   Both epidemiologic and experimental evidence are highly suggestive of an inverse relationship between vitamin A status and cancer induction. However, protection by vitamin A and retinoids has not been a universal finding, nor are the compounds equally effective in inhibiting cancer induction at all organ sites. Although the experimental evidence for a protective effect of retinoids is especially strong for mammary cancer, the epidemiologic evidence is less convincing. Chronic pharmacologic administration of retinoids may be limited by their potential toxicity; such potential toxicity is particularly important in light of the expectation that, in order to achieve effective anticarcinogenesis in a clinical setting, administration of retinoids may be required at relatively high doses for extended periods. Clinical trials to determine the efficacy of several retinoids as cancer preventive agents are only in the early stages. Meanwhile, experimentation to develop synthetic vitamin A analogs with increased activity, increased target organ specificity, and reduced toxicity must continue. The question of increasing anticarcinogenic activity by increasing vitamin A intake in populations whose vitamin A status is normal is more difficult to assess. The vast majority of epidemiologic studies indicate that groups with a relatively high intake of carotenoids are at a reduced risk for cancer in several target tissues. However, in populations whose vitamin A status is not deficient, increases in vitamin A and carotene intake are not well correlated with increases in serum vitamin A.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I141,I141)","v":8382073},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B141:D141)","v":6},1993,"Breast cancer chemoprevention.","Costa",8382073,"Breast cancer chemoprevention.    Abstract:   Cancer chemoprevention is a new challenging issue for oncology. For breast cancer, different strategies for risk avoidance, chemopreventive measures and chemosuppressive interventions are being investigated. Attention is presently focused on two compounds, the synthetic retinoid fenretinide (4-HPR) and the antioestrogen tamoxifen, and their possible synergism. More data are now available on the expression and regulation of retinoic acid receptors in human breast cancer cells and on the consequences of the interaction of retinoids with plasma retinol binding protein. Mechanistic relationships between retinoids and growth factors like transforming growth factor-beta have been demonstrated in the frame of a central regulatory system of the state of differentiation and proliferation, in which tamoxifen is involved as well. Recent data from different trials using tamoxifen as adjuvant treatment have shown a decrease in the incidence of contralateral new primaries and that it could soon become unethical not to prescribe this drug to all node-negative oestrogen receptor-positive postmenopausal patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I142,I142)","v":8145203},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B142:D142)","v":6},1993,"Embryo-uterine interactions in pigs during week 2 of pregnancy.","Roberts",8145203,"Embryo-uterine interactions in pigs during week 2 of pregnancy.    Abstract:   The second week of pregnancy is a particularly critical period for embryonic survival in pigs. Within that time, conceptus oestrogen synthesis is initiated, spacing and final placement of conceptuses is completed, and the signal for extending the functional lifespan of the corpora lutea is received by the mother. There is also a marked increase in blood flow to the uterus and the uterine endometrium produces and secretes nutrient histotrophe. Conceptus-derived oestrogen has been implicated in many of these events. It is also during this period that the trophoblast elongates dramatically and the inner cell mass starts to differentiate into the embryo proper. Here, we critically review the evidence that oestrogen is the sole factor initiating long-term corpus luteum maintenance in pigs. We also review the functions and general properties of the major secretory proteins in histotrophe and the role of oestrogen in controlling their expression. It is now generally accepted that asynchrony within a litter underlies much of the losses of conceptuses that are otherwise genetically normal, but which are lagging in their development; however, the underlying mechanisms remain unclear. Here we hypothesize that oestrogenic compounds derived from more advanced conceptuses or provided prematurely, either by injection or in the diet, trigger a massive increase in uterine expression and secretion of retinol-binding protein laden with retinol. We propose that less developed, smaller conceptuses are least able to contend with the sudden exposure to this potential teratogen at a time when they are particularly susceptible to imbalance in retinol supply. Hence, even though their growth proceeds for a few days, their developmental potential is irrevocably compromised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I143,I143)","v":3896699},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B143:D143)","v":6},1985,"Retinoids and mammary gland differentiation.","Moon",3896699,"Retinoids and mammary gland differentiation.    Abstract:   Certain retinoids serve as effective chemopreventive agents against breast cancer. The effective retinoids are also antiproliferative agents for the mammary gland both in vivo and in vitro. N-(4-hydroxyphenyl)retinamide (HPR) can inhibit the occurrence of hyperplastic alveolar nodules in C3H mice in vivo and 7,12-dimethylbenz[a]anthracene-induced nodule-like alveolar lesions in vitro. Moreover, HPR can also inhibit the phorbol ester-induced promotion of hyperplastic alveolar nodule development in vitro. HPR is metabolized by the mammary gland in vitro and one of the metabolites competes for the cytosolic retinoic acid-binding protein although the metabolite is not all-trans-retinoic acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I144,I144)","v":6349358},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B144:D144)","v":6},1983,"Vitamin A.","Schoeff",6349358,"Vitamin A.    Abstract:   Vitamin A refers collectively to a number of compounds, the most biologically active of which is retinol. Named after its earliest discovered function, visual excitation, retinol is also needed for growth and reproduction, and differentiation of epithelial tissue. A closely related form, retinoic acid, has selective biologic activity for normal growth and epithelial differentiation. The term retinoids has been used in recent years to include both natural and synthetic analogs of vitamin A. Carotene and carotenoids refer to vitamin A precursors (pro-vitamins) of vegetable origin. Following a brief historical account of vitamin A and description of dietary information this article focuses on the chemistry and physiology of retinoids. The biological roles of vitamin A compounds are elaborated, as well as the clinical significance of vitamin A deficiency and excess. Discussion of retinoids in therapy includes their use as anti-cancer agents and as therapeutics for dermatological disorders. Finally, a review of analytical techniques for laboratory assessment of vitamin A is presented."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I145,I145)","v":22827398},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B145:D145)","v":5},2012,"Immunity and inflammation in the uterus.","Turner",22827398,"Immunity and inflammation in the uterus.    Abstract:   Microbes often infect the uterus and particularly the endometrium of animals. Infections are most commonly associated with natural service, pregnancy and the post-partum period, leading to inflammation with the elaboration of cytokines, chemokines and prostaglandins. Clinical diseases such as metritis, endometritis and abortion are important causes of infertility. The adaptive immune response to infection has been characterized previously, so the present review aims to highlight the emerging role for innate immunity in the endometrium. The detection of microbes and the innate immune response depends on the detection of pathogen-associated molecular patterns by pattern recognition receptors. The main families of pattern recognition receptors are Toll-like receptors (TLRs), nucleotide oligomerization domain-like receptors, retinoic acid-inducible gene I-like receptors and C-type lectin receptors. These receptors are most often expressed by hematopoietic cells, but the epithelial and stromal cells of the endometrium also possess functional receptors. For example, endometrial cells express TLR4 for recognition of the lipopolysaccharide endotoxin of Gram-negative bacteria, leading to secretion of IL-6, IL-8 and prostaglandin E(2) . It is likely that the epithelial and stromal cells provide a first line of defence in the endometrium to alert hematopoietic cells to the presence of microbes within the uterus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I146,I146)","v":22594552},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B146:D146)","v":5},2012,"Maternal nutrition among women from Sub-Saharan Africa, with a focus on Nigeria, and potential implications for pregnancy outcomes among immigrant populations in developed countries.","Lindsay",22594552,"Maternal nutrition among women from Sub-Saharan Africa, with a focus on Nigeria, and potential implications for pregnancy outcomes among immigrant populations in developed countries.    Abstract:   Pregnant women in countries of Sub-Saharan Africa (SSA) are at risk of poor nutritional status and adverse outcomes as a result of poverty, food insecurity, sub-optimal healthcare facilities, frequent infections and frequent pregnancies. Studies from Nigeria, for example, have revealed a high prevalence of both under- and over-nutrition, as well as nutrient deficiencies, including iron, folate, vitamin D and vitamin A. Subsequently, obstetric complications, including hypertension, anaemia, neural tube defects, night-blindness, low birth weight and maternal and perinatal mortality, are common. Migration patterns from SSA to the Western world are on the rise in recent years, with Nigerians now representing the most prevalent immigrant African population in many developed countries. However, the effect of immigration, if any, on the nutritional status and pregnancy outcomes of these women in their host countries has not yet been studied. Consequently, it is unknown to what extent the nutritional deficiencies and pregnancy complications occurring in Nigeria, and other countries of SSA, present in these women post-emigration. This may result in missed opportunities for appropriate antenatal care of a potential high-risk group in pregnancy. The present review discusses the literature regarding nutrition in pregnancy among SSA women, using Nigeria as an example, the common nutrition-related complications that arise and the subsequent obstetric outcomes. The concept of dietary acculturation among immigrant groups is also discussed and deficiencies in the literature regarding studies on the diets of pregnant immigrant women are highlighted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I147,I147)","v":22500077},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B147:D147)","v":5},2012,"Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk?","Cazzaniga",22500077,"Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk?    Abstract:   The incidence and mortality of breast cancer have been recently influenced by several new therapeutic strategies. In particular our knowledge on cancer precursors, risk biomarkers, and genetics has considerably increased, and prevention strategies are being successfully explored. Since their discovery, retinoids, the natural and synthetic derivatives of vitamin A, have been known to play a crucial role in cell and tissue differentiation and their ability to inhibit carcinogenesis has made them the ideal chemopreventive agents studied in several preclinical and clinical trials. Fenretinide (4-HPR) is the most studied retinoid in breast cancer chemoprevention clinical trials due to its selective accumulation in breast tissue and its favorable toxicological profile. This agent showed a significative reduction of the incidence of second breast tumors in premenopausal women confirmed after 15-year followups. Considering Fenretinide protective action, a similar trend on ovarian cancer, this drug warrants reevaluations as a preventive agent for high-risk young women, such as BRCA-1 and 2 mutation carriers or with a high familial risk. This favorable effect therefore provides a strong rationale for a primary prevention trial in these unaffected cohort of women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I148,I148)","v":22052311},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B148:D148)","v":5},2011,"A review of the chemopreventative effects of oral retinoids for internal neoplasms.","Bhutani",22052311,"A review of the chemopreventative effects of oral retinoids for internal neoplasms.    Abstract:   With the recent data showing that psoriasis patients are at higher risk for systemic malignancies, there is a growing awareness for the need to minimize cancer risks in psoriasis patients. Retinoids as a class of medication have been widely studied as potential agents for cancer chemoprevention. Since they act by inducing cell differentiation and maturation, they may help reverse the pathogenesis of malignancies. Through an extensive literature review, this paper provides an update on the available data on retinoids and their systemic anti-cancer properties. Retinoids appear to be beneficial in the prevention of cutaneous T-cell lymphoma, acute promyelocytic leukemia, head and neck cancers, hepatocellular carcinoma, breast cancer and neuroblastoma. So far the data does not support anti-cancer efficacy of retinoids in the prevention of prostate or pancreatic cancer and may possibly have harmful effects in the pathogenesis of lung cancer in smokers. J Drugs Dermatol. 2011;10(11):1292-1298."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I149,I149)","v":20638138},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B149:D149)","v":5},2010,"Development of canal cholesteatoma in a patient with prenatal isotretinoin exposure.","Van Abel",20638138,"Development of canal cholesteatoma in a patient with prenatal isotretinoin exposure.    Abstract:    PURPOSE : To describe the clinical and radiologic findings in a case of isotretinoin embryopathy-like syndrome and discuss management of hearing loss, congenital external auditory canal (EAC) stenosis, and EAC cholesteatoma.  METHODS : Review of medical, audiological, and radiological records.  RESULTS : An 8 year old female presented with bilateral moderate conductive hearing loss, bilateral microtia, left EAC stenosis, and right EAC atresia, secondary to prenatal isotretinoin exposure. Comorbidities included developmental delay, ventricular septal defect, hypotonia, and retinal maldevelopment. The left EAC was sharply upsloping with a 2mm-diameter meatus. Computed tomography (CT) scan of the temporal bone demonstrated normal middle and inner ears bilaterally; serial CT scans over 6 years demonstrated progressive development of left canal cholesteatoma. Implantation of a right BAHA system was performed, followed by left canalplasty and excision of cholesteatoma with facial nerve monitoring. An endaural incision was utilized to avoid compromising future microtia repair. Postoperative left-sided hearing improved to mild low-frequency conductive hearing loss rising to normal at 2000 Hz and above.  CONCLUSIONS : Despite extensive precautions for its use, isotretinoin remains a cause of major birth defects, including sensorineural, conductive or mixed hearing loss. Congenital EAC stenosis is much less common than congenital atresia or acquired stenosis; optimal surgical approaches vary depending on hearing status and facial nerve anatomy. Close monitoring for development of canal cholesteatoma is necessary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I150,I150)","v":19386214},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B150:D150)","v":5},2009,"Dermatologic medication in pregnancy.","Turcić",19386214,"Dermatologic medication in pregnancy.    Abstract:   In female body, a vast number of skin changes occur during pregnancy. Some of them are quite distressing to many women. Therefore, performing treatment for physiologic skin changes during pregnancy with antiinfective agents, glucocorticosteroids, topical immunomodulators, retinoids, minoxidil, etc., is discussed. Drug administration during pregnancy must be reasonable."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I151,I151)","v":19275755},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B151:D151)","v":5},2009,"The novel RARbeta isoform (beta5) is a potential target of retinoids in breast cancer.","Christov",19275755,"The novel RARbeta isoform (beta5) is a potential target of retinoids in breast cancer.    Abstract:   Retinoic acid receptor beta 2 (RARbeta2) isoform has been considered a putative tumor suppressor because it is expressed in normal cells but is lacking in most tumors, including breast cancer. Recently, we identified a novel RARbeta isoform (beta5) in breast cancer cells, which may sereve as a potential target of retinoids in cancer prevention and therapy studies. In this review are summarized the data on the expression of RARbeta5 and of the previously identified RARbeta4 and RARbeta isoforms in various breast cancer cell lines. We found that RARbeta5 may serve as a potential biomarker of resistance of breast cancer cells to retinoids and thus may have clinical implication in selecting patients that may benefit the most from clinical trials with retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I152,I152)","v":19136457},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B152:D152)","v":5},2009,"Reproductive outcome after bariatric surgery: a critical review.","Guelinckx",19136457,"Reproductive outcome after bariatric surgery: a critical review.    Abstract:    BACKGROUND : After many cycles of weight loss and weight gain, more and more morbidly obese patients undergo bariatric surgery, like gastric banding or gastric bypass, as the ultimate treatment for their obesity-problem. Since women of reproductive age are candidates for bariatric surgery, concerns arise regarding the potential impact on future pregnancy.  METHODS : English-language articles were identified in a PUBMED search from 1982 to January 2008 using the keywords for pregnancy and bariatric surgery or gastric bypass or gastric banding.  RESULTS : The few reported case-control and cohort studies clearly show improved fertility and a reduced risk in obstetrical complications, including gestational diabetes, macrosomia and hypertensive disorders of pregnancy, in women after operatively induced weight loss when compared with morbidly obesity women. The incidence of intrauterine growth restriction (IUGR) appears to be increased, however. No conclusions can be drawn concerning the risk for preterm labour and miscarriage, although these risks are probably increased compared with controls matched for body mass index. Operative complications are not uncommon with bariatric surgery and several cases have pointed to the increased risk for intestinal hernias and nutritional deficiencies in subsequent pregnancy. Deficiencies in iron, vitamin A, vitamin B(12), vitamin K, folate and calcium can result in both maternal complications, such as severe anaemia, and fetal complications, such as congenital abnormalities, IUGR and failure to thrive.  CONCLUSIONS : Close supervision before, during and after pregnancy following bariatric surgery and nutrient supplementation adapted to the patients individual requirements can help to prevent nutrition-related complications and improve maternal and fetal health, in this high-risk obstetric population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I153,I153)","v":18957339},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B153:D153)","v":5},2008,"[Alcohol and pregnancy: diagnostic aspects and abnormalities in the placental vitamin A pathway].","Sapin",18957339,"[Alcohol and pregnancy: diagnostic aspects and abnormalities in the placental vitamin A pathway].    Abstract:   Maternal alcohol drinking during pregnancy is a reality in France leading to new-born specific clinical signs called quot;Fetal alcoholic syndrome/FASquot; in 1.5 per 1000 births and to common clinical signs grouped into quot;Fetal Linked to Alcohol Spectrum Disordersquot; in 5 per 1000 births. Our works presented for the attribution of the SFBC 2007 price talked about two aspects of this public health problem. The first presented the recent evaluation of the alcohol consumption during pregnancy in Auvergne by the realization of the DATAMATER clinical and biological study on more than 800 quot;mother/babyquot; couples. We confirmed the reality of such maternal drinking (1.8 FAS per 1000 births) and also the useless of biological tools to help the diagnosis of the clinician where the clinical signs did not clearly belonged to FAS and when the maternal consumption was asked. The second aspect reviewed the placental abnormalities occurring during the FAS, which could explain the intra-uterine growth retardation. To better understand the genesis of such alterations, we proposed a new physio-pathological mechanism. The alcohol could alter the retinol (vitamin A) activation into retinoic acid, a fundamental morphogenic molecule for the optimal development and functions of the placenta."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I154,I154)","v":18854810},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B154:D154)","v":5},2008,"[Is micronutrients supplementation useful in pregnancy?].","De Leo",18854810,"[Is micronutrients supplementation useful in pregnancy?].    Abstract:   Use of micronutrients in pregnancy appears to be useful in prevention of some pregnancy related pathologies if used continuously before and during all nine months of pregnancy. The assumption of specific micronutrients, with vitamins and mineral salt inside, could be use to correct some deficiencies and prevent the onset of specific pregnancy related diseases. An adequate support of micronutrients can ensure physiological fetal growth contributing to the development of various fetal organs. Besides folic acid administered in appropriate doses (gt;400 mug), that it is able to prevent some fetal diseases, such as the closure of the neural tube, other vitamins such as vitamin A are very effective in ensuring an optimal state of health of the mother and slowing the growth of uterine myomas."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I155,I155)","v":17168722},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B155:D155)","v":5},2006,"Nuclear retinoic acid receptor beta as a tool in chemoprevention trials.","Pavan",17168722,"Nuclear retinoic acid receptor beta as a tool in chemoprevention trials.    Abstract:   Retinoic acid (RA) and its natural and synthetic derivatives (retinoids) are important dietary factors which regulate cellular differentiation and growth, so that they are thought to be particularly effective at preventing the development of several tumours. They play this role as ligands of the RAR and RXR nuclear retinoic acid receptors, including the RA receptor isoforms alpha, beta, and gamma. These ligand-activated nuclear receptors induce the transcription of target genes by binding to RA-responsive elements in the promoter regions. Among these target genes, the RARbeta gene is of great interest, being able to encode a potential tumour suppressor. It should be emphasized that most breast carcinomas and breast cancer cell lines show loss or down-regulation of RARbeta receptor expression, whereas RARalpha and gamma, as well as retinoid X receptors, appear to be variably expressed in both normal and tumour cells. It is also interesting to note that basal and RA-induced RARbeta mRNA levels tend to increase with senescence of normal cells. This information provides further support for the hypothesis that genetic events involved in cellular senescence may also play a significant role in tumour suppression in humans. The aim of this review is to clarify whether expression of RARbeta could be modulated by chemopreventive intervention and may therefore serve as an intermediate biomarker in chemoprevention trials for some cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I156,I156)","v":16984470},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B156:D156)","v":5},2006,"Bovine early embryonic development and vitamin A.","Gómez",16984470,"Bovine early embryonic development and vitamin A.    Abstract:   Vitamin A and its derivatives, collectively termed as retinoids, have been paid attention in recent years because of their effects in bovine reproduction. However, the role of retinoids in the pre-implantation period continues to be largely unexplored, in contrast to later stages of development. Retinoids control cell growth, differentiation and death through binding to specific nuclear receptors by retinoic acid and other active metabolites. This paper reviews how retinoids can influence early embryonic development in cattle through their influence on the follicle, the extrafollicular oocyte and the pre-implantation embryo itself."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I157,I157)","v":15773539},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B157:D157)","v":5},2005,"An update on the safety and efficacy of topical retinoids.","Phillips",15773539,"An update on the safety and efficacy of topical retinoids.    Abstract:   Adapalene, tazarotene, and tretinoin are topical retinoids that are approved by the US Food and Drug Administration (FDA) and have overall favorable safety profiles. These agents are effective in a variety of skin disorders. Local adverse events, seen especially during the early course of treatment, include peeling, erythema, dryness, burning, and itching. The degree of local skin intolerance varies among patients and may relate to the vehicle formulation used. These local effects can be minimized by decreasing exposure to sunlight, avoiding extreme temperatures, and using moisturizers. Use of these agents has been found to be advantageous over current systemic retinoids from a toxicologic perspective. This article reviews the safety, efficacy, and photostability of the available topical retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I158,I158)","v":15049600},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B158:D158)","v":5},2004,"[Prescription of retinoids in psoriasis].","Brun",15049600,"[Prescription of retinoids in psoriasis].    Abstract:   Systemic retinoids inhibit keratinisation and have anti-inflammatory properties. In 30 years, they have revolutionised numerous aspects of dermatological practice, particularly in the management of psoriasis. In the management strategy of severe psoriasis, acitretin has first place of the medications currently available. It is the on-going treatment par excellence. It is even more effective and better tolerated when doses are progressively increased in steps to reach the optimal effective dose that corresponds to the maximum tolerated dose. The dose is adjusted according to this tolerance and not to standardise doses. With this precondition, the secondary effects are benign, sometimes bothersome with an increasing fragility of the mucous membranes of the epithelia and the phaneres, bearing witness to the medication impregnation of tissues and the interference with the natural retinoids. Due to their teratogenic risk, the only restriction concerns women of childbearing age in whom all prescription of retinoids is subject to some legal considerations that are indispensable to respect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I159,I159)","v":12730490},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B159:D159)","v":5},2003,"Cigarette smoking, alcohol use and adverse pregnancy outcomes: implications for micronutrient supplementation.","Cogswell",12730490,"Cigarette smoking, alcohol use and adverse pregnancy outcomes: implications for micronutrient supplementation.    Abstract:   This literature review examines whether smoking or alcohol use during pregnancy increases maternal micronutrient requirements and whether smoking or alcohol use interacts with micronutrient deficiencies to affect pregnancy outcomes. Studies suggest that vitamin C requirements increase for pregnant smokers. Studies also indicate that beta-carotene, vitamin B-12, vitamin B-6 and folate concentrations appear lower in pregnant smokers than in pregnant nonsmokers, although it is unclear whether lower serum concentrations are due to increased requirements, lower dietary or supplement intakes or other factors. Experimental animal studies suggest that iron supplementation partially ameliorates impaired fetal growth caused by cadmium, a heavy metal inhaled from cigarette smoke, but studies in humans have not substantiated cadmiums effect on fetal growth. Animal studies also suggest chronic alcohol consumption at levels of 20-50% of energy intake during pregnancy may mobilize fetal vitamin A concentration from the liver and result in increases in vitamin A in fetal organs and subsequent defects. Evidence is lacking, however, on whether zinc metabolism is altered by alcohol intake during pregnancy. Health care practitioners should consider increasing nutrient levels in pregnant women who do not meet the Recommended Dietary Allowances through their diet. Future studies that examine the nutrient levels of women exposed to cigarette smoke and alcohol should control for dietary intake. In addition, randomized controlled studies of the health impact of micronutrient supplementation in pregnant women should consider stratification by exposure to cigarette smoke and alcohol use."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I160,I160)","v":12076484},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B160:D160)","v":5},2002,"Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.","Brocklehurst",12076484,"Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus (HIV). This includes 1.4 million children less than 15 years of age. This is one of several reviews assessing the available evidence for preventing mother-to-child transmission of HIV infection. The other reviews will address other interventions, including Caesarean section, breast feeding, vaginal lavage and vitamin A supplementation.  OBJECTIVES : To assess which antiretroviral therapies may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. We also searched conference abstracts from the International AIDS Conferences and Conference on Retroviruses and Opportunistic Infections.  SELECTION CRITERIA : Randomised trials comparing any antiretroviral therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection with placebo or no treatment, or any two or more antiretroviral therapies or regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection.  DATA COLLECTION AND ANALYSIS : Two reviewers independently extracted data and assessed trial quality.  MAIN RESULTS : Zidovudine monotherapy Based on four trials any zidovudine regimen versus placebo significantly reduces the risk of mother-to-child transmission (Peto odds ratio (OR) 0.46, 95% confidence interval (CI) 0.35 to 0.60). Zidovudine also appears to decrease the risk of infant death within the first year of birth (OR 0.57, 95% CI 0.38 to 0.85) and the risk of maternal death (OR 0.32, 95% CI 0.16 to 0.66). There is no evidence that zidovudine influences the incidence of premature delivery (OR 0.86, 95% CI 0.57 to 1.29) or low birth weight (OR 0.74, 95% CI 0.53 to 1.04). The risk of transmission using a short-short course of zidovudine (from 35 weeks in pregnancy for the mother and for the baby until 3 days old) was higher than the risk using a long-long course (from 28 weeks in pregnancy for the mother and for the baby until 6 weeks old), (OR 2.33, 95% CI 1.16 to 4.68). However, the effectiveness of the long-short course (from 28 weeks in pregnancy for the mother and for the baby until 3 days old) and the short-long course (from 35 weeks in pregnancy for the mother and for the baby until 6 weeks old) did not differ from that of the long-long course. Nevirapine One large randomised controlled trial demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine (OR 0.51, 95% CI 0.33 to 0.79). When nevirapine is given to mothers already receiving standard antiretroviral therapy, however, there appears to be no additional advantage (OR 1.10, 95% CI 0.42 to 2.86). Combination Therapy Preliminary findings of the effect of combination therapy using zidovudine and lamivudine (3TC) suggest a decrease in the risk of transmission when the combination is given during the antenatal and intrapartum period or during the intrapartum and postpartum period compared with placebo. There is no evidence that intrapartum zidovudine and lamivudine alone are sufficient to decrease the risk of transmission compared with placebo.  REVIEWERS CONCLUSIONS : Implications for practice The randomised trials included in this review provide evidence that short course zidovudine and single-dose nevirapine are effective therapies for reducing mother-to-child transmission of HIV. The challenge for low and middle income countries will be to institute this therapy in practice. In industrialised countries practice has already moved on from the current evidence and combination antiretroviral therapy aimed primarily at preventing disease progression in the mother is the standard of care. Implications for research The potential value of nevirapine used for longer durations in breastfeeding populations should be considered as it may further reduce the risk of mother-to-child transmission, particularly if combined with early weaning. On-going evaluation of combination antiretroviral therapy is essential and will have an immediate benefit for countries with the resources to adopt such treatment. The search for effective, affordable, safe and acceptable alternatives to antiretroviral therapy for reducing mother-to-child transmission in resource poor countries should remain on the research agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I161,I161)","v":11869666},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B161:D161)","v":5},2002,"Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.","Brocklehurst",11869666,"Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus (HIV). This includes 1.4 million children less than 15 years of age. This is one of several reviews assessing the available evidence for preventing mother-to-child transmission of HIV infection. The other reviews will address other interventions, including Caesarean section, breast feeding, vaginal lavage and vitamin A supplementation.  OBJECTIVES : To assess which antiretroviral therapies may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. We also searched conference abstracts from the International AIDS Conferences and Conference on Retroviruses and Opportunistic Infections.  SELECTION CRITERIA : Randomised trials comparing any antiretroviral therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection with placebo or no treatment, or any two or more antiretroviral therapies or regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection.  DATA COLLECTION AND ANALYSIS : Two reviewers independently extracted data and assessed trial quality.  MAIN RESULTS : Zidovudine monotherapy Any zidovudine regimen versus placebo significantly reduces the risk of mother-to-child transmission (Peto odds ratio (OR) 0.46, 95% confidence interval (CI) 0.35 to 0.60). Zidovudine also appears to decrease the risk of infant death within the first year of birth (OR 0.57, 95% CI 0.38 to 0.85) and the risk of maternal death (OR 0.32, 95% CI 0.16 to 0.66). There is no evidence that zidovudine influences the incidence of premature delivery (OR 0.86, 95% CI 0.57 to 1.29) or low birth weight (OR 0.74, 95% CI 0.53 to 1.04). The risk of transmission using a short-short course of zidovudine (from 35 weeks in pregnancy for the mother and for the baby until 3 days old) was higher than the risk using a long-long course (from 28 weeks in pregnancy for the mother and for the baby until 6 weeks old), (OR 2.55, 95% CI 1.26 to 5.18). However, the effectiveness of the long-short course (from 28 weeks in pregnancy for the mother and for the baby until 3 days old) and the short-long course (from 35 weeks in pregnancy for the mother and for the baby until 6 weeks old) did not differ from that of the long-long course. Nevirapine One large randomised controlled trial demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine (OR 0.51, 95% CI 0.33 to 0.79). When nevirapine is given to mothers already receiving standard antiretroviral therapy, however, there appears to be no additional advantage (OR 1.10, 95% CI 0.42 to 2.86). Combination Therapy Preliminary findings of the effect of combination therapy using zidovudine and lamivudine (3TC) suggest a decrease in the risk of transmission when the combination is given during the antenatal and intrapartum period or during the intrapartum and postpartum period compared with placebo. There is no evidence that intrapartum zidovudine and lamivudine alone are sufficient to decrease the risk of transmission compared with placebo.  REVIEWERS CONCLUSIONS : Implications for practice The randomised trials included in this review provide evidence that short course zidovudine and single-dose nevirapine are effective therapies for reducing mother-to-child transmission of HIV. The challenge for low and middle income countries will be to institute this therapy in practice. In industrialised countries practice has already moved on from the current evidence and combination antiretroviral therapy aimed primarily at preventing disease progression in the mother is the standard of care. Implications for research The potential value of nevirapine used for longer durations in breastfeeding populations should be considered as it may further reduce the risk of mother-to-child transmission, particularly if combined with early weaning. On-going evaluation of combination antiretroviral therapy is essential and will have an immediate benefit for countries with the resources to adopt such treatment. The search for effective, affordable, safe and acceptable alternatives to antiretroviral therapy for reducing mother-to-child transmission in resource poor countries should remain on the research agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I162,I162)","v":11130478},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B162:D162)","v":5},2000,"Symptom control in the pregnant cancer patient.","MacDougall",11130478,"Symptom control in the pregnant cancer patient.    Abstract:   While much attention has been devoted to cytotoxic drugs and radiation therapy in the pregnant cancer patient, the drugs used for management of symptoms and complications related to cancer during pregnancy have been overlooked. There is substantial overlap between the symptoms of cancer and cancer management and the symptoms related to pregnancy. The mainstay of symptom management is drug therapy and the potential for a drug to be embryotoxic or teratogenic depends on when it is given. In general, drugs not proven safe in pregnancy should be withheld, especially during the first trimester. The few drugs that have been proven to be teratogenic are alcohol, thalidomide, the folic acid antagonists (which includes methotrexate), diethylstilbestrol, and the vitamin A isomers, but there is a good deal of uncertainty about many other therapeutic agents. Placental transport of drugs from mother to fetus must be taken into consideration from the fifth week of gestation to parturition. Although the first trimester is the time of most organ development in the fetus, the brain continues to develop throughout pregnancy and may be damaged later in pregnancy, resulting in diminished intelligence or behavioral problems. This review will focus on the treatment of the most common symptoms of cancer in a pregnant patient and the potential for fetal damage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I163,I163)","v":11122852},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B163:D163)","v":5},2000,"Fenretinide and cancer prevention.","Torrisi",11122852,"Fenretinide and cancer prevention.    Abstract:   A characteristic feature of fenretinide is the ability to inhibit cell growth through the induction of apoptosis with mechanisms that may be both receptor-dependent and receptor-independent. Chemopreventive efficacy of fenretinide has been investigated in clinical trials targeted at different organs. Results of a phase III secondary prevention trial suggest a benefit in preventing second breast malignancies in premenopausal women with early breast cancer. A potential benefit of fenretinide with ovarian cancer and a reduction of new occurrences of leukoplakia have also been observed in clinical trials with this agent. However, no effects on DNA content of urothelial cells from bladder washings and on recurrence rate were noted in a study of patients with superficial bladder tumors. Future trials using surrogate biomarkers may aid in rapid evaluation of the chemopreventive activity of fenretinide with various targeted organs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I164,I164)","v":10979152},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B164:D164)","v":5},2000,"Vitamin A and causes of maternal mortality: association and biological plausibility.","Faisel",10979152,"Vitamin A and causes of maternal mortality: association and biological plausibility.    Abstract:    OBJECTIVE : To review the association between major causes of maternal mortality and vitamin A, trying to determine if these associations are causal in nature, and to highlight possible biological pathways that may explain vitamin A effects.  DESIGN : Literature review, observational studies and clinical trials. The strength of association was determined by applying Bradford Hill criteria of causality.  RESULTS : In a vitamin A deficient population, vitamin A is essential for adequate treatment of anaemia. While vitamin A does not seem to be capable of preventing uterine atony, obstetric or surgical trauma, which are important causes of haemorrhage, it might be capable of preventing or decreasing coagulopathy. Possible effects on the placenta as regards implantation, site and size are not clear. As regards pregnancy-related infections, vitamin A supplementation can improve wound healing by decreasing fibrosis and increasing transforming growth factor-beta (TFG-beta). It can increase resistance to infection by increasing mucosal integrity, increasing surface immunoglobulin A (sIgA) and enhancing adequate neutrophil function. If infection occurs, vitamin A can act as an immune enhancer, increasing the adequacy of natural killer (NK) cells and increasing antibody production. beta-carotene in its provitamin form can act as an antioxidant by decreasing endothelial cell damage (the pathognomonic feature of pre-eclampsia) and promote the vasodilator effect of nitric oxide that might bring about a better outcome of toxaemia in pregnancy. It is unlikely that vitamin A or beta-carotene has an effect on obstructed labour.  CONCLUSIONS : Plausible biomedical pathways can only be constructed for obstetric haemorrhage, anaemia in pregnancy, hypertension in pregnancy and pregnancy-related infections. A 40% reduction in the maternal mortality ratio, as observed in Nepal, is unlikely to be solely explained through the aforementioned pathways."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I165,I165)","v":10885324},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B165:D165)","v":5},2000,"Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects.","Prakash",10885324,"Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects.    Abstract:   Cancer of the breast is the most common incident cancer and cause of death from cancer in women. Several epidemiologic studies have reported a significant inverse relationship between the intake of vitamin A and/or provitamin A-rich foods and the incidence of certain cancers, including breast cancer. A large number of studies have been conducted to determine the effect of retinoids (all-trans-retinoic acid, in particular), and to a lesser extent of carotenoids, on breast cancer using cell culture models. In general, the results of these studies demonstrate beneficial effects of all-trans-retinoic acid on different breast cancer cells. This review compares studies conducted in different laboratories using retinoids and carotenoids as treatments for breast cancer cells and suggests what may be the underlying reasons for the differential effects of these compounds on the same cell lines."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I166,I166)","v":10874923},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B166:D166)","v":5},2000,"[Acne today. Whats new?].","Auffret",10874923,"[Acne today. Whats new?].    Abstract:   WELL-CONDUCTED TREATMENT: Acne is a common condition in adolescents and requires careful management both in terms of therapeutic care and psychological support. Treatment is long and requires strict compliance. A well-conducted treatment can be expected to provide major improvement in most patients. LOCAL CARE: Local care is often sufficient for retentional or discretely inflammatory acne. A retinoid and/or a benzoyl peroxide can be associated with a local antibiotic. SEVERE FORMS: An oral antibiotic regimen for at least 3 months is proposed in association with the local treatment (retinoid, benzoyl peroxide, local antibiotic) in case of severe acne. ISOTRETINOIN: In case of unsuccessful treatment for nodular or conglobata acne, isotretinoin can be proposed in an oral preparation. This highly teratogenic drug must not be prescribed for women of reproductive age unless a well proven contraception has been instituted for more than 1 month and maintained for the entire duration of the treatment and 1 month after discontinuation. The patient must be informed of the risk in case of pregnancy and consent to regular monitoring of beta hCG less than 3 days before treatment onset, every 2 months during treatment and 5 weeks after treatment withdrawal)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I167,I167)","v":10668477},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B167:D167)","v":5},1999,"Progress in cancer chemoprevention.","Kelloff",10668477,"Progress in cancer chemoprevention.    Abstract:   More than 40 promising agents and agent combinations are being evaluated clinically as chemopreventive drugs for major cancer targets. A few have been in vanguard, large-scale intervention trials--for example, the studies of tamoxifen and fenretinide in breast, 13-cis-retinoic acid in head and neck, vitamin E and selenium in prostate, and calcium in colon. These and other agents are currently in phase II chemoprevention trials to establish the scope of their chemopreventive efficacy and to develop intermediate biomarkers as surrogate end points for cancer incidence in future studies. In this group are fenretinide, 2-difluoromethylornithine, and oltipraz. Nonsteroidal anti-inflammatories (NSAID) are also in this group because of their colon cancer chemopreventive effects in clinical intervention, epidemiological, and animal studies. New agents are continually considered for development as chemopreventive drugs. Preventive strategies with antiandrogens are evolving for prostate cancer. Anti-inflammatories that selectively inhibit inducible cyclooxygenase (COX)-2 are being investigated in colon as alternatives to the NSAID, which inhibit both COX-1 and COX-2 and derive their toxicity from COX-1 inhibition. Newer retinoids with reduced toxicity, increased efficacy, or both (e.g., 9-cis-retinoic acid) are being investigated. Promising chemopreventive drugs are also being developed from dietary substances (e.g., green and black tea polyphenols, soy isoflavones, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol). Basic and translational research necessary to progress in chemopreventive agent development includes, for example, (1) molecular and genomic biomarkers that can be used for risk assessment and as surrogate end points in clinical studies, (2) animal carcinogenesis models that mimic human disease (including transgenic and gene knockout mice), and (3) novel agent treatment regimens (e.g., local delivery to cancer targets, agent combinations, and pharmacodynamically guided dosing)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I168,I168)","v":9857270},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B168:D168)","v":5},1998,"Safety of vitamin A: recent results.","Wiegand",9857270,"Safety of vitamin A: recent results.    Abstract:   A still unresolved public health concern is that excessive vitamin A intake, like vitamin A deficiency, possibly causes birth defects not only in animals but also in man. Due to the low incidence of possibly vitamin A-related malformations in man, available data cannot convincingly define the upper safe limit of periconceptional vitamin A intake. Direct human intervention studies are not feasible for ethical reasons. Therefore, a novel approach in addressing this issue was chosen by combining teratogenicity data from a validated animal model with data on systemic exposure to vitamin A and its major metabolites in female volunteers. In a study in pregnant women endogenous plasma concentrations of vitamin A metabolites during early pregnancy ranged from 0.26 to 7.72 ng/ml. Since they did not cause any foetal malformations, retinoid plasma levels in this range can be considered non-teratogenic. Results of a trial in non-pregnant women document that daily oral vitamin A supplements of 4000, 10,000 and 30,000 IU given for 3 weeks were in the range or slightly above the range of endogenous plasma levels seen in early pregnancy. Even after a 3-week treatment with 30,000 IU/day, peak plasma levels of retinoic acid and isotretinoin were within or just slightly above the range of their physiological levels. In cynomolgus monkeys (average weight: 3-4 kg), a NOAEL (no observed adverse effect level) of 7500 IU per kg body weight and a LOAEL (lowest observed adverse effect level) for developmental toxicity of 20,000 IU/kg was found. Considering these results in the cynomolgus monkey, a dose of 30,000 IU/day should also be considered as non-teratogenic in man."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I169,I169)","v":9802541},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B169:D169)","v":5},1998,"The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome.","Zachman",9802541,"The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome.    Abstract:   The mechanism of the fetal embryopathology resulting from ethanol ingestion during pregnancy is not established. This review summarizes recent research on the interaction of ethanol and vitamin A in models that explore if an interaction between these two compounds might potentially be the mechanism for fetal alcohol syndrome. The rationale for this hypothesis includes the known facts that: (1) in adults, ethanol ingestion alters vitamin A metabolism and tissue distribution; (2) there are many phenotypic similarities between fetal alcohol syndrome and malformations of both vitamin A toxicity and deficiency; and (3) the vitamin A metabolite, retinoic acid (RA), is a potent mediator in embryogenesis and differentiation. One interaction that could possibly alter fetal development is that the synthesis of RA from retinol, catalyzed by alcohol dehydrogenase, might be competitively inhibited by ethanol leading to RA deficiency. Controversy over this hypothesis continues. Another model demonstrates in vivo effects of pregnant rat mothers ethanol consumption on retinol, retinyl ester, RA content, RA receptor (RAR) binding, and the levels of RAR expression in developing fetal organs. The variable responses in this model still need clarification, and specific defects resulting from specific RAR changes have not yet been identified. In a quail embryo model, ethanol treatment mimics vitamin A deficiency, and RA appears to prevent the adverse effects of ethanol. Finally, RA and ethanol reverse or block each others effects in studies on isolated neuroblastoma cells. Taken together, these experiments show definite interactions between ethanol and vitamin A. Further studies are needed to determine if any of these mechanisms significantly contribute to prenatal ethanol consumption embryopathy; but, clearly this hypothesis is gaining experimental support."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I170,I170)","v":9380470},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B170:D170)","v":5},1997,"Childhood vitamin A status and the risk of otitis media.","Durand",9380470,"Childhood vitamin A status and the risk of otitis media.    Abstract:    BACKGROUND : It has been suggested that vitamin A deficiency may predispose to otitis media.  METHODS : We conducted a prospective, observational study of 200 children, ages 3 to 5 years, on the island of Saipan in the Commonwealth of the Northern Mariana Islands. Baseline measurements of serum retinol concentrations were obtained from the children, and incidence of otitis media was determined during the following year by review of medical records. The sera were also tested for concentration of other carotenoids (beta-carotene, alpha-carotene, lutein and zeaxanthin, beta-cryptoxanthin, lycopene), and alpha-tocopherol and baseline concentrations of these compounds were also examined for relationship to incidence of otitis media.  RESULTS : Serum retinol concentrations of the children ranged from 13 to 58 microg/dl. Episodes of otitis media occurred in 22% of children during the follow-up period. Children with low serum retinol concentrations did not have an excess of episodes of otitis media (chi square for trend, 0.438; P = 0.508 for children grouped by serum retinol concentration; mean serum retinol concentrations were 29.1 and 28.6 microg/dl, respectively, for children who had and did not have a subsequent episode of otitis media). Controlling for potential confounding variables (duration of breast feeding, smoking in the household, illness or live virus vaccination in the 2 weeks before serum collection, day-care attendance) did not substantially alter this finding. Baseline serum concentrations of the other carotenoids and alpha-tocopherol also demonstrated no relation to incidence of otitis media.  CONCLUSION : In the range of serum vitamin concentrations found in this population, the status of vitamin A and related compounds in children appeared to have no effect on the incidence of otitis media."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I171,I171)","v":7762914},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B171:D171)","v":5},1995,"Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis.","Boumpas",7762914,"Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis.    Abstract:    PURPOSE : To review 1) advances in the pathogenesis, diagnosis, and management of dermatologic and joint disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus; 2) controversies related to pregnancy and hormonal therapy and to morbidity and mortality in these patients; and 3) current views on the pathogenesis of systemic lupus erythematosus.  DATA SOURCES AND STUDY SELECTION : Review of the English-language medical literature with emphasis on articles published within the last 5 years. More than 400 articles were reviewed.  DATA SYNTHESIS : Despite considerable overlap, cutaneous lesions specific to lupus erythematosus may be divided into subsets with distinct clinical, histologic, and immunofluorescent features. A recent short-term, prospective, uncontrolled trial found hydroxychloroquine and retinoids to be of similar efficacy in the treatment of cutaneous lupus erythematosus. Optimal treatment for patients with lupus and the anticardiolipin antibody syndrome remains to be defined; uncontrolled, retrospective, and treatment-withdrawal studies suggest that warfarin may be more protective than aspirin. Whether pregnancy induces lupus flares has not yet been established; existing data suggest both that it does and that it does not. Oral contraceptive use and postmenopausal estrogen replacement therapy appear not to cause clinical deterioration in patients with lupus. Recent studies have documented a substantial improvement in the survival of patients with systemic lupus erythematosus; they found 5-year survival rates of 90% or more and 10-year survival rates of more than 80%. Most data suggest that systemic lupus erythematosus results from the activation of self-reactive T cells and B cells by genetic or environmental factors.  CONCLUSIONS : The optimal treatment for dermatologic disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus remains unknown. Although mortality has decreased substantially, the morbidity related to the disease itself and to complications of therapy is still considerable. More studies are needed to further elucidate the effects of pregnancy on this condition and the pathogenetic mechanisms responsible for the development of this disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I172,I172)","v":8142111},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B172:D172)","v":5},1993,"Evaluation of the teratogenic risk of cutaneously administered retinoids.","Buchan",8142111,"Evaluation of the teratogenic risk of cutaneously administered retinoids.    Abstract:   In current cutaneous retinoid therapy systemic exposure is low and the risk of teratogenesis appears to be limited. However, new indications, altered posologies and the introduction of new synthetic retinoids demand continuous assessment of the teratogenic risk. Teratogenicity testing of new substances in animals is only of value if accompanied by detailed pharmacokinetic analysis to establish the relationships between the levels of parent compound and metabolite in both maternal plasma and fetal tissues and teratogenic events. This information should be compared to the maximum of relevant pharmacokinetic data which can be ethically obtained in man or from human tissues. The presence or absence of teratogenic effects following cutaneous administration of retinoids in animals has, as such, little direct bearing on the risk in man. Two special cases exist where teratogenic risk can be evaluated directly in man without reference to animal studies. The first concerns substances whose teratogenic potential has been established in man by other routes of administration permitting a comparison with the cutaneous route on a pharmacokinetic basis. The second concerns the cutaneous administration of endogenously occurring substances and their eventual disturbance of systemic retinoid equilibrium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I173,I173)","v":1525060},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B173:D173)","v":5},1992,"Experimental studies with liarozole (R 75,251): an antitumoral agent which inhibits retinoic acid breakdown.","De Coster",1525060,"Experimental studies with liarozole (R 75,251): an antitumoral agent which inhibits retinoic acid breakdown.    Abstract:   Liarozole reduced tumor growth in the androgen-dependent Dunning-G and the androgen-independent Dunning MatLu rat prostate carcinoma models as well as in patients with metastatic prostate cancer who had relapsed after orchiectomy. In vitro, liarozole did not have cytostatic properties, as measured by cell proliferation in breast MCF-7 and prostate DU145 and LNCaP carcinoma cell lines. It did not alter the metabolism of labeled testosterone i.e. the 5 alpha-reductase in cultured rat prostatic cells. In mouse F9 teratocarcinoma cells liarozole did not show any retinoid-like properties but enhanced the plasminogen activator production induced by retinoic acid. Furthermore, liarozole and retinoic acid similarly reduced the growth of the androgen-dependent Dunning-G tumor in nude mice and inhibited tumor promotion elicited by phorbol ester in mouse skin. These data have raised the hypothesis that the antitumoral properties of liarozole may be related to inhibition of retinoic acid degradation, catalyzed by a P-450-dependent enzyme that is blocked by the drug."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I174,I174)","v":2653031},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B174:D174)","v":5},1989,"An overview of the retinoids.","Boyd",2653031,"An overview of the retinoids.    Abstract:   The retinoids, a group of compounds consisting of vitamin A and its derivatives, have been the subject of intense investigation over the past 30 years. These molecules have shown beneficial effects in the areas of acne, psoriasis, neoplastic processes and, most recently, reversal of extrinsically aged skin. Additional retinoids are currently under development. Adverse reactions to these drugs include mucocutaneous irritation, hyperlipidemia, and profound teratogenicity. Appropriate patient selection is imperative before beginning therapy with these medications. An overview of retinoid metabolism and the currently available compounds is presented. The newest class of retinoids, the arotinoids, is also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I175,I175)","v":3280622},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B175:D175)","v":5},1988,"Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System.","Bigby",3280622,"Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System.    Abstract:   Between October 1982 and June 1985 the Adverse Drug Reaction Reporting System received reports of 104 suspected adverse reactions occurring in 93 patients who took isotretinoin. Adverse reactions involving the skin and mucous membranes (29 reports), central nervous system (23), musculoskeletal system (12), pregnancy (11), and eyes (8) were most commonly reported. Severe headache was the most frequently reported adverse reaction (15 reports). In four cases headaches were attributed to pseudotumor cerebri. Some of the reported reactions, for example, a disulfiram (Antabuse)-like reaction and oculogyric crisis, have not been described previously in the literature. Other reports, such as congenital malformations, serve to emphasize some of the serious reactions that are known to occur. These spontaneous reports of adverse reactions associated with isotretinoin use, together with the literature we review, may help alert physicians to the diverse spectrum of adverse reactions that may develop in patients taking isotretinoin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I176,I176)","v":3422131},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B176:D176)","v":5},1988,"Hidradenitis suppurativa of the anogenital region: response to isotretinoin.","Brown",3422131,"Hidradenitis suppurativa of the anogenital region: response to isotretinoin.    Abstract:   Hidradenitis suppurativa, a chronic relapsing disease of apocrine gland-bearing areas, most frequently occurs in the axillae, groin, perineal, and perianal regions. Hidradenitis of vulva is frequently misdiagnosed and inadequately treated. The case of a 15-year-old nulliparous black female adolescent referred for evaluation of multiple draining fistulas of the anogenital region is presented. Diagnostic studies for granulomatous disease were negative. Results of a barium enema were normal and biopsies were compatible with the diagnosis of hidradenitis suppurativa. She was treated for 22 weeks with isotretinoin, 1 mg/kg daily, with an excellent response. Side effects were minor and included cheilitis, mild xerosis, and a transient elevation of serum alkaline phosphatase levels. Few patients with severe hidradenitis have been responsive to this synthetic vitamin A derivative. A review of the literature indicates that the results of treatment with isotretinoin for hidradenitis have been at best equivocal. Isotretinoin should never be used during pregnancy because of known teratogenic effects. Women of childbearing age must use effective contraception during treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I177,I177)","v":6266310},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B177:D177)","v":5},1981,"Antiproliferative effects of retinoids related to the cell cycle-specific inhibition of ornithine decarboxylase.","Russell",6266310,"Antiproliferative effects of retinoids related to the cell cycle-specific inhibition of ornithine decarboxylase.    Abstract:   The induction of ornithine decarboxylase (ODC) during G1 phase of the cell cycle appears to be universal and essential for cell cycle progression. This induction has been demonstrated in at least 23 cell types in response to various growth stimuli. Further, specific inhibitors of ODC added to several of these cell lines resulted in inhibition of cell proliferation. The studies of the effects of retinoids to inhibit Chinese hamster ovary (CHO) cell growth indicate that the cells are blocked in G1 of cell cycle, and that there is a concentration-dependent inhibition of ODC induction. Retinoids only inhibit the induction of ODC activity when added in the first 2-3 hr of G1 progression. It is postulated that ODC induction is a requirement for G1 progression and that the antiproliferative properties of retinoids are related to the specific ability to inhibit this expression. Since retinoids do not dramatically alter the rate of protein synthesis, their ability to inhibit ODC may be related to their ability to inhibit messenger RNa synthesis for ODC."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I178,I178)","v":6999318},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B178:D178)","v":5},1980,"Retinoids for the prevention of epithelial cancers: current status and future potential.","Clamon",6999318,"Retinoids for the prevention of epithelial cancers: current status and future potential.    Abstract:   Prevention of epithelial cancers is needed, as the treatment of such cancers in the advanced state has failed. Vitamin A and its structural analogs called retinoids will prevent cancers of the lung, breast, bladder, stomach, and cervix in animals exposed to carcinogens. Synthetic retinoids, offer less toxicity than natural retinoids and may be acceptable to human trials. Identification of a suitable group at risk for an epithelial cancer which might be reasonably expected to benefit from retinoids should precede planning of a clinical trial."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I179,I179)","v":26806040},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B179:D179)","v":4},2016,"Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors.","Qi",26806040,"Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors.    Abstract:   We present a review of recent investigations of anticancer drug bexarotene in this article. As one of the novel synthetic analogs of retinoids, bexarotene selectively binds to and activates the retinoid X receptor (RXRs) subfamilies, exerting a prophylactic and therapeutic effect on a large series of tumors in vitro and in vivo covering cutaneous lesions, lung and breast cancers, nervous system diseases etc. Bexarotene has been proved to have a specifically favorable therapeutic profile in clinical dermatology or oncology with mild or absent retinoids side effects, especially in combination with other therapies. It is noteworthy that numerous previous outstanding researches have contributed to the chemical, biological, preclinical and clinical examinations of bexarotene during the past decades, with a relatively deficient progress of bexarotene in the field of pharmacy. In this review, the positive therapeutic results of bexarotene used as a monotherapy or combination therapy both in preclinical and clinical studies are reported based on relevant medical data; the distinct acting mechanisms of bexarotene are described; the potential studies and prospects of bexarotene in pharmaceutical domain are discussed. All the reports above collectively present bexarotene as a promising anti-cancer agent."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I180,I180)","v":26621538},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B180:D180)","v":4},2015,"Erythrocyte exchange and leukapheresis in pregnancy.","Perseghin",26621538,"Erythrocyte exchange and leukapheresis in pregnancy.    Abstract:   Hematological diseases in pregnancy should be carefully managed with a multidisciplinary approach, which should include obstetrics, hematology and, in selected patients, apheresis professionals. Hematological malignancies in pregnant women are rare, but the attending physicians should be aware that the use of cytotoxic drugs, tyrosine-kinase inhibitors or differentiating agents such as all-trans retinoic acid (ATRA) during the first trimester of pregnancy might be teratogenic and, in turn, induce fetal abnormalities or abortion. Thus, in pregnant patients with either acute or chronic leukemia presenting with symptomatic hyperleukocytosis, leukocytapheresis (LA) could be considered as a bridge therapeutic option. Furthermore, sickle cell disease (SCD) in pregnant women is usually managed only with supportive care, i.e. packed red blood cell (RBC) transfusion to prevent excessive hemoglobin decrease, hydration and prevention of acute sickling crisis. Nevertheless, selected patients at high risk for placental detachment due to vasoocclusive acute crisis or with multiple pregnancies may benefit from prophylactic erythrocyte exchange (EEX). Both LA and EEX must be carried out by well trained personnel and the patients (and the fetus) must be under close clinical and instrumental monitoring. In the present paper, recent indications for performing either LA or EEX in pregnant patients are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I181,I181)","v":26503498},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B181:D181)","v":4},2015,"Vitamin A supplementation during pregnancy for maternal and newborn outcomes.","McCauley",26503498,"Vitamin A supplementation during pregnancy for maternal and newborn outcomes.    Abstract:    BACKGROUND : The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin A deficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.    OBJECTIVES : To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes.  SEARCH METHODS : We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (30 March 2015) and reference lists of retrieved studies.  SELECTION CRITERIA : All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women.  DATA COLLECTION AND ANALYSIS : Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.  MAIN RESULTS : We reviewed 106 reports of 35 trials, published between 1931 and 2015. We included 19 trials including over 310,000 women, excluded 15 trials and one is ongoing. Overall, seven trials were judged to be of low risk of bias, three were high risk of bias and for nine it was unclear. 1) Vitamin A alone versus placebo or no treatmentOverall, when trial results are pooled, vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.65 to 1.20; four trials Ghana, Nepal, Bangladesh, UK, high quality evidence), perinatal mortality (RR 1.01, 95% CI 0.95 to 1.07; one study, high quality evidence), neonatal mortality, stillbirth, neonatal anaemia, preterm birth (RR 0.98, 95% CI 0.94 to 1.01, five studies, high quality evidence), or the risk of having a low birthweight baby.Vitamin A supplementation reduces the risk of maternal night blindness (RR 0.79, 95% CI 0.64 to 0.98; two trials). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.45, 95% CI 0.20 to 0.99, five trials; South Africa, Nepal, Indonesia, Tanzania, UK, low quality evidence) and maternal anaemia (RR 0.64, 95% CI 0.43 to 0.94; three studies, moderate quality evidence). 2) Vitamin A alone versus micronutrient supplements without vitamin AVitamin A alone compared to micronutrient supplements without vitamin A does not decrease maternal clinical infection (RR 0.99, 95% CI 0.83 to 1.18, two trials, 591 women). No other primary or secondary outcomes were reported 3) Vitamin A with other micronutrients versus micronutrient supplements without vitamin AVitamin A supplementation (with other micronutrients) does not decrease perinatal mortality (RR 0.51, 95% CI 0.10 to 2.69; one study, low quality evidence), maternal anaemia (RR 0.86, 95% CI 0.68 to 1.09; three studies, low quality evidence), maternal clinical infection (RR 0.95, 95% CI 0.80 to 1.13; I² = 45%, two studies, low quality evidence) or preterm birth (RR 0.39, 95% CI 0.08 to 1.93; one study, low quality evidence).In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (lt; 2.5 kg) in the supplemented group in one study (RR 0.67, 95% CI 0.47 to 0.96; one study, 594 women).  AUTHORS CONCLUSIONS : The pooled results of three large trials in Nepal, Ghana and Bangladesh (with over 153,500 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However, the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal night blindness, maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I182,I182)","v":26149091},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B182:D182)","v":4},2015,"Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments.","Bangsgaard",26149091,"Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments.    Abstract:   Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I183,I183)","v":25488886},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B183:D183)","v":4},2014,"A successful spontaneous pregnancy in abetalipoproteinemia: Amsterdam or the art of vitamin replacement?","Ferreira",25488886,"A successful spontaneous pregnancy in abetalipoproteinemia: Amsterdam or the art of vitamin replacement?    Abstract:   Abetalipoproteinemia is a rare metabolic disorder that causes disturbed lipid absorption with consequent hypocholesterolaemia and liposoluble avitaminosis. The broad spectrum of presentations includes malabsorption, failure to thrive and acanthocytosis in children, while later in life expected manifestations include coagulopathy, myopathy, retinitis pigmentosa, peripheral neuropathy, hyporeflexia and ataxia. These neurological complications stem from demyelination secondary to vitamin E deficiency. Another complication is reduced fertility in women. In the event of a successful conception, issues arise in vitamin supplementation, the mainstay of treatment of abetalipoproteinemia. The skilful clinician must master the delicate balance between the teratogenic effects on the fetus of over as well as under replacement of vitamins, pregnancy complications such as premature rupture of membranes and eclampsia, and, finally, maternal complications such as corneal ulcers. We describe the management of a patient ranging from pubertal growth to bearing a successful spontaneous pregnancy with an outcome of a completely healthy mother and child."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I184,I184)","v":25042865},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B184:D184)","v":4},2014,"Interplay between estrogen and retinoid signaling in breast cancer--current and future perspectives.","Ribeiro",25042865,"Interplay between estrogen and retinoid signaling in breast cancer--current and future perspectives.    Abstract:   All-trans-retinoic acid (RA) is a promising agent for breast cancer treatment, but it induces several adverse effects and the few clinical trials performed up to now in breast cancer patients have provided disappointing results. The combination of RA and antiestrogenic compounds, such as tamoxifen, synergistically decreases the proliferation of breast cancer cells and an interplay between retinoid and estrogen signaling has begun to be unraveled, turning these combinations into an appealing strategy for breast cancer treatment. This review focus on the current knowledge regarding the interplay between retinoid and estrogen signaling in breast cancer and the combinations of RA with antiestrogens, aiming their future utilization in cancer therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I185,I185)","v":24594504},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B185:D185)","v":4},2014,"Aldehyde dehydrogenase 1A1: friend or foe to female metabolism?","Petrosino",24594504,"Aldehyde dehydrogenase 1A1: friend or foe to female metabolism?    Abstract:   In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a quot;horizontal transfer of signalingquot; from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1-/- preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I186,I186)","v":22005522},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B186:D186)","v":4},2012,"Vitamin A and risk of cervical cancer: a meta-analysis.","Zhang",22005522,"Vitamin A and risk of cervical cancer: a meta-analysis.    Abstract:    OBJECTIVE : To conduct a systematic review with meta-analysis of studies assessing the association of vitamin A (retinol, carotene and other carotenoids) intake or blood (serum or plasma) levels of vitamin A (retinol and carotene) with risk of cervical cancer.  METHODS : We evaluated the studies published in English and Chinese on diet or blood vitamin A for the risk of cervical cancer. We also reviewed reference lists from retrieved articles. Meta-analysis was applied to calculate the combined effect values and their 95% confidence intervals. The risk of bias was assessed by the Egger regression asymmetry test.  RESULTS : As many as 11 articles on dietary vitamin A and 4 articles on blood vitamin A were selected according to the eligibility criteria and were included in the meta-analysis, for a total of 12,136 participants. The pooled odds ratios (ORs) of cervical cancer were 0.59 (95% CI, 0.49-0.72) for total vitamin A intake and 0.60 (95% CI, 0.41-0.89) for blood vitamin A levels. The combined ORs of cervical cancer were 0.80 (95% CI, 0.64-1.00), 0.51 (95% CI, 0.35-0.73) and 0.60 (95% CI, 0.43-0.84) for retinol, carotene and other carotenoid intake, and 1.14 (95% CI, 0.83-1.56) and 0.48 (95% CI, 0.30-0.77) for blood retinol and carotene.  CONCLUSIONS : Vitamin A intake and blood vitamin A levels were inversely associated with the risk of cervical cancer in this meta-analysis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I187,I187)","v":21158950},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B187:D187)","v":4},2011,"Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.","Schaefer",21158950,"Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.    Abstract:   Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I188,I188)","v":21069707},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B188:D188)","v":4},2010,"Vitamin A supplementation during pregnancy for maternal and newborn outcomes.","van den Broek",21069707,"Vitamin A supplementation during pregnancy for maternal and newborn outcomes.    Abstract:    BACKGROUND : The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin A deficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.    OBJECTIVES : To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (15 July 2010).  SELECTION CRITERIA : All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women.  DATA COLLECTION AND ANALYSIS : Two review authors independently assessed all studies for inclusion and resolved any disagreement through discussion with a third person. We used pre-prepared data extraction sheets.  MAIN RESULTS : We examined 88 reports of 31 trials, published between 1931 and 2010, for inclusion in this review. We included 16 trials, excluded 14, and one is awaiting assessment.Overall when trial results are pooled, Vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.55 to 1.10, 3 studies, Nepal, Ghana,UK ), perinatal mortality, neonatal mortality, stillbirth, neonatal anaemia, preterm birth or the risk of having a low birthweight baby. Vitamin A supplementation reduces the risk of maternal night blindness (risk ratio (RR) 0.70, 95% CI 0.60 to 0.82, 1 trial Nepal). In vitamin A deficient populations and HIV-positive women, vitamin A supplementation reduces maternal anaemia (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.43 to 0.94, 3 trials, Indonesia, Nepal,Tanzania ). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.37, 95% CI 0.18 to 0.77, 3 trials, South Africa, Nepal and UK).In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (lt; 2.5 kg) in the supplemented group in one study (RR 0.67, CI 0.47 to 0.96).  AUTHORS CONCLUSIONS : The pooled results of two large trials in Nepal and Ghana (with almost 95,000 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I189,I189)","v":21069669},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B189:D189)","v":4},2010,"WITHDRAWN: Vitamin A supplementation during pregnancy.","van den Broek",21069669,"WITHDRAWN: Vitamin A supplementation during pregnancy.    Abstract:    BACKGROUND : Vitamin A supplements have been recommended in pregnancy to improve outcomes that include maternal mortality and morbidity.  OBJECTIVES : To review the effectiveness of vitamin A supplementation during pregnancy, alone or in combination with other supplements, on maternal and newborn clinical and laboratory outcomes.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Groups specialised register of controlled trials (April 2002) and the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2002).  SELECTION CRITERIA : All randomised or quasi-randomised trials evaluating the effect of vitamin A supplementation in pregnant women. The types of intervention included vitamin A supplementation alone or in combination with other micro-nutrients.  DATA COLLECTION AND ANALYSIS : We assessed trials for methodological quality using the standard Cochrane criteria of adequacy of concealment. At least two review authors independently assessed the trials for inclusion and extracted data. We collected information on blinding, loss to follow-up, setting, number of women, exclusion after randomisation and follow-up as well as supplementation type, dose and frequency. The outcomes we sought included maternal and neonatal clinical and laboratory outcomes.  MAIN RESULTS : Five trials involving 23,426 women were included. Because the trials were heterogeneous with regard to type of supplement given, duration of supplement use and outcomes measured, pooled results using meta analysis could not be performed. One large population based trial in Nepal showed a possible beneficial effect on maternal mortality after weekly vitamin A supplements. In this study a reduction was noted in all cause maternal mortality up to 12 weeks postpartum with Vitamin A supplementation (RR 0.60, 95% CI 0.37-0.97). Night-blindness was assessed in a nested case-control study within this trial and found to be reduced but not eliminated. Three trials examined the effect of vitamin A supplementation on haemoglobin levels. The trial from Indonesia showed a beneficial effect in women who were anaemic ([Hb] lt;11.0 g/dl). After supplementation, the proportion of women who became non-anaemic was 35% in the Vitamin A supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both Vitamin A and iron and 16% in the placebo group. The two trials from Malawi did not corroborate these positive findings.  AUTHORS CONCLUSIONS : Although the two trials from Nepal and Indonesia suggested beneficial effects of vitamin A supplementation, further trials are needed to determine whether vitamin A supplements can reduce maternal mortality and morbidity and by what mechanism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I190,I190)","v":20486545},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B190:D190)","v":4},2010,"[Obesity among women. Pregnancy after bariatric surgery: a qualitative review].","Kanadys",20486545,"[Obesity among women. Pregnancy after bariatric surgery: a qualitative review].    Abstract:   Bariatric surgery is a safe and most effective method of achieving substantial long-term weight loss. Surgery should be considered in case of all patients with a BMI of more than 40 kg/m2 and for those with a BMI of over 35 kg/m2 with obesity-related co-morbidities, after conventional treatment failure. The most frequently used procedures in surgical treatment of obesity performed mostly laparoscopically are restrictive operations limiting energy intake by reducing gastric capacity (vertical banded gastroplasty adjustable gastric band, sleeve gastrectomy) and restrictive/ malabsorptive surgeries also inducing decreased absorption of nutrients by shortening the functional length of the small intestine (Roux-en-Y gastric bypass). Frequent complications following surgery may include hyperemesis, intragastric band migration, gastric perforation, nutritional deficiencies, anastomotic leak, bleeding, anastomotic stricture, internal hernia, wound infection. It is generally recommended for women after bariatric surgery to wait approximately at least 12 months before becoming pregnant. There exists considerable threat that rapid weight loss (relative starvation phase) may be unhealthy for a mother and a baby. Pregnancy after weight loss surgery is not only safe for the mother and the baby but may also be less risky than pregnancy in morbidly obese patients. Postoperative nutrient supplementation and close supervision before, during, and after pregnancy adjusted to individual requirements of a woman can help to prevent nutrition-related complications such as deficiencies in iron, vitamin A, vitamin B12, vitamin K, folate and calcium, and improve maternal and fetal health."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I191,I191)","v":19853185},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B191:D191)","v":4},2009,"The role of retinoid deficiency and estrogens as cofactors in cervical cancer.","Gariglio",19853185,"The role of retinoid deficiency and estrogens as cofactors in cervical cancer.    Abstract:   Persistent infection with high-risk human papillomaviruses (HR-HPVs) is involved in cervical cancer (CC), a major cause of cancer mortality worldwide. Infection occurs primarily at the transformation zone (TZ), the most estrogen- and retinoid-sensitive region of the cervix. Development of CC affects a small percentage of HR-HPV-infected women and often takes decades after infection, suggesting that HR-HPV is a necessary but not sufficient cause of CC. Thus, other cofactors are necessary for progression from cervical HR-HPV infection to cancer such as long-term use of hormonal contraceptives, multiparity, smoking, as well as micronutrient depletion and in particular retinoid deficiency, which alters epithelial differentiation, cellular growth and apoptosis of malignant cells. Therefore, early detection of HR-HPV and management of precancerous lesions together with a profound understanding of additional risk factors could be a strategy to avoid this disease. In this review we focus on the synergic effect of estrogens, retinoid deficiency and HR-HPVs in the development of CC. These risk factors may act in concert to induce neoplastic transformation in squamous epithelium of the cervix, setting the stage for secondary genetic or epigenetic events leading to cervical cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I192,I192)","v":19381305},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B192:D192)","v":4},2009,"Function of retinoic acid receptors during embryonic development.","Mark",19381305,"Function of retinoic acid receptors during embryonic development.    Abstract:   Retinoids, the active metabolites of vitamin A, regulate complex gene networks involved in vertebrate morphogenesis, growth, cellular differentiation and homeostasis. Studies performed in vitro, using either acellular systems or transfected cells, have shown that retinoid actions are mediated through heterodimers between the RAR and RXR nuclear receptors. However, in vitro studies indicate what is possible, but not necessarily what is actually occurring in vivo, because they are performed under non-physiological conditions. Therefore, genetic approaches in the animal have been be used to determine the physiological functions of retinoid receptors. Homologous recombination in embryonic stem cells has been used to generate germline null mutations of the RAR- and RXR-coding genes in the mouse. As reviewed here, the generation of such germline mutations, combined with pharmacological approaches to block the RA signalling pathway, has provided genetic evidence that RAR/RXR heterodimers are indeed the functional units transducing the RA signal during prenatal development. However, due to (i) the complexity in quot;hormonalquot; signalling through transduction by the multiple RARs and RXRs, (ii) the functional redundancies (possibly artefactually generated by the mutations) within receptor isotypes belonging to a given family, and (iii) in utero or early postnatal lethality of certain germline null mutations, these genetic studies have failed to reveal all the physiological functions of RARs and RXRs, notably in adults. Spatio-temporally-controlled somatic mutations generated in given cell types/tissues and at chosen times during postnatal life, will be required to reveal all the functions of RAR and RXR throughout the lifetime of the mouse."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I193,I193)","v":17974168},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B193:D193)","v":4},2007,"[Modern medico-biological nutritional requirements for pregnant women].","Baĭkova",17974168,"[Modern medico-biological nutritional requirements for pregnant women].    Abstract:   This review describes the basic physiological requirements, expert opinions and medico-biological recommendations for the optimal nutritional regime of pregnant women. In the first trimester of pregnancy the nutritional intake should be supplemented by about +68 kcal/24 h (the normal intake is 2000 kcal/24 h for non-pregnant women in the respective age group). In the second trimester the supplementation should be by +266 kcal/24 h, while in the III trimester--by up to +496 kcal/24 h. The requirements of folic acid and vitamin B6 during pregnancy are increased by 50%. The need for vitamin A is augmented up to 60%, while for vitamin C, niacin, vitamin B2 and B12--up to 30%. However, the requirements of iron and iodine are increased at most--100%. The weight gain in pregnant women should normally be in the range of 10-12.5 kg. During the I and II trimester it should be not substantial, while in the III trimester it should be about 350-400 g/per week. The risks associated with obesity and uncontrolled weight gain during pregnancy are discussed. Consulting physicians are provided with expert opinions about the individualization of the nutritional intake according to the specific metabolic changes during pregnancy and with definitions of an adequate in energy supply and nutritional balance diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I194,I194)","v":17121451},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B194:D194)","v":4},2006,"What is the best approach to reducing birth defects associated with isotretinoin?","Abroms",17121451,"What is the best approach to reducing birth defects associated with isotretinoin?    Abstract:    BACKGROUND TO THE DEBATE : Isotretinoin is an effective treatment for severe acne, a condition which can be physically, emotionally, and socially disabling. Because the drug is teratogenic, causing severe birth defects, women taking the drug are directed to avoid pregnancy. In the United States, a series of risk reduction programs have been implemented that aim to prevent pregnant women from taking the drug and to prevent women taking it from getting pregnant. The most recent, and most stringent, is an Internet-based, performance-linked system called iPLEDGE, which tries to ensure that the drug is dispensed only when there is documentary proof that the patient is not pregnant and is using two forms of birth control. Is iPLEDGE the best way to reduce isotretinoin birth defects, or is it an unproven and overly burdensome system?"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I195,I195)","v":16402912},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B195:D195)","v":4},2006,"Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis.","Mark",16402912,"Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis.    Abstract:   Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRalpha/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell type-restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I196,I196)","v":15883453},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B196:D196)","v":4},2005,"Multiple micronutrients in pregnancy and lactation: an overview.","Allen",15883453,"Multiple micronutrients in pregnancy and lactation: an overview.    Abstract:   This overview of multiple micronutrients during pregnancy and lactation emphasizes 2 relatively neglected issues. The first is that maternal micronutrient status in the periconceptional period, and throughout pregnancy and lactation, should be viewed as a continuum; too often these 3 stages are treated and discussed separately from both a scientific and a public health perspective. Iron and vitamin B-12 are included as examples to stress how status at conception affects maternal, fetal, and infant status and health until the child is weaned. The second issue is that while most attention has been focused on a few micronutrients, for example iron and folate as discussed elsewhere in this Supplement, multiple micronutrient deficiencies occur simultaneously when diets are poor. Some of these deserve more attention as causes of poor pregnancy outcome, including other B vitamin deficiencies that result in homocysteinemia, antioxidants, vitamin D, and iodine. In lactation, maternal status or intake of the B vitamins (except folate), vitamin A, selenium and iodine strongly affect the amount of these nutrients secreted in breast milk. This can result in the infant consuming substantially less than the recommended amounts and further depleting stores that were low at birth. While the optimal mode of meeting recommended micronutrient intakes is an adequate diet, in some situations supplementation is also important. Unfortunately, information is lacking on the optimal formulation of micronutrient supplements for pregnant women, and the need to continue these supplements during lactation is not recognized in many situations where maternal and infant health could benefit."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I197,I197)","v":14979475},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B197:D197)","v":4},2004,"Acute promyelocytic leukemia during pregnancy: report of 3 cases.","Consoli",14979475,"Acute promyelocytic leukemia during pregnancy: report of 3 cases.    Abstract:   Acute promyelocytic leukemia (APL) is characterized by onset at a young age and a life-threatening hemorrhagic diathesis, which is attributed to a disseminated intravascular coagulation (DIC)-like coagulopathy. The discovery of all-trans-retinoic acid has changed the course of APL treatment by reducing the onset of DIC and inducing a complete and durable remission in more than 90% of patients. The occurrence of APL during pregnancy is not a frequent event, but the management of these patients raises many therapeutic and ethical dilemmas and requires a careful clinical case evaluation of fetal and maternal risk, coagulation status, the parents wishes, and therapeutic options. Here we describe 3 patients with APL diagnosed during pregnancy. Clinical data and the therapeutic approaches are presented. In the discussion, we analyze clinical decisions and therapeutic options and compare our cases with those found in the literature."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I198,I198)","v":14608448},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B198:D198)","v":4},2003,"The use of folic acid for the prevention of neural tube defects and other congenital anomalies.","Wilson",14608448,"The use of folic acid for the prevention of neural tube defects and other congenital anomalies.    Abstract:    OBJECTIVE : To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal.  OUTCOMES : Folic acid supplementation has been proven to decrease or minimize specific birth defects.  EVIDENCE : A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC.  VALUES : Peer-review process within the committee structure.  BENEFITS, HARMS, AND COSTS : The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet.  RECOMMENDATIONS : 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canadas Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous pregnancy, family history, insulin-dependent diabetes, epilepsy treatment with valproic acid or carbamazepine) should be advised that high-dose folic acid (4.0 mg-5.0 mg daily) supplementation is recommended. This should be taken as folic acid alone, not in a multivitamin format, due to risk of excessive intake of other vitamins such as vitamin A. (I-A) 6. The choice of a 5 mg folic acid daily dose for women considering a pregnancy should be made under medical supervision after minimizing the risk of undiagnosed vitamin B12 deficiency (hypersegmentation of polymorphonuclear cells, macrocystic indices, large ovalocytes, leukopenia, thrombocytopenia, markedly elevated lactate dehydrogenase level, confirmed red blood cell folate level). (II-2A) 7. Signs or symptoms of vitamin B12 deficiency should be considered before initiating folic acid supplementation of doses greater than 1.0 mg. (III-A) 8. A three-generation pedigree on the families of both the pregnant woman and the biological father should be obtained to identify increased risk for congenital birth defects (i.e., NTD, cardiac, chromosomal, genetic). (III-A) 9. Women who become pregnant should be advised of the availability of noninvasive screening tests and invasive diagnostic tests for congenital birth defects (including NTDs): maternal serum quot;triple marker screenquot; at 15 to 20 weeks, ultrasound at 16 to 20 weeks, and amniocentesis after 15 weeks of pregnancy if a positive screening test is present. (I-A) VALIDATION: This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I199,I199)","v":12791426},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B199:D199)","v":4},2003,"Biomarkers and their use in cervical cancer chemoprevention.","Vlastos",12791426,"Biomarkers and their use in cervical cancer chemoprevention.    Abstract:   Cervical cancer chemoprevention agents under study include diet and micronutrients (particularly beta-carotene, folate, and vitamins A, C, and E); medications such as retinoids (retinyl acetate gel, all-trans-retinoic acid, and 4-hydroxyphenylretinamide) that are chemically related to micronutrients; and other chemopreventives meant to affect the carcinogenic process at the cellular level, including such polyamine synthesis inhibitors as alpha-difluoromethylornithine. Agents become reasonable candidates for study when they have a biologic rationale, they are of low toxicity, and they can be taken for a long period of time. Since the human papillomavirus (HPV) is the major etiologic agent, the medication should show activity against HPV-positive preinvasive and invasive cell lines. The medication needs to be of low toxicity because it may be taken for long periods of time and less toxicity is tolerated in the precancerous setting. Until 1995, none of the studies used surrogate end point biomarkers (SEBs), relying instead on histologic and colposcopic regression as end points. All studies typically included subjects with cervical intraepithelial neoplasia. Conclusions to be drawn from these studies include the following: Though micronutrients are logical candidates for chemoprevention, they havent worked consistently, and the reasons remain unclear. Furthermore, SEBs need to be validated in phase I trials. Finally, a better understanding of the role of HPV needs elucidation, including an understanding of the relationship of the medication to HPV status and of the immunobiology of HPV throughout the trial."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I200,I200)","v":12730475},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B200:D200)","v":4},2003,"Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm delivery: an overview of randomized controlled trials.","Villar",12730475,"Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm delivery: an overview of randomized controlled trials.    Abstract:   This overview assesses the effectiveness of nutritional interventions to prevent or treat maternal morbidity, mortality and preterm delivery. Cochrane systematic reviews and other up-to-date systematic reviews and individual randomized controlled trials were sought. Searches were carried out up to July 2002. Iron and folate supplements reduce anemia and should be included in antenatal care programs. Calcium supplementation to women at high risk of hypertension during pregnancy or low calcium intake reduced the incidence of both preeclampsia and hypertension. Fish oil and vitamins E and C are promising for preventing preeclampsia and preterm delivery and need further testing. Vitamin A and beta-carotene reduced maternal mortality in a large trial; ongoing trials should provide further evaluation. No specific nutrient supplementation was identified for reducing preterm delivery. Nutritional advice, magnesium, fish oil and zinc supplementation appear promising and should be tested alone or together in methodologically sound randomized controlled trials. Anema in pregnancy can be prevented and treated effectively. Considering the multifactorial etiology of the other conditions evaluated, it is unlikely that any specific nutrient on its own, blanket interventions or magic bullets will prevent or treat preeclampsia, hemorrhage, obstructed labor, infections, preterm delivery or death during pregnancy. The few promising interventions for specific outcomes should be tested or reconsidered when results of ongoing trials become available. Until then, women and their families should receive support to improve their diets as a general health rule, which is a basic human right."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I201,I201)","v":12519564},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B201:D201)","v":4},2002,"Vitamin A supplementation during pregnancy.","Van",12519564,"Vitamin A supplementation during pregnancy.    Abstract:    BACKGROUND : Vitamin A supplements have been recommended in pregnancy to improve outcomes that include maternal mortality and morbidity.  OBJECTIVES : To review the effectiveness of vitamin A supplementation during pregnancy, alone or in combination with other supplements, on maternal and newborn clinical and laboratory outcomes.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Groups specialised register of controlled trials (April 2002) and the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2002).  SELECTION CRITERIA : All randomised or quasi-randomised trials evaluating the effect of vitamin A supplementation in pregnant women. The types of intervention included vitamin A supplementation alone or in combination with other micro-nutrients.  DATA COLLECTION AND ANALYSIS : We assessed trials for methodological quality using the standard Cochrane criteria of adequacy of concealment. At least two reviewers independently assessed the trials for inclusion and extracted data. We collected information on blinding, loss to follow-up, setting, number of women, exclusion after randomisation and follow-up as well as supplementation type, dose and frequency. The outcomes we sought included maternal and neonatal clinical and laboratory outcomes.  MAIN RESULTS : Five trials involving 23,426 women were included. Because the trials were heterogeneous with regard to type of supplement given, duration of supplement use and outcomes measured, pooled results using meta analysis could not be performed. One large population based trial in Nepal showed a possible beneficial effect on maternal mortality after weekly vitamin A supplements. In this study a reduction was noted in all cause maternal mortality up to 12 weeks postpartum with Vitamin A supplementation (RR 0.60, 95% CI 0.37-0.97). Night-blindness was assessed in a nested case-control study within this trial and found to be reduced but not eliminated. Three trials examined the effect of vitamin A supplementation on haemoglobin levels. The trial from Indonesia showed a beneficial effect in women who were anaemic ([Hb] lt;11.0 g/dl). After supplementation, the proportion of women who became non-anaemic was 35% in the Vitamin A supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both Vitamin A and iron and 16% in the placebo group. The two trials from Malawi did not corroborate these positive findings.  REVIEWERS CONCLUSIONS : Although the two trials from Nepal and Indonesia suggested beneficial effects of vitamin A supplementation, further trials are needed to determine whether vitamin A supplements can reduce maternal mortality and morbidity and by what mechanism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I202,I202)","v":12137702},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B202:D202)","v":4},2002,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.","Shey",12137702,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : Mother-to-child transmission (MTCT) of HIV is the dominant mode of acquisition of HIV infection for children, currently resulting in about 1800 new paediatric HIV infections each day world-wide. This is one of several reviews assessing the available evidence for preventing HIV transmission from an HIV-infected woman to her child. The other reviews assess the effects of antiretroviral therapy, Caesarean section delivery, breast feeding, and vaginal lavage.  OBJECTIVES : To assess the effects of antenatal and intrapartum vitamin A supplementation, compared to an appropriate control group, on the risk of MTCT of HIV infection and infant and maternal mortality and morbidity, and the tolerability of vitamin A supplementation.  SEARCH STRATEGY : We searched the Cochrane Controlled Trials Register, Cochrane Pregnancy and Childbirth Register, PubMed, EMBASE, AIDSLINE, LILACS, AIDSTRIALS, and AIDSDRUGS, using standardised methodological filters for identifying trials. We also searched reference lists of identified articles, relevant editorials, expert opinions and letters to journal editors, and abstracts or proceedings of relevant conferences; and contacted subject experts, agencies, organisations, academic centres, and pharmaceutical companies. There were no language restrictions.  SELECTION CRITERIA : Randomised trials comparing vitamin A supplementation with no vitamin A supplementation in known HIV infected pregnant women. Trials had to include an estimate of the effect of vitamin A supplementation on MTCT of HIV and/or any other pre-specified adverse pregnancy outcome to be included.  DATA COLLECTION AND ANALYSIS : Two reviewers independently assessed trial eligibility and quality and extracted data. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for binary data and pooled using a fixed effect (Mantel-Haenszel) method. Heterogeneity between studies was examined by graphical inspection of results followed by a chi-square test of homogeneity.  MAIN RESULTS : We identified five eligible trials, only two of which included an estimated of the effect of vitamin A supplementation on at least one of the pre-specified outcomes. Based on the two trials, with a total of 1813 participants, there is no evidence that vitamin A supplementation has an effect on MTCT of HIV (OR 1.09, 95% confidence interval (CI) 0.81 to 1.45). There is no evidence of heterogeneity between the trials (p = 0.37), and no evidence of an effect of vitamin A supplementation in HIV-infected pregnant women on stillbirths (OR 1.07, 95% CI 0.63 to 1.80), very preterm births, i.e. born less than 34 weeks gestation (OR 0.86, 95% CI 0.57 to 1.31), all preterm births, i.e. born less than 37 weeks gestation (OR 0.88, 95% CI 0.68 to 1.13), low birth weight, i.e. weighing less than 2500g (OR 0.86, 95% CI 0.64 to 1.17), very low birthweight, i.e. weighing less than 2000g (OR 0.71, 95% CI 0.40 to 1.28), and postpartum CD4 levels (weighted mean difference -4.00, 95% CI -51.06 to 43.06). The effect of vitamin A on maternal mortality could not be assesssed, as there were only three maternal deaths.  REVIEWERS CONCLUSIONS : /                <AbstractText IMPLICATIONS FOR PRACTICE : At the present time there is no conclusive evidence that the antenatal and intrapartum use of vitamin A supplementation to reduce MTCT of HIV and adverse pregnancy outcomes among HIV-infected pregnant women should be recommended.  IMPLICATIONS FOR RESEARCH : The current review will be updated as soon as data from ongoing studies become available. This review and the review in progress on vitamin A supplementation in pregnant women of seronegative/unknown HIV status (Kulier 2002) should be considered together in order to shed more light on the effect of vitamin A supplementation on non-HIV related adverse pregnancy outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I203,I203)","v":12035861},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B203:D203)","v":4},2002,"Prepregnancy and pregnancy nutrition and its impact on womens health.","Oumachigui",12035861,"Prepregnancy and pregnancy nutrition and its impact on womens health.    Abstract:   The overall nutrition status of females remains deficient. Among female school children 13-18 years of age, calorie consumption ranged from 65-90% of the RDA (Recommended Dietary Allowance), protein consumption from 60-71% of RDA, and vitamin A intake was 50% of RDA. Prevalence of anemia ranged from 72-98% and that of intestinal parasitic infection ranged from 17-62%. Gender bias may adversely affect the nutrition of the female child. An adolescent is likely to begin pregnancy with a negative nutrition balance. In a multicentric study, 93,356 married women, aged 15-45 years, were interviewed at home in a community-based survey from 23 districts in India. Forty to eighty percent were married before 18 years of age, and the incidence of teenage pregnancy was 66%. The magnitude of the problem and the adverse effects malnutrition may have in later life requires well-designed studies in order to find solutions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I204,I204)","v":12035860},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B204:D204)","v":4},2002,"Maternal nutrition, health, and survival.","Christian",12035860,"Maternal nutrition, health, and survival.    Abstract:   The burden of maternal morbidity and mortality in developing countries is high. Each year, 600,000 women die from pregnancy-related causes and 62 million women suffer from morbidity and complications of pregnancy. The extent to which maternal nutrition can improve maternal health and survival is not well understood. Excluding deaths due to induced abortions, the other four main causes of maternal mortality (preeclampsia, hemorrhage, obstructed labor, and infection) may be amenable to nutrition interventions. The role of calcium in reducing the incidence of preeclampsia and hypertension is promising, but more research in deficient populations is urgently needed. Antenatal iron supplementation, although frequently recommended to prevent anemia during pregnancy, has had little program success. Severe anemia may be an important cause of maternal mortality, but convincing evidence is lacking on the health consequences of mild-to-moderate maternal anemia. Knowledge of the etiology of anemia is important in identifying effective strategies for combating it. Other vitamins such as folate, B12, and vitamin A may enhance the effect of iron supplementation in populations where multiple nutrition deficiencies exist. Maternal night blindness is widespread in South Asian women. In Nepal, this condition is associated with markedly increased risks of vitamin A deficiency, anemia, morbidity, and maternal and infant mortality. These findings need to be replicated elsewhere in South Asia. One study has shown vitamin A and beta carotene supplementation to reduce maternal mortality and morbidity. These findings need testing in different settings with emphasis on investigating the mechanisms of the effect. The area of prepregnancy nutrition and its influence on prolonged and obstructed labor is wide open for investigation. The scope for research in the area of maternal nutrition and health is large and the onus is on nutritionists to bring to the forefront the role of nutrition in maternal health and survival."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I205,I205)","v":12010859},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B205:D205)","v":4},2002,"Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.","Sato",12010859,"Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.    Abstract:   Previous prospective studies have raised the possibility that the antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the role of vitamin A (retinol) in cellular differentiation may be associated with a reduced risk of subsequent breast cancer. To investigate the association between serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha-tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a nested case control study was conducted among female residents of Washington County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases (n = 295) and controls (n = 295) were matched on age, race, menopausal status, and date of blood donation, and the analyses were stratified by cohort participation. Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively) and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95% confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI 0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P trend = 0.02) in the 1974 cohort. There was generally a protective association for other micronutrients in both cohorts, although none reached statistical significance. The results suggest that carotenoids may protect against the development of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I206,I206)","v":11949943},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B206:D206)","v":4},2002,"Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis.","Osteen",11949943,"Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis.    Abstract:   The endometrial lining of the human uterus is a highly specialized, steroid-sensitive tissue. Throughout the reproductive years, the endometrium undergoes dramatic cycles of growth, differentiation, and breakdown under the influence of ovarian steroids. In response to changes in steroid exposure throughout the menstrual cycle, the endometrium produces an array of bioactive growth factors and other cytokines that are critical components of paracrine communication. For example, cell-cell communication via paracrine factors directs the expression of matrix metalloproteinases (MMPs), enzymes that mediate tissue remodeling during the menstrual cycle. The disease endometriosis is thought to occur as a consequence of retrograde menstruation, and MMPs appear to contribute to the establishment and progression of ectopic endometrial growth in the peritoneal cavity. Although the risk for developing endometriosis is linked to a womans steroid exposure, locally produced paracrine factors can modify steroid action on multiple gene targets, including the MMPs. Estrogen-associated growth factors as well as inflammatory cytokines are potent stimulators of MMP expression and may contribute to the ability of endometrial fragments to invade the peritoneal surface and establish ectopic sites of growth. In contrast, paracrine factors associated with progesterone action during early pregnancy inhibit MMP expression and prevent ectopic endometrial growth in an experimental model. For example, locally produced retinoic acid and transforming growth factor-beta (TGF-beta) act in concert with progesterone to suppress MMPs, while enhancing expression of MMP inhibitors (TIMPs) during endometrial differentiation. Targeting pregnancy-associated factors that inhibit endometrial-specific MMP expression and action may enhance the effectiveness of progestin-related treatments for endometriosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I207,I207)","v":11787685},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B207:D207)","v":4},2001,"Development of a topical vaginal microbicide: lessons learned from human milk.","Isaacs",11787685,"Development of a topical vaginal microbicide: lessons learned from human milk.    Abstract:   Vaccines are not presently available to prevent adherence and transmission of many common pathogens at mucosal surfaces. As a result, sexually transmitted diseases were one of the most commonly reported infections in the US in 1999. New methods are needed to reduce the spread of mucosal infections. Providing nonspecific protective factors, such as lipids and retinoids found in human milk to mucosal surfaces could reduce mucosal infection caused by viruses, e.g., herpes simplex virus-1 (HSV-1) and bacteria, e.g., Pseudomonas aeruginosa. Human milk lipids enzymatically modified to produce monoglycerides were antimicrobial and inactivated enveloped viruses, as well as gram-positive and gram-negative bacteria. Enveloped viruses were inactivated in seconds following contact with antimicrobial lipids, and P. aeruginosa infectivity was reduced by 99.9% after 2 hours. Transmission of pathogens at mucosal surfaces can also be prevented using retinoids that inhibit viral replication. In a human embryonic intestinal cell line the retinoic acid (RA) derivatives all-trans-RA and 9-cis-RA (10 microg/mL) decreased the production of HSV-1 and Echo-6 viruses by 1-2 log10 over a 48-hour period. In addition, all-trans-RA inhibited HSV-1 replication in Vero cells as effectively as interferon beta, reducing viral production by 2.5log10. These studies indicate that lipids and retinoids could be part of a topical microbicide to prevent mucosal infections."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I208,I208)","v":11735646},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B208:D208)","v":4},2001,"Drug-induced congenital defects: strategies to reduce the incidence.","De Santis",11735646,"Drug-induced congenital defects: strategies to reduce the incidence.    Abstract:   Approximately 1% of congenital anomalies relate to pharmacological exposure and are. in theory, preventable. Prevention consists of controlled administration of drugs known to have teratogenic properties (e.g. retinoids, thalidomide). When possible, prevention could take the form of the use of alternative pharmacological therapies during the pre-conception period for certain specific pathologies, selecting the most appropriate agent for use during pregnancy [e.g. haloperidol or a tricyclic antidepressant instead of lithium; anticonvulsant drug monotherapy in place of multitherapy; propylthiouracil instead of thiamazole (methimazole)], and substitution with the most suitable therapy during pregnancy (e.g. insulin in place of oral antidiabetics; heparin in place of oral anticoagulants; alpha-methyldopa instead of ACE inhibitors). Another strategy is the administration of drugs during pregnancy taking into account the pharmacological effects in relation to the gestation period (e.g. avoidance of chemotherapy during the first trimester, avoidance of nonsteroidal anti-inflammatory drugs in the third trimester, and avoidance of high doses of benzodiazepines in the period imminent to prepartum)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I209,I209)","v":11040271},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B209:D209)","v":4},2000,"The retinoids and cancer prevention mechanisms.","Dragnev",11040271,"The retinoids and cancer prevention mechanisms.    Abstract:   Carcinogenesis is a multistep process that converts normal cells into malignant cells. Once transformed, malignant cells acquire the ability to invade and metastasize, leading to clinically evident disease. During this continuum from normal to metastatic cells, carcinogenic steps can be arrested or reversed through pharmacological treatments, known as cancer chemoprevention. Chemoprevention strategies represent therapeutic interventions at early stages of carcinogenesis, before the onset of invasive cancer. Effective chemoprevention should reduce or avoid the clinical consequences of overt malignancies by treating early neoplastic lesions before development of clinically apparent signs or symptoms. Preclinical, clinical, and epidemiological data provide considerable support for cancer chemoprevention as an attractive therapeutic strategy. This clinical approach was validated in the recent tamoxifen randomized trial, demonstrating that a selective estrogen receptor modulator reduces the risk of breast cancer in women at high risk for this malignancy. Derivatives of vitamin A, the retinoids, have reported activity in treating specific premalignant lesions and reducing incidence of second primary tumors in patients with prior head and neck, lung or liver cancers. Whether the retinoids will prevent primary cancers at these sites is not yet known. Notably, a carotenoid (beta-carotene) was shown as inactive in primary prevention of lung cancers in high-risk individuals. This underscores the need for relevant in vitro models to identify pathways signaling chemopreventive effects. These models should assess the activity of candidate chemoprevention agents before the conduct of large and costly prevention trials. An improved understanding of cancer prevention mechanisms should aid in the discovery of new therapeutic targets and chemoprevention agents. Ideally, these agents should have tolerable clinical toxicities suitable for chronic administration to individuals at high risk for developing primary or second cancers. This article reviews what is now known from clinical and preclinical studies about the retinoids as cancer prevention agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I210,I210)","v":10871590},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B210:D210)","v":4},2000,"Etiology of anemia in pregnancy in south Malawi.","van den Broek",10871590,"Etiology of anemia in pregnancy in south Malawi.    Abstract:    BACKGROUND : Anemia in pregnancy is a major public health problem in developing countries. In sub-Saharan Africa, such anemia is generally accepted as resulting from nutritional deficiencies, particularly iron deficiency.  OBJECTIVE : We comprehensively assessed the full spectrum of nutritional and nonnutritional factors associated with pregnancy anemia.  DESIGN : Iron, folate, vitamin B-12, and vitamin A were measured in serum in a cross-sectional study of 150 pregnant women in Blantyre, Malawi. Bone marrow aspirates were evaluated, peripheral blood films were examined for malaria parasites, stool and urine samples were examined for helminthic infection, and tests were done for genetic disorders and for HIV infection. C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates were measured as markers of inflammation.  RESULTS : Of the 150 anemic women, 23% were iron deficient with no evidence of folate, vitamin B-12, or vitamin A deficiencies; 32% were deficient in iron and one or more of the other micronutrients; 26% were not iron deficient but had evidence of one of the other micronutrient deficiencies, most often vitamin A; and 19% were not deficient in any of the micronutrients studied. CRP concentrations were notably high in 54% of the anemic women with no nutritional deficiencies and in 73.5% of the anemic women who were iron replete by bone marrow assessment.  CONCLUSION : The role of chronic inflammation as a possible contributing factor to anemia in pregnancy has important implications for the clinical evaluation and treatment of women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I211,I211)","v":10799410},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B211:D211)","v":4},2000,"Vitamin A in pregnancy: requirements and safety limits.","Azaïs-Braesco",10799410,"Vitamin A in pregnancy: requirements and safety limits.    Abstract:   Most of the functions of vitamin A are mediated through the binding of retinoic acid to specific nuclear receptors that regulate genomic expression. Recent experimental work in transgenic mice showed clearly that normal embryonic development depends on the correct spatial and temporal expression of the receptors in the differentiating cells and on the binding of specific forms of retinoic acid. This implies that the parent compound, vitamin A, is available in adequate forms and quantities. Excessive dietary intake of vitamin A has been associated with teratogenicity in humans in lt;20 reported cases over 30 y. However, caution must be exercised to avoid unnecessary supplementation of women of childbearing age. Hypovitaminosis A affects millions of women and children worldwide. The main consequence of a poor vitamin A supply during pregnancy is a low vitamin A status at birth and in the next few months. Vitamin A deficiency is strongly associated with depressed immune function and higher morbidity and mortality due to infectious diseases such as diarrhea, measles, and respiratory infections. Vitamin A deficiency is often associated with an increased mother-to-child transmission of HIV-1. The initiation of vitamin A supplementation should be carefully examined in each case according to the risk-to-benefit ratio. The final decision should take into account the estimated vitamin A status of the woman, the availability of vitamin A-rich foods in her diet, and whether supplementation can be supervised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I212,I212)","v":10497330},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B212:D212)","v":4},1999,"Heads or tails? Retinoic acid will decide.","Maden",10497330,"Heads or tails? Retinoic acid will decide.    Abstract:   A recent study (Niederreither et al. Nat Genet 1999;21:444-448 [Ref. 1]) describes the phenotype of a gene knockout for an enzyme, retinaldehyde dehydrogenase 2 (RALDH-2), that synthesizes retinoic acid (RA) in the early embryo. The effects generated by this single enzyme mutation are remarkably similar to those previously described in vitamin A-deprivation studies and compound retinoic acid receptor knockouts, which involve multiple systems of the embryo. With other data on the distribution of RA, its role in axial specification of the early embryo is considerably clarified. Surprisingly, it seems that head development is unaffected in these RALDH-2 knockout embryos; thus, the anterior of the embryo does not require RA, despite the observations that the hindbrain seems exquisitely sensitive to RA perturbation. Head development may be realised by a cytochrome P450 enzyme (CYP26), which has been described recently. Between these two opposing forces, the hindbrain develops."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I213,I213)","v":10325500},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B213:D213)","v":4},1999,"Retinoids in chemoprevention.","Whelan",10325500,"Retinoids in chemoprevention.    Abstract:   Over several decades, in vitro experimental studies have demonstrated that retinoids effect the process of carcinogenesis and tend towards the alteration of cells back to more normal differentiation. This hypothesis has formed the basis of several chemopreventive studies in breast cancer, cervical cancer, head and neck cancer and lung cancer. Experimental evidence exists to suggest that chemoprevention with retinoids may well have a beneficial effect in patients at high risk of acquiring prostate cancer. None of the studies, however, in any of the cancers have yet been definitive, but opportunities exist with newer retinoids that appear to be able to be given on a long-term basis with minimal toxic side effects, to explore this exciting potential treatment pathway."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I214,I214)","v":9989892},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B214:D214)","v":4},1998,"Nutritional interventions for the prevention of maternal morbidity.","Kulier",9989892,"Nutritional interventions for the prevention of maternal morbidity.    Abstract:    OBJECTIVE : To review the effectiveness of nutritional interventions to prevent maternal morbidity.  METHODS : This is an overview of systematic reviews and individual randomized controlled trials (if no systematic review available) of nutritional interventions during pregnancy. For each nutrient intervention the main maternal morbidity data reported were extracted. These were pre-eclampsia/eclampsia, pregnancy-induced hypertension, hemorrhage, anemia, infection and obstructed labor. In addition, the trial settings, the number of trials and participants characteristics were systematically extracted.  RESULTS : The systematic reviews considered in this paper had only few trials that reported the selected maternal outcomes. Outcome measures are based sometimes on one trial only. Most of the interventions compared single micronutrient supplementation with placebo/no treatment and did not show significant benefits for the supplementation groups. Calcium supplementation in women at high risk of pregnancy hypertension reduced the incidence of high blood pressure (RR, 0.35; 95% CI, 0.21-0.57) and pre-eclampsia (RR, 0.22; 95% CI, 0.11-0.43). Similarly, in women with low dietary calcium intake, calcium supplementation resulted in a significant reduction in the incidence of high blood pressure (RR, 0.49; 95% CI, 0.38-0.62) and pre-eclampsia (RR, 0.32; CI, 0.21-0.49). In women at low risk of pregnancy hypertension or with adequate baseline calcium intake, the beneficial effects of calcium supplementation are small and unlikely to be of clinical significance. Both, iron and folate supplementation reduced the number of women with low pre-delivery hemoglobin.  CONCLUSIONS : Routine calcium supplementation seems to be a promising intervention for pregnant women at risk of developing preeclampsia or have low calcium intake, but these findings need to be confirmed with a trial with adequate power in different settings. In populations with high incidence of nutritional anemia routine iron and folate supplementation should be recommended during ante-natal care. It is unclear at this stage if adding vitamin A to iron and folate supplementation in anemia prevalent areas provides further benefits. There is inadequate data on the benefits or harms of routine iron or folate supplementation in adequately nourished populations. With regard to other micronutrient supplementation, such as zinc, magnesium and fish oil, randomized controlled trials with sufficient power to detect clinically important differences in maternal and infant outcomes are needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I215,I215)","v":9781308},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B215:D215)","v":4},1998,"Flavonoids as hormones. A perspective from an analysis of molecular fossils.","Baker",9781308,"Flavonoids as hormones. A perspective from an analysis of molecular fossils.    Abstract:   Although for centuries plants have been known to have hormone-like actions in humans, the mechanism(s) by which plant-derived compounds act in humans is still being elucidated, a goal that has assumed more importance due to interest in the protective actions of fruits and vegetables in diseases such as cancer. Here I use the quot;molecular fossil recordquot; of amino acid sequences of proteins involved in regulating the actions steroids, retinoids, thyroid hormone and prostaglandins to propose some mechanisms by which flavonoids in fruits and vegetables can have hormone-like actions in humans. I focus on: i) hormone receptors that bind to DNA and regulate gene transcription and ii) the enzymes that regulate the concentrations of these hormones. Comparative analyses of amino acid sequences show that nuclear receptors for steroids, retinoids, thyroid hormone and prostaglandins in humans and insects are descended from a common ancestor. Similar analyses of dehydrogenases that regulate the concentrations of steroids, retinoids and prostaglandins reveal strong sequence similarity to enzymes in plants, insects, fungi, and bacteria. The similarity is sufficient to suggest that some compounds that bind receptors or enzymes in invertebrates, plants or unicellular organisms may also bind to mammalian homologs that are involved in endocrine physiology. Among the phytochemicals that are candidates for such activity are flavonoids because they are involved in plant-insect and plant-bacteria interactions and have some structural and chemical similarities to steroids, retinoids, thyroid hormone, prostaglandins and fatty acids. These similarities and the kinship of human, plant, insect and bacterial proteins involved in signal transduction provide a conceptual framework for investigating flavonoids for hormone-like actions in humans. Understanding these modes of action may be useful in developing protocols for preventing hormone-dependent diseases such as breast and prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I216,I216)","v":9524850},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B216:D216)","v":4},1998,"The significance of vitamin A and carotenoid status in persons infected by the human immunodeficiency virus.","Nimmagadda",9524850,"The significance of vitamin A and carotenoid status in persons infected by the human immunodeficiency virus.    Abstract:   Hyporetinemia is associated with increased childhood morbidity and mortality that is reversible with vitamin A supplementation. Although vitamin A deficiency is otherwise rare in developed countries, the prevalence of hyporetinemia in human immunodeficiency virus (HIV)-infected persons is up to 29%. Hyporetinemic HIV-infected patients have a 3.5-5-fold increased risk of death. Furthermore, HIV-infected patients with very low or very high intake of vitamin A and beta-carotene (a vitamin A precursor) have greater rates of disease progression than do patients with intermediate intake. In developing countries up to 60% of HIV-infected pregnant women are hyporetinemic. In such women the relative risk of perinatal HIV transmission may be increased more than fourfold. These data indicate that vitamin A deficiency is common in HIV-infected patients in the developed world and strongly suggest that vitamin A supplementation may be especially useful in adjunctive therapy for HIV-infected pregnant women who reside in the developing world."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I217,I217)","v":8949994},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B217:D217)","v":4},1996,"Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.","Piamsomboon",8949994,"Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.    Abstract:   Recurrent and metastatic cervical carcinoma has very poor prognosis, mainly because there is no effective systemic therapy which would increase the duration of survival. Biologic agents have recently been found to have activity in cervical carcinoma. The combination of interferon (IFN)-alpha and 13-cis-retinoic acid had additive and synergistic antitumor activity. Both have antiviral, immunoregulatory and antiangiogenic properties, and are known to modulate malignant cell differentiation and proliferation. We report two patients with recurrent squamous cell carcinoma (SCC) of the cervix who had small-volume progressive metastatic disease, and were treated with a combination of IFN-alpha and 13-cis-retinoic acid. The first patient had pelvic lymph node metastases and the other had lung metastases. The previously progressive diseases remained stable for a prolonged period of time, 3 and 4 years, with a good quality of life. These cases suggest the possibility of using IFN-alpha and 13-cis-retinoic acid as a treatment for small-volume residual disease or as postinduction therapy in patients at high risk for disease recurrence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I218,I218)","v":7831583},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B218:D218)","v":4},1994,"Retinoic acid and interferon in human cancer: mechanistic and clinical studies.","Moore",7831583,"Retinoic acid and interferon in human cancer: mechanistic and clinical studies.    Abstract:   Various combinations of retinoids, metabolic and synthetic derivatives of vitamin A, and interferons (IFNs) have demonstrated synergistic antiproliferative, differentiating, and antiangiogenic activity in some human hematologic and solid-tumor systems. This synergistic antitumor activity may be due to enhanced gene expression. In several cell systems, the actions of IFNs are enhanced by differentiation of cells with retinoic acid (RA). Combined RA-IFN effects have been correlated with the induction of higher levels of IFN-stimulated genes than the levels induced by either agent alone. Natural and synthetic retinoids have been found to augment the antiproliferative activity of IFNs in several squamous cell carcinoma (SCC) and breast tumor cell lines. Results of recent clinical trials indicate substantial activity of 13-cis-RA (13cRA) combined with IFN against advanced SCC of the skin and cervix, and possibly against other solid tumors. Two phase II trials have confirmed activity against locally advanced SCC of the cervix. Successful integration of this regimen with radiotherapy appears to be the most probable means of optimizing clinical outcome. Further studies are needed to determine the mechanistic details of the RA-IFN interaction."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I219,I219)","v":7925185},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B219:D219)","v":4},1994,"Developmental neurotoxicity induced by therapeutic and illicit drugs.","Vorhees",7925185,"Developmental neurotoxicity induced by therapeutic and illicit drugs.    Abstract:   The developmental neurotoxicity of phenytoin, isotretinoin, and methamphetamine has been reviewed to illustrate effects from both therapeutic and illicit drugs to which people are exposed and which either induce or show the potential for inducing learning disabilities following in utero exposure. In each case both human and experimental animal data are presented and compared where possible. The findings point to several conclusions. First, some drugs in current use induce developmental neurotoxicity, and it cannot safely be assumed that there are not more as yet unidentified. Second, of the types of neurotoxicity induced by drugs, learning disabilities figure prominently. Third, the effects observed are dependent on both the drugs mechanism of action and the period of brain development during which exposure occurs. Fourth, with the exception of CNS teratogens, it is not yet possible to predict which periods of brain development are the most vulnerable for the induction of learning disabilities, as seen by the different patterns of critical periods for phenytoin and isotretinoin compared to methamphetamine. Fifth, as seen with isotretinoin, existing drugs that cause developmental neurotoxicity are not the only problem; new drugs with such effects are still being introduced. Sixth, only a small fraction of the drugs currently in use have ever been examined for developmental neurotoxicity; hence, the full scope of the problem cannot even be accurately estimated based on current information. It is concluded that prevention of new cases caused by drugs such as isotretinoin should be a high priority for future regulatory action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I220,I220)","v":8151328},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B220:D220)","v":4},1994,"Cancer chemoprevention.","Lippman",8151328,"Cancer chemoprevention.    Abstract:    PURPOSE : To review the most important recent advances in clinical trials and biologic studies within the growing field of chemoprevention.  METHODS : The most critical methods issue concerns the definitive end point of phase III trials, which is now cancer incidence. This end point usually needs thousands of subjects monitored for 5 to 10 or more years to determine efficacy. Biologic markers of potential intermediate end points are under intensive study and may one day replace cancer incidence. Validated intermediate end point biomarkers could greatly reduce phase III trial populations, durations, and costs.  RESULTS : Randomized clinical trials over the last 5 years have produced significant activity in reversing oral, skin, colon, and cervical premalignancy; in preventing primary skin and stomach cancer; and in preventing second primary tumors associated with head and neck and lung cancer. These clinical advances have been paralleled at the basic science level by elegant molecular studies of premalignant carcinogenesis and of chemopreventive agents mechanisms of action. One major laboratory advance is the discovery of nuclear retinoic acid receptors and strong evidence of their roles both in carcinogenic progression and in its response to retinoids.  CONCLUSION : Chemoprevention has matured greatly in recent years with the significant reversal or suppression of premalignancy by chemopreventive agents in several sites. The future of chemoprevention will be determined largely by several ongoing phase III trials, including trials of retinoids, beta-carotene, and alpha-tocopherol in the aerodigestive tract, of tamoxifen and fenretinide in the breast, and of finasteride in the prostate."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I221,I221)","v":8494296},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B221:D221)","v":4},1993,"The role of the human placenta in embryonic nutrition. Impact of environmental and social factors.","Miller",8494296,"The role of the human placenta in embryonic nutrition. Impact of environmental and social factors.    Abstract:   The human placenta has been implicated in the poor growth and development of the embryo/fetus due to alterations in blood flow and reductions in the transfer of nutrients such as amino acids and carbohydrates. Deficiencies of such nutrients have been the principal of many research investigations. The role of micronutrients, however, may also be major factors in appropriate growth and development, and there may be a general reduction in the availability of such nutrients, for example, the role of folate supplementation during early pregnancy and the reduction in the incidence of neural tube defects. Vitamins are not all transported via a common mechanism. Therefore, the modulation of human placental transport can be different for different vitamins, for example, A and B12. It is apparent that the human placenta can oxidatively metabolize retinoids (isotretinoin and tretinoin) to more toxic or less toxic metabolites. These metabolites can then be transferred to the fetal circulation. Such metabolism/transfer is in contrast to how vitamin B12 is bound to transcobalamin proteins, which are produced by the placenta and directionally released into the maternal and fetal circulations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I222,I222)","v":8454548},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B222:D222)","v":4},1993,"Effects of supplemental beta-carotene and vitamin A on reproduction in swine.","Chew",8454548,"Effects of supplemental beta-carotene and vitamin A on reproduction in swine.    Abstract:   Since its discovery some 80 yr ago, many advances have been made in understanding the many diverse roles of vitamin A (retinoids). Among these are the critical roles that vitamin A plays in regulating reproduction in both the male and female. The identification of retinol-binding proteins produced by the pig uterus and conceptus marks an exciting event. It will be pivotal to future efforts in elucidating the mechanism by which retinoids regulate conceptus development and steroidogenesis. However, relatively little is known of the possible direct role played by its provitamin, beta-carotene, in controlling reproduction in the pig. However, future research likely will address this aspect of carotenoid function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I223,I223)","v":12288485},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B223:D223)","v":4},1992,"Vitamin A in pregnancy: a review.","Sharma",12288485,"Vitamin A in pregnancy: a review.    Abstract:   In recent years several studies have demonstrated the close association of vitamin A deficiency and increased neonatal and childhood morbidity. The breast-fed infant depends on its vitamin A supply solely from maternal milk. Neonatal serum concentration of vitamin A is about one half that found in their mothers. As long as adequate lactational levels of the vitamin are present, the infants vitamin A status improves over the first 12 months. If maternal vitamin A status is poor in pregnancy it may contribute to the high infant mortality observed in poorly nourished communities. Clinical proof was established only very recently demonstrating a strong correlation between vitamin A status of the mother and intake of the infant. Thus, an adequate vitamin A status during lactation prevents respiratory and diarrheal diseases in breast-fed infants and averts death caused by the diseases. The International Vitamin A Consultative Group (IVACG) suggested that the recommended daily allowance (RDA) of vitamin A in the diet of pregnant women should be 9.3 retinol equivalent (RE)/kg body weight + 100 RE. In marginally nourished populations such as western Rajasthan, it is recommended that daily supplemental doses of 3000 RE (10,000 IU) vitamin A be given during pregnancy provided that the dietary intake is inadequate. For lactating women, the goal is to maintain the highest vitamin A concentration in breast milk. The dietary RDA should be 9.3 RE/kg body weight + 350 RE, provided that the lactating woman did not enter the lactation period in a deficient state. If she did, megadoses of vitamin A (200,000-300,000 IU) may be safely given at parturition or within the first month after birth. This is adequate to maintain a normal range of vitamin A in maternal blood and milk for at least a month."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I224,I224)","v":1812131},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B224:D224)","v":4},1991,"Teratogenic effects of alcohol and isotretinoin on craniofacial development: an analysis of animal models.","Webster",1812131,"Teratogenic effects of alcohol and isotretinoin on craniofacial development: an analysis of animal models.    Abstract:   The teratogens alcohol and isotretinoin cause different patterns of facial dysmorphogenesis in the human. For isotretinoin the pattern is consistent with interference with the normal development of the cranial neural crest, particularly that destined for the second visceral arch. In vitro studies in the rat indicate that, at threshold levels of exposure to isotretinoin, the development of the second arch crest represents the most sensitive process of organogenic development. For alcohol, the facial abnormalities result from exposure very early in development, during the gastrulation process. There is no evidence that this is a peculiarly sensitive stage of development with respect to alcohol; animal studies indicate that other processes in the organogenic period are equally or more vulnerable. The emphasis given to the abnormal facial features in the fetal alcohol syndrome is considered a phenomenon associated with the exclusivity of syndromes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I225,I225)","v":2133256},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B225:D225)","v":4},1990,"Evaluation of N-4-(hydroxycarbophenyl) retinamide as a cancer prevention agent and as a cancer chemotherapeutic agent.","Han",2133256,"Evaluation of N-4-(hydroxycarbophenyl) retinamide as a cancer prevention agent and as a cancer chemotherapeutic agent.    Abstract:   In this review, a retinoid analogue (N-4-hydroxycarbophenyl) retinamide (R11) has been evaluated for its pharmacological and clinical properties. R11 has been studied both as a cancer prevention agent, as well as, a cancer chemotherapeutic agent. R11 alone and in combination with other agents can be used for the treatment of cervical dysplasia or leukemia. This review will examine novel strategies and mechanisms of action for retinoids in the treatment and prevention of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I226,I226)","v":2403415},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B226:D226)","v":4},1990,"Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review.","Boone",2403415,"Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review.    Abstract:   A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N-methyl-N-nitrosourea or 7,12-dimethylbenz(a)anthracene; hamster lung carcinoma induced by N-methyl-N-nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: beta-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I227,I227)","v":2122140},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B227:D227)","v":4},1990,"Cancer chemoprevention by supplemental carotenoids and synergism with retinol in mastodynia treatment.","Santamaria",2122140,"Cancer chemoprevention by supplemental carotenoids and synergism with retinol in mastodynia treatment.    Abstract:   Cancer chemoprevention with beta-carotene (BC), canthaxanthin (CX) and retinol-BC is reported with respect to skin, breast, gastric, colon carcinogeneses induced by benzo(a)pyrene (BP) with or without ultra violet radiation (UV-A, UV-B), dimethylbenzathracene (DMBA) +/- UVB, P-UVA, N-methyl-N-N-nitro-nitrosoguanidine (MNNG), dimethylhydrazine (DMH), and with respect to transplanted tumours. When animals were loaded with carotenoid supplementation one month before the carcinogenic induction (continued throughout the experiment), cancer prevention was observed up to 60-100%. The absence of provitamin A-activity in CX shows the carotenoid antioxidant property. Fifteen patients given BC + CX to prevent recurrences after radical removal of the primary neoplasia in organs like lung, breast, colon, urinary bladder, head and neck were studied in 1980-89. A longer than expected disease-free interval was preliminarily found. Supplementation of BC +/- retinol was also reported to prevent and treat oral leucoplakia. Supplementation and intermittent retinol administration was also tested in benign cyclical mastalgia with clear cut side effect free therapeutic results."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I228,I228)","v":2971690},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B228:D228)","v":4},1988,"Use of oral and topical agents for acne in pregnancy.","Rothman",2971690,"Use of oral and topical agents for acne in pregnancy.    Abstract:   Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy. Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy. Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies. Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies. Erythromycin, however, appears to be safe. Topical acne medications never have been implicated as a cause of fetal deformities in human beings. Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age. Prompt reporting of adverse effects is encouraged."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I229,I229)","v":3054428},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B229:D229)","v":4},1988,"Prenatal adverse effects of various drugs and chemicals. A review of substances of frequent concern to mothers in the community.","Bologa-Campeanu",3054428,"Prenatal adverse effects of various drugs and chemicals. A review of substances of frequent concern to mothers in the community.    Abstract:   Using the number of calls to the Canadian Motherisk Program as an indicator of the drugs and chemicals frequently of concern to mothers during pregnancy, the risks to the fetus of exposure to these compounds have been reviewed. The drugs which were of concern, and have been proven to be teratogenic, included alcohol, alkylating and antimetabolite agents, stilboestrol, disulfiram, heparin, lithium carbonate, phenytoin, tretinoin (retinoic acid), troxidone and valproic acid. For other compounds studied, there was either no data in the literature or no clear evidence of teratogenicity. The combination of doxylamine and pyridoxine, for example, has been associated with limb reduction defects in isolated case reports: cohort and case-control studies have failed to show a higher-than-baseline risk of malformations. In some cases of exposure to compounds with no known teratogenic potential, other adverse effects to the fetus are possible, and these effects are discussed in detail. In conclusion, when advising a pregnant woman about the potential teratogenic effect of a particular drug or chemical exposure, the health professional should also discuss other factors such as age, obstetric and medical history and the history of other exposures (including alcohol and smoking). In every pregnancy there is a 1 to 5% risk of mayor malformations, and even if the exposure does not appear to increase the teratogenic risk, such a risk still exists."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I230,I230)","v":3157194},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B230:D230)","v":4},1985,"Skeletal morphogenesis: comparative effects of a mutant gene and a teratogen.","Kochhar",3157194,"Skeletal morphogenesis: comparative effects of a mutant gene and a teratogen.    Abstract:   As a teratogenic agent retinoic acid (RA) produces severe limb reduction defects if administered at a certain stage of embryonic development. In vitro, RA is able to prevent chondrogenesis and this inhibitory effect is accompanied by the absence of cartilage specific proteoglycans in treated cultures. Such an effect is ruled out as a direct causative factor in teratogenesis for two reasons. First, the limbs of treated embryos show extensive chondrogenesis and this cartilage is normal as far as the expression of biochemical markers of differentiation are concerned. Second, the morphogenetic effects of a mutant gene, cmd, where there is a functional deficit of the proteoglycan core protein are very different from those associated with RA-induced teratogenesis. The differences between the two are not wholly reconciled by the fact that the effects of the mutant gene are cumulative and progressive while those of the RA insult are transitory. There are a number of developmental events which are, however, altered by RA in the mesenchymal cells of the early limb bud such as cell proliferation, cell death, and hyaluronic acid metabolism. Not only any one or more of these factors may secondarily inhibit chondrogenesis but, more importantly, may also have a number of other consequences in the developing embryo. Since a number of cell types besides mesenchymal cells respond to RA by altering their pattern of differentiation, it is conceivable that some fundamental molecular step in the process of differentiation provides a target for its action. In a recent review, Sporn and Roberts (1983) have suggested that to be compatible with the wide ranging effects of retinoids documented so far, any hypothesis put forward for its molecular mechanism of action must include a role in gene expression. No experimental work has yet directly addressed how retinoids might modify gene expression. We believe that along with teratocarcinoma stem cell lines, the use of retinoids as selective teratogens may open up another avenue in search of molecular mechanisms of cell differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I231,I231)","v":6385136},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B231:D231)","v":4},1984,"Vitamin A and carotene in animal nutrition.","Bondi",6385136,"Vitamin A and carotene in animal nutrition.    Abstract:   Vitamin A, an unsaturated 20 carbon cyclic alcohol, subserves a number of important physiological functions. However, the biochemical basis of these roles is not well understood. The main sources of retinol are liver, egg yolk and milk fat. Several carotenoids show vitamin A activity. The conversion of beta-carotene to retinol is affected by copper-containing dioxygenase and zinc-containing retinene reductase. The efficiency of conversion varies in different species. The latter is defined in units as the daily dose required to produce a weight gain of 3 g/week in young rats between the 4th and 8th week. Retinol is unstable on exposure to light or heat, particularly in the presence of heavy metal ions and water. Much recent work has focused on the absorption, metabolism and excretion of vitamin A. It is now recognized that plasma vitamin A levels do not reflect the nutritional status except in severe hypo- and hypervitaminosis A. Also, many dietary factors may influence vitamin A metabolism. These basic and applied aspects of vitamin A are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I232,I232)","v":26962240},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B232:D232)","v":3},2016,"Interventions To Prevent Retinopathy of Prematurity: A Meta-analysis.","Fang",26962240,"Interventions To Prevent Retinopathy of Prematurity: A Meta-analysis.    Abstract:    CONTEXT : The effectiveness of many interventions aimed at reducing the risk of retinopathy has not been well established.  OBJECTIVE : To estimate the effectiveness of nutritional interventions, oxygen saturation targeting, blood transfusion management, and infection prevention on the incidence of retinopathy of prematurity (ROP).  DATA SOURCES : A comprehensive search of several databases was conducted, including Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through March 2014.  STUDY SELECTION : We included studies that evaluated nutritional interventions, management of supplemental oxygen, blood transfusions, or infection reduction and reported the incidence of ROP and mortality in neonates born at lt;32 weeks.  DATA EXTRACTION : We extracted patient characteristics, interventions, and risk of bias indicators. Outcomes of interest were any stage ROP, severe ROP or ROP requiring treatment, and mortality.  RESULTS : We identified 67 studies enrolling 21 819 infants. Lower oxygen saturation targets reduced the risk of developing any stage ROP (relative risk [RR] 0.86, 95% confidence interval [CI], 0.77-0.97) and severe ROP or ROP requiring intervention (RR 0.58, 95% CI, 0.45-0.74) but increased mortality (RR 1.15, 95% CI, 1.04-1.29). Aggressive parenteral nutrition reduced the risk of any stage ROP but not severe ROP. Supplementation of vitamin A, E, or inositol and breast milk feeding were beneficial but only in observational studies. Use of transfusion guidelines, erythropoietin, and antifungal agents were not beneficial.  LIMITATIONS : Results of observational studies were not replicated in randomized trials. Interventions were heterogeneous across studies.  CONCLUSIONS : At the present time, there are no safe interventions supported with high quality evidence to prevent severe ROP."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I233,I233)","v":26425706},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B233:D233)","v":3},2015,"Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.","Lassi",26425706,"Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.    Abstract:    BACKGROUND : Evidence-based interventions and strategies are needed to improve child survival in countries with a high burden of neonatal and child mortality. An overview of systematic reviews can focus implementation on the most effective ways to increase child survival.  METHODS : In this overview we included published Cochrane and other systematic reviews of experimental and observational studies on antenatal, childbirth, postnatal and child health interventions aiming to prevent perinatal/neonatal and child mortality using the WHO list of essential interventions. We assessed the methodological quality of the reviews using the AMSTAR criteria and assessed the quality of the outcomes using the GRADE approach. Based on the findings from GRADE criteria, interventions were summarized as effective, promising or ineffective.  FINDINGS : The overview identified 148 Cochrane and other systematic reviews on 61 reproductive, maternal, newborn and child health interventions. Of these, only 57 reviews reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids for preventing neonatal respiratory distress syndrome in preterm infants; early initiation of breastfeeding; hygienic cord care; kangaroo care for preterm infants; provision and promotion of use of insecticide treated bed nets (ITNs) for children; and vitamin A supplementation for infants from six months of age, were identified as clearly effective interventions for reducing neonatal, infant or child mortality. Antenatal care, tetanus immunization in pregnancy, prophylactic antimalarials during pregnancy, induction of labour for prolonged pregnancy, case management of neonatal sepsis, meningitis and pneumonia, prophylactic and therapeutic use of surfactant, continuous positive airway pressure for neonatal resuscitation, case management of childhood malaria and pneumonia, vitamin A as part of treatment for measles associated pneumonia for children above 6 months, and home visits across the continuum of care, were identified as promising interventions for reducing neonatal, infant, child or perinatal mortality.  INTERPRETATION : Comprehensive adoption of the above six effective and 11 promising interventions can improve neonatal and child survival around the world. Choice of intervention and degree of implementation currently depends on resources available and policies in individual countries and geographical settings.  FUNDING : This review was part of doctoral thesis which was funded by University of Adelaide, Australia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I234,I234)","v":26132929},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B234:D234)","v":3},2015,"Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways.","Taylor",26132929,"Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways.    Abstract:   Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I235,I235)","v":26036904},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B235:D235)","v":3},2015,"Molecular biology of endometriosis: from aromatase to genomic abnormalities.","Bulun",26036904,"Molecular biology of endometriosis: from aromatase to genomic abnormalities.    Abstract:   Endometriosis has been initially described as the presence of ectopic endometrial tissue on pelvic organs or in extrapelvic sites; and this has been used as its key pathologic feature ever since. Endometriosis responds to fluctuations in estrogen and progesterone by growth and inflammation, leading to pain aggravated by menses. It was proposed that pelvic endometriosis primarily originate from retrograde menstruation of a critical number of eutopic endometrial cells with stem characteristics. This postulate is supported by the molecular defects found in ectopic endometriotic tissue. Genome-wide differences in CpG methylation between eutopic endometrial and endometriotic stromal cells are present. Defective CpG methylation affecting several genes that encode key transcription factors such as GATA6, steroidogenic factor-1, and estrogen receptor-β in endometriosis gives rise to overproduction of local estrogen and prostaglandins and suppression of progesterone receptor. Progesterone receptor deficiency leads to progesterone resistance, resulting in decreased retinol uptake and retinoic acid production and altered retinoic acid action. These molecular defects collectively give rise to poor cellular differentiation, enhanced survival, and increased inflammation, which are the biological hallmarks of endometriotic tissue."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I236,I236)","v":24759120},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B236:D236)","v":3},2014,"The effect of micronutrient supplements on male fertility.","Buhling",24759120,"The effect of micronutrient supplements on male fertility.    Abstract:    PURPOSE OF REVIEW : To describe the beneficial effects of micronutrient supplementation on male fertility.  RECENT FINDINGS : Several micronutrients have beneficial effects on sperm quality, as well on male fertility (e.g. pregnancy rate). A deliberate use of micronutrients might be helpful for infertile patients. Healthcare providers should be aware that supplements contain the studied dose.  SUMMARY : Male sterility is becoming increasingly important because of various factors. In addition to the avoidable risk factors (alcohol and smoking), unchangeable factors are also likely involved in the genesis. Modern reproductive medicine methods help resulting in decent pregnancy rates in subfertile men. However, in addition to reproductive medicine methods, factors other than cessation of smoking and alcohol consumption can influence the fertility of men. Several studies have reported a significant increase in sperm quality and pregnancy rates when the men were supplemented by specific vitamins and micronutrients.The present review gives an overview of the study results and discusses specific legal requirements (e.g. upper limits)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I237,I237)","v":23961521},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B237:D237)","v":3},2013,"Resolution of radiation-induced acneform eruption following treatment with tretinoin and minocycline: a case report.","Parr",23961521,"Resolution of radiation-induced acneform eruption following treatment with tretinoin and minocycline: a case report.    Abstract:   Postradiation comedogenesis is an uncommon side effect of radiation therapy, with few cases reported in the medical literature. The proposed etiology of this reaction is alteration of pilosebaceous unit secretions and retention of proliferating ductal keratinocytes due to stricture and scarring. We report a case of a 48-year-old woman who had been treated for infiltrating ductal carcinoma of the right breast with lumpectomy and radiation therapy. She subsequently developed open and closed comedones as well as tender inflammatory papules and papulopustules in the irradiated area. Our patient was treated with tretinoin cream and oral minocycline, with rapid improvement in symptoms and complete resolution of lesions after 2 months of therapy. We review the literature on the pathogenesis, clinical features, and treatment of postradiation acne, and discuss rapid resolution of a radiation-induced acneform eruption after combination treatment with tretinoin and minocycline."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I238,I238)","v":23914887},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B238:D238)","v":3},2013,"Treatment of acne vulgaris in pregnant patients.","Pugashetti",23914887,"Treatment of acne vulgaris in pregnant patients.    Abstract:   The management of acne vulgaris in the setting of pregnancy raises important clinical considerations regarding the efficacy and safety of acne treatments in this special patient population. Particular challenges include the absence of safety data, discrepancy in safety data between different safety rating systems, and lack of evidence-based recommendations for the treatment of acne during pregnancy. Nonetheless, many therapeutic options exist, and the treatment of acne in pregnant women can be safely and often effectively accomplished. For mild or moderate disease, patients can be treated with topical antimicrobial agents, anti-inflammatory agents, as well as glycolic and salicylic acid. Several topical agents, notably benzoyl peroxide, previously viewed as potentially dangerous are cited by many sources as being considered safe. When necessary, systemic therapies that can be safely added include penicillins, amoxicillin, cephalosporins, erythromycin, clindamycin, and tetracyclines or sulfonamides, depending on the stage of fetal development. Adjunct therapy may include phototherapy or laser treatments. Physicians should work with this often highly motivated, safety-conscious patient population to tailor an individualized treatment regimen. This treatment regimen will likely shift throughout the different stages of fetal development, as distinct safety considerations are raised prior to conception as well as during each of the trimesters of pregnancy. Important considerations regarding acne management in breast-feeding mothers is also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I239,I239)","v":23446290},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B239:D239)","v":3},2013,"Impetigo Herpetiformis during pregnancy: a case report and literature review.","Gao",23446290,"Impetigo Herpetiformis during pregnancy: a case report and literature review.    Abstract:    BACKGROUND : Impetigo herpetiformis (IH) is a rare pustular dermatosis that typically occurs in pregnant women with unknown etiology.  CASE REPORT : We report an 18-year-old primigravida who presented with IH at nearly 30 weeks gestation and was the first patient reported in mainland China. The patients condition deteriorated rapidly in spite of treatment with corticosteroids and antibiotics, so we decided to terminate the pregnancy by induction of labor. After vaginal delivery she developed fever and her skin lesions did not disappear naturally. Fortunately her symptoms were resolved with the treatment of antibiotics and acitretin, and at day 60 postpartum her skin lesions had completely disappeared.  CONCLUSION : Although IH is associated with high mortality and morbidity in both fetus and mother, a better prognosis could be achieved with an immediate diagnosis and proper treatment. The etiology of IH needs to be further explored and the process of diagnosis and therapy should be standardized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I240,I240)","v":23390117},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B240:D240)","v":3},2014,"Mid-hindbrain malformations due to drugs taken during pregnancy.","Merlini",23390117,"Mid-hindbrain malformations due to drugs taken during pregnancy.    Abstract:   Although genetic defects are the leading cause of central nervous system malformations including in the posterior fossa, specific malformative patterns should alert the clinician to consider rather a teratogenic etiology. We discuss the imaging features of 2 mid-hindbrain malformations consecutive to the intake of isotretinoin (Roaccuatane®; case 1) and misoprostol (Cytotec®; case 2) during pregnancy and review the pertinent literature. We correlate the morphological appearance of the mid-hindbrain malformation, as seen on high-resolution magnetic resonance imaging to possible drug-induced pathogenetical mechanisms. The recognition of characteristic imaging patterns enables diagnosis of and/or confirmation of suspected drug-induced hindbrain malformations. This has important medicolegal implications and also clinical significance to avoid unsuccessful and misleading genetic testing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I241,I241)","v":23232823},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B241:D241)","v":3},2013,"Vitamin a deficiency in pregnancy: perspectives after bariatric surgery.","Chagas",23232823,"Vitamin a deficiency in pregnancy: perspectives after bariatric surgery.    Abstract:   This study aims to describe the clinical consequences of vitamin A deficiency (VAD) in pregnant women after bariatric surgery. Included are studies on VAD during pregnancy and after bariatric surgery conducted in humans from 1993 to 2011. There are few investigations on the relationship between pregnancy and bariatric surgery and on the damage to the binomial mother-child resulting from VAD in this relationship. The high percentage of VAD in the postoperative period is a cause for concern, especially considering the function of this vitamin in certain biological moments and in moments of intense nutritional demand. This vitamin serum evaluation is recommended during the prenatal period."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I242,I242)","v":22963233},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B242:D242)","v":3},2013,"U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.","Scarisbrick",22963233,"U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.    Abstract:    BACKGROUND : Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments.  OBJECTIVES :   To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect.  METHODS :  Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature.  RESULTS :  The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting.  CONCLUSION :  Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I243,I243)","v":22610102},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B243:D243)","v":3},2012,"Biomarkers of teratogenesis: suggestions from animal studies.","Giavini",22610102,"Biomarkers of teratogenesis: suggestions from animal studies.    Abstract:   Biomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I244,I244)","v":22443072},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B244:D244)","v":3},2012,"[Advances on studies related to the requirement of vitamin A for infants, young and preschool children].","Yu",22443072,"[Advances on studies related to the requirement of vitamin A for infants, young and preschool children].    Abstract:   There are many factors that could affect the requirement of vitamin A including infections, parasites, protein-energy malnutrition, bioconversion efficiency of provitamin A, food matrix and so on. However, the toxicity of vitamin A should also be taken into account when establishing reference values for infants, young and preschool children. Serum and breast-milk retinol concentrations, retinol binding protein concentrations, the relative-dose-response test , the modified-relative-dose-response and the deuterated retinol isotope dilution test are the common tools to assess vitamin A status."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I245,I245)","v":22419344},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B245:D245)","v":3},2012,"Micronutrient supplementation in pregnant women with HIV infection.","Siegfried",22419344,"Micronutrient supplementation in pregnant women with HIV infection.    Abstract:    BACKGROUND : Micronutrient deficiencies are widespread and compound the effects of HIV disease; micronutrient supplements may be effective and safe in reducing this burden.  OBJECTIVES : To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in pregnant and lactating women with HIV infection and their infants.  SEARCH METHODS : The review has been updated three times since publication in 2005. In reviews prior to this update (2011), we searched the CENTRAL, EMBASE, PubMed, and GATEWAY databases to identify randomised controlled trials of micronutrient supplements using the search methods of the Cochrane HIV/AIDS Group. In the 2011 review the PubMed, EMBASE, and CENTRAL databases were searched in July 2011. As the GATEWAY database does not include conference abstracts after 2006, we also searched the AIDS-specific conference database, www.aegis.org, and contacted researchers and organisations active in the field of research to identify additional unpublished trials.  SELECTION CRITERIA : Randomised controlled trials were selected that compared the effects of micronutrient supplements (vitamins, trace elements, and combinations of these) with other supplements, placebo or no treatment on mortality, morbidity, pregnancy outcomes, immunologic indicators, and anthropometric measures in HIV-positive pregnant and lactating women. Any adverse effects of supplementation were recorded.  DATA COLLECTION AND ANALYSIS : Two reviewer authors independently selected trials, appraised trial quality for risk of bias using standardised criteria, and extracted data using standardised forms. Where disagreements arose, a third author, acted as arbiter.  MAIN RESULTS : One additional trial is included in this update in addition to the three trials included in the 2010 update of the initial Cochrane review. Four relatively large, well-conducted randomised controlled trials of the benefits of micronutrient supplementation have been conducted in pregnant and lactating women infected with HIV. Each of the trials evaluated a different micronutrient supplement and no direct comparisons or analyses can be made across the four trials. The four trials were conducted between 1995 and 2006. The trials have all been conducted by the same research team in Dar es Salaam in Tanzania, in an urban setting in hospital-based antenatal clinics. Pregnant women were recruited with gestational age ranging from 12 to 27 weeks in each of the trials. Sample sizes range from 400 to 1129 with a median of 1000 participants. Three of the trials were placebo-controlled. Different interventions have been evaluated in each trial, viz.:Vitamin A versus Vitamin A and multivitamins versus Multivitamins versus placebo; Selenium versus placebo; Zinc versus placebo; and Multiple RDA multivitamins versus Single RDA multivitamins. None of the women were receiving antiretrovrial therapy (ART).Multiple micronutrient supplements conferred multiple clinical benefits to pregnant women and their offspring. No significant adverse effects were reported.No significant clinical benefits were found from zinc supplementation of pregnant Tanzanian women.Selenium supplements given during and after pregnancy did not delay maternal HIV disease progression or improve pregnancy outcomes, but may improve child survival and decrease maternal diarrhoeal morbidity.There were no differences in maternal and infant outcomes when women received single RDA multivitamins or multiple RDA multivitamin supplementation.The evidence is lacking for the effects of micronutrient supplementation given concomitantly to pregnant women already initiated on antiretroviral therapy for treatment purposes.GRADE assessments were conducted on outcomes for each trial and included reviewing the data and the potential biases in each trial before grading the level of evidence. None of the trials were graded as providing high quality evidence primarily because there was no replication of results in other trials in other settings.  AUTHORS CONCLUSIONS : In keeping with previous World Health Organization (WHO) recommendations everything possible should be done to promote and support adequate dietary intake of micronutrients, while recognising that this may not be sufficient to correct specific micronutrient deficiencies in all HIV-infected individuals.Specific recommendations for pregnant and lactating women infected with HIV would be to include the provision of multivitamin supplements in single RDA formulations during the antenatal period and at least for 6 weeks post-partum, especially for women who are breast-feeding.There is no conclusive evidence to provide stand-alone zinc or selenium supplementation to HIV-infected pregnant and lactating women.Micronutrient supplementation should not be used as a substitute for provision of recommended antiretroviral medication for preventing mother-to-child transmission of HIV and treating maternal HIV infection when this is recommended.Further trials of single supplements are required to build the evidence base. The long-term clinical benefits, adverse effects, and optimal formulation of multiple micronutrient supplements require further investigation in pregnant women at different stages of HIV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I246,I246)","v":22146768},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B246:D246)","v":3},2012,"The use of retinoids in ovarian cancer: a review of the literature.","Whitworth",22146768,"The use of retinoids in ovarian cancer: a review of the literature.    Abstract:   Ovarian cancer is the deadliest of all gynecologic malignancies. The search for novel treatment modalities to augment traditional chemotherapy and improve quality of life is ongoing. Retinoids, a class of compounds composed of vitamin A, its natural derivatives, and synthetic analogs, have been studied extensively in both the prevention and treatment of gynecologic malignancies. In this article, we reviewed preclinical studies and clinical trials conducted using retinoids in ovarian cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I247,I247)","v":20842651},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B247:D247)","v":3},2010,"The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.","Pennimpede",20842651,"The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.    Abstract:   Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development. This review will discuss our current understanding of the role of RA in teratogenesis, with specific emphasis on the essential function of the RA catabolic CYP26 enzymes in preventing teratogenic consequences caused by uncontrolled distribution of RA. Particular focus will be paid to the RA-sensitive tissues of the caudal and cranial regions, the limb, and the testis, and how genetic mutation of factors controlling RA distribution have revealed important roles for RA during embryogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I248,I248)","v":20676546},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B248:D248)","v":3},2010,"[Vitamin A and gestational diabetes].","Lira",20676546,"[Vitamin A and gestational diabetes].    Abstract:   Diabetes mellitus (DM) a pathology with chronic evolution, has now acquired a connotation of global epidemic. Gestational diabetes, a condition associated with insulin resistance and decreased beta-cells function is also characterized by a high incidence in different populations and ethnic groups. Recently strong evidence has been found for involvement of retinol levels of pregnant women with DM due to the pathologys evolution. This condition makes these diabetics prone to have a marginal biochemical profile or a vitamin A deficiency when compared to those of healthy pregnant women. Therefore, with an awareness of the physiological role of vitamin A and consequences of diabetes during pregnancy, this review intends to clarify the impact of DM on retinol levels of these pregnant women and the consequences that vitamin A deficiency may cause to these women and their infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I249,I249)","v":22254040},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B249:D249)","v":3},2010,"Vitamin A-not for your eyes only: requirement for heart formation begins early in embryogenesis.","Zile",22254040,"Vitamin A-not for your eyes only: requirement for heart formation begins early in embryogenesis.    Abstract:   Vitamin A insufficiency has profound adverse effects on embryonic development. Major advances in understanding the role of vitamin A in vertebrate heart formation have been made since the discovery that the vitamin A active form, all-trans-retinoic acid, regulates many genes, including developmental genes. Among the experimental models used, the vitamin A-deficient avian embryo has been an important tool to study the function of vitamin A during early heart formation. A cluster of retinoic acid-regulated developmental genes have been identified that participate in building the heart. In the absence of retinoic acid the embryonic heart develops abnormally leading to embryolethality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I250,I250)","v":20415580},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B250:D250)","v":3},2010,"Micronutrients, birth weight, and survival.","Christian",20415580,"Micronutrients, birth weight, and survival.    Abstract:   Maternal micronutrient requirements during pregnancy increase to meet the physiologic changes in gestation and fetal demands for growth and development. Maternal micronutrient deficiencies are high and coexist in many settings, likely influencing birth and newborn outcomes. The only recommendation for pregnancy currently exists for iron and folic acid use. Evidence is convincing that maternal iron supplementation will improve birth weight and perhaps gestational length. In one randomized trial, iron supplementation during pregnancy reduced child mortality in the offspring compared with the control group. Few other single micronutrients given antenatally, including vitamin A, zinc, and folic acid, have been systematically shown to confer such a benefit. A meta-analysis of 12 trials of multiple micronutrient supplementation compared with iron-folic acid reveals an overall 11% reduction in low birth weight but no effect on preterm birth and perinatal or neonatal survival. Currently, data are unconvincing for replacing supplementation of antenatal iron-folic acid with multiple micronutrients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I251,I251)","v":20138179},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B251:D251)","v":3},2010,"Molecular and genetic studies suggest that thyroid hormone receptor is both necessary and sufficient to mediate the developmental effects of thyroid hormone.","Das",20138179,"Molecular and genetic studies suggest that thyroid hormone receptor is both necessary and sufficient to mediate the developmental effects of thyroid hormone.    Abstract:   Thyroid hormone (TH) affects diverse biological processes and can exert its effects through both gene regulation via binding the nuclear TH receptors (TRs) and non-genomic actions via binding to cell surface and cytoplasmic proteins. The critical importance of TH in vertebrate development has long been established, ranging from the formation of human cretins to the blockage of frog metamorphosis due the TH deficiency. How TH affects vertebrate development has been difficult to study in mammals due to the complications associated with the uterus-enclosed mammalian embryos. Anuran metamorphosis offers a unique opportunity to address such an issue. Using Xenopus as a model, we and others have shown that the expression of TRs and their heterodimerization partners RXRs (9-cis retinoic acid receptors) correlates temporally with metamorphosis in different organs in two highly related species, Xenopuslaevis and Xenopus tropicalis. In vivo molecular studies have shown that TR and RXR are bound to the TH response elements (TREs) located in TH-inducible genes in developing tadpoles of both species. More importantly, transgenic studies in X. laevis have demonstrated that TR function is both necessary and sufficient for mediating the metamorphic effects of TH. Thus, the non-genomic effects of TH have little or no roles during metamorphosis and likely during vertebrate development in general."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I252,I252)","v":19772370},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B252:D252)","v":3},2009,"Emerging drugs for acne.","James",19772370,"Emerging drugs for acne.    Abstract:   Acne vulgaris is a common skin disorder that affects most individuals at some point in their lives. It may result in significant morbidity, including cutaneous scarring and psychological impairment. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, and systemic isotretinoin. There are growing concerns of rising antibiotic resistance, significant side effects of isotretinoin therapy, and lack of safe and effective treatment for pregnant females. Recent advances in the pathogenesis of acne have led to a greater understanding of the underlying inflammatory mechanisms and the role the Propionibacterium acnes and biofilms. This has led to the development of new therapeutic targets. This article reviews emerging treatments of acne, including topical picolinic acid, topical antibiotic dapsone, systemic zinc salts, oral antibiotic lymecycline, new formulations of and synergistic combinations of benzoyl peroxide, photodynamic therapy with topical photosensitizers and potential acne vaccines."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I253,I253)","v":19760653},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B253:D253)","v":3},2009,"Vitamin A deficiency in an infant with PAGOD syndrome.","Gavrilova",19760653,"Vitamin A deficiency in an infant with PAGOD syndrome.    Abstract:   PAGOD syndrome is a rare condition characterized by multiple congenital anomalies including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic abnormalities, cardiac defects, omphalocele, and various genital anomalies. The etiology of this condition is unknown but the spectrum of birth defects is similar to the developmental anomalies observed in vitamin A deficiency animal models. We describe an infant with PAGOD syndrome phenotype. The patient had a normal male karyotype and no copy number changes were seen on chromosome genomic hybridization (CGH) microarray. Endocrine evaluation was consistent with primary hypogonadism. The testes and Müllerian structures were absent by imaging studies, raising the possibility of arrest of early gonadogenesis. The plasma free vitamin A was low, consistent with moderate to severe vitamin A deficiency; the maternal plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken up by retinol binding protein 4 (RBP4) which is expressed in the embryonic visceral endoderm from pregastrulational stages. This transport is mediated via the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6). STRA6 is widely expressed in human organ systems including the placenta during embryonic development. Mutations in the STRA6 gene result in Matthew-Wood syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome. Sequencing of STRA6 coding regions in our patient, revealed no mutations. We present a case of PAGOD syndrome with a review of the literature, posing the hypothesis that a vitamin A metabolic defect, other than transport mediated by STRA6 receptor, might have an etiological role in the development of this multiple congenital anomalies syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I254,I254)","v":19567449},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B254:D254)","v":3},2010,"Role of micronutrients in the periconceptional period.","Cetin",19567449,"Role of micronutrients in the periconceptional period.    Abstract:    BACKGROUND : Micronutrient deficiencies have been associated with significantly high reproductive risks, ranging from infertility to fetal structural defects and long-term diseases. In this review we focus on the reproductive risks related to some micronutrients during the periconceptional period, a critical step in determining fetal development and health due to the potential onset of several disorders.  METHODS : Embase Medline and PubMed databases, Google-indexed scientific literature and periodics from on-line University of Milan Bibliotecary Service were searched to identify relevant publications. In vivo human studies were mainly searched for, but when needed animal studies as well as in vitro and cell culture experiments were also considered.  RESULTS : Fertility, conception, implantation, fetal organogenesis and placentation are the critical stages potentially affected by nutrition during the periconceptional period. Reactive oxygen species (ROS) and total homocysteine (tHcy) plasma levels are factors involved in the respective mechanisms. The preconceptional period is particularly important since it affects both fertility and the early stages of gestation. Micronutrients dietary intake and maternal status affect the different phases of the onset and development of pregnancy as well as of the conceptus.  CONCLUSION : Although human studies are scarce, and conclusive evidence is provided solely for periconceptional folate and prevention of neural tube defects (NTDs), the overall data indicate that micronutrients may affects fertility, embryogenesis and placentation, and the prophylactic use of some micronutrients may be useful in preventing several adverse pregnancy outcomes. Efforts to increase awareness of a healthy diet should be strengthened not only throughout pregnancy but also before. However, further researches in humans are necessary to optimise periconceptional micronutrient requirements."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I255,I255)","v":19426466},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B255:D255)","v":3},2009,"Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy.","Yakoob",19426466,"Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy.    Abstract:    BACKGROUND : The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase womens risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.  METHODS : This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.  RESULTS : From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.  CONCLUSION : Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care - particularly including diagnosis and management of high-risk pregnancies - that pregnant women receive."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I256,I256)","v":19321586},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B256:D256)","v":3},2009,"Provision of multiple rather than two or fewer micronutrients more effectively improves growth and other outcomes in micronutrient-deficient children and adults.","Allen",19321586,"Provision of multiple rather than two or fewer micronutrients more effectively improves growth and other outcomes in micronutrient-deficient children and adults.    Abstract:   Deficiencies of multiple micronutrients (MMN) usually coexist in developing countries, but supplements have usually provided only 1 or 2 micronutrients (MN). To inform policy, in this article we compared the relative benefits of supplying MMN vs. a placebo or 1 or 2 MN on the following: childrens growth, health, and development; pregnancy outcome; nutritional status; and HIV/AIDS mortality and morbidity in adults. Sufficient data were available to perform random-effects meta-analyses of randomized controlled trials (RCT) for the effects of MMN on child growth and nutritional status. Results for other outcomes are presented as effect sizes (ES) when available. In children, MMN interventions resulted in small but significantly greater improvements in length or height (ES = 0.13; 95% CI: 0.055, 0.21) and weight (ES = 0.14; 95% CI: 0.029, 0.25), hemoglobin (ES = 0.39; 95% CI: 0.25, 0.53), serum zinc (ES = 0.23; 95% CI: 0.18, 0.43), serum retinol (ES = 0.33; 95% CI: 0.050, 0.61), and motor development. A Cochrane review reported that compared with no supplementation or a placebo, MMN supplementation during pregnancy reduced the relative risk of low birth weight (0.83), small-for-gestational age (0.92), and anemia (0.61); however, MMN were not more effective than iron + folic acid alone. There is some evidence that MMN supplementation improves CD4 counts and HIV-related morbidity and mortality in adults. The efficacy of MMN varies across trials, but overall there is evidence that outcomes are better than when providing lt; or =2 MN. The policy implications of these studies are discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I257,I257)","v":19213559},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B257:D257)","v":3},2009,"Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype.","Sogno",19213559,"Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype.    Abstract:   Several cancer chemopreventive agents have been demonstrated to exert antiangiogenic effects. Blocking tumor angiogenesis, a process critical for tumor mass expansion and metastasis, represents an intriguing approach not only to cancer therapy, but also to cancer chemoprevention. We found that angiogenesis is a common and key target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in premalignant tumors, a concept we termed quot;angioprevention.quot; In this manuscript we use as an example the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR), a molecule with confirmed clinical applications in breast cancer adjuvant therapy to prevent cancer recurrence and under evaluation in neuroblastoma and glioblastoma treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I258,I258)","v":18682377},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B258:D258)","v":3},2008,"Prenatal nutritional deficiency and risk of adult schizophrenia.","Brown",18682377,"Prenatal nutritional deficiency and risk of adult schizophrenia.    Abstract:   Converging evidence suggests that a neurodevelopmental disruption plays a role in the vulnerability to schizophrenia. The authors review evidence supporting in utero exposure to nutritional deficiency as a determinant of schizophrenia. We first describe studies demonstrating that early gestational exposure to the Dutch Hunger Winter of 1944--1945 and to a severe famine in China are each associated with an increased risk of schizophrenia in offspring. The plausibility of several candidate micronutrients as potential risk factors for schizophrenia and the biological mechanisms that may underlie these associations are then reviewed. These nutrients include folate, essential fatty acids, retinoids, vitamin D, and iron. Following this discussion, we describe the methodology and results of an epidemiologic study based on a large birth cohort that has tested the association between prenatal homocysteine, an indicator of serum folate, and schizophrenia risk. The study capitalized on the use of archived prenatal serum specimens that make it possible to obtain direct, prospective biomarkers of prenatal insults, including levels of various nutrients during pregnancy. Finally, we discuss several strategies for subjecting the prenatal nutritional hypothesis of schizophrenia to further testing. These approaches include direct assessment of additional prenatal nutritional biomarkers in relation to schizophrenia in large birth cohorts, studies of epigenetic effects of prenatal starvation, association studies of genes relevant to folate and other micronutrient deficiencies, and animal models. Given the relatively high prevalence of nutritional deficiencies during pregnancy, this work has the potential to offer substantial benefits for the prevention of schizophrenia in the population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I259,I259)","v":18373954},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B259:D259)","v":3},2008,"Molecular genetics and racial disparities of uterine leiomyomas.","Othman",18373954,"Molecular genetics and racial disparities of uterine leiomyomas.    Abstract:   Uterine leiomyomas (ULMs) are benign oestrogen-dependent tumours of the myometrium. They are the most common tumours of the female genital tract, affecting around 77% of the female population. ULMs are more common in Black women than White women. These tumours tend to develop earlier and be more numerous, larger in size and more symptomatic in Black women than other ethnic groups. The molecular mechanism underlying this ethnic disparity is not fully understood. Polymorphism of genes involved in oestrogen synthesis and/or metabolism (COMT, CYP17), variation in the expression levels or function of oestrogen and progesterone receptors or retinoic acid nuclear receptors (retinoid acid receptor-alpha, retinoid X receptor-alpha), or aberrant expression of micro-RNAs are some of the molecular mechanisms that may be involved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I260,I260)","v":17665093},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B260:D260)","v":3},2007,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.","Strobel",17665093,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.    Abstract:   Vitamin A is essential for growth and differentiation of a number of cells and tissues. Notably during pregnancy and throughout the breastfeeding period, vitamin A has an important role in the healthy development of the fetus and the newborn, with lung development and maturation being particularly important. The German Nutrition Society (DGE) recommends a 40% increase in vitamin A intake for pregnant women and a 90% increase for breastfeeding women. However, pregnant women or those considering becoming pregnant are generally advised to avoid the intake of vitamin A rich liver and liver foods, based upon unsupported scientific findings. As a result, the provitamin A carotenoid beta-carotene remains their essential source of vitamin A. Basic sources of provitamin A are orange and dark green vegetables, followed by fortified beverages which represent between 20% and 40% of the daily supply. The average intake of beta-carotene in Germany is about 1.5-2 mg a day. Assuming a vitamin A conversion rate for beta-carotene for juices of 4:1, and fruit and vegetables between 12:1 and 26:1; the total vitamin A contribution from beta-carotene intake represents 10-15% of the RDA. The American Pediatrics Association cites vitamin A as one of the most critical vitamins during pregnancy and the breastfeeding period, especially in terms of lung function and maturation. If the vitamin A supply of the mother is inadequate, her supply to the fetus will also be inadequate, as will later be her milk. These inadequacies cannot be compensated by postnatal supplementation. A clinical study in pregnant women with short birth intervals or multiple births showed that almost 1/3 of the women had plasma retinol levels below 1.4 micromol/l corresponding to a borderline deficiency. Despite the fact that vitamin A and beta-carotene rich food is generally available, risk groups for low vitamin A supply exist in the western world. It is therefore highly critical to restrict the beta-carotene supply from diet, particularly from sources of beta-carotene with high consumer acceptance such as fortified juices (e.g. quot;ACE juicesquot;) or dietary supplements (e.g. multivitamins for pregnant women). For the part of the population unable to meet vitamin A requirements according to the DACH recommendations, sufficient intake of beta-carotene may be crucial to help improve and maintain adequate vitamin A status and prevention of developmental disorders. At this time it has to be urgently advised against restricting the beta-carotene supply or putting warning labels on beta-carotene fortified products. It is, however, highly recommended to improve the available data on nutrient intakes in Germany, especially for pregnant and breastfeeding women. For them, recommendations to be aware of potential nutrient intake inadequacies might prove useful."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I261,I261)","v":17368317},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B261:D261)","v":3},2007,"Vitamin A supplementation and retinoic acid treatment in the regulation of antibody responses in vivo.","Ross",17368317,"Vitamin A supplementation and retinoic acid treatment in the regulation of antibody responses in vivo.    Abstract:   Vitamin A (VA, retinol) is essential for normal immune system maturation, but the effect of VA(1) on antibody production, the hallmark of successful vaccination, is still not well understood. In countries where VA deficiency is a public health problem, many children worldwide are now receiving VA along with immunizations against poliovirus, measles, diphtheria, pertussis, and tetanus. The primary goal has been to provide enough VA to protect against the development of VA deficiency for a period of 4-6 months. However, it is also possible that VA might promote the vaccine antibody response. Several community studies, generally of small size, have been conducted in children supplemented with VA at the time of immunization, as promoted by the World Health Organization/UNICEF. However, only a few studies have reported differences in antibody titers or seroconversion rates due to VA. However, VA status was not directly assessed, and in some communities children were often breast fed, another strategy for preventing VA deficiency. Some of the vaccines used induced a high rate of seroconversion, even without VA. In children likely to have been VA deficient, oral polio vaccine seroconversion rate was increased by VA. In animal models, where VA status was controlled and VA deficiency confirmed, the antibody response to T-cell-dependent (TD) and polysaccharide antigens was significantly reduced, congruent with other defects in innate and adaptive immunity. Moreover, the active metabolite of VA, retinoic acid (RA) can potentiate antibody production to TD antigens in normal adult and neonatal animals. We speculate that numerous animal studies have correctly identified VA deficiency as a risk factor for low antibody production. A lack of effect of VA in human studies could be due to a low rate of VA deficiency in the populations studied or low sample numbers. The ability to detect differences in antibody response may also depend on the vaccine-adjuvant combination used. Future studies of VA supplementation and immunization should include assessment of VA status and a sufficiently large sample size. It would also be worthwhile to test the effect of neonatal VA supplementation on the response to immunization given after 6 months to 1 year of age, as VA supplementation, by preventing the onset of VA deficiency, may improve the response to immunizations given later on."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I262,I262)","v":17097400},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B262:D262)","v":3},2006,"The treatment of melasma: a review of clinical trials.","Gupta",17097400,"The treatment of melasma: a review of clinical trials.    Abstract:   Melasma is an irregular brown or grayish-brown facial hypermelanosis, often affecting women, especially those living in areas of intense UV radiation. The precise cause of melasma remains unknown; however, there are many possible contributing factors. Because of its dermal component and tendency to relapse, melasma is often difficult to treat. The use of broad-spectrum (UVA + UVB) sunscreen is important, as is topical hydroquinone, the most common treatment for melasma. Other lightening agents include retinoic acid (tretinoin) and azelaic acid. Combination therapies such as hydroquinone, tretinoin, and corticosteroids have been used in the treatment of melasma, and are thought to increase efficacy as compared with monotherapy. Kojic acid, isopropylcatechol, N-acetyl-4-cysteaminylphenol, and flavonoid extracts are other compounds that have been investigated for their ability to produce hypopigmentation, but their efficacy, safety, or trial design indicates that the interventions would need further study before they could be recommended. Chemical peels, laser treatments, and intense pulsed light therapy are additional therapeutic modalities that have been used to treat melasma."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I263,I263)","v":16936753},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B263:D263)","v":3},2006,"Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid.","Soprano",16936753,"Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid.    Abstract:   Despite a number of attempts to improve treatment of ovarian cancer, it remains the most common cause of death from gynecological cancers. Thus, it is very important to identify more effective drugs for treatment and prevention of ovarian cancer. All-trans-retinoic acid (ATRA) has been shown to arrest the growth of ovarian carcinoma cells in G0/G1 and to significantly elevate levels of Rb2/p130 protein, a member of the retinoblastoma family of tumor suppressors. As ATRA treatment leads to a significant increase in the amount of Rb2/p130 protein but not mRNA, the elevated levels of Rb2/p130 protein is likely the result of increased stability. In studies to elucidate the mechanism by which ATRA alters Rb2/p130 stability in ovarian cancer cells, it was determined that PP2A, a serine/threonine phosphatase, binds and dephosphorylates Rb2/p130. Dephosphorylated Rb2/p130 exhibits decreased ubiquitination and thus is not degraded by the proteasome. The sites at which PP2A catalytic subunit (PP2Ac) interacts with Rb2/p130 have been localized to the NLS in the C-terminus of Rb2/p130. These sites are also involved in the interaction of Rb/p130 with importin beta and importin alpha, members of the nuclear transport machinery. It is known that importin alpha recognizes a NLS on a target protein and importin beta binds the nuclear pore complex. Moreover, it has been shown that the binding of importin alpha to NLS significantly decreases with phosphorylation of NLS. In ATRA-treated ovarian carcinoma cells, PP2A binds to Rb2/p130 and dephosphorylates the NLS of Rb2/p130 leading to the interaction of importin alpha with Rb2/p130. Importin beta then binds to the importin alpha-Rb2/p130 complex, leading to the translocation of the Rb2/p130 to the nucleus where it acts to arrest ovarian cancer cells in G1 and suppress proliferation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I264,I264)","v":16790941},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B264:D264)","v":3},2006,"Is interferon-alpha and retinoic acid combination along with radiation superior to chemo-radiation in the treatment of advanced carcinoma of cervix?","Basu",16790941,"Is interferon-alpha and retinoic acid combination along with radiation superior to chemo-radiation in the treatment of advanced carcinoma of cervix?    Abstract:   Locally advanced cervical cancers comprise a large majority of the gynecologic cancers in India and other developing countries. Concurrent chemo-radiation has improved the survival of high risk stage I and stage II cervical cancers. There is no evidence that the same survival benefit has been achieved with chemo-radiation in stage III and stage IV disease. Interferon-alpha and Retinoic acid have synergistic anti-proliferative activity. In combination with radiation, they substantially enhance the sensitivity of the squamous carcinoma cells to radiation. Based on these observations from the in vitro studies, a few clinical trials have evaluated the combination of interferon-alpha and Retinoic acid, concomitant with radiation, to treat cervical cancers. The results from these early trials were encouraging and the combination had minimal toxicities. However, till date, no phase III randomized controlled trial has been done to evaluate this therapeutic modality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I265,I265)","v":15662707},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B265:D265)","v":3},2004,"Mechanisms regulating toxicant disposition to the embryo during early pregnancy: an interspecies comparison.","Carney",15662707,"Mechanisms regulating toxicant disposition to the embryo during early pregnancy: an interspecies comparison.    Abstract:   The dose of toxicant reaching the embryo is a critical determinant of developmental toxicity, and is likely to be a key factor responsible for interspecies variability in response to many test agents. This review compares the mechanisms regulating disposition of toxicants from the maternal circulation to the embryo during organogenesis in humans and the two species used predominantly in regulatory developmental toxicity testing, rats and rabbits. These three species utilize fundamentally different strategies for maternal-embryonic exchange during early pregnancy. Early postimplantation rat embryos rely on the inverted visceral yolk sac placenta, which is in intimate contact with the uterine epithelium and is equipped with an extensive repertoire of transport mechanisms, such as pinocytosis, endocytosis, and specific transporter proteins. Also, the rat yolk sac completely surrounds the embryo, such that the fluid-filled exocoelom survives through most of the period of organogenesis, and can concentrate compounds such as certain weak acids due to pH differences between maternal blood and exocelomic fluid. The early postimplantation rabbit conceptus differs from the rat in that the yolk sac is not closely apposed to the uterus during early organogenesis and does not completely enclose the embryo until relatively later in development (approximately GD13). This suggests that the early rabbit yolk sac might be a relatively inefficient transporter, a conclusion supported by limited data with ethylene glycol and one of its predominant metabolites, glycolic acid, given to GD9 rabbits. In humans, maternal-embryo exchange is thought to occur via the chorioallantoic placenta, although it has recently been conjectured that a supplemental route of transfer could occur via absorption into the yolk sac. Knowledge of the mechanisms underlying species-specific embryonic disposition, factored together with other pharmacokinetic characteristics of the test compound and knowledge of critical periods of susceptibility, can be used on a case-by-case basis to make more accurate extrapolations of test animal data to the human."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I266,I266)","v":15384917},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B266:D266)","v":3},2004,"Micronutrients and adverse pregnancy outcomes in the context of HIV infection.","Fawzi",15384917,"Micronutrients and adverse pregnancy outcomes in the context of HIV infection.    Abstract:   HIV infection is a global public health problem, particularly in Africa. Concurrently, micronutrient deficiencies and adverse pregnancy outcomes are prevalent in the same settings. Supplements containing B complex and vitamins C and E were efficacious in reducing adverse pregnancy outcomes, including fetal loss, low birth weight, and prematurity among HIV-infected women; the generalizability of this finding to uninfected women is being examined. There is little encouragement from published studies to provide prenatal vitamin A supplements in HIV infection, particularly in light of significantly higher risk of mother-to-child transmission observed in one trial. The efficacy and safety of prenatal zinc and selenium supplements on these outcomes need to be examined in randomized trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I267,I267)","v":15056048},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B267:D267)","v":3},2004,"Bexarotene: a clinical review.","Farol",15056048,"Bexarotene: a clinical review.    Abstract:   Bexarotene (Targretin, Ligand Pharmaceuticals Inc.) is a synthetic retinoid analog with specific affinity for the retinoid X receptor and belongs to a group of compounds called rexinoids. Early clinical trials of this drug demonstrated activity in cutaneous T-cell lymphoma. Subsequent Phase II/III trials have demonstrated a greater than 50% response rate in patients with all stages of cutaneous T-cell lymphoma who were refractory or intolerant to the previous therapy. The principal toxicities of bexarotene include central hypothyroidism, xeroderma and elevation of cholesterol and triglycerides. These toxicities can be managed with dose attenuation or addition of atorvastatin (Lipitor, Pfizer) or fenofibrate (TriCor, Abbott Laboratories). Since bexarotene has little bone marrow toxicity, it is an excellent candidate for combination therapy with other modalities useful in the treatment of cutaneous T-cell lymphoma. These include ultraviolet B irradiation, psoralen and ultraviolet A photochemotherapy, interferons, denileukin diftitox (Ontak, Ligand Pharmaceuticals Inc.) and cytotoxic chemotherapy. Bexarotene has also been investigated in the treatment of breast cancer and non-small cell carcinoma of the lung with promising early results."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I268,I268)","v":12959189},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B268:D268)","v":3},2003,"New insights regarding pharmacologic approaches for ovarian cancer prevention.","Rodriguez",12959189,"New insights regarding pharmacologic approaches for ovarian cancer prevention.    Abstract:   The pathogenesis of epithelial ovarian cancer is not completely understood, but it commonly is believed that the process of recurrent ovulation (incessant ovulation) causes genetic damage in ovarian epithelial cells and that sufficient genetic damage can lead to ovarian cancer in susceptible individuals. Under this model, it has been suggested that reproductive and hormonal factors, such as pregnancy and oral contraceptive use, decrease ovarian cancer risk mainly via their inhibitory effects on ovulation. There is mounting evidence that the ovarian epithelium is a hormonally responsive target organ whose biology can be impacted strongly by the local hormonal environment. Progestin-mediated apoptotic effects may be a major mechanism underlying the ovarian cancer protective effects of pregnancy (a high progestin state) and oral contraceptive pill use. Similarly, retinoids, vitamin D, and non-steroidal anti-inflammatory drugs may have biologic effects on the ovarian epithelium that are cancer preventive, whereas androgens may have stimulatory effects on the ovarian epithelium, leading to an increased ovarian cancer risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I269,I269)","v":11949945},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B269:D269)","v":3},2002,"Regulation and modulation of abnormal immune responses in endometriosis.","Sidell",11949945,"Regulation and modulation of abnormal immune responses in endometriosis.    Abstract:   There is ample evidence demonstrating that endometriosis is accompanied by inflammatory reactions in the peritoneum, resulting in abnormal levels of a variety of cytokines and chemokines in the peritoneal fluid. Among the immunological parameters that have been shown to be altered in the peritoneal cavity of women with endometriosis, an increase in the number of activated nonadherent macrophages that show reduced surface expression of scavenger receptors has been observed. The cause-and-effect relationship between aberrant peritoneal macrophage activity and endometriosis is still unknown. We have demonstrated that steroid hormone receptor agonists and antagonists [e.g., retinoids, antiglucocorticoids, ligands to peroxisome proliferator activated receptors (PPARs)] can regulate macrophage functions in ways that could either suppress or stimulate the growth of ectopic endometrial lesions. Our studies include a number of relevant findings: (1) RU486, acting as an antioxidant, can suppress activation of NFkappaB, a nuclear transcription factor that affects the expression of several inflammatory genes such as those for MCP-1, GM-CSF, CSF-1, and various adhesion molecules; (2) IL-6 secretion from a variety of cell types including endometrial cells is inhibited by retinoic acid; and (3) retinoids and PPARgamma ligands can upregulate the expression of scavenger receptors in cells of the monocyte/macrophage lineage. These observations, combined with the possibility that macrophage activity may play a fundamental role in endometriosis, suggest that pharmacologic manipulation of macrophage function may provide a novel mechanism for treating this disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I270,I270)","v":11155466},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B270:D270)","v":3},2000,"[Importance of chemoprevention in oncology].","Aragona",11155466,"[Importance of chemoprevention in oncology].    Abstract:   The therapeutic approach to cancer is generally limited to the advanced phases of disease. The preventive strategies aim at eliminating or reducing the exposition to known carcinogenes. We act with pharmacological and/or with an accurate dietary education to induce cellular differentiation phenomena, cytostasis and apoptosis. Chemoprevention acts both on the inductive phase (metabolic activation, DNA adducts), as well as on the promotion/proliferation of the long pre-clinical period of latency (antioxidants, anti-inflammatory, retinoids, carotenoids, vitamins and micronutrients, hormones and hormonal inhibitors, polyamine inhibitors, ditholetions, isothiocyanates, telomerase inhibitors, etc). Unanimous agreement has been reached on the preventive role of retinoids in head and neck tumors and of the cervical uterus, of hormonal inhibitors in breast and prostate cancer, and of anti-inflammatory in colorectal cancer. New and more accurate parameters for the evaluation of results and individual applications of chemopreventive strategies are linked to the biological research of high-risk subjects (genetic damage) or increased individual susceptibility. Caution, instead, should be applied in the clinical trial planning. An increased risk in developing and dying of lung tumor in smokers has been shown for the use vitamin A. Many clinical studies have been started in order to establish an efficient chemoprevention in oncology, and with the early diagnostic programs, and the evaluation of genotypic and phenotypic alterations, encouraging results will be reached for the next millennium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I271,I271)","v":10918511},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B271:D271)","v":3},2000,"Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents.","Hendrickx",10918511,"Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents.    Abstract:   There are close physiologic similarities between humans and macaques that make them well suited for preclinical testing of biopharmaceutics. These include menstrual cycles of similar length and hormonal control, comparable cellular and endocrine processes of implantation, and similar timetables of prenatal development. Three teratogenic agents have induced abnormal development of the macaque thymus that is a key organ in the development of the fetal immune system. Embryonic exposure to triamcinolone acetonide, a potent corticosteroid, during critical periods of thymus development caused marked hypoplasia, depletion of thymic lymphocytes, and reduction of epithelial elements. Aplasia and hypoplasia of the thymus were a distinct feature of the quot;retinoid syndromequot; in cynomolgus macaques following exposure to 13-cis-retinoic acid (Accutane) in early pregnancy, the time of neural crest migration. Experimentally induced zinc deficiency in rhesus macaques from conception to 1-year of age caused severe alterations in immunocompetence. More recent studies have shown that the levels of IgG and IgA in cervicovaginal lavages of the rhesus macaque exhibit specific temporal patterns during the normal menstrual cycle. Taken together, theses data suggest that several macaque species are appropriate animal models for preclinical safety assessment of immunomodulatory drugs. Current teratology protocols in these models may require slight modifications to adequately assess the safety of these biologics."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I272,I272)","v":10762741},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B272:D272)","v":3},2000,"Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer.","Decensi",10762741,"Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer.    Abstract:   Chemoprevention is a recently introduced and rapidly growing area of oncology that is identifying agents with a potentially preventive role in cancer. Several clinical trials have recently shown the feasibility of this approach in reducing the risk of major human cancers. In the USA, a large trial that demonstrated a reduction of approximately 50% in the risk of developing breast cancer led to Food and Drug Administration (FDA) approval of tamoxifen as a preventive agent in women at increased risk. Although the results could not be reproduced in two smaller European trials, further investigations into this agent are clearly warranted. Raloxifene, another selective oestrogen receptor modulator which has reduced the risk of breast cancer in a trial in women with osteoporosis, is being compared with tamoxifen in a large primary prevention trial in at-risk women. Retinoids are a group of compounds that have proved especially effective in reducing the occurrence of second primary tumours in subjects with skin, head and neck or liver cancer. Fenretinide, a synthetic retinoic acid derivative, has recently been shown to decrease the occurrence of a second breast malignancy in premenopausal women. Results with non-steroidal anti-inflammatory drugs (NSAIDs) have proved consistently encouraging in epidemiological studies in lowering the incidence of colorectal cancer. Clinical trials with selective cyclo-oxygenase inhibitors potentially devoid of gastrointestinal (GI) toxicity are currently underway in at-risk subjects. Calcium and selenium have also received much attention as chemopreventive agents. Originally investigated against skin cancer, selenium showed efficacy in reducing prostate, lung and colon cancer incidence. Similarly, vitamin E was effective in reducing prostate cancer incidence and mortality in a lung cancer prevention trial in heavy smokers. The challenges of conducting well-designed and unequivocal chemoprevention trials are considerable, but advances in techniques of identification of at-risk subjects and establishing surrogate endpoint biomarkers should contribute greatly to future studies. Current knowledge suggests that a pharmacological approach to preventing cancer, using natural or synthetic agents, could become an important way forward."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I273,I273)","v":10680075},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B273:D273)","v":3},2000,"Chemoprevention of breast cancer in the older patient.","Minton",10680075,"Chemoprevention of breast cancer in the older patient.    Abstract:   Age is the most important risk factor for the development of breast cancer. The risk of breast cancer continues to increase in American women until the age of 80 years. A family history of breast cancer helps identify those who possibly have the highest risk of developing breast cancer; however, most women who develop breast cancer do not have a first-degree relative with a history of breast cancer. Currently, the Gail model is a commonly used model to identify risk, and this model has now been validated in several populations of women undergoing screening for breast cancer. The first large-scale breast cancer prevention trial investigating the preventive effects of tamoxifen has demonstrated a decrease in the development of breast cancer by almost 50% in the women in the tamoxifen treatment arm as compared with those receiving placebo. The NSABP P-1 trial was the largest of the three tamoxifen breast cancer prevention trials and had the greatest power to detect a difference between the two treatment groups in breast cancer events. This trial also included the largest percentage of postmenopausal women. It is unclear why the Italian and Royal Marsden Hospital trials had negative results regarding the preventive effects of tamoxifen. These two trials were strikingly different from the NSABP P-1 trial, however, and they included a different population of women. The issues surrounding the use of HRT for treatment of hot flashes in the Italian and Royal Marsden Hospital trials adds to the controversy concerning the negative results of these trials. The new SERM, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. The STAR trial will open soon and will evaluate the efficacy of raloxifene in preventing breast cancer in a prospective fashion, comparing its efficacy with tamoxifen treatment. Other endpoints will evaluate side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding serum lipids and incidence of osteoporotic bone fractures. The development of SERMs results from an understanding of novel mechanisms of ER modulation and allows targeting for favorable effects in specific tissues. The challenge is to develop an ideal SERM that is effective in preventing breast cancer and does not increase the risk of endometrial cancer, while providing beneficial estrogenic effects on serum lipids and bone mineral density changes. Estrogen receptor-mediated intracellular processes are complex. There are at least two different types of estrogen receptors. The alpha receptors predominate in the breast and uterus, and the beta receptors predominate in the bone and blood vessels. Many proteins also interact with these receptors as co-activators or co-repressors. Transcription-activating factors modulate the effects of estrogen on its target genes. Future prevention strategies may use a combined targeted approach to inhibit ER-mediated cancer progression pathways. The retinoids are under investigation in prevention studies for a multitude of cancers, because they have been shown to inhibit cellular proliferation and to induce cellular differentiation. The retinoid 4HPR was selected for use in breast cancer prevention studies because of its low toxicity profile and prevention efficacy in preclinical studies. It is now being used in combination with tamoxifin in a phase II breast cancer prevention trial. Multiple surrogate endpoint biomarkers are being measured before and after treatment, including measurement of serum IGF-I levels. Future directions in breast cancer prevention include the development of more potent hormonal therapies that completely inhibit ER-mediated cancer progression and, ultimately, multitargeted therapies involving agents that work synergistically."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I274,I274)","v":10668982},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B274:D274)","v":3},1999,"Morphogenetic action of retinoids and estrogens.","van der Burg",10668982,"Morphogenetic action of retinoids and estrogens.    Abstract:   Retinoids and estrogens are small lipophilic compounds fulfilling important biological roles in vertebrate development, reproduction and homeostasis. Both types of ligands are regulators of gene transcription by binding to (nuclear) proteins acting as ligand-activatable transcription factors, members of the nuclear receptor gene superfamily. Retinoids and their multiple receptors (RARs/RXRs) are particularly well-known for their role in early development and spermatogenesis, while much less is known about the two estrogen receptors (ERalpha/beta) during development. In this article we describe some of our previous and present work in both areas of research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I275,I275)","v":10452726},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B275:D275)","v":3},1999,"Vitamin A deficiency in Bangladesh: a review and recommendations for improvement.","Ahmed",10452726,"Vitamin A deficiency in Bangladesh: a review and recommendations for improvement.    Abstract:    OBJECTIVE : This article provides a comprehensive review of the change in vitamin A status and the extent of vitamin A deficiency among different population groups in Bangladesh up to the present time. The result of experience with different strategies and interventions designed to improve vitamin A status are then reviewed, leading to a discussion of key options for action, as well as important areas for research and evaluation.  DESIGN AND SETTING : All the available data have been examined in detail, including data from nationally representative samples and nationwide surveys, as well as small studies in different population groups. Reports on the effectiveness of different intervention programmes have been used.  RESULTS : Over the past three decades a number of studies, which include national nutrition surveys, have been carried out to investigate the prevalence of vitamin A deficiency among different population groups in Bangladesh, and they have demonstrated a significant public health problem. Studies have shown that the prevalence of severe deficiency, based on the prevalence of night blindness in preschool children, decreased from 3.6% in 1982-83 to 1.78% in 1989 and 0.6% in 1996. However, there is still a high prevalence of subclinical vitamin A deficiency, based on the biochemical assessment of serum retinol levels in preschool children, estimated mainly from hospital-based groups. Night blindness and Bitots spot are also found to exist among school-age children and adolescents. Recent reports indicate that night blindness among rural mothers is as high as 1.4%. Only a limited number of studies, with small sample sizes, are available where serum retinol has been reported for school-age children, adolescents and pregnant women. Nevertheless, these studies confirm the presence of low levels of serum retinol and hence, the existence of subclinical vitamin A deficiency. Furthermore, the dietary intake of vitamin A in each population group has been found to be less than the Recommended Daily Allowance (RDA), indicating a significant risk of deficient intakes of vitamin A. To address the problem of vitamin A deficiency, the government of Bangladesh started the Nutritional Blindness Programme in 1973. The main activities of the programme include vitamin A capsule (VAC) supplementation to children of 6 months to 6 years old, nutrition education to increase the production and consumption of vitamin A rich foods, and training of primary health-care workers on the clinical diagnosis and treatment of vitamin A deficiency, VAC distribution and nutrition education. Since 1988, as a long-term strategy, Helen Keller International has been implementing community home gardening promotion projects. To date, the possibility that foods may be fortified with vitamin A, has not been explored as a possible approach in Bangladesh.  CONCLUSION : Although short- to long-term prevention and control programmes are to some extent in place, to improve the situation of vitamin A deficiency, Bangladesh needs a more appropriate mix of interventions for the entire population. More operational research and evaluation are needed if a fully effective programme to alleviate the problem of vitamin A deficiency is to be developed. Finally, to achieve the goal of virtual elimination of vitamin A deficiency will require an integrated approach which brings together appropriate actions at every level, within and across the many sectors of society."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I276,I276)","v":10338266},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B276:D276)","v":3},1999,"A lifetime of healthy skin: implications for women.","Bergfeld",10338266,"A lifetime of healthy skin: implications for women.    Abstract:   During her lifetime, a woman faces the possibility of seeking dermatological assistance for a myriad of conditions, including acne, rosacea, striae, photodamage, and skin cancers. It is important for clinicians and patients to be aware of the symptoms of these conditions as well as the most beneficial approaches for prevention, diagnosis, treatment, and management. The life expectancy of women has increased and predictions for the year 2050 estimate the average age at 81 years. This will place women at greater risk for dermatological problems, especially photodamage and skin cancer. In addition, various ethnic groups may manifest these conditions differently. Although acne is most prevalent among teenaged males, most can expect clearing by age 25. Females may continue to experience acne into the adult years, sometimes beyond the age of 40. Although it is not a life-threatening disease, acne may have psychosocial and quality-of-life consequences. Treatments for acne can be topical or systemic, and include retinoids, antibiotics, benzoyl peroxide, azelaic acid, and hormonal therapy. Rosacea is more common in women (especially during menopause) than in men. It is a chronic condition that can cause complications, including telangiectasia, conjunctivitis, and blepharitis. Although there is no cure, rosacea can be managed and controlled with medication. Topical antibiotics, such as metronidazole, and systemic antibiotics, such as tetracycline, clarithromycin, and doxycycline, are used to manage rosacea. Striae, or stretch marks, occur most frequently in pregnant women, adolescents experiencing growth spurts, weight lifters, and the obese. Although not a health threat, they can be psychologically distressing. There are not many treatment options for striae, but topical tretinoin and the pulsed dye laser offer promising results. Intrinsic, or normal, aging of the skin results from the process of chronological aging. Photodamage is skin damage caused by chronic exposure to ultraviolet (UV) light. It is the leading cause of extrinsic aging, or alterations of the skin due to environmental exposure. Estimates indicate that almost half of a persons UV exposure occurs by age 18. Photoaging causes numerous histologic, physiologic, and clinical changes; it also increases the risk for skin cancer. Photodamage can be prevented through the use of sun screens, protective clothing, and avoidance of the sun during peak intensity time. The only product approved by the FDA for the treatment of photodamage (fine wrinkles, mottled hyperpigmentation, and skin roughness), topical tretinoin emollient cream, may help prevent additional photoaging when it is used to treat existing photoaging. Other management options for photodamaged skin include alpha-hydroxy acids, antioxidants, antiandrogens, moisturizers, and exfoliants. In patients with excessive manifestations of photodamage, surgical management may be needed, including dermabrasion, chemical peels, soft tissue augmentation, laser resurfacing, botulism toxin, and Gortex threads. Clinicians must educate their patients about the most appropriate skin care regimen as well as approaches for preventing and treating common afflictions. In this way, women will have the best opportunity for having and maintaining healthy skin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I277,I277)","v":9842220},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B277:D277)","v":3},1998,"New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.","Sciarra",9842220,"New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.    Abstract:   Three new different aspects of prostate cancer have been considered in this review: the existence of an hereditary form, the role of estrogens as predisposing factors and the efficacy of differentiation therapies. Prostate cancer shows a stronger familial aggregation than colon and breast carcinoma. Hereditary prostate cancer is distinguished by early age at onset and autosomal dominant inheritance within families. However, only 2% of all prostate cancer in United States white men occur in those 55 years old or younger. Thus, the impact of hereditary prostate cancer in the population is the greatest at younger ages but this accounts for only a small proportion of the total disease burden. Using the developmentally estrogenized mouse model, an alternative role for estrogens as a predisposing factor for prostate diseases was proposed: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to neoplasia. A combination therapy employing both differentiation therapy and hormone therapy may be effective in the treatment of advanced prostate cancers. Recent advances in the field of differentiation therapy have resulted in the development of novel retinoic acid metabolism blocking agents. Unlike previous differentiating agents such as the retinoids, these agents increase the endogenous levels of retinoic acid by inhibiting its breakdown in cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I278,I278)","v":9787988},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B278:D278)","v":3},1998,"Pharmacologic profile of tazarotene.","Duvic",9787988,"Pharmacologic profile of tazarotene.    Abstract:   The majority of patients with psoriasis exhibit a mild to moderate form of the disease. While topically applied agents represent the ideal therapeutic approach for these patients, our treatment options have been hampered by their inconsistent or limited efficacy, expense, and cosmetic properties. Furthermore, some of the topically applied preparations have the potential for systemic absorption and associated adverse events. Tazarotene is the first synthetically developed retinoid indicated for the topical treatment of patients with psoriasis. Pharmacologically, tazarotene affects the three primary abnormalities associated with psoriasis: it normalizes epidermal differentiation, it exhibits a potent antiproliferative effect, and it decreases epidermal inflammation. Following topical application, tazarotene is rapidly metabolized in the skin to tazarotenic acid, its primary and active metabolite. While tazarotenic acid achieves measurable levels in the systemic circulation, no drug-related hematologic, ophthalmologic, or metabolic adverse events have been observed. Only a minimal amount of tazarotene is absorbed into the circulation. While animal studies have found tazarotene to be nonmutagenic and nonteratogenic, women of child-bearing potential should be counseled regarding the potential risks of retinoid use during pregnancy. In summary, animal and clinical patient trials have found tazarotene to be effective, safe, and well-tolerated. The availability of such an agent in a topical formulation is a welcome treatment alternative for the management of patients with psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I279,I279)","v":9652687},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B279:D279)","v":3},1998,"Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.","Carr",9652687,"Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.    Abstract:   HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndromes pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I280,I280)","v":9447344},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B280:D280)","v":3},1997,"Adequate nutrition in pregnancy does matter.","Hautvast",9447344,"Adequate nutrition in pregnancy does matter.    Abstract:   This paper highlights briefly several nutrition issues in pregnancy which at present are receiving much attention in research and nutritional health policy. Nutritional status and health in pregnancy will become an area of more research in future. This is amongst others directed by the hypothesis that health in later life may already partly be determined by childrens intra-uterine growth and development patterns."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I281,I281)","v":9364869},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B281:D281)","v":3},1997,"[A neonate born to a mother with acute promyelocytic leukemia treated by all-trans retinoic acid].","Maeda",9364869,"[A neonate born to a mother with acute promyelocytic leukemia treated by all-trans retinoic acid].    Abstract:   We report a female neonate delivered in week 32 of gestation by a mother who had acute promyelocytic leukemia (APL) treated by all-trans retinoic acid (ATRA). APL was diagnosed in week 29 of gestation and was treated with ATRA from week 30. Physical examination and laboratory tests showed no abnormalities at birth. The girl has since shown normal development, with no peripheral blood abnormalities at 2 years old. Hypersegmented neutrophils, which often appear during ATRA treatment, were seen in the peripheral blood of the mother and cord blood but not peripheral blood of the neonate on the day of birth. ATRA is known to cross the placenta, and has been revealed to be teratogenic in animal studies. There have been eight neonates born to the mothers with APL who were treated with ATRA during pregnancy. All infants, including this one, have shown normal growth without any complications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I282,I282)","v":8981600},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B282:D282)","v":3},1996,"Similarities in genetic mental retardation and neuroteratogenic syndromes.","Adams",8981600,"Similarities in genetic mental retardation and neuroteratogenic syndromes.    Abstract:   Principles and mechanisms of neurobehavioral teratogenesis are used to show commonalities between manifestations of abnormal development consequent to genetic abnormality or teratogenic exposure. A comparison and contrast of both the neuropathological and neuropsychological characteristics of children with early embryonic exposure to isotretinoin (Accutane) or with selected mental retardation syndromes is presented. Putative mechanisms of retinoid teratogenesis through the disruption of normal retinoid-triggered embryogenesis and the alteration of homeobox gene expression are discussed. Interference with homeobox gene expression as an avenue to the perturbation of early developmental processes and the production of hindbrain and craniofacial abnormalities is then proposed as a common basis for the translation and expression of several genetic mental retardation syndromes. Finally, dose-response effects and other modulators of vulnerability to abnormal development are used to provide a conceptual framework for the understanding of variability in the expression of genetically caused abnormalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I283,I283)","v":8923025},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B283:D283)","v":3},1996,"Adverse effects of preventive therapy in humans.","La Vecchia",8923025,"Adverse effects of preventive therapy in humans.    Abstract:   The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I284,I284)","v":8778807},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B284:D284)","v":3},1996,"Influence of diet on tumors of hormonal tissues.","Rao",8778807,"Influence of diet on tumors of hormonal tissues.    Abstract:   Approximately 20% of all deaths in the United States are due to cancer. Cancers of the hormonal tissues such as breast, uterus, ovary in women and prostate in men account for about 8% and 5% of total mortality and 30% and 11% of cancer mortality in women and men, respectively. Diet is considered to be a major and important environmental factor contributing to cancers of hormonal tissues. Breast, uterus, and ovary cancers in women and prostate cancers in men were positively correlated with high fat consumption, high body weight (body mass), body fat, and obesity. A major mechanism for development of these cancers appears to be mediated through increased levels of hormones, especially estrogens. Adipose tissue is considered to be one of the major sources of extraglandular estrogen, produced by aromatization of androgen precursors. Weight reduction decreases the estrogen levels possibly due to a decrease in body fat, thus decreasing the risk for cancers of the hormonal tissues. Dietary fiber may modify the risk for these cancers by influencing estrogen metabolism, recirculation, and excretion. Vitamin A and its precursors may decrease the risk for prostate cancer. Iodine deficiency may increase the risk for thyroid neoplasms in humans and experimental animals. Tumors of the hormonal tissues are the most common tumors in laboratory rodents, especially rats and mice. Incidences of mammary and anterior pituitary tumors had significant and positive correlation with body weight in rats and mice. Lowering the body weight by either decreased caloric intake or other means (e.g., exercise, increased fiber consumption) markedly lowered the incidences of these tumors in laboratory rodents. Laboratory studies indicated that mammary tumor rates in rats may not depend on the amount of fat consumed per day. The mammary tumor-promoting effect of fat may be due to complex interactions involving energy intake and energy retention (body mass) mediated through paracrine, endocrine, and neurohormonal mechanisms. Dietary protein may influence chemically induced tumors by affecting the metabolism of chemicals through enzyme induction. Thus, environmental factors such as diet are considered to be major and important factors for tumors of the hormonal tissues such as breast, uterus, and ovary in women and prostate in men. Diet and associated body weight are considered to be the major factors for tumors of hormonal tissues such as mammary and pituitary glands in rodents, especially rats. Modification of diet and a decrease in caloric intake may markedly decrease the incidence or delay the development of tumors of hormonal tissues in humans and in experimental animals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I285,I285)","v":8603034},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B285:D285)","v":3},1996,"P450-dependent enzymes as targets for prostate cancer therapy.","De Coster",8603034,"P450-dependent enzymes as targets for prostate cancer therapy.    Abstract:   Metastatic prostate adenocarcinoma is a leading cause of cancer-related deaths among men. First line treatment is primarily aimed at blocking the synthesis and action of androgens. As primary endocrine treatment, androgen deprivation is usually achieved by orchidectomy or LHRH analogues, frequently combined with androgen receptor antagonists in order to block the residual adrenal androgens. However, nearly all the patients will eventually relapse. Available or potential second line therapies include, among others, alternative endocrine manipulations and chemotherapy. Cytochrome P450-dependent enzymes are involved in the synthesis and/or degradation of many endogenous compounds, such as steroids and retinoic acid. Some of these enzymes represent suitable targets for the treatment of prostate cancer. In first line therapy, inhibitors of the P450-dependent 17,20-lyase may achieve a maximal androgen ablation with a single drug treatment. Ketoconazole at high dose blocks both testicular and adrenal androgen biosynthesis but its side-effects, mainly gastric discomfort, limit its widespread use. A series of newly synthesized, more selective, steroidal 17,20-lyase inhibitors related to 17-(3-pyridyl)androsta-5,16-dien-3beta-ol, may open new perspectives in this field. In prostate cancer patients who relapse after surgical or medical castration, therapies aiming at suppressing the remaining adrenal androgen biosynthesis (ketoconazole) or producing a medical adrenalectomy (aminoglutethimide+hydrocortisone) have been used, but are becoming obsolete with the generalization of maximal androgen blockade in first line treatment. The role of inhibition of aromatase in prostate cancer therapy, which was postulated for aminoglutethimide, could not be confirmed by the use of more selective aromatase inhibitors, such as formestane. An alternative approach is represented by liarozole fumarate (LIA), a compound that blocks the P450-dependent catabolism of retinoic acid (RA). In vitro, it enhances the antiproliferative and differentiation effects of RA in cell lines that express RA metabolism, such as F9 teratocarcinoma and MCF-7 breast carcinoma cells. In vivo, monotherapy with LIA increases RA plasma levels and, to a greater extent, endogenous tissue RA levels leading to retinoid-mimetic effects. In the rat Dunning prostate cancer models, it inhibits the growth of androgen-independent as well as androgen-dependent carcinomas relapsing after castration. Concurrently, changes in the pattern of cytokeratins characteristic of increased differentiation were observed. Early clinical trials show that LIA, in second or third line therapy in metastatic prostate cancer, induces PSA responses in about 30% of unselected patients. In some patients regression of soft tissue metastasis ha been observed. In a subgroup of patients, an important relief of metastatic bone pain was also noted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I286,I286)","v":8522241},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B286:D286)","v":3},1995,"[Retinoids--drugs with a strong teratogenic side effect].","Jendryczko",8522241,"[Retinoids--drugs with a strong teratogenic side effect].    Abstract:   The derivatives of the vitamin A--retinoids, are very precious drugs used in dermatology. Forever, they are very strong teratogens and their applications in case of women before the menopause may cause serious deformations of the fetus. So we presented the recommendations so as to applications of the retinoids in such women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I287,I287)","v":8747399},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B287:D287)","v":3},1995,"Molecular approaches to prevention and detection of epithelial ovarian cancer.","Bast",8747399,"Molecular approaches to prevention and detection of epithelial ovarian cancer.    Abstract:   More than 90% of epithelial ovarian cancers arise from single cells. Malignant transformation can be associated with a number of molecular alterations including upregulation of tyrosine kinases and phosphatases, physiologic activation o ras, mutation of p53, amplification of myc, and increased activity of matrix metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be enhanced through the persistence of autocrine growth stimulation by TGF-alpha, loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid. Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which induces apoptosis in malignant ovarian epithelial cells, but not in normal ovarian surface epithelium. Proliferation of surface epithelial cells following ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral contraceptives that suppress ovulation has been associated with reduced risk of ovarian cancer in later life. Retinoids also deserve further evaluation for chemoprevention. Treatment with fenretinide was associated with decreased incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor cell proliferation has been observed with TGF-beta in combination with all-trans-retinoic acid. Early detection of ovarian cancer could improve survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have been evaluated in multiple clinical trials. The former lacks adequate specificity, whereas the latter is not sufficiently sensitive. Use of multiple serum markers can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected gt; 95% of Stage I ovarian cancers. If similar results are obtained with different data sets, multiple serum markers could be used to trigger the performance of TVS, providing a potentially cost effective screening strategy. Prospective trials will be required to demonstrate that screening for early stage ovarian actually impacts on survival."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I288,I288)","v":8747372},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B288:D288)","v":3},1995,"Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary.","Kelloff",8747372,"Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary.    Abstract:   Well-designed and conducted Phase II clinical trials are very important to cancer chemoprevention drug development. Three critical aspects govern the design and conduct of these trials--well-characterized agents, suitable cohorts, and reliable biomarkers for measuring efficacy that can serve as surrogate endpoints for cancer incidence. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. Agents that meet these criteria for chemoprevention of cervical cancer include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids, folic acid, antioxidant vitamins and other agents that prevent cellular oxidative damage. Because of the significant cervical cancer risk associated with human papilloma virus (HPV) infection, agents that interfere with the activity of HPV products may also prove to be effective chemopreventives. In endometrium, unopposed estrogen exposure has been associated with cancer incidence. Thus, pure antiestrogens and progestins may be chemopreventive in this tissue. Ovarian cancer risk is correlated to ovulation frequency; therefore, oral contraceptives are potentially chemopreventive in the ovary. Recent clinical observations also suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may be chemopreventive in this tissue. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in endometrium, patients with atypical hyperplasia, fit these criteria. Defining a cohort for a Phase II trial in the ovary is more difficult. This tissue is less accessible for biopsy; consequently, the presence of precancerous lesions is more difficult to confirm. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decrease cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, perhaps appearing on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid solely on biomarkers that do not describe cancer but represent isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis. Chemoprevention trials should be designed to evaluate fully the two or three biomarkers that appear to be the best models of the cancer. Additional biomarkers should be considered only if they can be analyzed efficiently and the sample size allows more important biomarkers to be evaluated completely. Two types of biomarkers that stand out regarding their high correlation to cancer and their ability to be quantified are measures of intraepithelial neoplasia and indicators of cellular proliferation. Measurements made by computer-assisted image analysis that are potentially useful as surrogate endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape (roundness), and texture (DNA distribution patterns); nucleolar size and number of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase fraction and PCNA..."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I289,I289)","v":7632866},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B289:D289)","v":3},1995,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.","Johnston",7632866,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.    Abstract:   Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: quot;growth factorsquot; (e.g., FGF and TGFalpha) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues. Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome(FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGF alpha s, RAR alpha s, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzons syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I290,I290)","v":7934156},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B290:D290)","v":3},1994,"Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid tumors.","Man",7934156,"Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid tumors.    Abstract:   Preclinical data indicate that the combination of retinoids and interferons have synergistic antiproliferative and differentiating effects in some hematologic and solid tumor models. These observations have led to clinical trials in which 13-cis-retinoic acid (13cRA) 1 mg/kg/day was combined with interferon alpha-2a (IFN alpha) 3 or 6 x 10(6) U/day. The first two such trials produced exciting results: 50% response rate in patients with previously untreated stages IB-IVA cervix cancer and 68% in patients with advanced squamous cell skin cancer. These data led to a number of additional trials of the combination, but the high response rates seen in the initial cervix and skin trials have not been duplicated in the other squamous tumors tested (head and neck, lung, pretreated cervix). In addition, trials in two non-squamous histologies were negative (lung and melanoma). However, the regimen was not always studied in an optimal population of previously untreated patients and the negative results in pretreated cervix patients point to the relevance of this consideration. Nevertheless, the observation that the combination of 13cRA and IFN alpha (both of which bind to specific receptors and change gene expression) is able to induce regression in advanced tumors, must be regarded as highly important. Key questions to be addressed include an understanding of the biologic mechanism of specific tumor sensitivity (why some squamous tumors and not others?), and mechanisms of resistance in sensitive tumor types (e.g. cervix). Such data may lead to trials targeted to tumor types with defined biologic features having a high likelihood of clinical benefit. In the meantime, studies integrating this combination with other active treatment modalities such as radiation is warranted in cervix and skin carcinomas."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I291,I291)","v":7999471},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B291:D291)","v":3},1994,"Prevention of breast cancer in premenopausal women.","Love",7999471,"Prevention of breast cancer in premenopausal women.    Abstract:   While all-inclusive complete models for breast cancer development are not available, four concepts are likely to be critical to creation of well-grounded breast cancer prevention efforts: 1) step-by-step progressive development, 2) involving multiple factors, 3) over several years, and 4) during a long period of which the process may be reversible. Interventions to prevent breast cancer must have a comprehensive biological rationale, an absence of serious toxic effects, and long-term acceptability by women. Prophylactic mastectomy may be beneficial in some women, but identification of individuals at very high risk for breast cancer remains elusive. At present, greater attention to four manipulable risk factors is appropriate: radiation, smoking, alcohol, and lactation. Clinical trials are in the process of studying a synthetic retinoid (4-hydroxyphenylretinamide), tamoxifen, and a low-fat diet. Other breast cancer prevention strategies in various phases of preclinical trial evaluation include: pseudopregnancy, an quot;idealquot; combination oral contraceptive, luteinizing hormone-releasing hormone (LHRH) agonist oophorectomy, modification of estrogen metabolism, suppression of ornithine decarboxylase induction, and manipulation of growth factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I292,I292)","v":8260265},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B292:D292)","v":3},1993,"Retinoic acid and interferon combination studies in human cancer.","Lippman",8260265,"Retinoic acid and interferon combination studies in human cancer.    Abstract:   Retinoic acid and interferon-alpha have limited single-agent activity in advanced cancer. Cell culture data indicate that in combination these agents have enhanced activity (modulating growth and differentiation) in a number of malignant cell types. Recent clinical work in advanced squamous cell carcinoma reports major activity with this regimen. This paper reviews the preclinical and clinical data testing retinoic acid in combination with interferons and presents recent work integrating these agents with radiotherapy in locally advanced cervical cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I293,I293)","v":1330304},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B293:D293)","v":3},1992,"Mechanistic interrelationships between two superfamilies: the steroid/retinoid receptors and transforming growth factor-beta.","Roberts",1330304,"Mechanistic interrelationships between two superfamilies: the steroid/retinoid receptors and transforming growth factor-beta.    Abstract:   The fields of endocrinology and peptide growth factors can no longer be studied independently, nor can hypotheses about the modes of action of hormones and growth factors be constrained by outmoded classic definitions. Although much is still to be learned about the mechanisms of induction of TGF-beta activity by steroids/retinoids, about the involvement of specific nuclear receptors and about the factors regulating the differential effects of steroids/retinoids on the various isoforms of TGF-beta, it is clear that the identification of the interrelationships between these two superfamilies of multi-functional effectors has heralded a new era of discovery of the underlying regulatory events controlling cellular proliferation and differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I294,I294)","v":2663306},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B294:D294)","v":3},1989,"Deleterious effects of drugs on the developing nervous system.","Dodson",2663306,"Deleterious effects of drugs on the developing nervous system.    Abstract:   In the past two decades, several categories of drugs have emerged as serious neuroteratogens. These include vitamin A congeners, isotretinoin and etretinate, certain antiepileptic drugs, especially trimethadione, and valproic acid. Other antiepileptic drugs have low teratogenic potential and variably affect the developing CNS. When multiple antiepileptics are administered during pregnancy, however, the risk to the fetus increases considerably."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I295,I295)","v":3772906},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B295:D295)","v":3},1986,"Contraceptive steroid effects on nonreproductive organ systems.","Corson",3772906,"Contraceptive steroid effects on nonreproductive organ systems.    Abstract:   Oral contraceptives affect many organ systems in addition to the reproductive tract. In some cases the alteration is just a clinical laboratory test result value; in others it represents a true alteration in metabolism, with the induction of increased enzyme activity. Even with the markedly reduced steroid content of todays oral contraceptives, the practitioner must continue to be aware of these potential and real effects on nonreproductive organ systems. How oral contraceptives (OCs) affect the nonreproductive organ systems depends on both the dose and choice of the estrogenic and progestational components and the interaction between the 2. Several animal model systems have been used to measure the potencies of these agents and their estrogenic-androgenic metabolic effects. These test results have been combined with human data from delay-of-menses tests and gonadotropin-suppression studies to differentiate between commercially available combinations. There has been a tendency to place less importance on animal studies because the data correlate poorly with human experience. Ongoing studies provide particularly valuable information. In a study conducted at the Northwest Lipid Research Clinic at the University of Washington, Seattle, the clinical chemistries of women using OCs and replacement estrogen were compared with those of nonusers. OC users and those on estrogen replacement therapy had lower levels of alkaline phosphates than nonusers when adjusted age-specific values were compared. Mean SGOT and bilirubin levels were statistically lower than in OC users. Knopp, with the same group, also investigated the effects of pregnancy and OC use on clinical serum chemistry. OC users and women who were 36 weeks pregnant were compared with nonpregnant women who did not use OCs. Total plasma bilirubin concentration was lower in OC users (29%) and pregnant women (32%). Plasma glucose levels showed a wider variation: 3% lower in OC users and 17% lower in pregnant women as compared with the controls. Discordancy was noted for SGOT levels, with a 9% decrease in OC users but a 27% increase in pregnancy. Commonly used biochemical indexes are influenced differently by the estrogen and progestin components of the pill. Yet, even recently published longitudinal studies evaluated doses no longer commonly used. Because some of these changes seem to be dose related in part, it is necessary to continue to study the newer preparations. In 1975, Wynn reviewed the issue of OC use and vitamins. He noted that vitamin A was increased 30-80% in OC users as a consequence of an estrogen-mediated increase in retinol-binding protein. Thiamine (B1) and pyridoxine (B6) were decreased; vitamin C was decreased by 30-40% in OC users but not enough to reach deficiency ranges. In 1966 Shearman called attention to post-pill amenorrhea. 9 of 86 patients with secondary amenorrhea had experienced the onset after cessation of OC use. Conversely, in 1977 Jacobs et al. analyzed 131 consecutive cases of secondary amenorrhea and concluded that OC use did not cause that disorder. Dickey and Berger discussed the incidence of post-pill amenorrhea over various time periods and reported an estimated 2-2.6% at 6 months after cessation of OCs. Bennion et al. demonstrated the effect of OCs on bile composition in 22 women; OCs increased gall bladder bile cholesterol saturation. Because OCs markedly decrease the ovarian production of androgens, decrease adrenal production of the precursors, and increase sex-binding globulin, its therapeutic effect is broad based."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I296,I296)","v":4076026},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B296:D296)","v":3},1985,"Vitamin A status of pregnant and lactating women as assessed by serum levels in Machakos area, Kenya.","Kusin",4076026,"Vitamin A status of pregnant and lactating women as assessed by serum levels in Machakos area, Kenya.    Abstract:   In a sample of 100 pregnant and 106 lactating women, the serum levels of vitamin A, carotene, retinol-binding protein (RBP), and pre-albumin (PA) were analyzed. The study was in response to the problem of inadequate hepatic reserves and serum vitamin A levels of newborns. On the presumption that these levels are related to the Vitamin A status of mothers during pregnancy, and the Vitamin A content of breast milk during lactation, attention was given to the Vitamin A status of pregnant and lactating women in studies of maternal and child nutrition in Machakos. The women were selected at random from the total population of pregnant and lactating women with infants of 0-12 months. Blood was taken before the midday meal, centrifuged, and sera were deep frozen. Mean serum levels of the 4 biochemical parameters of vitamin A status were in the range for well-nourished population groups. Correlations of r=0.76-0.85 were found between RBP and PA, but between Vitamin A and RBP the correlation was r=0.32-0.40. Some seasonal variations reflected crop availability. A review of very little available literature shows that Vitamin A status of lactating women in Ethiopia is poorer among less privileged women. Dietary intake of retinol equivalents in West African countries being adequate, reported serum levels in these countries are also generally adequate. Xerophthalmia among young children in Machakos is rare, with the possible explanation that seasonal intake of carotene-rich foods is enough to replenish liver stores, and protein status (RBP and PA serum levels) is adequate as well."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I297,I297)","v":27638711},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B297:D297)","v":2},2016,"Carotenoids: biochemistry, pharmacology and treatment.","Milani",27638711,"Carotenoids: biochemistry, pharmacology and treatment.    Abstract:    NlmCategory=UNASSIGNEDCarotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I298,I298)","v":27320329},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B298:D298)","v":2},2016,"Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.","Muccio",27320329,"Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.    Abstract:    NlmCategory=UNASSIGNEDThis review focuses on our efforts to translate a low-toxicity retinoid X receptor-selective agonist, UAB30, to the clinic for the prevention of breast cancers. The review is divided into several sections. First, the current status of breast cancer prevention is discussed. Next, preclinical studies are presented that support translation of rexinoids to the clinic for cancer prevention. While current FDA-approved retinoids and rexinoids demonstrate profound effects in treating cancers, they lack sufficient safety for long term use in the high risk population that is otherwise disease free. The review stresses the need to identify cancer preventive drugs that are effective and safe in order to gain wide use in the clinic. Due to the heterogeneity of the disease, UAB30 is evaluated for the prevention of ER-positive and ER-negative mammary cancers. Since selective estrogen receptor modulators and aromatase inhibitors are used clinically to prevent and treat ER-positive breast cancers, preclinical studies also must demonstrate efficacy of UAB30 in combination with existing drugs under use in the clinic. To support an Investigational New Drug Application to the FDA, data on pharmacology and toxicity as well as mutagenicity is gathered prior to human trials. The review concludes with a discussion of the outcomes of human Phase 0/1 clinical trials that determine the safety and pharmacology of UAB30. These studies are essential before this agent is evaluated for efficacy in phase 2 trials. Success in phase 2 evaluation is critical before long-term and costly phase 3 trials are undertaken. The lack of surrogate biomarkers as endpoints for phase 2 evaluation of rexinoid preventive agents is discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I299,I299)","v":26484581},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B299:D299)","v":2},2015,"Minireview: Familiar Faces in Unfamiliar Places: The Emerging Role of Nuclear Receptors in Lung Cancer.","Yenerall",26484581,"Minireview: Familiar Faces in Unfamiliar Places: The Emerging Role of Nuclear Receptors in Lung Cancer.    Abstract:   Nuclear hormone receptors (NRs) are a superfamily of 48 transcription factors that are frequently modulated by ligands and control various cancer-relevant cellular pathways, such as differentiation, proliferation, migration, and metabolism. These properties make them excellent therapeutic targets in cancers dependent upon their activity, and as such, 3 NRs, estrogen receptor-α, androgen receptor, and retinoic acid receptor-α (more specifically, the promyelocytic leukemia-retinoic acid receptor-α translocation), have been targeted clinically in breast cancer, prostate cancer, and acute promyelocytic leukemia, respectively. Recently, a number of studies have highlighted a putative role for NRs in nonsmall cell lung cancer (NSCLC), a highly lethal type of lung cancer with relatively few targeted agents. Here, we review the potential roles of selected NRs in NSCLC and offer insights on how NRs may be leveraged in NSCLC to improve patient outcomes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I300,I300)","v":26451736},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B300:D300)","v":2},2015,"Promoter Methylation of the Retinoic Acid Receptor Beta2 (RARβ2) Is Associated with Increased Risk of Breast Cancer: A PRISMA Compliant Meta-Analysis.","Fang",26451736,"Promoter Methylation of the Retinoic Acid Receptor Beta2 (RARβ2) Is Associated with Increased Risk of Breast Cancer: A PRISMA Compliant Meta-Analysis.    Abstract:    BACKGROUND : Epigenetic studies demonstrate that an association may exist between methylation of the retinoic acid receptor beta2 (RARβ2) gene promoter and breast cancer onset risk, tumor stage, and histological grade, however the results of these studies are not consistent. Hence, we performed this meta-analysis to ascertain a more comprehensive and accurate association.  MATERIALS AND METHODS : Relevant studies were retrieved from the PubMed, Embase and Chinese National Knowledge Infrastructure databases up to February 28, 2015. After two independent reviewers screened the studies and extracted the necessary data, meta-analysis was performed using Review Manager 5.2 software.  RESULTS : Nineteen eligible articles, including 20 studies, were included in our analysis. Compared to non-cancerous controls, the frequency of RARβ2 methylation was 7.27 times higher in patients with breast cancer (odds ratio (OR) = 7.27, 95% confidence interval (CI) = 3.01-17.52). Compared to late-stage RARβ2 methylated patients, the pooled OR of early-stage ones was 0.81 (OR = 0.81, 95% CI = 0.55-1.17). The OR of low-grade RARβ2 methylated patients was 0.96 (OR = 0.96, 95% CI = 0.74-1.25) compared to high-grade RARβ2 methylated patients.  CONCLUSION : RARβ2 methylation is significantly increased in breast cancer samples when compared to non-cancerous controls. RARβ2 could serve as a potential epigenetic marker for breast cancer detection and management."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I301,I301)","v":26029163},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B301:D301)","v":2},2015,"Reporter Cell Lines for the Characterization of the Interactions between Human Nuclear Receptors and Endocrine Disruptors.","Grimaldi",26029163,"Reporter Cell Lines for the Characterization of the Interactions between Human Nuclear Receptors and Endocrine Disruptors.    Abstract:   Endocrine-disrupting chemicals (EDCs) are exogenous substances interfering with hormone biosynthesis, metabolism, or action, and consequently causing disturbances in the endocrine system. Various pathways are activated by EDCs, including interactions with nuclear receptors (NRs), which are primary targets of numerous environmental contaminants. The main NRs targeted by environmental contaminants are the estrogen (ER α, β) and the androgen (AR) receptors. ERs and AR have pleiotropic regulatory roles in a diverse range of tissues, notably in the mammary gland, the uterus, and the prostate. Thus, dysfunctional ERs and AR signaling due to inappropriate exposure to environmental pollutants may lead to hormonal cancers and infertility. The pregnane X receptor (PXR) is also recognized by many environmental molecules. PXR has a protective role of the body through its ability to regulate proteins involved in the metabolism, the conjugation, and the transport of many exogenous and endogenous compounds. However, the permanent activation of this receptor by xenobiotics may lead to premature drug metabolism, the formation, and accumulation of toxic metabolites and defects in hormones homeostasis. The activity of other NRs can also be affected by environmental molecules. Compounds capable of inhibiting or activating the estrogen related (ERRγ), the thyroid hormone (TRα, β), the retinoid X receptors (RXRα, β, γ), and peroxisome proliferator-activated (PPAR α, γ) receptors have been identified and are highly suspected to promote developmental, reproductive, neurological, or metabolic diseases in humans and wildlife. In this review, we provide an overview of reporter cell lines established to characterize the human NR activities of a large panel of EDCs including natural as well as industrial compounds such as pesticides, plasticizers, surfactants, flame retardants, and cosmetics."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I302,I302)","v":25683035},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B302:D302)","v":2},2015,"Triorganotin compounds--ligands for quot;rexinoidquot; inducible transcription factors: biological effects.","Brtko",25683035,"Triorganotin compounds--ligands for quot;rexinoidquot; inducible transcription factors: biological effects.    Abstract:   We review trialkyltin and triaryltin compounds, representing a class of organometallic compounds that function as nuclear retinoid X receptors (RXR) agonists due to their capability to bind to the ligand-binding domain of RXR subtypes and function as transcriptional activators. RXRs act predominantly as heterodimers with other nuclear receptors as permissive heterodimers with peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptor, pregnane X receptor and constitutive androstan receptor or as non-permissive heterodimer with vitamin D receptor, and as conditional heterodimers with retinoid receptors, and thyroid hormone receptors. RXR - quot;partnerquot; receptor heterodimers are considered to be ligand-activated, DNA-binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Tributyltin at even pico- or nanomolar concentrations may cause the superimposition of male genitalia on female in several aquatic organisms, since they are DNA-targeted, mitotic, and their actions are occurring through target gene(s)-mediated pathways. They may cause molecular interactions with reproductive system in mammals, and as potent environmental obesogens, they promote adipocyte differentiation. Organotin compounds become known also for their immunotoxicity, neurotoxicity, for their effects on reproduction and/or development. We also review effects of organotins with respect to levels and activities of hepatic P450s and aromatase activity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I303,I303)","v":25621293},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B303:D303)","v":2},2014,"The emerging roles of GPRC5A in diseases.","Zhou",25621293,"The emerging roles of GPRC5A in diseases.    Abstract:   The Retinoic Acid-Inducible G-protein-coupled receptors or RAIG are a group comprising the four orphan receptors GPRC5A, GPRC5B, GPRC5C and GPRC5D. As the name implies, their expression is induced by retinoic acid but beyond that very little is known about their function. In recent years, one member, GPRC5A, has been receiving increasing attention as it was shown to play important roles in human cancers. As a matter of fact, dysregulation of GPRC5A has been associated with several cancers including lung cancer, breast cancer, colorectal cancer, and pancreatic cancer. Here we review the current state of knowledge about the heterogeneity and evolution of GPRC5A, its regulation, its molecular functions, and its involvement in human disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I304,I304)","v":25517754},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B304:D304)","v":2},2015,"Dermatologic therapy in pregnancy.","Tyler",25517754,"Dermatologic therapy in pregnancy.    Abstract:   Patients present during pregnancy with a variety of dermatologic conditions, most of which can be treated conservatively with topical medication by a primary obstetrician if he or she is familiar with common treatment options. Patients with moderate to severe forms of dermatologic disease or those requiring systemic therapy should be treated in consultation with a dermatologist. Dermatologic surgery can be performed safely in the second trimester using local anesthesia if needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I305,I305)","v":24953623},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B305:D305)","v":2},2014,"[Management of chronic hand eczema].","Lahfa",24953623,"[Management of chronic hand eczema].    Abstract:   The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I306,I306)","v":24506350},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B306:D306)","v":2},2013,"[Dietary supplements as a treatment for cervical cancer: a systematic review].","Arellano Ortiz",24506350,"[Dietary supplements as a treatment for cervical cancer: a systematic review].    Abstract:    INTRODUCTION : Cervical cancer and cervical intraepithelial neoplasia (CIN) require a careful selection of conventional and complementary therapies. The inclusion of dietary supplements within the aforementioned treatments set the tone within treatments. However, there are no reports of what kind of supplements could be used to provide a better response to the disease in these patients.  OBJECTIVE : In this review, we analyze clinical trials of the past 20 years that evaluated dietary supplements on this population, with the objective to raise awareness on which of them are viable to be administered.  METHODS : We performed a search for clinical trials that used a dietary supplement in women with cervical cancer and some degree of NIC analyzing them how to use the supplement, the conventional treatment, deficiency of the nutrient or compound to be evaluated, the characteristics of the population, the clinical trial and the supplement, as well as dosage and their effects.  RESULTS : Twenty were in total the number of studies reviewed. The articles were classified according to the nature of the supplement: Retinoids, vitamin E, probiotics, indoles, multivitamin, folic acid and selenium.  CONCLUSION : Some supplements were found to be effective in the treatment of cervical cancer and CIN. However, their effect depends on specific factors of the disease. The correct management of dietary supplements is an effective aid to help the patient with cancer and therefore, it is important to define what complementary therapies can be used for this population. Introducción: En el cáncer cervicouterino (CaCu) y neoplasias intraepiteliales cervicales (NIC) se requiere de una cuidadosa selección de terapias convencionales y complementarias, la inclusión de suplementos dietéticos dentro de ellas marcaría la pauta dentro de los tratamientos. Sin embargo, no se tiene algún reporte de qué tipo de suplementos pudieran ser utilizados para brindar una mejor respuesta ante la enfermedad por estas pacientes. Objetivo: En la presente revisión se analizan los ensayos clínicos de los últimos 20 años que evaluaron suplementos dietéticos en esta población, con el objetivo de dar a conocer cuáles de ellos son viables para ser administrados. Metodología: Se realizó una búsqueda de ensayos clínicos que utilizaron algún suplemento dietario en mujeres con CaCu y algún grado de NIC analizando en ellos el modo de utilización del suplemento; el tratamiento convencional; si existe una deficiencia del nutriente ó compuesto a evaluar; las características de la población, del ensayo clínico y del suplemento; así como la dosis y los efectos esperados. Resultados: Veinte fueron en total el número de estudios analizados. Los artículos fueron clasificados según la naturaleza del suplemento: Retinoides, vitamina E, probióticos, indoles, multivitamínico, ácido fólico y selenio. Conclusión: Para el tratamiento de CaCu y NIC resultaron efectivos algunos de los suplementos encontrados en esta revisión, sin embargo su efecto dependerá de diferentes factores propios de la enfermedad. Debido a esto, es necesario el manejo correcto de los suplementos dietéticos para poder ser utilizados eficientemente como tratamiento complementario en esta población."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I307,I307)","v":24504207},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B307:D307)","v":2},2014,"Interventions to address maternal and childhood undernutrition: current evidence.","Bhutta",24504207,"Interventions to address maternal and childhood undernutrition: current evidence.    Abstract:   The global burden of undernutrition remains high with little evidence of change in many countries. We reviewed the evidence of the potential nutritional interventions and estimated their effect on nutrition-related outcomes of women and children. Among the maternal interventions, daily iron supplementation results in a 69% reduction in incidence of anemia, 20% in incidence of low birthweight (LBW) and improves mean birthweight. MMN supplementation during pregnancy has been shown to significantly decrease the number of LBW infants by 14% and small for gestational age (SGA) by 13%. Balanced protein-energy supplementation reduces the incidence of SGA by 32% and risk of stillbirths by 38%. Antimalarials when given to pregnant women increase the mean birthweight significantly and were associated with a 43% reduction in LBW and severe antenatal anemia by 38%. Among the neonatal and child interventions, educational/counseling interventions increased exclusive breastfeeding by 43% at 4-6 weeks and 137% at 6 months. Vitamin A supplementation (VAS) reduces all-cause mortality by 24% and results in a 14% reduction in the risk of infant mortality at 6 months. Intermittent iron supplementation in children reduces the risk of anemia by 49% and iron deficiency by 76%, and significantly improves hemoglobin and ferritin concentration. Preventive zinc supplementation in populations at risk of zinc deficiency decreases morbidity from childhood diarrhea and acute lower respiratory infections, and increases linear growth and weight gain among infants and young children. Among the supportive interventions, hand washing with soap significantly reduces diarrhea morbidity by 48%, though it depends on access to water. The effect of water treatment on diarrhea morbidity also appears similarly large with a 17% reduction. Recent research has established linkages of preconception interventions with improved maternal, perinatal and neonatal health outcomes, and it has been suggested that several proven interventions recommended during pregnancy may be even more effective if implemented before conception. These proven interventions, if scaled up have the potential to reduce the global burden of undernutrition substantially."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I308,I308)","v":25924463},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B308:D308)","v":2},2013,"[Reference values of vitamin A for the Venezuelan population].","García-Casal",25924463,"[Reference values of vitamin A for the Venezuelan population].    Abstract:   Vitamin A deficiency is one of the most prevalent nutritional deficiencies worldwide, mainly affecting children and women. The cause of vitamin A deficiency is insufficient intake, especially in presence of infection and the consequences of the deficiency are xerophthalmia, night blindness, anemia, increased susceptibility to infections and the still controversial increase in infant mortality. National evidence at this point is insufficient to establish the recommendation, and as in the 2000 review of the Venezuelan RDAs, the actual recommendations are based on the reported for the United States population. The Recommended Dietary Allowances (RDA) for Venezuela are 400-500 RE/day for infants, 300-400 RE/day for children 600 RE/day for adolescents, 900 RE/day for men and 700 RE/day for women, increasing to 750 RE/day for pregnancy and to 1200-1300 RE/day during lactation, depending on the age. The estimated average requirement (EAR) is between 210 and 275 RE/day for children, 445 RE/day for male adolescents, 420 RE/day for female adolescents, 630 RE/day for men and 485 RE/day for women, increasing to 530-550 and 885-900 RE/ day during pregnancy and lactation, respectively. The tolerable upper intake levels (UL) for vitamin A are 600 RE/day for children, 1700 a 2800 RE/day for adolescents and 3000 RE/day for adults, males and females."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I309,I309)","v":23973941},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B309:D309)","v":2},2013,"Retinoid signaling in control of progenitor cell differentiation during mouse development.","Duester",23973941,"Retinoid signaling in control of progenitor cell differentiation during mouse development.    Abstract:   The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I310,I310)","v":23657872},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B310:D310)","v":2},2013,"Treatment of acne vulgaris during pregnancy and lactation.","Kong",23657872,"Treatment of acne vulgaris during pregnancy and lactation.    Abstract:   Acne vulgaris is a common problem encountered by pregnant and lactating women. Unfortunately, in clinical practice, treatment is often not optimized as a result of the lack of safety data and unified recommendations on the use of the various anti-acne therapies. In this narrative review, current data on their safety is summarized. We recommend the use of topical medications as first-line treatment for acne vulgaris in pregnant and lactating women. These include antibiotics (erythromycin, clindamycin, metronidazole and dapsone), benzoyl peroxide, azelaic acid and salicylic acid. Oral agents and/or light-based therapy may be considered as second-line treatment. The former consists of oral macrolides (erythromycin and azithromycin), cephalexin or zinc compounds. Blue-violet or red light phototherapy may be used as monotherapy or in addition to topical and/or oral therapies. Hormonal therapy, antibiotics consisting of tetracyclines, co-trimoxazole and fluoroquinolones, and both oral and topical retinoids should be avoided."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I311,I311)","v":23656452},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B311:D311)","v":2},2013,"Epidemiology of major congenital malformations with specific focus on teratogens.","Chaabane",23656452,"Epidemiology of major congenital malformations with specific focus on teratogens.    Abstract:    BACKGROUND : Major congenital malformations (MCMs) are a significant cause of infant morbidity and mortality and constitute an important societal and economic burden.  METHODS : We conducted a literature review to synthesize current evidence on MCMs. Specific objectives were to: 1) summarize internationally reported prevalence of MCMs based on registries and surveillance systems; 2) describe the epidemiology of different MCM types including critical periods and causative factors; 3) to identify the role played by principal known teratogens on the increase in the risk of MCMs; and 4) determine challenges associated with the epidemiologic assessment of potential risk factors for MCMs as well as potential preventive measures.  RESULTS : It is estimated that 7.9 million infants worldwide are born every year with a MCM, yet there is considerable variation in reported rates across countries. This may be attributable to varying definitions arising from heterogeneity among different classes with respect to critical periods for embryogenesis and organogenesis. There is also substantial etiologic heterogeneity among MCMs classes that potentially contribute to challenges in epidemiologic studies. Modifiable factors such as pharmacologic exposures have received considerable attention and a number of drugs have been shown to be teratogenic including folic acid antagonists, angiotensin converting enzyme inhibitors, antidepressants, anticonvulsants, coumarin derivatives and retinoids including isotretinoin.  CONCLUSION : The majority of MCMs are due to unexplained causes. Other contributing factors include genetics, environmental factors, multifactorial inheritance, maternal-related conditions, and maternal drug or chemical exposure. However, there remains a need to better understand the epidemiology of MCMs when studying drug effect during gestation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I312,I312)","v":23296582},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B312:D312)","v":2},2013,"Pregnancy and isotretinoin therapy.","Choi",23296582,"Pregnancy and isotretinoin therapy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I313,I313)","v":23085014},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B313:D313)","v":2},2013,"Vitamin D: health panacea or false prophet?","Glade",23085014,"Vitamin D: health panacea or false prophet?    Abstract:   Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkins lymphoma, non-Hodgkins lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohns disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimers disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individuals vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individuals serum 25-OHD(3) concentration may appear to be quot;lowquot; for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I314,I314)","v":22254103},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B314:D314)","v":2},2011,"Vitamin A in reproduction and development.","Clagett-Dame",22254103,"Vitamin A in reproduction and development.    Abstract:   The requirement for vitamin A in reproduction was first recognized in the early 1900s, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of carotene or supported on limiting quantities of RA early in organogenesis, embryos form but show a collection of defects called the vitamin A deficiency syndrome or late vitamin A deficiency. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signaling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally. Both nutritional and genetic approaches are being used to elucidate the vitamin A-dependent pathways upon which these processes depend."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I315,I315)","v":22075477},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B315:D315)","v":2},2012,"Initiating meiosis: the case for retinoic acid.","Griswold",22075477,"Initiating meiosis: the case for retinoic acid.    Abstract:   The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I316,I316)","v":20927743},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B316:D316)","v":2},2010,"Vitamin A supplementation for postpartum women.","Oliveira-Menegozzo",20927743,"Vitamin A supplementation for postpartum women.    Abstract:    BACKGROUND : In vitamin A deficient populations, the amount of vitamin A may be insufficient for maintenance of maternal health and levels in breast milk may be insufficient for breastfeeding infants needs.  OBJECTIVES : To assess the effects of postpartum maternal vitamin A supplementation on maternal and infant health.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (31 July 2010), LILACS (1982 to July 2010), Web of Science (1945 to July 2010) and Biological Abstracts (1998 to July 2010).  SELECTION CRITERIA : Randomised controlled trials evaluating the effects of postpartum maternal vitamin A supplementation.  DATA COLLECTION AND ANALYSIS : Two review authors assessed the studies independently.  MAIN RESULTS : We included 12 trials at moderate risk of bias, enrolling 25,465 mother-baby pairs and comparing several postpartum doses (200,000-400,000 IU) of vitamin A or 7.8 mg daily beta-carotene, with placebo, iron or no supplement; or higher (400,000 IU) versus lower dose (200,000 IU). The majority of infants in all studies were at least partially breastfed for six months.Maternal: we observed no impact of vitamin A on maternal mortality (two trials of 9,126 women), morbidity (one trial of 50 women) or adverse effects (subset of 786 women in one trial). Vitamin A enhanced serum and breast milk retinol at three months in five trials, but these improvements were generally not sustained.Infant: we observed no significant differences for infant mortality RR 1.14 95% CI 0.84 to 1.57 (five trials (6,170 infants) or morbidity (three trials) except for fewer episodes of fever with vitamin A in one small trial. No significant differences in infant vitamin A status were seen with maternal vitamin A supplementation (five trials).No beneficial effects for maternal or infant health were associated with higher compared to lower doses of vitamin A in two trials.  AUTHORS CONCLUSIONS : The lack of effect on maternal and infant mortality and morbidity, with exception of some improved infant morbidity in one small study, and the improvement in maternal vitamin A status, suggest that maternal postpartum vitamin A supplementation offers limited benefits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I317,I317)","v":20927663},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B317:D317)","v":2},2012,"Mechanisms of ethanol-induced death of cerebellar granule cells.","Luo",20927663,"Mechanisms of ethanol-induced death of cerebellar granule cells.    Abstract:   Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that are most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of N-methyl-D-aspartate receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I318,I318)","v":20633616},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B318:D318)","v":2},2010,"Are azole fungicides a teratogenic risk for human conceptus?","Giavini",20633616,"Are azole fungicides a teratogenic risk for human conceptus?    Abstract:   Azole fungicides are widely used in agriculture and in human mycosis. Their antifungal activity is based on their ability to inhibit CYP51, a key enzyme in the formation of fungal wall. Several azole fungicides tested in laboratory animals have been found to possess a common teratogenic potential to induce facial, axial skeleton, and limb defects. The mechanism of the teratogenic effect has been hypothesized to be related to the capability of these substances to alter embryonic retinoic acid catabolism. Although a number of human epidemiological studies were unable to demonstrate a definite relationship between azole exposure during pregnancy and birth defects, some case reports indicate a possible teratogenic effect of high doses of azoles in humans. Because of their common mechanism of action, azole fungicides should be regarded with caution for use in pregnant women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I319,I319)","v":20482689},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B319:D319)","v":2},2010,"[Antibiotics, azelaic acid and benzoyl peroxide in topical acne therapy].","Fluhr",20482689,"[Antibiotics, azelaic acid and benzoyl peroxide in topical acne therapy].    Abstract:   Benzoyl peroxide was introduced as a basic treatment already in acne therapy 1934. The mechanism of action is the reduction of anaerobe bacteria by strong oxidation processes. No resistancies have been ever reported. BPO is available in 2.5, 5 and 10 % formulations. Its efficacy is slightly related to the strength of concentrations, but the side effect profile with burning, erythema and desquamation is increasing with concentrations. BPO 5% mostly is efficient enough to control acne of grades I to II according to the Kligman amp; Plewig classification. BPO my bleach clothes and hair. It is the most costeffective topical drug in acne of grades I-II. Inflammatory acne of the papular-pustular type I-II can also be treated by topical antibiotics such as erythromycin, clindamycin, and, less frequent and today not anymore recommended tetracyclines. Mechanism of action is not alone an antibacterial but anti inflammatory effect. The efficacy and penetration of the topical antibiotics between the groups are similar. Randomized studies have shown that concentrations of 2-4% are equivalent to oral tetracycline and minocycline in mild to moderate acne. Combinatory formulations with BPO and with retinoids enhance the efficacy significantly. Topical antibiotics plus BPO show less bacterial resistancies as topical antibiotics alone. Antibiotics should therefore not be used as monotherapy. Moreover gram negative folliculitis may develop. Azelaic acid is acting as an antimicrobial and can also reduce comedones. It can also be used in pregnancy and during the lactation period."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I320,I320)","v":20419766},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B320:D320)","v":2},2010,"Epidemiologic and genetic aspects of spina bifida and other neural tube defects.","Au",20419766,"Epidemiologic and genetic aspects of spina bifida and other neural tube defects.    Abstract:   The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories: anencephaly and spina bifida (SB). Epidemiological studies have provided valuable insight for (a) researchers to identify nongenetic and genetic factors contributing to etiology, (b) public health officials to design and implement policies to prevent NTD pregnancies, and (c) individuals to take precautions to reduce the chance of having an NTD-affected pregnancy. Despite extensive research, our knowledge of the genetic etiology of human NTDs is limited. Although more than 200 small animal models with NTDs exist, most of these models do not replicate the human disease phenotype. Over a hundred candidate genes have been examined for risk association to human SB. The candidate genes studied include those important in folic acid metabolism, glucose metabolism, retinoid metabolism, and apoptosis. Many genes that regulate transcription in early embryogenesis and maintain planar cell polarity have also been tested as candidates. Additionally, genes identified through mouse models of NTDs have been explored as candidates. We do not know how many genes in the human genome may confer risk for NTDs in human. Less than 20% of the studied candidate genes have been determined to confer even a minor effect on risk association. Many studies have provided conflicting conclusions due to limitations in study design that potentially affect the power of statistical analysis. Future directions such as genomewide association studies (GWAS) and whole exome or even whole genome sequencing are discussed as possible avenues to identify genes that affect risk for human NTDs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I321,I321)","v":20204266},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B321:D321)","v":2},2010,"[Maternal and neonatal complications in a pregnant woman with biliopancreatic diversion].","Ocón Bretón",20204266,"[Maternal and neonatal complications in a pregnant woman with biliopancreatic diversion].    Abstract:   Biliopancreatic diversion (BPD) is a bariatric technique which can lead to the development of nutritional complications such as protein-calorie malnutrition and deficiencies in fat-soluble vitamins. Many women in childbearing age undergone DBP, pregnancy frequently occurs afterwards. Vitamin A is essential for the differentiation and growth of cell during embryonic development. Although BPD has shown beneficial effects in some obstetric and reproductive complications as infertility and macrosomia, several reports suggest a link between maternal malnutrition and fetal or neonatal complications. We present the case of a pregnant woman with a severe malnutrition associated with vitamin A deficiency as a result of a BPD. The patient delivered a premature infant, with low birth weight and significant eye and kidney malformations. We review and discuss the probable relationship between adverse neonatal outcome, malnutrition and vitamin A deficiency during pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I322,I322)","v":20082945},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B322:D322)","v":2},2010,"Hormonal therapy for acne: why not as first line therapy? facts and controversies.","Katsambas",20082945,"Hormonal therapy for acne: why not as first line therapy? facts and controversies.    Abstract:   Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I323,I323)","v":19547803},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B323:D323)","v":2},2009,"Vitamin A supplementation during puerperium: systematic review.","Caminha",19547803,"Vitamin A supplementation during puerperium: systematic review.    Abstract:   A systematic review on studies evaluating the effect of applying megadoses of vitamin A on the retinol concentrations in maternal milk and blood, as a short-term measure for preventing hypovitaminosis A, was conducted. Based on the strategy of the Brazilian Cochrane Center for randomized trials, 115 published papers were identified in PubMed. From these, through a set of inclusion/exclusion criteria, 14 articles published between 1993 and 2007 were selected. The effects of interventions with three posological regimens (200,000, 300,000 and 400,000 IU) of vitamin A were analyzed. Out of 11 experiments conducted on maternal milk, nine presented elevation of the retinol levels in comparison with the control group; out of nine that evaluated maternal blood, four showed elevation at varying times after applying megadoses of vitamin A. It was concluded that the results from administration of vitamin A at high doses were positive in 82% of the trials on maternal milk, but less notable in relation to maternal blood. No significant differences regarding the posological regimens applied were observed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I324,I324)","v":18793157},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B324:D324)","v":2},2008,"Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance.","Sugden",18793157,"Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance.    Abstract:   In healthy individuals, a hyperbolic relationship exists between whole-body insulin-sensitivity and insulin secretion. Thus, for any difference in insulin-sensitivity, a reciprocal proportionate change occurs in insulin secretion. Such a feedback loop is evident in healthy individuals ingesting diets high in saturated fat and in late pregnancy where, despite lipid-induced insulin resistance, glucose tolerance is maintained through augmented GSIS (glucose-stimulated insulin secretion). NRs (nuclear receptors) are members of a superfamily of ligand-regulated and orphan transcription factors. On activation by a cognate ligand, many ligand-activated NRs recruit the RXR (retinoid X receptor) for heterodimer formation. Such NRs include the PPARs (peroxisome-proliferator-activated receptors), which are involved in lipid sensing and liporegulation. PPARs exert important lipid-lowering effects in vivo, thereby opposing the development of lipid-induced insulin resistance by relieving the inhibition of insulin-stimulated glucose disposal by muscle and lowering the necessity for augmented GSIS to counter lipid-induced insulin resistance. Long-chain fatty acids are proposed as natural PPAR ligands and some specific endogenous pathways of lipid metabolism are believed to generate PPAR agonists. Other NRs, e.g. the LXR (liver X receptor), which senses expansion of the metabolically active pool of cholesterol, and the FXR (farnesoid X receptor; NR1H4), which, like the LXR, is involved in sterol metabolism, also modulate systemic lipid levels and insulin-sensitivity. In this review, we discuss how these NRs impact insulin secretion via effects on the insulin-sensitivity-insulin secretion feedback loop and, in some cases, via direct effects on the islet itself. In addition, we discuss interactions between these nutrient/metabolite-responsive NRs and NRs that are central to the action of metabolically important hormones, including (i) the glucocorticoid receptor, critical for maintaining glucose homoeostasis in stress, inflammation and during fasting, and (ii) the thyroid hormone receptors, vital for maintenance of oxidative functions. We present data indicating that the RXR occupies a key role in directly modulating islet function and that its heterodimerization with at least two of its partners modulates GSIS."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I325,I325)","v":18234138},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B325:D325)","v":2},2008,"Maternal and child nutrition in Sub-Saharan Africa: challenges and interventions.","Lartey",18234138,"Maternal and child nutrition in Sub-Saharan Africa: challenges and interventions.    Abstract:   Women of child-bearing age (especially pregnant and lactating women), infants and young children are in the most nutritionally-vulnerable stages of the life cycle. Maternal malnutrition is a major predisposing factor for morbidity and mortality among African women. The causes include inadequate food intake, poor nutritional quality of diets, frequent infections and short inter-pregnancy intervals. Evidence for maternal malnutrition is provided by the fact that between 5 and 20% of African women have a low BMI as a result of chronic hunger. Across the continent the prevalence of anaemia ranges from 21 to 80%, with similarly high values for both vitamin A and Zn deficiency levels. Another challenge is the high rates of HIV infection, which compromise maternal nutritional status. The consequences of poor maternal nutritional status are reflected in low pregnancy weight gain and high infant and maternal morbidity and mortality. Suboptimal infant feeding practices, poor quality of complementary foods, frequent infections and micronutrient deficiencies have largely contributed to the high mortality among infants and young children in the region. Feeding children whose mothers are infected with HIV continues to remain an issue requiring urgent attention. There are successful interventions to improve the nutrition of mothers, infants and young children, which will be addressed. Interventions to improve the nutrition of infants and young children, particularly in relation to the improvement of micronutrient intakes of young children, will be discussed. The recent release by WHO of new international growth standards for assessing the growth and nutritional status of children provides the tool for early detection of growth faltering and for appropriate intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I326,I326)","v":17600781},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B326:D326)","v":2},2007,"Retinoic acid regulation of the somitogenesis clock.","Duester",17600781,"Retinoic acid regulation of the somitogenesis clock.    Abstract:   Retinoic acid (RA) is a signaling molecule synthesized from vitamin A that controls gene expression at the transcriptional level by functioning as a ligand for nuclear RA receptors. RA plays an essential role during embryonic development in higher animals by regulating key genes involved in pattern formation. RA is required for induction of several Hox genes involved in patterning of the hindbrain and spinal cord as neuroectoderm emerges from the primitive streak. Recent findings indicate that RA is also required to ensure bilaterally symmetrical generation of left and right somites as presomitic mesoderm emerges from the primitive streak. RA may control somitogenesis through its ability to repress posterior ectodermal expression of fibroblast growth factor-8 (Fgf8) for a short period of time during the late primitive streak stage when the somitogenesis clock initiates. During this tight temporal window, RA is required to limit Fgf8 expression to the most posterior ectoderm (epiblast), thus preventing ectopic Fgf8 expression in more anterior ectoderm including the node ectoderm and neuroectoderm. Although Fgf8 is required for the node to impart left-right asymmetry on specific tissues (heart, visceral organs, etc.), excess Fgf8 signaling following a loss of RA may stimulate the node to generate asymmetry also in presomitic mesoderm, leading to left-right asymmetry in the somitogenesis clock. These findings suggest that human vertebral birth defects such as scoliosis, an abnormal left-right bending of the vertebral column, may be caused by a defect in RA signaling during somitogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I327,I327)","v":17519397},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B327:D327)","v":2},2007,"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.","Jenkins",17519397,"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.    Abstract:   Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I328,I328)","v":17419303},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B328:D328)","v":2},2007,"[Polycystic ovary syndrome in 2006].","Vrbíková",17419303,"[Polycystic ovary syndrome in 2006].    Abstract:   Polycystic ovary syndrome was defined as the combination of anovulation and hyperandrogenaemia (NIH 1990). Another definition used the combination of ultrasonographic appearance of polycystic ovaries and/or anovulation and/or hyperandrogenaemia or cutaneous manifestations of hyperandrogenism (Rotterdam). The population defined according to NIH is probably in greater risk of insulin resistance and obesity. Pathogenesis of PCOS is not clear till now. Dysregulation of ovarian steroidogenesis could be one of the causes of the full-blown syndrome. Up-regulation of steroidogenic enzymes, probably due to the exaggerated expression of transcription factors such as GATA-6 or retinoids could be involved. Insulin sensitisators are now widely used in the therapy. They could beneficially modify not only insulin resistance and dyslipidaemia, but also ovarian and adrenal steroidogenesis. Metformin and glitazones improve anovulation however the studies conducted till now were not representative concerning the point of successful pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I329,I329)","v":17368322},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B329:D329)","v":2},2007,"Effects of vitamins, including vitamin A, on HIV/AIDS patients.","Mehta",17368322,"Effects of vitamins, including vitamin A, on HIV/AIDS patients.    Abstract:   An estimated 25 million lives have been lost to acquired immune-deficiency syndrome (AIDS) since the immunodeficiency syndrome was first described in 1981. The progress made in the field of treatment in the form of antiretroviral therapy (ART) for HIV disease/AIDS has prolonged as well as improved the quality of life of HIV-infected individuals. However, access to such treatment remains a major concern in most parts of the world, especially in the developing countries. Hence, there is a constant need to find low-cost interventions to complement the role of ART in prevention of HIV infection and slowing clinical disease progression. Nutritional interventions, particularly vitamin supplementation, have the potential to be a low-cost method for being such an intervention by virtue of their modulation of the immune system. Among all the vitamins, the role of vitamin A has been studied most extensively; most observational studies have found that low vitamin A levels are associated with increased risk of transmission of HIV from mother to child. This finding has not been supported by large randomized trials of vitamin A supplementation; on the contrary, these trials have found that vitamin A supplementation increases the risk of mother-to-child transmission (MTCT). There are a number of potential mechanisms that might explain these contradictory findings. One is the issue of reverse causality in observational studies-for instance, advanced HIV disease may suppress release of vitamin A from the liver. This would lead to low levels of vitamin A in the plasma despite the body having enough vitamin A liver stores. Further, advanced HIV disease is likely to increase the risk of MTCT, and hence it would appear that low serum vitamin A levels are associated with increased MTCT. The HIV genome also has a retinoic acid receptor element-hence, vitamin A may increase HIV replication via interacting with this element, thus increasing risk of MTCT. Finally, vitamin A is known to increase lymphoid cell differentiation, which leads to an increase in CCR5 receptors. These receptors are essential for attachment of HIV to the lymphocytes and therefore, an increase in their number is likely to increase HIV replication. Vitamin A supplementation in HIV-infected children, on the other hand, has been associated with protective effects against mortality and morbidity, similar to that seen in HIV-negative children. The risk for lower respiratory tract infection and severe watery diarrhea has been shown to be lower in HIV-infected children supplemented with vitamin A. All-cause mortality and AIDS-related deaths have also been found to be lower in vitamin A-supplemented HIV-infected children. The benefits of multivitamin supplementation, particularly vitamins B, C, and E, have been more consistent across studies. Multivitamin supplementation in HIV-infected pregnant mothers has been shown to reduce the incidence of adverse pregnancy outcomes such as fetal loss and low birth weight. It also has been shown to decrease rates of MTCT among women who have poor nutritional or immunologic status. Further, multivitamin supplementation reduces the rate of HIV disease progression among patients in early stage of disease, thus delaying the need for ART by prolonging the pre-ART stage. In brief, there is no evidence to recommend vitamin A supplementation of HIV-infected pregnant women; however, periodic vitamin A supplementation of HIV-infected infants and children is beneficial in reducing all-cause mortality and morbidity and is recommended. Similarly, multivitamin supplementation of people infected with HIV, particularly pregnant women, is strongly suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I330,I330)","v":17022912},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B330:D330)","v":2},2006,"Fat-soluble vitamin deficiency in pregnancy: a case report and review of abetalipoproteinemia.","Gaudet",17022912,"Fat-soluble vitamin deficiency in pregnancy: a case report and review of abetalipoproteinemia.    Abstract:    BACKGROUND : Abetalipoproteinemia (ABL) is a metabolic disorder resulting in poor absorption of fat-soluble vitamins.  CASE : Two pregnancies in a woman with ABL are reported, contrasting outcomes with subtherapeutic and normal vitamin levels.  CONCLUSION : Fat-soluble vitamin levels in pregnancy are critical for many aspects of fetal development. This report details a congenital ophthalmologic finding that may be associated with vitamin A deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I331,I331)","v":17016954},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B331:D331)","v":2},2003,"Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania.","Latham",17016954,"Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania.    Abstract:   Traditionally, the main strategies used to control micronutrient deficiencies have been food diversification, consumption of medicinal supplements, and food fortification. In Tanzania, we conducted efficacy trials using a dietary supplement as a fourth approach. These were randomized, double-blind, placebo-controlled efficacy trials conducted separately first in children and later in pregnant women. The dietary supplement was a powder used to prepare an orange-flavored beverage. In the school trial, children consumed 25 g per school day attended. In the pregnancy trial, women consumed the contents of two 25-g sachets per day with meals. This dietary supplement, unlike most medicinal supplements, provided 11 micronutrients, including iron and vitamin A, in physiologic amounts. In both trials we compared changes in subjects consuming either the fortified or the nonfortified supplement. Measures of iron and vitamin A status were similar in the groups at the baseline examination, but significantly different at follow-up, always in favor of the fortified groups. Children receiving the fortified supplement had significantly improved anthropometric measures when compared with controls. At four weeks postpartum, the breast milk of a supplemented group of women had significantly higher mean retinol content than did the milk of mothers consuming the nonfortified supplement. The advantages of using a fortified dietary supplement, compared with other approaches, include its ability to control several micronutrient deficiencies simultaneously; the use of physiologic amounts of nutrients, rather than megadoses that require medical supervision; and the likelihood of better compliance than with the use of pills because subjects liked the beverage used in these trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I332,I332)","v":17016949},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B332:D332)","v":2},2003,"Vitamin A deficiency disorders in children and women.","West",17016949,"Vitamin A deficiency disorders in children and women.    Abstract:   Vitamin A deficiency is an endemic nutrition problem throughout much of the developing world, especially affecting the health and survival of infants, young children, and pregnant and lactating women. These age and life-stage groups represent periods when both nutrition stress is high and diet likely to be chronically deficient in vitamin A. Approximately 127 million preschool-aged children and 7 million pregnant women are vitamin A deficient. Health consequences of vitamin A deficiency include mild to severe systemic effects on innate and acquired mechanisms of host resistance to infection and growth, increased burden of infectious morbidity, mild to severe (blinding) stages of xerophthalmia, and increased risk of mortality. These consequences are defined as vitamin A deficiency disorders (VADD). Globally, 4.4 million preschool children have xerophthalmia and 6 million mothers suffer night blindness during pregnancy. Both conditions are associated with increased risk of morbidity and mortality. While reductions of child mortality of 19-54% following vitamin A treatment have been widely reported, more recent work suggests that dosing newborns with vitamin A may, in some settings, lower infant mortality. Among women, one large trial has so far reported a gt; or = 40% reduction in mortality related to pregnancy with weekly, low-dose vitamin A supplementation. Epidemiologic data on vitamin A deficiency disorders can be useful in planning, designing, and targeting interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I333,I333)","v":16469975},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B333:D333)","v":2},2006,"The acute and chronic toxic effects of vitamin A.","Penniston",16469975,"The acute and chronic toxic effects of vitamin A.    Abstract:   The acute and chronic effects of vitamin A toxicity are well documented in the literature. Emerging evidence suggests that subtoxicity without clinical signs of toxicity may be a growing concern, because intake from preformed sources of vitamin A often exceeds the recommended dietary allowances (RDA) for adults, especially in developed countries. Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA. Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are nonsensitive indicators in this range of liver vitamin A reserves. The metabolism in well-nourished persons of preformed vitamin A, provided by either liver or supplements, has been studied by several research groups. To control vitamin A deficiency, large therapeutic doses are administered in developing countries to women and children, who often are undernourished. Nevertheless, little attention has been given to the short-term kinetics (ie, after absorption but before storage) of a large dose of vitamin A or to the short- and long-term effects of such a dose given to lactating women on serum and breast-milk concentrations of retinol and its metabolites. Moreover, appropriate dosing regimens have not been systematically evaluated to ascertain the quantitative improvement in vitamin A status of the women and children who receive these supplements. The known acute and chronic effects of vitamin A toxicity have been reported previously. However, further research is needed to ascertain the areas of the world in which subclinical toxicity exists and to evaluate its effects on overall health and well-being."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I334,I334)","v":15956766},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B334:D334)","v":2},2005,"Genesis of alcohol-induced craniofacial dysmorphism.","Sulik",15956766,"Genesis of alcohol-induced craniofacial dysmorphism.    Abstract:   The initial diagnosis of fetal alcohol syndrome (FAS) in the United States was made because of the facial features common to the first cohort of patients. This article reviews the development of an FAS mouse model whose craniofacial features are remarkably similar to those of affected humans. The model is based on short-term maternal treatment with a high dosage of ethanol at stages of pregnancy that are equivalent to Weeks 3 and 4 of human gestation. At these early stages of development, alcohols insult to the developing face is concurrent with that to the brain, eyes, and inner ear. That facial and central nervous system defects consistent with FAS can be induced by more quot;realisticquot; alcohol dosages as illustrated with data from an oral alcohol intake mouse model in which maternal blood alcohol levels do not exceed 200 mg/dl. The ethanol-induced pathogenesis involves apoptosis that occurs within 12 hrs of alcohol exposure in selected cell populations of Day 7, 8, and 9 mouse embryos. Experimental evidence from other species also shows that apoptosis underlies ethanol-induced malformations. With knowledge of sensitive and resistant cell populations at specific developmental stages, studies designed to identify the basis for these differing cellular responses and, therefore, to determine the primary mechanisms of ethanols teratogenesis are possible. For example, microarray comparisons of sensitive and resistant embryonic cell populations have been made, as have in situ studies of gene expression patterns in the populations of interest. Studies that illustrate agents that are effective in diminishing or exacerbating ethanols teratogenesis have also been helpful in determining mechanisms. Among these agents are antioxidants, sonic hedgehog protein, retinoids, and the peptides SAL and NAP."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I335,I335)","v":15838445},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B335:D335)","v":2},2005,"Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.","Morrison",15838445,"Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.    Abstract:    INTRODUCTION : Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis.  METHODS : Retrospective review of patient records.  RESULTS : Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic.  DISCUSSION : Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure.  CONCLUSION : RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I336,I336)","v":15799239},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B336:D336)","v":2},2004,"Mammalian target of rapamycin.","Meric-Bernstam",15799239,"Mammalian target of rapamycin.    Abstract:   Targeted molecular therapeutics are tailored toward the genetic abnormalities that cause tumor progression. Modulation of certain signaling pathways that are aberrant in cancer cells has the potential to provide an effective, nontoxic approach to therapy in a broad range of cancers. Agents targeting BCR-ABL (imatinib mesylate [formerly known as STI-571], Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ), retinoid receptor fusion proteins (all-trans retinoic acid), ErbB-2 or HER2/neu (trastuzumab, Herceptin; Genentech, Inc, South San Francisco, CA), epidermal growth factor receptor (IMC-C225 and ZD1839), and the phosphatidylinositol 3-kinase pathway (CCI-779) have all induced remarkable, nontoxic responses in a subset of patients with cancer and abnormalities in the corresponding signal transduction cascades. To achieve successful individualized therapy, the specific components within the aberrant signaling pathways that are driving the pathophysiology of the tumors must be identified in each patient. Molecular diagnostics can identify patients in whom the target is aberrant; linking molecular diagnostics with effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for patients with cancer. In addition, intermediary markers and/or molecular imaging techniques must be used to identify the biologically relevant dose that is sufficient to inhibit the target of interest. This review focuses on the P13K pathway, and novel molecules targeting this pathway, to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast and ovarian cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I337,I337)","v":15750294},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B337:D337)","v":2},2005,"The roles of vitamin A for cytoplasmic maturation of bovine oocytes.","Ikeda",15750294,"The roles of vitamin A for cytoplasmic maturation of bovine oocytes.    Abstract:   Vitamin A is one of the micronutrients which have been implicated in cattle reproduction. In cattle, ingested vitamin A, mainly as beta-carotene (BC) from forages and retinol ester from formula feed, is metabolized and transported to the oocytes and cumulus-granulosa cells in ovarian follicles through binding to various interacting molecules. The active form of vitamin A, retinoic acid (RA), functions as a regulator of gene expression in these targets. Early research showed the positive effects of vitamin A supplementation on bovine fertility in artificial insemination, and several studies on effects of vitamin A metabolites used in other artificial reproductive techniques (ART), including superovulation, ovum pick up, and in vitro maturation culture have provided evidence for the specific roles of vitamin A in oocyte cytoplasmic maturation (acquisition of developmental competence of oocytes during their meiotic maturation period for the embryonic development after fertilization). BC may enhance cytoplasmic maturation by its antioxidant properties which cannot be replaced by RA. Furthermore, RA may promote cytoplasmic maturation of bovine oocytes via its modulatory effects on the gene expression of gonadotrophin receptors, midkine, cyclooxygenase-2, and nitric oxide synthase in cumulus-granulosa cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I338,I338)","v":15236946},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B338:D338)","v":2},2004,"Gene-nutrient interactions: importance of folates and retinoids during early embryogenesis.","Finnell",15236946,"Gene-nutrient interactions: importance of folates and retinoids during early embryogenesis.    Abstract:   The role that nutritional factors play in mammalian development has received renewed attention over the past two decades, as the scientific literature exploded with reports of retinoid compounds disrupting craniofacial development, and with other reports that folic acid supplementation in the periconceptional period can protect embryos from highly significant malformations. As was often the case, the situation became far more complicated, as the interaction between nutritional factors with selected genes was recognized. In this review, we attempt to summarize a complex clinical and experimental literature of nutritional factors, their biological transport mechanisms, and the impact that they have during early embryogenesis. Although not exhaustive, our goal was to provide an overview of important gene-nutrient interactions and a framework for their investigation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I339,I339)","v":15169985},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B339:D339)","v":2},2004,"Advances in chemoprevention of head and neck cancer.","Rhee",15169985,"Advances in chemoprevention of head and neck cancer.    Abstract:   Head and neck squamous cell carcinoma is a devastating disease with a poor outcome in advanced stages, accounting for approximately 3% of all malignancies, with an estimated 37200 new cases and 11000 deaths annually in the U.S. Second primary tumors are estimated to occur at an annual rate of 3%-10% and are significant threats to long-term survivors. Chemoprevention is an appealing strategy, and its success has been demonstrated in breast cancer and familial adenomatous polyposis. High-dose retinoids have been shown to be active against oral premalignant lesions and in prevention of second primary tumors in the head and neck. New targets include the epidermal growth factor receptor, cyclooxygenase-2, and other molecular targets. Challenges in future head and neck cancer chemoprevention investigations include achieving long-lasting efficacy with retinoids and/or new agents, and determining the optimal dose and duration of therapy while maintaining acceptable toxicities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I340,I340)","v":14711761},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B340:D340)","v":2},2003,"Anaemia and micronutrient deficiencies.","van den Broek",14711761,"Anaemia and micronutrient deficiencies.    Abstract:   Anaemia in pregnancy is a common and worldwide problem that deserves more attention. For many developing countries, prevalence rates of up to 75% are reported. Anaemia is frequently severe in these situations and can be expected to contribute significantly to maternal mortality and morbidity. After a discussion of definitions, screening for anaemia and prevalence, the relationship between anaemia and maternal mortality and morbidity will be reviewed. Micronutrient deficiency and especially iron deficiency is believed to be the main underlying cause for anaemia. More recently the role of vitamin A deficiency as a contributing factor to anaemia has also been examined. The difficulties of assessment of micronutrient sufficiency or deficiency in pregnancy are described, as is the interaction between infection and micronutrient deficiency states."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I341,I341)","v":14613030},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B341:D341)","v":2},2003,"Linking molecular diagnostics to molecular therapeutics: targeting the PI3K pathway in breast cancer.","Mills",14613030,"Linking molecular diagnostics to molecular therapeutics: targeting the PI3K pathway in breast cancer.    Abstract:   Modulation of the signaling pathways that are aberrant in cancer cells has the potential to provide an effective nontoxic approach to patient management in a broad range of cancers. This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Support for the concept of targeting products of fusion genes found in specific cancers was first provided by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia where the RARalpha all-trans retinoic acid target is the target of multiple different chromosomal rearrangements. In breast cancer, trastuzumab, which alters the function of the HER2 proto-oncogene overexpressed in a portion of breast cancers, provides an additional example of targeting specific molecular aberrations present in cancer cells. Although the target for these signal transduction modulators is functional in normal cells, acceptable therapeutic indices sufficient to prevent tumor growth without unacceptable toxicities have been observed. Whether STI-571 and other signal transduction modulators also target the stroma, and specifically the neovasculature, in addition to the tumor remains an open question. The presence of the target in the cancer cells or in the surrounding stroma appears to be required but not sufficient for the action of molecular therapeutics. Thus, linking molecular diagnostics to identify patients where the target is amplified or activated and driving the pathophysiology of the patients tumor to effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for breast cancer patients. This review will focus on the phosphatidylinositol 3-kinase pathway and novel molecules targeting this pathway to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I342,I342)","v":14594936},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B342:D342)","v":2},2003,"Chemoprevention of cancer--focusing on clinical trials.","Kakizoe",14594936,"Chemoprevention of cancer--focusing on clinical trials.    Abstract:   Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I343,I343)","v":14587863},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B343:D343)","v":2},2003,"Novel agents for the prevention of breast cancer: targeting transcription factors and signal transduction pathways.","Shen",14587863,"Novel agents for the prevention of breast cancer: targeting transcription factors and signal transduction pathways.    Abstract:   Transformation of breast cells occurs through loss or mutation of tumor suppressor genes, or activation or amplification of oncogenes, leading to deregulation of signal transduction pathways, abnormal amplification of growth signals, and aberrant expression of genes that ultimately transform the cells into invasive cancer. The goal of cancer preventive therapy, or quot;chemoprevention,quot; is to eliminate premalignant cells or to block the progression of normal cells into cancer. Multiple alterations in signal pathways and transcription factors are observed in mammary gland tumorigenesis. In particular, estrogen receptor (ER) deregulation plays a critical role in breast cancer development and progress, and targeting ER with selective ER modulators (SERMs) has achieved significant reduction of breast cancer incidence in women at high risk for breast cancer. However, not all breast cancer is prevented by SERMs, because 30-40% of the tumors are ER-negative. Other receptors for retinoids, vitamin D analogs and peroxisome proliferator-activiator, along with transcription factors such as AP-1, NF-kappaB, and STATs (signal transducers and activators of transcription) affect breast tumorigenesis. This is also true for the signal transduction pathways, for example cyclooxygenase 2 (Cox-2), HER2/neu, mitogen-activated protein kinase (MAPK), and PI3K/Akt. Therefore, proteins in pathways that are altered during the process of mammary tumorigenesis may be promising targets of future chemopreventive drugs. Many newly-developed synthetic or natural compounds/agents are now under testing in preclinical studies and clinical trials. Receptor selective retinoids, receptor tyrosine kinase inhibitors (TKIs), SERMs, Cox-2 inhibitors, and others are some of the promising novel agents for the prevention of breast cancer. The chemopreventive activity of these agents and other novel signal transduction inhibitors are discussed in this chapter."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I344,I344)","v":12854100},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B344:D344)","v":2},2003,"The prevention of breast cancer.","Prichard",12854100,"The prevention of breast cancer.    Abstract:    BACKGROUND : Despite advances in the early detection and treatment of breast carcinoma, the mortality and morbidity rates associated with this disease remain high. Primary prevention, therefore, offers the best chance of making a major impact on outcome.  METHODS : The aim was to review the rationale, current stage of development and adverse effects of the strategies involved in the primary prevention of breast carcinoma. A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2002 without language restrictions.  RESULTS AND CONCLUSION : Currently, the only agent to have general approval for chemoprevention of breast carcinoma is tamoxifen. Women who derive the greatest benefit in terms of risk reduction from tamoxifen are premenopausal with a 5-year Gail risk factor of more than 1.66 per cent, postmenopausal with a 5-year Gail risk factor of more than 3 per cent, and postmenopausal without a uterus. In these specific subgroups, tamoxifen should be considered for the chemoprevention of breast carcinoma. Raloxifene, retinoids, aromatase inhibitors and cyclo-oxygenase 2 inhibitors require further clinical investigation before adoption in this context. Surgical intervention should largely be limited to those women who have a BRCA1 or BRCA2 mutation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I345,I345)","v":12848275},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B345:D345)","v":2},2003,"The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants.","Crawford",12848275,"The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants.    Abstract:   The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to gt; 200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very-low-birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long-term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very-low-birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postnatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I346,I346)","v":12771347},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B346:D346)","v":2},2003,"Micronutrients and reproductive health issues: an international perspective.","Christian",12771347,"Micronutrients and reproductive health issues: an international perspective.    Abstract:   Micronutrients may have a role in enhancing reproductive health of women living in the developing world. Two illustrative micronutrients, zinc and vitamin A, have received some attention in this regard. Numerous animal experiments and observational studies suggest the potential role of zinc deficiency in labor and delivery-related complications such as premature rupture of membrane, placental abruption, preterm labor and inefficient uterine contraction. These associations have not been confirmed in supplementation studies. Zinc does not appear to be a limiting factor in intrauterine growth in the developing world, contrary to some evidence of its suggested benefit among women residing in industrialized countries. One study in Nepal found that maternal vitamin A or beta-carotene supplementation reduces pregnancy-related mortality but not infant mortality. These findings are corroborated by observations of the significantly higher risk of mortality among night-blind women compared to non-night-blind women long after the termination of pregnancy and the resolution of night blindness. Maternal multiple micronutrient supplementation needs more careful evaluation before its use in large-scale programs. Two recent trials indicated that a prenatal multiple micronutrient supplement provides no added advantage over iron and folate in reducing outcomes such as low birth weight and probably no survival benefit. Data are also suggestive that adding zinc may negate the beneficial effect of iron and folic acid on birth weight. Research is needed to further our understanding of nutrient-nutrient interactions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I347,I347)","v":12730478},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B347:D347)","v":2},2003,"Potential cost-effectiveness of nutrition interventions to prevent adverse pregnancy outcomes in the developing world.","Rouse",12730478,"Potential cost-effectiveness of nutrition interventions to prevent adverse pregnancy outcomes in the developing world.    Abstract:   The potential cost-effectiveness of antenatal nutrition interventions to improve pregnancy outcomes in the developing world has not undergone formal evaluation. Furthermore, the effectiveness of antenatal care in improving maternal or fetal and neonatal health has been questioned. However, reasonably compelling evidence from randomized trials shows that nutrition interventions can prevent both infant (iodine supplementation) and maternal (vitamin A and beta-carotene supplementation) deaths, and informal analysis suggests that the cost-effectiveness of nutrition interventions would be comparable and, in some cases, markedly superior to several standard antenatal interventions. Future efforts to establish the cost-effectiveness of nutrition interventions in developing countries will depend on conducting large, pragmatic clinical trials that use region- and resource-appropriate interventions with mortality or valid, incontrovertibly severe morbidity endpoints. If such trials establish effectiveness, credible cost-effectiveness analyses can then be performed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I348,I348)","v":12728784},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B348:D348)","v":2},2003,"[Breakthrough in breast cancer chemoprevention].","Kahán",12728784,"[Breakthrough in breast cancer chemoprevention].    Abstract:   Breast cancer is the most frequent female malignant disease in developed countries. Various approaches are being developed for breast cancer prevention. Medical prevention called chemoprevention is reviewed. Prior to any intervention estimation of breast cancer risk is mandatory. For practical reasons distinction of two risk groups is useful. In the high risk group inherited gene mutation showing high penetrance may be suspected, while in the medium risk group hormonal factors play an important role. The antiestrogen tamoxifen has been extensively investigated in breast cancer and also tested for the prevention of breast cancer. The results of four randomized tamoxifen prevention studies have been published. In the largest, American trial the number of invasive or quot;in situquot; breast cancers was halved by tamoxifen. Particularly estrogen receptor positive and relatively good prognosis breast cancers were reduced. Similar results were obtained in the quot;International Breast Intervention Studyquot;. Tamoxifen has been registered for breast cancer prevention for high risk individuals in the United States. The Italian and English (quot;Royal Marsden Hospitalquot;) studies did not prove significant preventative effect for tamoxifen that may be explained by the characteristics of the study protocols and study populations. Increased rates of endometrial cancer, thromboembolic events and cataract were observed under tamoxifen treatment, especially over the age of 50. Prevention has an increased importance in gene mutation carriers. Besides prophylactic mastectomy and close surveillance tamoxifen and bilateral oophorectomy or the use of gonadotropin releasing-hormone analogs seem efficient in this group. Various new chemoprevention strategies are under testing. Raloxifene and the aromatase inhibitors show advantage in menopausal women, the retinoid fenretinide and the gonadotropin releasing-hormone analogs seem promising for premenopausal individuals. The use of these agents are investigated in clinical trials. It is likely that not one single method will be applied for breast cancer prevention in the future. Preferably individual prevention strategies based on individual risk assessment will be developed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I349,I349)","v":12682772},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B349:D349)","v":2},2003,"Evolving strategies for prostate cancer chemoprevention trials.","Lieberman",12682772,"Evolving strategies for prostate cancer chemoprevention trials.    Abstract:   Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I350,I350)","v":12528989},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B350:D350)","v":2},2003,"Cancer chemoprevention drug targets.","Krishnan",12528989,"Cancer chemoprevention drug targets.    Abstract:   Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Chemoprevention can either prevent DNA damage that initiates the neoplastic transformation process or reverses the progression of pre-invasive lesions. Epidemiological observations, experimental evidence from animal carcinogenesis models, knock-out models, cancer cell lines and clinical trials have shown the efficacy of this approach. Recent advances in our understanding of carcinogenesis have led to the synthesis of new drugs that target specific receptors. Non-steroidal anti-inflammatory drugs target the prostaglandin pathway. The identification of the role of cyclooxygenase-2 in epithelial carcinogenesis led to the synthesis of selective cyclooxygenase-2 inhibitors (Celecoxib). Celecoxib was subsequently approved for the prevention of colon polyps in familial adenomatous polyposis after the completion of a randomized clinical trial. The large chemoprevention clinical trial with the selective estrogen receptor modulator, tamoxifen, showed the benefit of tamoxifen in the prevention of breast cancer in high-risk women. Retinoids and rexinoids target the retinoid receptors and have a role in chemoprevention of aerodigestive, hepatic and cervical neoplasia. Selenium, an inhibitor of the glutathione peroxidase system, is being tested in the chemoprevention of prostate cancer and lung cancer. The different isoforms of vitamin E (tocopherols) may be chemopreventive. Recent evidence indicates that gamma-tocopherol may be a more powerful chemopreventive than the alpha-tocopherol. The review details the rationale, experimental and clinical evidence and the drug targets of the chemopreventive agents that are currently in various phases of clinical development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I351,I351)","v":12514311},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B351:D351)","v":2},2003,"Retinoids and alcohol-related carcinogenesis.","Wang",12514311,"Retinoids and alcohol-related carcinogenesis.    Abstract:   Chronic and excessive alcohol intake is associated with an increased incidence of a variety of cancers (e.g., liver, oral cavity, esophagus, colorectal and breast). Long-term alcohol intake results in impaired nutritional status of retinoic acid (RA), the most active derivative of vitamin A, which may provide a promoting environment for tumor formation. Recent studies demonstrate that chronic alcohol-induced hepatocellular proliferation, which may convert hepatocytes from a state of resistance to a carcinogen to a state of high susceptibility, is due to alcohol-impaired RA metabolism and signaling and crosstalk with the Jun N-terminal kinases-dependent signaling pathway. Further, the restoration of hepatic RA homeostasis by treatment with either RA supplementation or inhibitors of RA catabolism can suppress alcohol-induced hepatocyte hyperproliferation and restore alcohol-deregulated apoptosis, thereby reducing the risk of alcohol-promoted hepatocellular carcinogenesis. These studies indicate the importance of RA actions in the prevention and/or treatment of alcohol-related carcinogenic process in the liver and other organs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I352,I352)","v":12505260},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B352:D352)","v":2},2002,"Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.","Kurian",12505260,"Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.    Abstract:   A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3) 10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel for breast cancer. Replicate bone marrow aspirate karyotypes contained a translocation between the long arms of chromosomes 15 and 17, but not at breakpoints typical for APL. Fluorescence in situ hybridization paints and RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17 were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the patient received induction chemotherapy and a several month trial of all-trans retinoic acid (ATRA), there was no clinical improvement or hematological remission. We suspect that this patient developed postchemotherapy secondary APL with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I353,I353)","v":12476050},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B353:D353)","v":2},2002,"Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells.","Hohn",12476050,"Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells.    Abstract:   The establishment of pregnancy in the human decisively depends on the competence of the early trophoblast to interact during implantation with (1). the uterine epithelium and subsequently (2). with the endometrial stroma and blood vessels. In the interaction with uterine epithelium cell-to-cell adhesion appears to be a critical element, involving initially (and astonishingly) apical cell poles of both epithelia. The subsequent invasion of the stroma includes both adhesive interactions with and degradation of extracellular matrix. How these different processes are regulated in detail remains largely unknown. While the invasiveness of the trophoblast is known to be regulated in local and temporal terms it has remained unclear so far whether trophoblast adhesiveness to cells and/or matrix is subject to a coupled regulation or whether both properties involve different, maybe sequentially effective, control mechanisms. It is also not known how the regulation of these activities is related to the differentiation pathways leading to the formation of noninvasive villous trophoblast serving endocrine as well as nutritive functions. This communication reviews experiments using normal cytotrophoblast cells isolated from first trimester or term placentae as well as malignant trophoblast (choriocarcinoma) cells treated with a panel of compounds known to modulate cell differentiation [retinoic acid, methotrexate, dibutyryl-cAMP, phorbol-(12-myristoyl-13-acetyl)-diester]. Parameters indicative of trophoblast differentiation [in particular chorionic gonadotrophin (hCG) secretion] as well as adhesion to uterine epithelial cells and invasion into extracellular matrix in vitro were monitored. While expression of differentiation parameters was increased by all drug treatments, adhesion to uterine epithelial cells in vitro was reduced. Modulation of invasiveness, however, followed a different pattern: while it was reduced in normal trophoblast cells it was even increased in choriocarcinoma cells with various substances. The response of cells with respect to production of extracellular matrix proteins or matrix-degrading proteinases showed a complex pattern that again lacked a stringent correlation with hCG production and adhesion, and in addition also with invasive behavior. These results suggest that adhesiveness of trophoblast to uterine epithelial cells and invasiveness into the uterine stroma (extracellular matrix) are subject to different control mechanisms. They support the view that trophoblast-endometrium interactions involve a cascade of various adhesion and migration processes whose cellular and molecular basis is complex but accessible to experimental investigation using a variety of available in vitro systems."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I354,I354)","v":12456342},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B354:D354)","v":2},2003,"Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression.","Osteen",12456342,"Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression.    Abstract:   The endometrium is a unique adult tissue which, in the absence of pregnancy or disease, undergoes cyclic breakdown and regrowth approximately 400 times during a womans reproductive life. The chances of reproductive success during each cycle depends on appropriate, cell-specific responses to steroids, including expression of matrix metalloproteinases (MMPs). Normal endometrial MMP regulation in response to either estrogen or progesterone requires additional, cell-specific interactions mediated by various growth factors and cytokines. During endometrial maturation, progesterone, retinoic acid and TGF-beta act cooperatively, providing a remarkable biological balance to regulate expression of MMPs in the highly steroid-sensitive endometrium. Exploring the regulatory actions of locally produced growth factors and cytokines on members of the MMP family and their inhibitors will allow a better understanding of the unique physiology of the human endometrium under the influence of progesterone."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I355,I355)","v":12416085},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B355:D355)","v":2},2002,"Preconception counseling about nutrition and exercise.","Ross",12416085,"Preconception counseling about nutrition and exercise.    Abstract:   Being overweight and being underweight can both cause problems during pregnancy. Corrective intervention should be addressed during the preconception period. Preconception counseling is of particular importance for women on special diets or those who have conditions such as pica, anorexia nervosa, bulimia, and lactose intolerance. Supplements of folic acid and iron should be considered. Excesses of vitamin A, vitamin D, and caffeine should be avoided. Appropriate levels of exercise may be maintained during pregnancy and should be encouraged."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I356,I356)","v":12242693},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B356:D356)","v":2},2002,"Role of insulin-like growth factor binding protein-3 in breast cancer cell growth.","Schedlich",12242693,"Role of insulin-like growth factor binding protein-3 in breast cancer cell growth.    Abstract:   The mitogenic effects of insulin-like growth factors (IGFs) are regulated by a family of insulin-like growth factor binding proteins (IGFBPs). One member of this family, IGFBP-3, mediates the growth-inhibitory and apoptosis-inducing effects of a number of growth factors and hormones such as transforming growth factor-beta, retinoic acid, and 1,25-dihydroxyvitamin D3. IGFBP-3 may act in an IGF-dependent manner by attenuating the interaction of pericellular IGFs with the type-I IGF receptor. It may also act in an IGF-independent manner by initiating intracellular signaling from a cell surface receptor, or by direct nuclear action, or both. The possibility of a membrane-bound receptor is strengthened by recent studies which have identified members of the transforming growth factor-beta receptor family as having a role, either directly or indirectly, in signaling from the cell surface by IGFBP-3. A number of growth factors and hormones stimulate the expression and secretion of cellular IGFBP-3, which then signals from the cell surface to bring about some of the effects attributed to the primary agents. Within the cell, the apoptosis-inducing tumor suppressor, p53, can also induce IGFBP-3 expression and secretion. Since IGFBP-3 upregulates the cell cycle inhibitor, p21(Waf1), and increases the ratio of proapoptotic to antiapoptotic members of the Bcl family, it appears to exert the same effects on major downstream targets of cell signaling as p53 does. The nuclear localization of IGFBP-3 has been described in a number of cell types. IGFBP-3 may act to import IGFs or other nuclear localization signal-deficient signaling molecules into the nucleus. It may also act directly in the nucleus by enhancing the activity of retinoid X receptor-alpha and thereby promote apoptosis. All of the above phenomena will be discussed with particular emphasis on the growth of breast cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I357,I357)","v":12137703},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B357:D357)","v":2},2002,"Vaginal disinfection during labour for reducing the risk of mother-to-child transmission of HIV infection.","Shey",12137703,"Vaginal disinfection during labour for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : Mother-to-child transmission (MTCT) of HIV infection is one of the most tragic consequences of the HIV epidemic, especially in resource-limited countries, resulting in about 650 000 new paediatric HIV infections each year world-wide. The paediatric HIV epidemic threatens to seriously undermine decade-old child survival programmes. This is one of several reviews assessing the available evidence for preventing HIV transmission from an HIV-infected woman to her child. The other reviews assess the effects of antiretroviral therapy, Caesarean section delivery, breast feeding, and vitamin A supplementation.  OBJECTIVES : To estimate the effect of vaginal lavage on the risk of MTCT of HIV and infant and maternal mortality and morbidity, as well as tolerability of vaginal lavage in HIV infected women.  SEARCH STRATEGY : We searched the Cochrane Controlled Trials Register, Cochrane Pregnancy and Childbirth Register, PubMed, EMBASE, AIDSLINE, LILACS, AIDSTRIALS, and AIDSDRUGS, using standardised methodological filters for identifying trials. We also searched reference lists of identified articles, relevant editorials, expert opinions and letters to journal editors, and abstracts and proceedings of relevant conferences, and contacted subject experts and pharmaceutical companies. There were no language restrictions.  SELECTION CRITERIA : Randomised trials or clinical trials comparing vaginal disinfection during labour with placebo or no treatment, in known HIV infected pregnant women. Trials had to include an estimate of the effect of vaginal disinfection on MTCT of HIV and/or any other pre-specified adverse pregnancy outcome to be included.  DATA COLLECTION AND ANALYSIS : Two reviewers independently assessed trial eligibility and quality, and extracted data.  MAIN RESULTS : Only one low quality trial included an estimate of the effect of vaginal disinfection on at least one pre-specified outcome. There was no evidence of an effect of vaginal disinfection on MTCT of HIV (odds ratio 0.93, 95% confidence interval 0.63 to 1.38), and no information was available on the other pre-specified outcomes.  REVIEWERS CONCLUSIONS : There is a need for well-designed randomised controlled trials to estimate the effects of vaginal disinfection on MTCT of HIV."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I358,I358)","v":12036800},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B358:D358)","v":2},2002,"Micronutrients and vertical transmission of HIV-1.","Dreyfuss",12036800,"Micronutrients and vertical transmission of HIV-1.    Abstract:   ABSTRACT Vertical transmission of HIV from mother to infant can occur during pregnancy, at the time of delivery, or post-natally through breast-feeding and is a major factor in the continuing spread of HIV infection. Inadequate nutritional status may increase the risk of vertical HIV transmission by influencing mater-nal and child factors for transmission. The potential effects on these factors include impaired systemic immune function in pregnant women, fetuses, and children; an increased rate of clinical, immunologic, and virologic disease progression; impaired epithelial integrity of the placenta and genital tract; increased viral shedding in breast milk from inflammation of breast tissue; increased risk of low birth weight and preterm birth; and impaired gastrointestinal immune function and integrity in fetuses and children. Micronutrient deficiencies are prevalent in many HIV-infected populations, and numerous studies have reported that these deficiencies impair immune responses, weaken epithelial integrity, and are associated with accelerated HIV disease progression. Although low serum vitamin A concentrations were shown to be associated with an increased risk of vertical HIV transmission in prospective cohort studies, randomized, placebo-controlled trials have reported that vitamin A and other vitamin supplements do not appear to have an effect on HIV transmission during pregnancy or the intrapartum period. However, the ability of prenatal and postpartum micronutrient supplements to reduce transmission during the breast-feeding period is still unknown."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I359,I359)","v":11980191},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B359:D359)","v":2},2001,"Histological and immunohistochemical events during placentation in pigs.","Dantzer",11980191,"Histological and immunohistochemical events during placentation in pigs.    Abstract:   The early morphological events in pig placental development are summarized and related to the known data on differences in placental vascular efficiency between Meishan and US breeds. The activation and localization of a number of factors, the ligands and their receptors, such as insulin-like growth factor (IGF), transforming growth factor beta (TGF beta), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), as well as retinoids and calcium, is described. The comparison between these factors gives a strong impression of their complex interactions and hormonal relationships during placentation and vascular development in pigs. This review also emphasizes that retinoids are of great importance for placental function and that the transport of vitamin A appears to take place in the areolar gland complex only, whereas based on histochemistry and electron energy dispersive analysis, the calcium transport may be confined to the interareolar route across the interhaemal barrier."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I360,I360)","v":11980189},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B360:D360)","v":2},2001,"Gene expression during pre- and peri-implantation embryonic development in pigs.","Maddox-Hyttel",11980189,"Gene expression during pre- and peri-implantation embryonic development in pigs.    Abstract:   Embryo technological procedures such as in vitro production and cloning by nuclear transfer are not as advanced in pigs as in cattle and cannot yet be applied under field conditions. The present paper focuses on genome activation in in vivo-derived, in vitro-produced and nuclear transfer pig embryos with special emphasis on the development of embryonic nucleoli, where the ribosomal RNA (rRNA) genes transcribed can be used as markers for genome activity. In addition, contemporary data on gene expression in in vivo-derived pig embryos are reviewed. In in vivo-derived pig embryos, pronounced transcription is initiated at the four-cell stage (the third cell cycle after fertilization), when nucleoli develop. In parallel with the development of the nucleoli as a result of rRNA gene activation, a cascade of other genes is also likely to be transcribed. However, apart from identification of transcripts for the oestrogen receptor at the blastocyst stage, reports on mRNAs resulting from initial transcription of the pig embryonic genome are lacking, in contrast to the situation in cattle and, in particular, mice. More information is available on gene expression during elongation of pig conceptuses, when the genes for steroidogenic enzymes, extracellular matrix receptors, oestrogen receptors, growth factors and their receptors, as well as retinol binding protein and retinoic acid receptors, are expressed. Nucleolus development appears to be disturbed in in vitro-produced pig embryos and in pig embryos reconstructed by nuclear transfer of granulosa cells to enucleated metaphase II oocytes produced by oocyte maturation in vivo or in vitro, which is indicative of disturbances in activation of rRNA genes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I361,I361)","v":11871862},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B361:D361)","v":2},2001,"Breast cancer prevention: present and future.","Salih",11871862,"Breast cancer prevention: present and future.    Abstract:   Increased risk of breast cancer may result from modifiable factors such as endogenous hormone levels, obesity, HRT, and non-lactation, or non-modifiable factors such as genetic susceptibility or increasing age. Those factors that are easiest to modify may have a limited impact on the totality of breast cancer. The Gail model, based on known factors may be useful for estimating life-time risk in some individuals. Tamoxifen prevention still remains contentious. In the NSABP-P1 study, there was a 49% reduction in risk of breast cancer in women given tamoxifen but in the Italian and Royal Marsden trials, no effect on breast cancer incidence was detected, possibly because of the different case-mix in these studies. Raloxifene, tested in the MORE trial reduced the incidence of breast cancer by 65%. The effect was restricted to ER positive tumours: no reduction in ER negative cancers was seen. Life-style factors such as diet, obesity, exercise, and age of first full term pregnancy and number of pregnancies have a mild to moderate impact on risk and so may have little effect on the incidence of breast cancer. Reduction of alcohol intake could lead to a modest reduction in the risk of breast cancer but possibly adversely affect other diseases. So far, studies of retinoids have not shown a benefit in terms of breast cancer risk reduction. Fat reduction and GnRH analogues reduce mammographic density but have not yet been shown to affect risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I362,I362)","v":11743608},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B362:D362)","v":2},2002,"Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review.","Bortman",11743608,"Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review.    Abstract:   The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the active form of vitamin D3, is an important regulator of calcium homeostasis, exerts antiproliferative effects on various cell systems and can induce differentiation in some kinds of hematopoietic cells. These effects are triggered by its receptor, vitamin D receptor (VDR), a phosphoprotein member of the nuclear receptor superfamily, which functions as a transcriptional factor. VDR binds as a heterodimer with retinoid X receptor (R X R) to hexameric repeats, characterized as vitamin D-responsive elements present in the regulatory region of target genes such as osteocalcin, osteopontin, calbindin-D28K, calbindin-D9K, p21WAF1/CIP1, TGF-beta2 and vitamin D 24-hydroxylase. Many factors such as glucocorticoids, estrogens, retinoids, proliferation rate and cell transformation can modulate VDR levels. VDR is expressed in mammary tissue and breast cancer cells, which are potential targets to hormone action. Besides having antiproliferative properties, vitamin D might also reduce the invasiveness of cancer cells and act as an anti-angiogenesis agent. All of these antitumoral features suggest that the properties of vitamin D could be explored for chemopreventive and therapeutic purposes in cancer. However, hypercalcemia is an undesirable side effect associated with pharmacological doses of 1,25-(OH)2D3. Some promising 1,25-(OH)2D3 analogs have been developed, which are less hypercalcemic in spite of being potent antiproliferative agents. They represent a new field of investigation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I363,I363)","v":11708649},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B363:D363)","v":2},2001,"Use of transgenic mice model for understanding the placentation: towards clinical applications in human obstetrical pathologies?","Sapin",11708649,"Use of transgenic mice model for understanding the placentation: towards clinical applications in human obstetrical pathologies?    Abstract:   The mammalian embryo and fetus are unable to develop without a well-established, functional placenta. This transitory yet indispensable structure attaches the conceptus to the uterus and establishes the vascular connections necessary for nutrient and gaseous exchange between maternal and fetal compartments. Genetic targeting strategy allows the generation of mice lacking a specific gene. Such approaches reveal: (i) the high incidence of mutant embryonic or fetal death in utero, and (ii) the extraembryonic (placental) causes of these deaths. Due to the similarities presented between mouse and human placenta, we propose to use the potential of mouse targeting experiments as a model in order to understand human obstetrical pathologies. In this paper, we first review genes that have been demonstrated to be required in mice for implantation, choriovitelline and chorioallantoic placentation. Using examples (integrins, homeoboxs, hepatocyte growth factor or epidermal growth factor receptor...) we demonstrate the reality and efficiency of such an approach. Other candidate genes (receptor of leukemia inhibitory factor, Wnt2 or retinoic acid receptor alpha...) in order to understand, prevent and treat human obstetrical pathologies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I364,I364)","v":11509096},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B364:D364)","v":2},2001,"Nutrition and maternal morbidity and mortality.","Tomkins",11509096,"Nutrition and maternal morbidity and mortality.    Abstract:   Nearly 600 000 women die every year from pregnancy related conditions and the maternal mortality rates (MMR = deaths per 100 000 live births) in developing countries may be as high as 1000 compared with less than ten in industrialised countries. In the light of the striking impact of deficiencies of micronutrients such as vitamin A and zinc on immune function, morbidity and mortality in children it seems reasonable to suggest that such deficiencies might play a contributing role in the high rates of morbidity and mortality in mothers. Hitherto, there has been rather little published on the contribution of malnutrition to maternal morbidity or mortality but recent results of micronutrient supplementation show a major effect of vitamin A or beta carotene supplementation on maternal mortality in Nepal and an impressive effect of a multiple micronutrient mixture on pregnancy outcome in Tanzania. There is now data showing that subclinical mastitis, a potential risk factor for mother to child transmission of HIV by increasing levels of virus in breast milk, is influenced by maternal diet in Tanzania and feeding patterns in South Africa. Considering the massive tragedy of maternal mortality the recent data provides opportunities for new, innovative nutritional interventions for the reduction of the global burden of maternal morbidity and mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I365,I365)","v":11470927},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B365:D365)","v":2},2001,"Familiar drugs may prevent cancer.","Sharma",11470927,"Familiar drugs may prevent cancer.    Abstract:   Despite positive results in large scale chemoprevention trials, many physicians are unaware of the potential cancer preventive properties of drugs in common usage. The antioestrogen tamoxifen and the selective cyclo-oxygenase-2 inhibitor celecoxib have been licensed in the USA for the chemoprevention of breast and colorectal cancers respectively in selected high risk individuals. Similarly, folate and retinol have been shown to decrease the incidence of colorectal cancer and squamous cell carcinoma of the skin respectively in large scale intervention trials. Other retinoids have proved efficacious in the tertiary chemoprevention of cancers of the breast and head/neck. Epidemiological evidence also exists in favour of aspirin, non-steroidal anti-inflammatory drugs, and angiotensin converting enzyme inhibitors preventing certain cancers. Phytochemicals may represent less toxic alternatives to these agents. Although some of these drugs are available without prescription and most are not yet licensed for use in cancer chemoprevention, physicians and students of medicine should be aware of this accumulating evidence base. Practitioners should be amenable to patient referral to discuss complex issues such as risk estimation or potential benefit from intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I366,I366)","v":11465069},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B366:D366)","v":2},2000,"Protein kinase C as a drug target: implications for drug or diet prevention and treatment of cancer.","Carter",11465069,"Protein kinase C as a drug target: implications for drug or diet prevention and treatment of cancer.    Abstract:   Protein kinase C (PKC) isoforms are serine/threonine kinases involved in signal transduction pathways that govern a wide range of physiological processes including differentiation, proliferation, gene expression, brain function, membrane transport and the organization of cytoskeletal and extracellular matrix proteins. PKC isoforms are often overexpressed in disease states such as cancer. In this review, PKC in a variety of cancers is discussed along with some specific cell biological mechanisms by which PKC exerts its function(s). The PKC family consists of several isoforms comprising three groups: classical, novel and atypical. Although PKC has been investigated for around 2 decades, only recently has the specific function of each isoform started to be elucidated and the isoforms evaluated for use as targets of drug action. Phorbol esters such as the tumor-promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol (DAG) activate classical and novel PKC isoforms. Naturally occurring retinoids, antisense oligonucleotides against specific PKC isoforms and specific PKC inhibitors can block this activation. Beta carotene and retinoid derivatives act as anticarcinogenic agents and can antagonize some of the biological actions of phorbol esters and oxidants. Another important area of investigation is the use of antisense oligonucleotides to inhibit specific PKC isoforms. These compounds have proven effective in reducing specific types of cancer in rodents and humans and are currently used in clinical trials. This review examines PKC isoforms as a target of drug action with special emphasis on their use in cancer therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I367,I367)","v":11055498},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B367:D367)","v":2},2000,"Retinoids in breast cancer prevention and treatment. A review of the literature.","Baj",11055498,"Retinoids in breast cancer prevention and treatment. A review of the literature.    Abstract:   During the last three decades, research focused on cancer treatment has led to the development of many cytotoxic agents. Despite the fact that these efforts have significantly improved the prognosis of certain malignancies such as some lymphomas, leukemias and testicular carcinomas, other tumors such as ovarian, lung and metastatic breast cancer are still associated with a poor prognosis. An innovative approach has recently emerged, thanks to a better understanding of tumor cell biology and many efforts are aimed at finding compounds capable of restoring a more differentiated phenotype to tumor cells, thereby reducing the tumors aggressiveness and ultimately reverting it to its normal counterpart [1, 2]. Retinoids are the prototype of this new therapeutical approach called quot;differentiation therapyquot;."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I368,I368)","v":10941247},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B368:D368)","v":2},2000,"[Nonhormonal prevention of breast cancer].","Jonat",10941247,"[Nonhormonal prevention of breast cancer].    Abstract:    BACKGROUND : Despite the use of currently available drug therapies, the life expectancy of patients with metastasized breast cancer can still only be extended by about 14 to 16 months in comparison to a completely untreated patient population. In light of these figures, and the associated economic costs, all possible means to reduce the incidence of the disease are of great potential importance and must be examined seriously.  PREVENTION : Increased consumption of alcohol is a risk factor for breast cancer. Increased intake of phytoestrogens, dietary fiber, and beta-carotene as well as regular physical activity and normal body weight lower the risk of breast cancer. The increased risk of breast cancer associated with alcohol consumption can be reduced by adequate intake of folate. The significance of retinoids is at present ambiguous.  CONCLUSION : Effective preventive measures, along with adequate early detection schemes, are the best means of reducing mortality due to breast cancer. Both folate and retinoids deserve to be subjected to further studies. It would also be desirable to supplement currently ongoing adjuvant therapy trials with studies examining the use of folate versus placebo."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I369,I369)","v":10791768},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B369:D369)","v":2},2000,"Insulin-like growth factor (IGF) system in the bovine mammary gland and milk.","Baumrucker",10791768,"Insulin-like growth factor (IGF) system in the bovine mammary gland and milk.    Abstract:   Primary bovine mammary cells express the two IGF receptors (IGF-IR, IGF-IIR), insulin receptor, and four IGFBPs (IGFBP-2, -3, -4, and -5). Examination of the IGF-IR during the mammary gland lactation cycle shows that IGF-IR number declines at parturition, a change that coincides with decreases in the blood level of its ligand, IGF-I. IGF-II and IGF-IIR are largely unchanged. IGFBP-3 is the predominant mammary IGFBP and its concentration also declines in blood and milk during lactation compared to prepartum and involution periods. Time of lactation and pregnancy were the main determinants of milk but not blood IGFBP-3 levels. IGFBP-3 binds to membrane proteins of bovine mammary tissue; an IGFBP-3 binding protein has been identified as bovine lactoferrin. Lactoferrin has the capacity to compete with IGF binding to IGFBP-3. Appearance of both IGFBP-3 and lactoferrin in conditioned media of primary cultures of bovine mammary cells was stimulated by all trans retinoic acid (atRA). Furthermore, atRA was necessary for the entry of exogenously added lactoferrin into the mammary cell nucleus, while IGFBP-3 entry into the nuclei of atRA treated cells required the presence of lactoferrin. These findings reveal a novel role for lactoferrin, suggesting that lactoferrin is critically involved in the regulation of the IGF system during the involution period."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I370,I370)","v":10762023},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B370:D370)","v":2},2000,"Criteria for implementation of large and multiagent clinical chemoprevention trials.","Meyskens",10762023,"Criteria for implementation of large and multiagent clinical chemoprevention trials.    Abstract:   If one were to wait for the perfect set of experimental results before launching a multi-agent chemoprevention or large risk reduction study, the trial would never be launched. On the other hand, non-scientific considerations have led to the premature launching of at least three prominent studies (CARET, Carotene and Retinol Efficacy Trial; ATBC, Apha Tocopherol Beta Carotene; PCPT, Prostate Cancer Prevention Trial) and the much delayed start-up of another, BCPT, the Breast Cancer Prevention Trial. Strong epidemiologic data by itself should not be adequate to justify starting a large trial; experimental and/or clinical data should be developed. On the other hand fear of secondary adverse events that are of low incidence should not be enough to delay a trial if the overall health benefit could be high. The development of multiagent chemoprevention trials requires that each agent is active and additively or synergistically so in combination in preclinical models. Additionally, side effects of each agent should be non-overlapping and low to non-existent, preferably a feature determined in formal phase IIa and IIb trials. These principles will be discussed in the context of prior (CARET, ATBC) and ongoing (EUROSCAN, acetylcysteine/retinol), as well as proposed future trials (difluromethyl/sulindac)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I371,I371)","v":10762020},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B371:D371)","v":2},2000,"Chemoprevention of breast cancer: the Italian experience.","Decensi",10762020,"Chemoprevention of breast cancer: the Italian experience.    Abstract:   The activity of our group is focused on the conduction of chemoprevention clinical trials of breast cancer in at-risk subjects, among which we include women on hormone replacement therapy (HRT). The role of the insulin-like growth factor (IGF) system and of mammographic breast density as surrogate biomarkers for breast cancer prevention is also being investigated. The IGF system is involved in human carcinogenesis of several solid tumors. IGF-I is a potent mitogen for breast cancer cells; elevated circulating IGF-I levels have been associated with a higher risk of premenopausal breast cancer, prostate and colorectal cancer in prospective studies. Both tamoxifen and the synthetic retinoid fenretinide (4-HPR) have been shown to decrease plasma IGF-I levels. A trial of their combination is ongoing in premenopausal women with increased risk for breast cancer. Mammographic breast density has also been associated with an increased risk of breast cancer in several prospective studies. In this article, we discuss the rationale for selection of appropriate cohorts, candidate agents, and putative surrogate biomarkers in our breast cancer prevention trials. Moreover, updated results of the secondary prevention trial of 4-H PR and of the primary prevention trial of tamoxifen are presented. Finally, the rationale for a reduction of tamoxifen dose in future prevention trials is provided."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I372,I372)","v":10540891},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B372:D372)","v":2},1999,"[Vitamins in pregnancy].","Yoshioka",10540891,"[Vitamins in pregnancy].    Abstract:   Vitamins are essential for the growth and normal function of human body. There are very few reports on vitamin A deficiency in pregnant women and newborn. Vitamin B complex includes various fractions essential to proper nutrition. The absence of vitamin C results Barlow disease in newborn. Vitamin D, the antirachitic Vitamin, is of great importance in safeguarding the mother and fetus from its relation to calcium and phosphorus metabolism. Vitamin E is also useful for the treatment of toxemia of pregnancy, intra-uterine growth retardation (IUGR), and neonatal jaundice. Vitamin K is well known for the protection of neonatal hemorrhage. The 6th recommended dietary allowances for Japanese in 1999 is shown in the table."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I373,I373)","v":10540883},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B373:D373)","v":2},1999,"[Vitamin deficiencies and hypervitaminosis].","Mino",10540883,"[Vitamin deficiencies and hypervitaminosis].    Abstract:   There have recently been very few deficiencies with respect to fat soluble and water soluble vitamins in Japan All-trans-retinoic acid as induction or maintenance treatment improves disease free and overall survival against acute promyelocytic leukemia. In the isolated vitamin E deficiencies gene mutation has been cleared for alpha-tocopherol transferprotein. Recently, a relation of nutritional vitamin K intake and senile osteoporosis in women was epidemiologically demonstrated on a prospective study. Thiamin was yet noticed as development of deficiency in alcoholism, while the importance of supplemental folic acid during pregnancy has become especially clear in light of studies showing that folic acid supplements reduce the risk of neural tube defects in the fetus. With respect to hypervitaminosis, the Council for Responsible Nutrition (CRN), USA, has established safe intakes by identifying the NOAEL (No Observed Adverse Effect Level) and LOAEL (Lowest Observed Adverse Effect Level). Summaries of NOAEL and LOAEL for individual vitamins were shown."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I374,I374)","v":10505667},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B374:D374)","v":2},1999,"Regulation of lactoferrin gene expression by estrogen and epidermal growth factor: molecular mechanism.","Teng",10505667,"Regulation of lactoferrin gene expression by estrogen and epidermal growth factor: molecular mechanism.    Abstract:   Lactoferrin (LF) is a member of the transferrin gene family. Its expression in the mouse uterus is regulated by estrogen and epidermal growth factor (EGF). The author et al. cloned the LF gene promoter/enhancer region, and demonstrated that multihormone signaling pathways are involved in modulating LF gene activity. Three short but complex modules, within 400 bp from the transcription initiation site of the mouse LF gene, contain the response elements that are responsible for estrogen, retinoic acid, mitogen, and growth factor stimulation. These elements have been identified and characterized, using reporter constructs transiently transfected into human endometrial carcinoma RL95-2 cells. The author et al. used molecular approaches, such as deletion, insertion, and site-directed mutagenesis, to determine the relationship between the response elements, and to fine-map the crucial nucleotides within them. This article reviews the characterization of the estrogen and EGF response elements of the mouse LF gene promoter."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I375,I375)","v":10487397},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B375:D375)","v":2},1999,"Drug-induced nail disorders: incidence, management and prognosis.","Piraccini",10487397,"Drug-induced nail disorders: incidence, management and prognosis.    Abstract:   A large number of drugs of different classes, ranging from antibacterials to chemotherapeutic agents to psoralens, can be responsible for the development of nail changes. Drug-induced nail changes usually involve several or all 20 nails and appear in temporal correlation with drug intake. Some nail changes are asymptomatic and only cause cosmetic problems, while others cause pain and discomfort and impair manual activities or deambulation. Drug-induced nail abnormalities are usually transitory and disappear with drug withdrawal, but sometimes persist in time. The pathogenesis of the nail changes is usually a toxic effect of the drug on the different nail constituents, but other mechanisms can be involved. Drugs that are well known to produce nail abnormalities include cancer chemotherapeutic agents, psoralens, retinoids, tetracyclines, antimalarials and zidovudine. Arsenic poisoning is also always associated with nail changes that have medico-legal importance. Some drugs taken during pregnancy may impair nail development of the fetus, and nail hypoplasia or other nail dystrophies will be evident in the newborn."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I376,I376)","v":10476692},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B376:D376)","v":2},1999,"Cytokines and the regulation of apoptosis in reproductive tissues: a review.","Lea",10476692,"Cytokines and the regulation of apoptosis in reproductive tissues: a review.    Abstract:    PROBLEM : To determine the role of apoptosis-regulating genes bax and bcl-2 in reproduction.  METHOD OF STUDY : Review of literature and current data.  RESULTS : The bcl-2 family of apoptotic regulatory gene products interact and form dimers of anti- and pro-apoptotic proteins (e.g., bcl-2 and bax respectively), the ratio of which determines cell death or survival. Menses is associated with increased apoptosis in the glands, a change in bcl-2:bax ratio and increased levels of the pro-apoptotic cytokine TNFalpha. Apoptosis occurs in all placental cell types and increases from first to third trimester. Placental apoptosis is induced by TNFalpha in vitro and increased levels in utero characterize most failing pregnancies, intra-uterine growth restriction (IUGR) and labour. An increased bcl-2:bax ratio and apoptosis in the syncytiotrophoblast characterizes failing first trimester pregnancies. Apoptosis in the syncytiotrophoblast is also associated with IUGR. In a rat model, maternal vitamin A deficiency perturbs fetal development. This is associated with a placental infiltrate of TNFalpha positive neutrophils (day 20) and increased placental apoptosis in areas of infiltration. A similar infiltrate occurs in a mouse model of early pregnancy loss. In the fetal membranes, clusters of bcl-2 negative chorion trophoblast cells undergo apoptosis. This may allow passage of myometrial stimulatory factors that induce labour.  CONCLUSION : The ratio of bcl-2:bax is crucial in the regulation of apoptosis, particularly in the human placenta. Changes in trophoblast apoptosis characterize (1) early pregnancy failure, (2) IUGR and (3) pre-term and term labour. Regardless of gestational age, TNFalpha plays a major role in the induction of placental apoptosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I377,I377)","v":10419022},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B377:D377)","v":2},1999,"Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7.","Peltoketo",10419022,"Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7.    Abstract:   Two 17beta-hydroxysteroid dehydrogenases (17HSDs), type 1 and type 7, are enzymes of estradiol biosynthesis, in addition to which rodent type 1 enzymes are also able to catalyze androgens. Both of the 17HSDs are abundantly expressed in ovaries, the type 1 enzyme in granulosa cells and type 7 in luteinized cells. The expression of 17HSD7, which has also been described as a prolactin receptor-associated protein (PRAP), is particularly up-regulated in corpus luteum during the second half of rodent pregnancy. A moderate or slight signal for mouse 17HSD7/PRAP mRNA has also been demonstrated in samples of placenta and mammary gland, for example. Human, but not rodent, 17HSD1 is expressed in placenta, breast epithelium and endometrium in addition to ovaries. A cell-specific enhancer, silencer and promoter in the hHSD17B1 gene participate in the regulation of type 1 enzyme expression. The enhancer consists of several subunits, including a retinoic acid response element, the silencer has a binding motif for GATA factors, and the proximal promoter contains adjacent and competing AP-2 and Sp binding sites."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I378,I378)","v":10221607},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B378:D378)","v":2},1999,"Dietary vitamin A and teratogenic risk: European Teratology Society discussion paper.","Dolk",10221607,"Dietary vitamin A and teratogenic risk: European Teratology Society discussion paper.    Abstract:   This review discusses the predictive value of animal models in assessment of possible risk from excess vitamin A consumption during pregnancy and the human evidence concerning risk of congenital malformations from excess vitamin A in the diet, consumed either as a constituent of normal foods or in the form of dietary vitamin supplements. Other sources of exposure to vitamin A include medicines (dermal and oral preparations) and cosmetics, but these are not further considered here. Conservative estimates of the likely safe intake of vitamin A during pregnancy are available, based on results from scientific research to date. However, current uncertainties are such that further research is needed to more clearly define intakes which may be on the borderline between those which are beneficial and those which may pose a risk to the developing embryo and fetus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I379,I379)","v":10218141},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B379:D379)","v":2},1999,"Prevention of ovarian cancer.","Brewer",10218141,"Prevention of ovarian cancer.    Abstract:   Chemoprevention trials with OCP and retinoids will be important to determine if these drugs are effective in selected populations. Further work will be critical to understanding the mechanism of action of OCP in preventing ovarian cancer and if this protective effect will be upheld in the high-risk population. Initial results in the Milan study are promising for the retinoids in prevention of ovarian cancer and will be used in chemoprevention trials both alone and in combination with OCPs to determine if there might be an additive effect with these drugs. As yet, little is known about preinvasive changes in the ovary to predict which women are at risk for developing ovarian cancer. We can now identify high-risk women by genetic counseling and testing, yet ultrasound and serum markers are the only modality available to evaluate these women. Research is focusing on developing ways of evaluating women, particularly those at high risk for ovarian cancer, to better understand the neoplastic process in the ovary and thus identify these women prior to their developing advanced ovarian cancer. Research is also focusing on understanding chemoprevention for ovarian cancer so that women can receive the optimal chemopreventive agent when diagnosed as high risk. Prognosis with advanced disease is so poor that early diagnosis and chemoprevention are the only methods at the current time to significantly improve survival in epithelial ovarian cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I380,I380)","v":9706339},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B380:D380)","v":2},1998,"Orofacial cleft defects: inference from nature and nurture.","Houdayer",9706339,"Orofacial cleft defects: inference from nature and nurture.    Abstract:   Cleft lip with or without cleft palate (CL/P), and cleft palate (CP) are most common congenital malformation conditions. Prognosis mainly rests on the possibility of associated symptoms, since more than a hundred recognised Mendelian disorders involve this orofacial defect (thereby defining syndromic CL/P, or CP). Multiplex non-syndromic CL/P, or CP families indicate that genetic factors are likely involved in causation. Inheritance is generally regarded as multigenic, allelic variation at different loci (TGF alpha, TGF beta 3, RARA) determining a fraction of the genetic risk, as demonstrated by association or transmission/disequilibrium non-parametric tests. Some pedigrees are however clearly monogenic, consistent with either autosomal dominant or recessive inheritance. X-linked recessive CP (with or without ankyloglossia) is an additional possibility. Significant linkage to 6p23 (EDN1) or 19q13 (BCL3) could be achieved using parametric models with reduced penetrance. Environmental exposures were also demonstrated to interfere with lip and/or palatal formation when present during the first trimester of pregnancy. Whereas ethanol, retinoids or folate antagonists are clearly teratogenic, indictment of more common exposures such as caffeine is merely tentative. The development of animal models allowed to confirm the genetic bases of CL/P, or CP, exemplify the role of teratogens, and study the interaction of nature and nurture."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I381,I381)","v":9678068},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B381:D381)","v":2},1998,"Hormonal contraception and the skin.","Giannotti",9678068,"Hormonal contraception and the skin.    Abstract:   The use of hormonal contraception is of great interest in dermatological therapy because of the effectiveness of hormonal contraception with its antiandrogenic properties in the treatment of androgen-dependent dermatological disease and because of the need for a pregnancy prevention strategy in dermatological treatments with teratogenic potential (retinoids, thalidomide, methotrexate). We discuss here the main indications for the use of hormonal contraception in dermatology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I382,I382)","v":9488752},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B382:D382)","v":2},1997,"[Treatment of acne].","Delanoë",9488752,"[Treatment of acne].    Abstract:   The treatment of acne is based upon simple pathogenic arguments, but needs to be adapted to the type of acne. Patients must always be informed that it is long and difficult and that no significant response will be expected before 2 to 3 months of regular treatment. The authors present the different therapeutic agents and strategies. Isotretinoin should be used only in severe acne after failure of at least 3 months of a well conducted classical treatment and in nodulo-cystic acne; because of its major side effect of teratogenicity its use in adolescent girls requires pregnancy testings before and during treatment and an effective contraception."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I383,I383)","v":9480037},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B383:D383)","v":2},1997,"[Vitamin A deficiency: epidemiological aspects and control methods].","Ag Bendech",9480037,"[Vitamin A deficiency: epidemiological aspects and control methods].    Abstract:   Vitamin A deficiency is one of the most common nutrient deficiency syndromes in children from developing countries. It is also correlated with the increased severity and incidence of certain infections. Until recently, vitamin A research was focused on preventing xerophthalmia and blindness in Third World Countries and on the development of synthetic retinoid molecules, with lower toxicity than vitamin A, for the treatment of skin diseases. However, there has been a major shift of emphasis in the last five to ten years. There is a risk of death from xerophthalmia, primarily from complications with infectious diseases. Intermittent treatment with the very large doses of vitamin A prescribed to combat blindness was shown to be effective. This suggests that vitamin A may affect specific elements of the immune system. High-dose vitamin A supplements have been given, at widely-spaced time intervals, to preschool children in communities where vitamin A deficiency causes xerophthalmia and blindness, over the last 20 to 30 years. A strong correlation between mortality and xerophthalmia was identified. Death then became the principal outcome measured because it was easier to detect than xerophthalmia, particularly in large clinical trials in high risk regions where clinical expertise was minimal and vitamin A deficiency was a commoner cause of death than blindness. Other, food-based approaches to the treatment and prevention of vitamin A deficiency, involving foods naturally rich in retinol or carotenoid, or foods artificially fortified with these nutrients, should be developed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I384,I384)","v":9434866},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B384:D384)","v":2},1997,"Cell death/apoptosis: normal, chemically induced, and teratogenic effect.","Zakeri",9434866,"Cell death/apoptosis: normal, chemically induced, and teratogenic effect.    Abstract:   Cell death is an integral part of a variety of biological processes including cell proliferation, differentiation, and morphogenesis. We review here the morphological and biochemical nature as well as the genetic basis for cell death during normal and abnormal development. Most often referred to in normal development as programmed cell death, this controlled process determines the size, patterning, and function of many tissues. The importance of its proper genetic regulation is demonstrated by the discovery of cell death-specific genes and the several disorders including cancer and teratogenesis that result from repression or enhancement of cell death. In our studies we employed the developing mouse limb, which provides a defined window of active cell death, to elucidate mechanisms of cell death. We have developed markers that reveal in the developing normal limb an apoptotic morphology with phagocytosis and DNA fragmentation. In the limb deformity mutant Hammertoe there is a defective (restricted) cell death pattern, but the morphology remains apoptotic. By the use of these markers, we were able to observe that the teratogen retinoic acid produced enhanced apoptotic cell death. Most interestingly, retinoic acid-induced cell death in the Hammertoe mutant resulted in correction of the mutant phenotype. Future studies will determine the relationship between exogenous agents and endogenous signaling pathways as well as indicate how these interactions can alter the fate of a given cell and potentially ameliorate a genetic abnormality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I385,I385)","v":9167139},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B385:D385)","v":2},1997,"Vitamins and cancer chemoprevention.","Giacosa",9167139,"Vitamins and cancer chemoprevention.    Abstract:   Chemoprevention is in an area of cancer research with perhaps the greatest potential for reducing cancer mortality. Several agents, and in particular antioxidant vitamins, appear to be effective against early rather than later steps of the premalignant process at different sites. Particular attention must be paid to possible side effects and safety of the agents and to optimal doses in long-term administration regimens. The results of numerous trials on the preventive role of vitamins (e.g. beta-carotene, retinols, retinoids, alpha-tocopherol, ascorbic acid, folic acid) are contradictory and far from conclusive. Multiple primary and secondary intervention trials currently under way should assess in the coming years the role of some vitamins in the prevention of various cancers (oral cavity, pharynx, oesophagus, colon, lung, breast, skin, cervix, bladder)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I386,I386)","v":7492140},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B386:D386)","v":2},1995,"Melasma. Etiologic and therapeutic considerations.","Grimes",7492140,"Melasma. Etiologic and therapeutic considerations.    Abstract:    BACKGROUND : Melasma is a common acquired symmetric hypermelanosis characterized by irregular light- to gray-brown macules and patches involving sun-exposed areas of skin. Etiologic factors in the pathogenesis of melasma include genetic influences, exposure to UV radiation, pregnancy, hormonal therapies, cosmetics, phototoxic drugs, and antiseizure medications.  OBSERVATIONS : Melasma is often a therapeutically challenging disease, and current treatments include hypopigmenting agents, chemical peels, and lasers. Hypopigmenting agents include phenolic and nonphenolic derivatives. Phenolic agents include hydroquinone and hydroquinone combination preparations. Despite controversies regarding the issue of hydroquinone-induced ochronosis, hydroquinone remains the most effective topically applied bleaching agent approved by the Food and Drug Administration for the treatment of melasma. Nonphenolic bleaching agents include tretinoin and azelaic acid. Superficial, medium, and deep chemical peels are more often used in lighter-complexioned patients. Such peels should be used with caution in blacks. Although lasers have demonstrated significant efficacy in the treatment of a variety of hyperpigmentary disorders, their precise efficacy and place in the therapy of melasma have yet to be established.  CONCLUSIONS : In the hierarchy of therapies for melasma, the treating physician must consider the devastating psychosocial impact of pigmentary imperfections within the realm of the benefits and risks associated with each treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I387,I387)","v":8589015},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B387:D387)","v":2},1995,"Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.","Hoffmann",8589015,"Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.    Abstract:    BACKGROUND : The development of therapy-related acute myeloid leukemia (t-AML) with balanced translocations to chromosome bands 11q23 and 21q22 has recently been significantly related to previous treatment with several cytostatic drugs poisoning DNA topoisomerase II. A similar association was suspected for other balanced chromosomal aberrations such as the t(15;17) characteristic of acute promyelocytic leukemia (APL).  PATIENTS AND METHODS : Two cases of acute promyelocytic leukemia were observed following treatment for seminoma with etoposide, cisplatin, and bleomycin and treatment for breast cancer with 4-epi-doxorubicin and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil followed by radiotherapy. Both cases presented a t(15;17) (q22;q12) and were examined for the characteristic chimeric rearrangement of the RAR alpha and PML genes observed in acute promyelocytic leukemia de-novo.  RESULTS : In both cases the characteristic chimeric rearrangement was demonstrated. Case no. 2 in addition to the t(15;17) showed an inversion of the long arm of a chromosome no. 5 and a del(7)(q22) in all abnormal mitoses studied. Despite these findings the patient obtained a complete morphological and cytogenetic remission of the leukemia following treatment with all-trans-retinoic acid.  CONCLUSIONS : Based on these two cases and a review of the literature it is concluded that the development of t-APL with the balanced translocation t(15;17) is related to previous treatment with cytostatic drugs targeting DNA topoisomerase II and that additional abnormalities of the long arms of chromosomes no. 5 and no. 7 do not interfere with the induction of remission with all-trans-retinoic acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I388,I388)","v":8526344},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B388:D388)","v":2},1995,"Retinoids in cancer chemoprevention. Clinical trials with the synthetic analogue fenretinide.","Costa",8526344,"Retinoids in cancer chemoprevention. Clinical trials with the synthetic analogue fenretinide.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I389,I389)","v":8600562},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B389:D389)","v":2},1995,"[Vitamin and mineral deficiency in Mexico. A critical review of the state of the art. II. Vitamin deficiency].","Rosado",8600562,"[Vitamin and mineral deficiency in Mexico. A critical review of the state of the art. II. Vitamin deficiency].    Abstract:   We carried out a review of the studies related to vitamin deficiencies in the Mexican population published since 1950. Forty four studies were published from which we can conclude that: a) dietary intake data suggest that ascorbic acid, riboflavin and retinol intake are deficient: reported intakes were 40-70%, 35-64% and 20-72% of the recommended daily amounts respectively; niacin intake was also deficient in some studies; b) about 10% of Mexican children in rural areas had deficient values of plasma retinol (lt; 100 ng/ml) and about 25 to 30% had low values (100-200 ng/ml); this prevalence is reduced in children with a higher socioeconomic level; c) some studies were found that show the existence of marginal deficiencies of vitamin E, riboflavin and vitamin B12 in apparently healthy populations. Further studies are required to identify the magnitude of these and perhaps other vitamin deficiencies and their potential effects on the health and function of the Mexican population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I390,I390)","v":8747385},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B390:D390)","v":2},1995,"Surrogate endpoint biomarkers for cervical cancer chemopreventive trials.","Ruffin",8747385,"Surrogate endpoint biomarkers for cervical cancer chemopreventive trials.    Abstract:   Cervical intraepithelial neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve a both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention progression. In planning chemoprevention trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I391,I391)","v":8747384},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B391:D391)","v":2},1995,"Chemoprevention trials in the cervix: design, feasibility, and recruitment.","Mitchell",8747384,"Chemoprevention trials in the cervix: design, feasibility, and recruitment.    Abstract:   The cervix is an ideal organ for chemoprevention studies and the study of squamous carcinogenesis. In chemoprevention trial design, four factors are important: high-risk cohorts must be identified; suitable agents must be selected; study designs should include Phase 1, II, and III; and studies should include the use of surrogate endpoint biomarkers. High-risk cohorts can be selected for Phase I, II and III trials in the cervix, for example, patients with high grade lesions such as cervical intraepithelial neoplasia (CIN) grade 3 and carcinoma in situ (CIS). A Phase III trial might also include patients with lesions infected with oncogenic HPV types. The cervix is accessible and can be safely followed with Papanicolaou (Pap) smears and colposcopy. Suitable agents include those likely to work in squamous lesions, including retinoids, difluoromethylornithine, beta-carotene, and others. In Phase I chemopreventive studies, does are de-escalated rather than escalated, determining toxicity and optimal dose schedule. Phase II studies looking at effectiveness need placebo control groups since regression of high-risk lesions is possible. Phase III studies, now multicentric, should be carefully designed and include wide patient representation in order to evaluate the risk-benefit ratio of therapy, focusing on cancer incidence reduction. Surrogate endpoint biomarkers include quantitative histopathology, biologic measures of proliferation, regulation, differentiation, genetic instability, and fluorescence emission. Quantitative histopathologic markers include nuclear grading (i.e., shape, area, optical density, texture), nuclear pleomorphism, ploidy, and nucleolar size and position. Biomarkers under study at the present time in the cervix include proliferation markers (PCNA), regulation marker (EGFR, ras, myc, p53, retinoic acid receptors, ODC, spermidine/spermine ratios), differentiation markers (involucrin, cornifin, keratins), and markers of genetic instability (chromosome polysomy). Fluorescent spectroscopy uses light to probe the biochemical properties of tissue. This technique provides an automated diagnosis in real time with comparable sensitivity and specificity to colposcopy and can be used to monitor lesions in chemoprevention trials. Recruitment designs for cervix studies need to include a large referral population and patients with sufficiently large lesions. Clinicians involved in such studies need to stress contraception and smoking cessation, deal with language barriers, and provide compensation for child care and parking to patients in order to increase compliance."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I392,I392)","v":8747374},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B392:D392)","v":2},1995,"A phase II chemoprevention trial design to identify surrogate endpoint biomarkers in breast cancer.","Dhingra",8747374,"A phase II chemoprevention trial design to identify surrogate endpoint biomarkers in breast cancer.    Abstract:   Surrogate biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of conducting chemoprevention trials. In addition to criteria of sensitivity, specificity, quantifiability, and reproducibility applicable to most potential biomarkers, there are additional specific constraints in developing biomarkers for specific organ sites. In the case of breast tissue, these difficulties include lack of a consensus on the nature of premalignant lesions and the histologic criteria used to define them; even when such a consensus can be evolved, there are limitations in visualizing such lesions without invasive biopsies. Also, knowledge of specific genetic and biochemical changes in premalignant lesions is limited. In addition, the physiology of breast tissue is cyclic, no proven, relevant markers can be studied in a randomly obtained needle aspirate. The earliest determinate lesion that can be recognized in breast tissue is ductal carcinoma in situ (DCIS). At the University of Texas M.D. Anderson Cancer Center, we have initiated a study to develop biomarkers for tamoxifen and 4-hydroxyphenylretinamide by administering one or both of these drugs to women with DCIS or small invasive lesions in the interval between the initial diagnostic core biopsy and definitive surgery. The treatment is to be administered for 2-4 weeks. Proposed biomarkers to be studied include: (a) markers associated with neoplastic phenotypes, e.g., excessive proliferation, alternations of nuclear morphology and angiogenesis; (b) proteins likely to be required for response to the putative chemopreventive agents, e.g., estrogen receptor, nuclear retinoid receptors; (c) markers indicative of intact downstream response pathways, e.g., progesterone receptors; (d) oncogenes and tumor suppressor genes regulated by the proposed chemopreventive agents, e.g., neu, TGF-beta; and (e) potential novel markers of genetic instability that could be studied in randomly obtained needle aspirates, i.e., random chromosomal gains and losses in high risk mammary epithelium. The experience gained in designing and conducting this trial is expected to facilitate development of future chemoprevention trials of breast, as well as other organ site cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I393,I393)","v":8001523},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B393:D393)","v":2},1994,"Seasonal variations in vitamins A, C, riboflavin and folate intakes and status of pregnant and lactating women in a rural Gambian community: some possible implications.","Bates",8001523,"Seasonal variations in vitamins A, C, riboflavin and folate intakes and status of pregnant and lactating women in a rural Gambian community: some possible implications.    Abstract:    OBJECTIVE : To relate measured intake of vitamins A, C, folate and riboflavin to biochemical indicators of nutritional status for these micronutrients, and to examine seasonal variations.  SETTING : MRC Dunn Nutrition Unit Field Station, Keneba, The Gambia, which has heavy rainfall in August, and little or no rain between late September and mid-June. Data were collected during 1978-80.  SUBJECTS : Pregnant or lactating women in a rural farming community whose diet has been studied throughout the year.  RESULTS : Mean daily intake of vitamin C varied from virtually nil during the rainy season to about 100 mg/d in May, while plasma ascorbate ranged from 0.2 to 1.2 mg/dl, and breast-milk ascorbate from 2 to 6 mg/dl, changing synchronously with changing intake. Intake of retinol equivalents ranged from 120 micrograms/d in December to 900 micrograms/d in June, and plasma carotenoids showed synchronous fluctuation from 60 to 180 micrograms/dl, whereas plasma retinol was virtually unchanged throughout the year at 30 micrograms/dl. Intake of riboflavin was very low throughout the year, but erythrocyte glutathione reductase activation coefficient ranged from a minimum of 1.5 in July to a maximum of 1.9 between December and March. Obstetric outcome also exhibited seasonal variation with lowest birthweights during the rainy season. Intakes of food energy are assumed to be the major dietary influence on birthweight, but micronutrient intakes and status may have additional effects, and seasonality clearly affects ascorbate intakes by suckling infants.  CONCLUSIONS : In countries such as The Gambia seasonality is a major determinant of micronutrient status. However, dietary intake is not the only factor which determines micronutrient status: thus there are seasonal fluctuations in riboflavin status which, for example, may relate to changes in the balance between energy intake and output, rather than to seasonal changes in riboflavin intake."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I394,I394)","v":7968931},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B394:D394)","v":2},1994,"[Nutritional principles for the pregnant diabetic].","Strata",7968931,"[Nutritional principles for the pregnant diabetic].    Abstract:   After a short account on alimentation in pregnant women, the authors examine in detail the correct alimentation in pregnant women affected by different types of diabetes. As general lines for a correct nutritional approach, a total caloric intake of 2200-2500 kcal daily (9196-10450 Kj) (which enclose 35-40 kcal/pro/kg ideal weight and a caloric surplus for pregnancy) is recommended. In over-weight women the caloric intake will be reduced till 1500 kcal (6270 Kj) checking constantly metabolic situation (increase of weight should be for the first ten weeks of 100 g weekly, than of 300 g weekly). Altogether weight increase should be from 9 to 12 kg. 15-20% of caloric intake should be represented for proteins, very important for pregnancy and good growth of fetus. Carbohydrate intake should be 55-60% of caloric intake represented for 75-80% by complex glucides and for 20-25% simple glucides to support a suitable amount of dietary fibres (25-30%). The lipid intake recommended should be 25-30% of the daily calories with a third of monounsaturated fat acids, a third of polyunsaturated fat acids and a third of saturated fat acids, with a cholesterol amount under 300 mg/die. In additional the nutritional plan should consist of a adequate amount of quot;non energetic nutrientsquot; (minerals and vitamins), particularly the calcium intake must be 1200 mg/die and 18 mg/die that of iron and folic acid, vitamin A, D and B intake must be increased. Finally, the authors advise against alcoholic beverages and recommend a regular subdivision of the meals.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I395,I395)","v":8304290},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B395:D395)","v":2},1994,"Maternal vitamin A status and its importance in infancy and early childhood.","Underwood",8304290,"Maternal vitamin A status and its importance in infancy and early childhood.    Abstract:   Early fetal vitamin A supplies must be regulated to avoid teratogenic consequences from too little or too much. Late in gestation, adequate maternal vitamin A status is important for newborn reserves and for sustaining adequate breast-milk concentrations. Vitamin A supplements are not needed for most pregnant women in Western countries who consume the recommended dietary allowance during their reproductive years. Increased consumption of vitamin A-rich foods can meet increased needs during lactation. Women in developing countries whose habitual intakes are near basal needs should receive an additional 100 micrograms retinol equivalents (RE) during pregnancy and 300 micrograms RE during lactation. Supplements not above 3000 micrograms RE (10,000 IU) daily are safe for fertile women where circumstances preclude obtaining the needed increment through diet. The first postpartum month is the only safe period during which to provide deficient lactating women with a single high-dose supplement to benefit the mother and breast-feeding infant for several months."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I396,I396)","v":8202283},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B396:D396)","v":2},1994,"Vitamin A and cancers of the breast, large bowel, and prostate: epidemiologic evidence.","Willett",8202283,"Vitamin A and cancers of the breast, large bowel, and prostate: epidemiologic evidence.    Abstract:   In this review we have examined epidemiological data from a variety of sources to assess the relation between vitamin A intake and cancer risk. The potential for recall bias in case-control studies makes their interpretation difficult, particularly if we are searching for modest associations. Prospective data are preferable, but sparse. Studies of blood levels of carotenoids may be informative if the blood is stored at ultra-low temperatures; however, studies of blood retinol levels are largely uninformative as an index of dietary intake because blood retinol is not well correlated with intake except in vitamin A-deficient populations. We have also reviewed the evidence for an influence of vitamin A intake on the incidence of cancer at the three major cancer sites accounting for a substantial portion of cancers in developed countries. The available data are compatible with a modest inverse association between intake of vitamin A and breast cancer, although it is not clear whether this effect may be due to preformed vitamin A, carotenoids, or both. The evidence that vitamin A protects against colon cancer is unconvincing. In the case of prostate cancer, early suggestions that vitamin A may increase incidence have not been confirmed by subsequent studies. Fortunately, prospective data from a number of large ongoing cohort studies in the United States and Europe should be available within the next 5 years or so. These data will permit further assessment of potential correlations between vitamin A and cancer at various sites by analysis of much larger numbers of cases than are presently available.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I397,I397)","v":8005023},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B397:D397)","v":2},1994,"Vitamins, folic acid and the cause and prevention of neural tube defects.","Seller",8005023,"Vitamins, folic acid and the cause and prevention of neural tube defects.    Abstract:   Primary prevention of neural tube defects has been demonstrated in humans by maternal therapy with multivitamins and folic acid or folic acid alone. It has also been shown in several animal models of neural tube defects. One of these, the curly tail mouse, has been used extensively to study which agents will prevent neural tube defects in embryos when administered to the mother in early pregnancy. Prevention is achieved with retinoic acid, inositol and the DNA inhibitors hydroxyurea, mitomycin C, 5-fluorouracil and cytosine arabinoside. In no case were neural tube defects prevented in every embryo. A possible preventive effect was seen with riboflavin, vitamin C and vitamin D2. Despite the use of a variety of dose levels, no prevention was achieved with folic acid, folinic acid, Pregnavite Forte F tablets, pyridoxine or vitamin B12, or triamcinolone and cycloheximide (inhibitors of mRNA and protein synthesis, respectively), zinc, homocysteine, methionine and thymidine. Various studies have investigated whether there is a biochemical lesion in folate metabolism in women who have had children with neural tube defects. While there is no difference in their dietary intake of folate compared with control patients, the correlation between their dietary folate and the level of folate in both serum and red blood cells is distorted. Also they are less efficient at raising their folate levels after a folate load. The effects are minor but may hint at a lesion which, if identified, could act as a marker for at risk women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I398,I398)","v":8401248},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B398:D398)","v":2},1993,"An appraisal of strategies to reduce the incidence of breast cancer.","Jordan",8401248,"An appraisal of strategies to reduce the incidence of breast cancer.    Abstract:   The current focus of breast cancer research is to develop a novel strategy to prevent the disease. In this review a potential model of breast cancer development is proposed based upon the results of laboratory models of the induction of mammary carcinogenesis. It is clear that susceptibility to initiation occurs in young female animals, and a preventive strategy is more effective the sooner it is started after initiation occurs. In humans we do not know the timing or the nature of the carcinogenic insult, but epidemiologic studies suggest that the process is long and initiation is most likely to occur in young adults. Hormones are the key to promotion of the carcinogenic process and it would appear that strategically the earlier an intervention is applied after initiation the better will be the general effect on the population. Hormonal contraception could prevent breast cancer if the appropriate formulation was chosen and used by all young women. This inhibitory strategy might protect women without the need to preselect based on risk factors. Breast cancer prevention would be a side effect of the contraceptive method. Alternatively, tamoxifen, an antiestrogen, is known to prevent mammary carcinogenesis in animals and prevent the appearance of second primary breast cancers in women. This well tested therapeutic agent is currently being evaluated in clinical trials of selected high-risk women aged 35 and above. Finally, retinoids have shown promise as agents in the laboratory to prevent cell replication and inhibit mammary tumorigenesis. A trial of retinoids to prevent second primary tumors in node negative breast cancer patients is currently underway in Italy. The review discusses the relative merits and concerns about these prevention strategies and proposes additional studies to be undertaken."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I399,I399)","v":8243382},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B399:D399)","v":2},1993,"Impact of the environment on reproduction from conception to parturition.","Sullivan",8243382,"Impact of the environment on reproduction from conception to parturition.    Abstract:   Consideration of environmental influences on human reproduction must include an investigation of the socioeconomic factors that play an important role in embryo-fetal development. Nutritional factors are of prime importance, and modern methods of food production and supply have led to new hazards for pregnant women. For example, pregnant women have been advised in a number of European countries not to eat liver due to the very high concentration (frequently exceeding 100,000 IU per 100 g) of vitamin A. The clear demonstration that periconceptional vitamin supplementation can dramatically reduce the recurrence rate of neural tube defects suggests that folic acid deficiency may be common even in otherwise well-nourished women. Modern methods of food production manufacture and sale have increased the risks of Salmonella and Listeria infections in pregnancy. The dangers of social drug use, especially alcohol and tobacco, are discussed. The types of adverse effect that can result from chemical exposure during the different stages of pregnancy is reviewed with a discussion of some of the problems of epidemiological studies in attempting to identify toxic chemicals. The extent of the ignorance concerning the reproductive toxicity of industrial and environmental chemicals is emphasized by the fact that data are available on only a small percentage of even the high-production volume (1000 tons/year) chemicals. The evidence of reproductive toxicity from exposure to lead, methyl mercury, polychlorinated biphenyls, polychlorinated dibenzofurans, and hexachlorobenzene are briefly reviewed. Some areas of research needs are discussed with emphasis on nutrition, food production, preparation, and storage and the new problems that may be introduced by genetic manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I400,I400)","v":8377392},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B400:D400)","v":2},1993,"[Oncology 1992. Association with ophthalmology and brief status evaluation].","Lohri",8377392,"[Oncology 1992. Association with ophthalmology and brief status evaluation].    Abstract:   Several clinical situations require the cooperation of ophthalmologist and medical oncologist. Systemic metastasis spreading from an ocular primary tumor may rarely pose a problem. Liver metastasis from an ocular melanoma can be treated with intrahepatic chemoembolization and local palliation can be achieved. Disseminated tumors such as breast cancer or leukemias may spread to the eye and require local therapy. Per continuitatem orbital infiltrations of i.e. nasopharyngeal carcinomas need a cooperative management. Ocular side effects from chemo/radiotherapy may be especially severe in high dose therapies such as preparative regimes for allogeneic bone marrow transplants (BMT). A Sjögren-type sicca syndrome, cataracts and a microvasculopathy with cotton wool spots are associated with total body irradiation and the immunosuppression needed in BMT. Cancer research over the past ten years was increasingly influenced by molecular biology which has added to our understanding of tumor biology. The retinoblastoma gene is a typical example of a tumor suppressor gene. It regulates cell growth in its normal physiological state. Deletions may occur, that lead to tumor formation. The detection of oncogenes helps in the diagnosis of leukemias or lymphomas. Growth factors such as the Granulocyte Colony Stimulating Factor (G-CSF) were introduced recently. The differentiation therapy with retinoids has brought a new dimension into the field of cancer treatment and probably also of cancer prophylaxis. Taxol, an alkaloid from the yew tree is a novel cytostatic compound with very promising activity in tumors such as refractory ovarian or breast cancer. High dose therapy with BMT today is an established treatment for certain leukemias.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I401,I401)","v":1457516},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B401:D401)","v":2},1992,"Early detection, epidemiology, and prevention of breast cancer.","Vogel",1457516,"Early detection, epidemiology, and prevention of breast cancer.    Abstract:   Control of breast cancer will ultimately be achieved through a better understanding of the epidemiology of the disease and application of primary prevention. Until then, use of screening mammography offers the promise of a 30% reduction in breast cancer mortality, which continues to be shown by screening studies with prolonged follow-up. Biologic markers of cancer risk, including nipple aspirates and cyst fluid, suggest that a complete risk profile can be developed using fluid and tissue obtained from the normal breast. Epidemiologic studies of dietary factors and geographic differences in breast cancer risk continue to provide promising leads relating to the etiology of the disease. Increasing evidence suggests that circulating androgens and estrogens affect breast cancer risk, whereas exogenous estrogen therapy does not increase risk except for small subgroups of women at risk. Increasing understanding of the genetics of breast cancer will have an impact on the disease in the near future. The greatest impact in the short term will come from the use of tamoxifen for primary prevention of breast cancer. The retinoids, particularly N-(4-hydroxyphenyl)retinamide, hold great promise as agents for primary prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I402,I402)","v":1570803},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B402:D402)","v":2},1992,"The cost of successful adolescent growth and development in girls in relation to iron and vitamin A status.","Brabin",1570803,"The cost of successful adolescent growth and development in girls in relation to iron and vitamin A status.    Abstract:   The role of iron and vitamin A in adolescent growth and development is not well described. During adolescence iron requirements are increased, reaching a maximum at peak growth, but after menarche, menstrual iron loss must also be replaced. An observed rise in retinol-binding protein concentrations at puberty level 4 indicates a role for vitamin A in sexual maturation. Iron and vitamin A deficiencies may slow the tempo of growth. Conversely, for girls on marginal diets, an extended catch-up growth period may lead to depletion of these nutrients. The costs of achieving growth may also include cephalopelvic disproportion in girls becoming pregnant and increased risk of menorrhagia. Few studies have investigated how nutrients such as iron and vitamin A promote adolescent growth or whether the effort of catching up on growth may result in a reduction of iron and vitamin A stores. The intake of these nutrients probably does not rise along with maturational requirements in many developing countries. In situations where adolescent females have a heavy workload, low social status, low priority in food distribution, and high infectious disease rates, growth may be achieved, but at the cost of reductions in stores of certain nutrients. Womens health will be compromised during pregnancy. It is proposed in this paper that growth requirements increase demands for iron and vitamin A and that deficiencies of these nutrients may be a consequence of growth and sexual development in adolescent females on marginal diets. One consequence of reduced iron and vitamin A stores in nonpregnant adolescents may be increased risk of menorrhagia, which contributes further to the problems of anemia in poorly nourished girls in their prereproductive years and beyond. The costs of achieving growth may also include cephalopelvic disproportion in girls becoming pregnant. Sections discuss iron and vitamin A requirements during adolescence, the cost of successful growth, and interactions of vitamin A and iron."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I403,I403)","v":2408256},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B403:D403)","v":2},1990,"Nutritional needs assessment of rural agricultural migrants of southern Brazil: designing, implementing and evaluating a nutrition education program.","Desai",2408256,"Nutritional needs assessment of rural agricultural migrants of southern Brazil: designing, implementing and evaluating a nutrition education program.    Abstract:   A nutritional needs assessment was conducted among rural agricultural migrant women (target group) and children (less than 5 years). The study was conducted in Vila Diogo, a slum located on the periphery of Nuporanga, a village in Sao Paulo state, Brazil. A nutrition education program was designed on the basis of evidence obtained from demographic/socioeconomic information of the study population and a nutritional needs assessment of women (target group) and children less than 5 years of age. The nutritional needs assessment consisted of anthropometry, dietary assessment, and nutrition knowledge, attitudes, and beliefs questionnaires. Formative and summative evaluation of the nutrition education program, using appropriately selected criteria and comparisons of nutrition knowledge scores before and after the program, were used to determine program effectiveness. Major findings of the study were: Diets of Vila Diogo residents were generally simplistic, consisting primarily of rice, beans, and coffee with sugar. Vila Diogo women appeared to be at a relatively high risk for vitamin A, iron, calcium, ascorbic, and riboflavin deficiencies, based on comparisons of 24-hour dietary intake data with FAO recommendations. Children (2-5 years) appeared at high risk for vitamin A, iron, and ascorbic acid deficiencies, based on comparisons of 24-hour dietary intake data with FAO recommendations. All children less than 5 years of age had been breast-fed at birth, but more than one half of children had been weaned by the third month. Infant feeding practices during fever and diarrhea were nutritionally detrimental. Women generally recognized a relationship between dietary intake during pregnancy and fetal nourishment. Using weight-for-height index, a significant number of women were probably undernourished; a small percentage of women, however, were overweight or obese. Although children less than 5 years of age did not generally appear malnourished, a relatively large number were stunted in growth. Although Vila Diogo women reported many food taboos during various physiological states (menstruation, pregnancy, immediately post partum, lactation), relatively few food taboos had potentially negative nutritional consequences. For women who participated in the nutrition education program, nutrition knowledge scores after the program showed improvement which was statistically significant at alpha = 0.05, using Wilcoxon signed rank test."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I404,I404)","v":2109595},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B404:D404)","v":2},1990,"Suppression of tumor promotion by inhibitors of poly(ADP)ribose formation.","Troll",2109595,"Suppression of tumor promotion by inhibitors of poly(ADP)ribose formation.    Abstract:   Tumor promoters, such as phorbol esters or hormones, cause many biological effects which may contribute to the expression of cancer. The mechanism of cancer expression may have a common theme. One method of learning about this common mechanism is the identification of chemicals that interfere with tumor development. That there is actually a common theme between very different substances, such as inflammatory skin tumor promoters and estradiol causing breast cancer, was shown by the fact that both skin and breast cancers are suppressed by the same agents, e.g., protease inhibitors and retinoids. In addition to skin and breast, protease inhibitors suppress colon, bladder, and liver cancers. The substances that crossed over in suppressing many varieties of cancer were found to inhibit oxygen radical formation by tumor promoter-activated neutrophils and ras oncogene expression in NIH 3T3 cells. Poly(ADP)ribose polymerase (PADPR polymerase) may serve as the connecting link between oxygen radicals that cause its activation and oncogene expression. PADPR polymerase is inhibited by retinoids, antioxidants, and some protease inhibitors. Benzamide, an inhibitor of PADPR polymerase, is also a chymotrypsin inhibitor which suppresses oxygen radical formation by tumor promoter-activated neutrophils. The inhibition of PADPR polymerase causes the expulsion of some oncogenes from NIH 3T3 cells at definite times after oncogene transfection. Further work is required to find what are the contributions of PADPR polymerase to tumor promotion and of its inhibitors to suppression of oncogene expression."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I405,I405)","v":2667986},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B405:D405)","v":2},1989,"Protease inhibitors interfere with the necessary factors of carcinogenesis.","Troll",2667986,"Protease inhibitors interfere with the necessary factors of carcinogenesis.    Abstract:   Many tumor promoters are inflammatory agents that stimulate the formation of oxygen radicals (.O2-) and hydrogen peroxide (H2O2) in phagocytic neutrophils. The neutrophils use the oxygen radicals to kill bacteria, which are recognized by the cell membrane of phagocytic cells causing a signal to mount the oxygen response. The tumor promoter isolated from croton oil, 12-O-tetradecanoylphorbol-13-acetate (TPA), mimics the signal, causing an oxygen radical release that is intended to kill bacteria; instead, it injures cells in the host. Oxygen radicals cause single strand breaks in DNA and modify DNA bases. These damaging reactions appear to be related to tumor promotion, as three types of chemopreventive agents, retinoids, onion oil, and protease inhibitors, suppress the induction of oxygen radicals in phagocytic neutrophils and suppress tumor promotion in skin cancer in mice. Protease inhibitors also suppress breast and colon cancers in mice. Protease inhibitors capable of inhibiting chymotrypsin show a greater suppression of the oxygen effect and are better suppressors of tumor promotion. In addition, oxygen radicals may be one of the many agents that cause activation of oncogenes. Since retinoids and protease inhibitors suppress the expression of the ras oncogene in NIH 3T3 cells, NIH 3T3 cells may serve as a relatively facile model for finding and measuring chemopreventive agents that interfere with the carcinogenic process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I406,I406)","v":2654619},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B406:D406)","v":2},1989,"[Exogenous causes of disordered embryonal morphogenesis].","Kunze",2654619,"[Exogenous causes of disordered embryonal morphogenesis].    Abstract:   Recent advances in exogenous factors known to cause embryopathies are reviewed. Among the non-infectious agents alcohol is the most important, followed by a combination of anticonvulsant drugs, valproic acid, retinoic acid, lithium, coumarin derivates, methyl mercury, aminopterin and methotrexate, cocaine and amniogenic bands. Rubella embryopathy is well known. Varicella zoster and herpes simplex type II viruses are now also known to be teratogenic in some cases. Erythema infectiosum has recently been detected as a cause of embryonic death. Diabetic women and women with phenylketonuria must be carefully examined before and during pregnancy. There does not seem to be a world trend towards increased frequency of genetically and non genetically conditioned malformations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I407,I407)","v":2553467},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B407:D407)","v":2},1989,"Toward a dietary prevention of cancer.","Freudenheim",2553467,"Toward a dietary prevention of cancer.    Abstract:   Clearly, there is a need for further elucidation of the role in carcinogenesis of dietary factors. On the epidemiologic level, studies of the last few years indicate the need to investigate further the potential role of fats as related to all the major sites of cancer, to distinguish the effects of various fractions of fiber as well as of fibers deriving from fruits, vegetables and grains, and to examine more closely carotenoids as opposed to retinoids to explore further the proposition that although carotenoids may reduce risk for a number of cancers, retinoids may play no part. Future studies must also reflect more carefully the human experience regarding diet. Because humans do not ingest foods singly, but rather as groups, patterns of intake of groups of foods and nutrients may provide insight into types of diet that affect risk. In nutritional science, there is an increasing appreciation of the complexity of interaction of nutrients both in absorption and in metabolism; future epidemiologic studies of biologic materials as well as of nutrient interactions may be beneficial. Interindividual differences in response to diet which may identify subgroups who are more or less susceptible to particular dietary factors should also be examined. Since dietary exposures affect virtually everyone, the public health implications of even small differences in risk are important. For example, a well substantiated relative risk of 1.2 for a nutrient associated with breast cancer is not trivial. Speculation as to the proportion of total cancer attributable to diet is so tenuous as to be almost frivolous.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I408,I408)","v":2432054},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B408:D408)","v":2},1985,"The role of nutrients in cancer causation.","Newberne",2432054,"The role of nutrients in cancer causation.    Abstract:   The role of nutrients in cancer causation has been a subject of considerable interest, research, and public discussion in recent years. Results from epidemiologic, clinical, and animal studies have suggested that: 1) a reduction in total calories decreases risk for a number of tumor types; 2) dietary protein is directly correlated with liver, prostate, and colon cancer, among others, with increasing dietary protein increasing the risk; 3) increased dietary fat is correlated with increased risk for breast cancer; the evidence for an effect of fat on colon cancer is equivocal in human and animal studies; 4) a deficiency of vitamin A may enhance lung and colon tumors in animal experiments but in human this is equivocal. Increasing vitamin A above normal levels, as an anticarcinogenic effect, has not been satisfactorily demonstrated in animal models. The synthetic retinoid, 13-cis retinoic acid, inhibits both colon and lung cancer in animal models; 5) zinc deficiency is associated with enhanced esophageal cancer in humans and markedly enhances animal tumors; selenium inhibits this form of neoplasia in animals, 6) diets low in lipotropes enhance liver cancer induced by a variety of hepatocarcinogens. Our data from studies in animal models agree in some cases with epidemiological observations, but disagree with others, particularly fat and colon cancer. Overall, some forms of cancer are enhanced by excessive calories, increased dietary protein and fat, and by deficiencies of vitamin A, selenium, zinc, and lipotropes. Decreasing total intake of calories, protein, and fat, and ensuring adequate dietary levels of vitamin A, selenium, zinc, and lipotropes decreases risk for some forms of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I409,I409)","v":6303065},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B409:D409)","v":2},1983,"Cellular retinol- and retinoic acid-binding proteins.","Chytil",6303065,"Cellular retinol- and retinoic acid-binding proteins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I410,I410)","v":7031543},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B410:D410)","v":2},1981,"Risks and benefits of nutritional supplements during pregnancy.","Moghissi",7031543,"Risks and benefits of nutritional supplements during pregnancy.    Abstract:   This review emphasizes the role of minerals and vitamins in pregnancy. Of the trace elements, iron, copper, zinc, and iodine have a fundamental role in human nutrition. Supplementation of iron, zinc, and iodine in the diet of all pregnant women, when dietary deficiencies exist, seems justified. The average diet in developed countries contains sufficient amounts of various vitamins, with the exception of folic acid, which may require supplementation. However, in developing nations and among poor populations in which the diet is inadequate, additional supplies of micronutrients are advisable."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I411,I411)","v":6116096},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B411:D411)","v":2},1981,"Breastfeeding in developing countries.","Villar",6116096,"Breastfeeding in developing countries.    Abstract:   The calculated protein and calorie requirements and nutritional status of intrauterine-growth-retarded infants of poor mothers in underdeveloped countries were compared with the estimated amounts of protein and calories supplied in the mothers milk and their nutritional status both before and during lactation. These mothers were only able to provide 69% of the infants protein requirements at birth, falling to 51% at three months of age 123% of calorie requirements were supplied at birth, falling to 55% at three months. Conversely, in terms of g protein per 100 kcal, 56% of requirements were met at birth, rising to 95% at three months-figures which reflect the decreasing protein requirement with age. Socioeconomic factors determine nutritional status in developing countries and it is the responsibility of governments to ensure the health and adequate nutrition of mothers and infants. Mothers should be able to lay down nutritional reserves during pregnancy, and to remain well fed throughout lactation. This is not the case in developing countries, where poorly nourished mothers gave birth to low birth weight infants in a much higher percentage than in developed countries (17% versus 6%). In some areas 75% of infants are intrauterine-growth-retarded (IUGR); these are the infants most at risk of perinatal death and illness. The protein requirements for IUGR infants has been calculated to be 2.53 g/kg/body weight at 1 month, and 2.16 and 1.92 at 2 and at 3 months, respectively. A malnourished mother usually gains only 5-7 kgs during pregnancy, which means not enough stored fat, and her daily intake of nutrients falls below the recommended level; the volume of milk produced is not enough, and its protein, caloric and aminoacid content not sufficient; these facts may help explain the high mortality rate in wholly breastfed infants in some developing countries. Studies conducted in third world countries showed that malnourished mothers were able to provide only 69% of the infants protein requirements at birth, and only 51% at 3 months; while 123% of calorie requirements were supplied at birth only 55% were supplied at 3 months. In terms of g pretein per 100 kcal 56% of requirements were met at birth, and 95% at 3 months, showing the decreased protein requirements with age. Low levels of vitamin A, B, and C, and of calcium have also been found in the milk of mothers from developing countries. Since the nutritional status of mothers and infants depends mostly on socioeconomic factors, it should be up to governments to secure adequate nutrition to mothers and babies alike."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I412,I412)","v":389022},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B412:D412)","v":2},1979,"Retinoic acid--a review.","Ott",389022,"Retinoic acid--a review.    Abstract:   Retinoic acid (RA) is now considered anormal metabolite of vitamin A. It has been established that RA maintains health and supports growth in animals but differs from other forms of vitamin A in that RA does not function in visual or reproductive processes. RA and RA analogs also differ from other forms of vitamin A in: absorption, transport, metabolism, storage, turnover, biochemical functions, excretion, pharmacology, and toxicology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I413,I413)","v":327356},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B413:D413)","v":2},1977,"Cellular retinol and retinoic acid binding proteins.","Jelliffe",327356,"Cellular retinol and retinoic acid binding proteins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I414,I414)","v":812958},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B414:D414)","v":2},1975,"[A case of Goldenhar syndrome: acute vitamin A intoxication in the mother during pregnancy].","Mounoud",812958,"[A case of Goldenhar syndrome: acute vitamin A intoxication in the mother during pregnancy].    Abstract:   The authors describe the case of a boy aged 2 1/2, who showed at birth a bilateral epibulbar dermoid, preauricular appendices on the left side and other malformations suggesting Goldenhars syndrome. The history disclosed that in the second month of pregnancy the mother had accidentally swallowed 10 ml of an oily solution of Vitamin A during a laboratory manipulation. In their discussion, the autonrs analyse the teratogenic action of Vitamin A during embryonic development and review the aetiologies found in cases of Goldenhars syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I415,I415)","v":27609747},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B415:D415)","v":1},2016,"Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy.","Dandawate",27609747,"Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy.    Abstract:    NlmCategory=UNASSIGNEDBreast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3-di-indolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I416,I416)","v":27282881},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B416:D416)","v":1},2016,"Steroid receptor RNA activator: Biologic function and role in disease.","Liu",27282881,"Steroid receptor RNA activator: Biologic function and role in disease.    Abstract:   Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I417,I417)","v":27200367},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B417:D417)","v":1},2015,"Pan-cancer analyses of the nuclear receptor superfamily.","Long",27200367,"Pan-cancer analyses of the nuclear receptor superfamily.    Abstract:    NlmCategory=UNASSIGNEDNuclear receptors (NR) act as an integrated conduit for environmental and hormonal signals to govern genomic responses, which relate to cell fate decisions. We review how their integrated actions with each other, shared co-factors and other transcription factors are disrupted in cancer. Steroid hormone nuclear receptors are oncogenic drivers in breast and prostate cancer and blockade of signaling is a major therapeutic goal. By contrast to blockade of receptors, in other cancers enhanced receptor function is attractive, as illustrated initially with targeting of retinoic acid receptors in leukemia. In the post-genomic era large consortia, such as The Cancer Genome Atlas, have developed a remarkable volume of genomic data with which to examine multiple aspects of nuclear receptor status in a pan-cancer manner. Therefore to extend the review of NR function we have also undertaken bioinformatics analyses of NR expression in over 3000 tumors, spread across six different tumor types (bladder, breast, colon, head and neck, liver and prostate). Specifically, to ask how the NR expression was distorted (altered expression, mutation and CNV) we have applied bootstrapping approaches to simulate data for comparison, and also compared these NR findings to 12 other transcription factor families. Nuclear receptors were uniquely and uniformly downregulated across all six tumor types, more than predicted by chance. These approaches also revealed that each tumor type had a specific NR expression profile but these were most similar between breast and prostate cancer. Some NRs were down-regulated in at least five tumor types (e.g. NR3C2/MR and NR5A2/LRH-1)) whereas others were uniquely down-regulated in one tumor (e.g. NR1B3/RARG). The downregulation was not driven by copy number variation or mutation and epigenetic mechanisms maybe responsible for the altered nuclear receptor expression."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I418,I418)","v":27149979},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B418:D418)","v":1},2016,"Protein pathways working in human follicular fluid: the future for tailored IVF?","Bianchi",27149979,"Protein pathways working in human follicular fluid: the future for tailored IVF?    Abstract:   The human follicular fluid (HFF) contains molecules and proteins that may affect follicle growth, oocyte maturation and competence acquiring. Despite the numerous studies, an integrated broad overview on biomolecular and patho/physiological processes that are proved or supposed to take place in HFF during folliculogenesis and oocyte development is still missing. In this review we report, for the first time, all the proteins unambiguously detected in HFF and, applying DAVID (Database for Annotation, Visualization and Integrated Discovery) and MetaCore bioinformatic resources, we shed new lights on their functional correlation, delineating protein patterns and pathways with reasonable potentialities for oocyte quality estimation in in vitro fertilisation (IVF) programs. Performing a rigorous PubMed search, we redacted a list of 617 unique proteins unambiguously-annotated as HFF components. Their functional processing suggested the occurrence in HFF of a tight and highly dynamic functional-network, which is balanced by specific effectors, primarily involved in extracellular matrix degradation and remodelling, inflammation and coagulation. Metalloproteinases, thrombin and vitamin-D-receptor/retinoid-X-receptor-alpha resulted as the main key factors in the nets and their differential activity may be indicative of ovarian health and oocyte quality. Despite future accurate clinical investigations are absolutely needed, the present analysis may provide a starting point for more accurate oocyte quality estimation and for defining personalised therapies in reproductive medicine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I419,I419)","v":26982298},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B419:D419)","v":1},2015,"Vitamin A supplementation in Brazilian pregnant and postpartum women: a systematic review.","Neves",26982298,"Vitamin A supplementation in Brazilian pregnant and postpartum women: a systematic review.    Abstract:    OBJECTIVE : To assess the impact of vitamin A supplementation on adult pregnant and puerperal women in Brazil regarding the content of vitamin A and secretory immunoglobulin A on colostrum and breast milk, in childs health conditions, and in mother-child binomial vitamin A status.  METHODS : A research was conducted in Medline, Scopus, Web of Science, and Lilacs electronic databases for the studies published between January 2000 and January 2014. The methodological quality of the studies was assessed according to Jadad scale. The study search was conducted in January 2014, independently by two authors.  RESULTS : Seven studies were found concerning the effects of vitamin A supplementation in the puerperal period on breast milk and infant morbidity. No study regarding pregnant women supplementation was found. The supplementation in the puerperal period raised the retinol content on breast milk, thus increasing the offer of vitamin A for the child and the concentration of secretory immunoglobulin A on colostrum. There was no description of effects on infant morbidity.  CONCLUSION : It seems that the advantages of postpartum supplementation were not established in the Brazilian program, although the supplementation contributes to a better nutritional status of vitamin A for both the child and the puerperal woman and increases the offer of vitamin A for the newborn through the breast milk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I420,I420)","v":26844556},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B420:D420)","v":1},2016,"Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment.","Huang",26844556,"Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment.    Abstract:   Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I421,I421)","v":26648652},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B421:D421)","v":1},2015,"Drugs in breastfeeding.","Hotham",26648652,"Drugs in breastfeeding.    Abstract:   Most commonly used drugs are relatively safe for breastfed babies. The dose received via milk is generally small and much less than the known safe doses of the same drug given directly to neonates and infants. Drugs contraindicated during breastfeeding include anticancer drugs, lithium, oral retinoids, iodine, amiodarone and gold salts. An understanding of the principles underlying the transfer into breast milk is important, as is an awareness of the potential adverse effects on the infant. Discussion with the mother about the possibility of either negative product information or ill-informed advice from others will reduce the confusion and anxiety that may be generated. Good resources about medicines and breastfeeding are available and include state-based medicines information services."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I422,I422)","v":26469117},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B422:D422)","v":1},2015,"Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.","Zdrojewicz",26469117,"Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.    Abstract:   Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper). Both are responsible for sperm motility. Drugs such as thioridazine used in schizophrenia treatment and phenoxybenzamine (antihypertensive activity) exhibit a contraceptive effect. Similar action exhibits an analogue of lonidamine--adjudin and an antagonist of retinoic acid receptors (BMS-189453). Researchers are working on a contraceptive vaccine, whose active ingredient is epididymal protease inhibitor (Eppin). Another promising method acts by blocking Bromodomain testis-specific proteins (Brdt) involved in the process of spermatogenesis. JQ1-the Brdt inhibitor causes reversible infertility without affecting the endocrine signaling pathways. A recent discovery of Juno as the binding partner for Izumo1 identifies these proteins as the cell-surface receptor pair, essential for gamete recognition and this interaction can be inhibited by an anti-Juno monoclonal antibody. Our review shows that the situation of men can change and investigators are close to the optimal solution. In the near future men will be able to choose the best contraceptive suited to their needs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I423,I423)","v":26401661},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B423:D423)","v":1},2015,"From Sex Determination to Initial Folliculogenesis in Mammalian Ovaries: Morphogenetic Waves along the Anteroposterior and Dorsoventral Axes.","Suzuki",26401661,"From Sex Determination to Initial Folliculogenesis in Mammalian Ovaries: Morphogenetic Waves along the Anteroposterior and Dorsoventral Axes.    Abstract:   Gonadal sex in most mammals is determined based on sex differentiation of the supporting cell lineages. In mouse XY gonads, SRY induces SOX9 upregulation and subsequent FGF9 expression by embryonic day 11.5 (E11.5), leading to the differentiation of Sertoli cells. XX gonads, lacking SRY action, start on the ovarian program through the actions of WNT4 and FOXL2 from around E11.5-12.0. These 2 ovarian factors, together with retinoic acid (RA) action, promote feminization partially through the repression of the masculinizing activities of SOX9, FGF9 and DMRT1. RA initiates meiosis in female germ cell cysts, in which intercellular bridges between interconnected germ cells rapidly undergo cyst breakdown by E17.5. Ovarian morphogenesis is characterized by continuous recruitment of pre-granulosa progenitor cells from the coelomic epithelia during the embryonic stage, which results in the formation of ovigerous cords and tight packing of non-interconnected oocytes (i.e. oocyte nests) at the perinatal stages. At birth, the oocyte nests break down into single oocytes surrounded by granulosa cells, leading to the assembly of primordial follicles. This review focuses on recent advances in the molecular and cellular events of initial ovarian differentiation, meiotic initiation, germ cell nest breakdown, and primordial follicle formation based on anatomical and morphogenetic aspects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I424,I424)","v":26398295},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B424:D424)","v":1},2015,"Diet for a Healthy Lactating Woman.","Kolasa",26398295,"Diet for a Healthy Lactating Woman.    Abstract:   The nutrient and caloric requirements for lactation are set by the Institute of Medicine. The dietary pattern to meet those needs is found in the Dietary Guidelines for Americans. Only deficiency states for selected nutrients and/or prolonged inadequate caloric intake appear to affect the volume and quality of breast milk. Other dietary concerns of lactating women include quot;dietingquot; to return to prepregnancy weight; low maternal intake of selected nutrients due to health conditions or food choices; need for supplementation of calcium, vitamin D, and fatty acids; and use of non-nutritive sweeteners, caffeine, herbal supplements, and alcohol."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I425,I425)","v":26373900},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B425:D425)","v":1},2016,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.","Marcadier",26373900,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.    Abstract:   PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I426,I426)","v":26178026},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B426:D426)","v":1},2015,"Maternal micronutrient deficiencies and related adverse neonatal outcomes after bariatric surgery: a systematic review.","Jans",26178026,"Maternal micronutrient deficiencies and related adverse neonatal outcomes after bariatric surgery: a systematic review.    Abstract:   Pregnant and postpartum women with a history of bariatric surgery are at risk of micronutrient deficiencies as a result of the combination of physiologic changes related to pregnancy and iatrogenic postoperative alterations in the absorption and metabolism of crucial nutrients. This systematic review investigates micronutrient deficiencies and related adverse clinical outcomes in pregnant and postpartum women after bariatric surgery. A systematic approach involving critical appraisal was conducted independently by 2 researchers to examine deficiencies of phylloquinone, folate, iron, calcium, zinc, magnesium, iodide, copper, and vitamins A, D, and B-12 in pregnant and postpartum women after bariatric surgery, together with subsequent outcomes in the neonates. The search identified 29 relevant cases and 8 cohort studies. The quality of reporting among the case reports was weak according to the criteria based on the CARE (CAse REporting) guidelines as was that for the cohort studies based on the criteria from the Cohort Study Quality Assessment list of the Dutch Cochrane Center. The most common adverse neonatal outcomes related to maternal micronutrient deficiencies include visual complications (vitamin A), intracranial hemorrhage (phylloquinone), neurological and developmental impairment (vitamin B-12), and neural tube defects (folate). On the basis of the systematically collected information, we conclude that the evidence on micronutrient deficiencies in pregnant and postpartum women after bariatric surgery and subsequent adverse neonatal outcomes remains weak and inconclusive."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I427,I427)","v":26166560},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B427:D427)","v":1},2015,"Nutrition and maternal, neonatal, and child health.","Christian",26166560,"Nutrition and maternal, neonatal, and child health.    Abstract:   This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and young children to help advance the global MNCH agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I428,I428)","v":26149504},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B428:D428)","v":1},2015,"[Revaluation of the concept of developmental abnormality: the importance of faulty perinatal imprinting].","Csaba",26149504,"[Revaluation of the concept of developmental abnormality: the importance of faulty perinatal imprinting].    Abstract:   The classic definition of developmental abnormalities referred to malformations observed at birth. Later the functional teratogenicity was also recognized and accepted, which can be revealed in functional abnormalities caused by harms during the intrauterine development and can be manifested at any time of life. However, the ontogeny is not closed with the birth, because some systems or organs are developing for a long time after it, and can be influenced by different factors. From this aspect the perinatal period is especially important when the mutual adjustment of the receptor-hormone system is taking place and the hormonal imprinting develops. If this is faulty, it influences the hormone binding capacity of receptors that has consequences for life. The faulty hormonal imprinting is functionally teratogen; it provokes a fault up to the level of a malformation and aggravated with its heredity to the progenies. False imprinting is provoked (in animal experiments, proportioning to human doses) by drugs acting at receptor level, as oxytocin, steroid hormone analogues (pregnancy protectors, oral contraceptives, surfactants), vitamin A and D, environmental pollutant endocrine disruptors (benzpyrene, bisphenol A, pesticides, herbicides) and certain soybean components, etc. From this aspect these are functional teratogens, and their evasion in prevention as well as therapy seems to be vital. This means that the concept of developmental abnormality must be broadened, as developmental abnormalities: 1.) can originate not only in the intrauterine period, but also perinatally or even later, 2.) it can be manifested at any time of life, 3.) it can be present in a latent form which can be activated by inner or outer environmental factors, 4.) the faulty hormonal imprinting is a teratogen factor."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I429,I429)","v":26143434},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B429:D429)","v":1},2015,"Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.","Guidry",26143434,"Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.    Abstract:   Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I430,I430)","v":25806650},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B430:D430)","v":1},2016,"Preparing normal tissue cells for space flight experiments.","Koch",25806650,"Preparing normal tissue cells for space flight experiments.    Abstract:   Deterioration of health is a problem in modern space flight business. In order to develop countermeasures, research has been done on human bodies and also on single cells. Relevant experiments on human cells in vitro are feasible when microgravity is simulated by devices such as the Random Positioning Machine or generated for a short time during parabolic flights. However, they become difficult in regard to performance and interpretation when long-term experiments are designed that need a prolonged stay on the International Space Station (ISS). One huge problem is the transport of living cells from a laboratory on Earth to the ISS. For this reason, mainly rapidly growing, rather robust human cells such as cancer cells, embryonic cells, or progenitor cells have been investigated on the ISS up to now. Moreover, better knowledge on the behavior of normal mature cells, which mimic the in vivo situation, is strongly desirable. One solution to the problem could be the use of redifferentiable cells, which grow rapidly and behave like cancer cells in plain medium, but are reprogrammed to normal cells when substances like retinoic acid are added. A list of cells capable of redifferentiation is provided, together with names of suitable drugs, in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I431,I431)","v":25628116},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B431:D431)","v":1},2015,"Environmental aspects of congenital scoliosis.","Li",25628116,"Environmental aspects of congenital scoliosis.    Abstract:   Growing evidence has proved that many aspects of our lifestyle and the environment contribute to the development of congenital disease. Congenital spinal deformities are due to anomalous development of the vertebrae including failure of formation and segmentation during embryogenesis. The causes of congenital scoliosis have not been fully identified. A variety of factors are implicated in the development of vertebral abnormalities. Previous studies have demonstrated that both genetics and environmental factors are implicated in the development of vertebral abnormalities. However, no specific cause for congenital scoliosis has been identified. In our review, we focus on the environmental factors for the development of congenital scoliosis. Various maternal exposures during pregnancy including hypoxia, alcohol use, vitamin deficiency, valproic acid, boric acid, and hyperthermia have been observed to be associated with the occurrence of congenital scoliosis. This review describes the major environmental contributors of congenital scoliosis with an emphasis on treatment aspects associated with environmental disposition in congenital scoliosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I432,I432)","v":25455729},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B432:D432)","v":1},2014,"Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers.","Roshan-Moniri",25455729,"Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers.    Abstract:   Nuclear receptors (NRs), a family of 48 transcriptional factors, have been studied intensively for their roles in cancer development and progression. The presence of distinctive ligand binding sites capable of interacting with small molecules has made NRs attractive targets for developing cancer therapeutics. In particular, a number of drugs have been developed over the years to target human androgen- and estrogen receptors for the treatment of prostate cancer and breast cancer. In contrast, orphan nuclear receptors (ONRs), which in many cases lack known biological functions or ligands, are still largely under investigated. This review is a summary on ONRs that have been implicated in prostate and breast cancers, specifically retinoic acid-receptor-related orphan receptors (RORs), liver X receptors (LXRs), chicken ovalbumin upstream promoter transcription factors (COUP-TFs), estrogen related receptors (ERRs), nerve growth factor 1B-like receptors, and ‘‘dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1’’ (DAX1). Discovery and development of small molecules that can bind at various functional sites on these ONRs will help determine their biological functions. In addition, these molecules have the potential to act as prototypes for future drug development. Ultimately, the therapeutic value of targeting the ONRs may go well beyond prostate and breast cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I433,I433)","v":25372763},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B433:D433)","v":1},2014,"Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling.","Jørgensen",25372763,"Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling.    Abstract:   Meiosis is a unique type of cell division that is performed only by germ cells to form haploid gametes. The switch from mitosis to meiosis exhibits a distinct sex-specific difference in timing, with female germ cells entering meiosis during fetal development and male germ cells at puberty when spermatogenesis is initiated. During early fetal development, bipotential primordial germ cells migrate to the forming gonad where they remain sexually indifferent until the sex-specific differentiation of germ cells is initiated by cues from the somatic cells. This irreversible step in gonadal sex differentiation involves the initiation of meiosis in fetal ovaries and prevention of meiosis in the germ cells of fetal testes. During the last decade, major advances in the understanding of meiosis regulation have been accomplished, with the discovery of retinoic acid as an inducer of meiosis being the most prominent finding. Knowledge about the molecular mechanisms regulating meiosis signaling has mainly been established by studies in rodents, while this has not yet been extensively investigated in humans. In this review, the current knowledge about the regulation of meiosis signaling is summarized and placed in the context of fetal gonad development and germ cell differentiation, with emphasis on results obtained in humans. Furthermore, the consequences of dysregulated meiosis signaling in humans are briefly discussed in the context of selected pathologies, including testicular germ cell cancer and some forms of male infertility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I434,I434)","v":25333772},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B434:D434)","v":1},2014,"IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (review).","Durzyńska",25333772,"IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (review).    Abstract:   The insulin-like growth factor (IGF) axis promotes the growth of cells, tissues and organs. IGF-1 is mainly produced in the liver but is also secreted from local tissues. In the circulation, IGF-1 is bound to insulin-like binding proteins (IGFBPs), and when released it activates the insulin-like growth factor receptor (IGF-1R). The signal is further transmitted by intracellular signaling pathways leading to gene expression that regulates, among others, cell proliferation and survival. This review presents the IGF axis in the context of cell transformation and cancer development. Aspects involving IGF-1 deficiency and protection from cancer are also briefly described. Furthermore, human papillomaviruses (HPVs) interplaying with IGF axis components in cervical cancer development are described. These small dsDNA viruses are divided into low-risk and high-risk HPVs with regard to the potency of their oncogenic actions; they mainly infect epithelial or mucosal cells. Special attention is drawn to expression of two major HPV oncogenes (E6 and E7) initiating and maintaining cervical carcinogenesis, which is a multistep and multifactorial process; therefore, involvement of additional factors such as mitochondrial DNA changes, sex hormones, retinoic and folic acids are also discussed. Finally, IGF axis components and HPV oncogenes as targets in anticancer treatment are presented which include IGF-1R downregulation, RNA interference and anti-HPV therapeutic vaccines. The review concludes that despite an enormous advancement in research on IGF and HPV-related cancers, more molecular studies and clinical trials are needed before commercialized therapies are widely available for oncology patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I435,I435)","v":24829621},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B435:D435)","v":1},2014,"Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.","Litzenburger",24829621,"Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.    Abstract:   Preventing breast cancer is an effective strategy for reducing breast cancer deaths. The purpose of chemoprevention (also termed preventive therapy) is to reduce cancer incidence by use of natural, synthetic, or biological agents. The efficacy of tamoxifen, raloxifene, and exemestane as preventive therapy against estrogen-receptor (ER)-positive breast cancer is well established for women at increased risk for breast cancer. However, because breast cancer is a heterogeneous disease, distinct preventive approaches may be required for effective prevention of each subtype. Current research is, therefore, focused on identifying alternative mechanisms by which biologically active compounds can reduce the risk of all breast cancer subtypes including ER-negative breast cancer. Promising agents are currently being developed for prevention of HER2-positive and triple-negative breast cancer (TNBC) and include inhibitors of the ErbB family receptors, COX-2 inhibitors, metformin, retinoids, statins, poly(ADP-ribose) polymerase inhibitors, and natural compounds. This review focuses on recent progress in research to develop more effective preventive agents, in particular for prevention of ER-negative breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I436,I436)","v":24552013},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B436:D436)","v":1},2014,"[30 years with isotretinoin. quot;Miracle medicinequot; against acne with many side effects].","Mobacken",24552013,"[30 years with isotretinoin. quot;Miracle medicinequot; against acne with many side effects].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I437,I437)","v":24502598},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B437:D437)","v":1},2014,"Teratogenic activity of HDAC inhibitors.","Giavini",24502598,"Teratogenic activity of HDAC inhibitors.    Abstract:   Modification of the terminal tails of histones is considered one of the documented mechanisms for epigenetic control of gene expression. Histone deacetylase inhibitors (HDACi) lead to a state of hyperacetylation of histone, a condition that can affect normal gene transcription. Furthermore, HDACi have many other protein targets involved in regulation of gene expression, cell proliferation and cell death. For these properties some HDACi are nowadays used as anticancer drugs with promising results. Several molecules with HDACi properties (valproic acid, trichostatin A, apicidin, MS-275, sodium butyrate, boric acid, salicylic acid) have been found to induce congenital malformations associated with hyperacetylation of histones in the target organs. Cell death is the major event in the target organs a few hours after embryonic exposure to HDACi. Gene deregulation, oxidative stress, DNA demethylation, and/or retinoic acid imbalance are the modes of action postulated for HDACi-induced teratogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I438,I438)","v":25835237},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B438:D438)","v":1},2014,"The potential of orange-fleshed sweet potato to prevent vitamin A deficiency in Africa.","Gurmu",25835237,"The potential of orange-fleshed sweet potato to prevent vitamin A deficiency in Africa.    Abstract:    PURPOSE : Vitamin A deficiency is among major health problems worldwide that leads to blindness, retarded growth and death, particularly in developing countries. In these countries, vitamin A deficiency largely affects pre-school children, pregnant and lactating mothers, and the rural poor. For instance, the predicted prevalence of vitamin A deficiency for 36 sub-Saharan African countries is 19.1%.  METHODS : Different strategies, including vitamin A supplementation, food fortification and dietary diversification, have been used to combat this problem. However, these strategies are not sustainable due to their high costs.  RESULTS : Orange-fleshed sweet potato (Ipomoea batatas L. Lam) is a low priced crop, which is part of staple foods in most of sub-Saharan Africa that can be a year-round source of vitamin A. Most of the orange-fleshed sweet potato varieties contain 3000-16000 μg 100 g(-1) of β-carotene and this contributes to 250 to 1300 μg 100 g(-1) Retinol Activity Equivalents (RAE). Therefore, by using orange-fleshed sweet potato, it is possible to improve vitamin A status, increase the bio-availability of different micro-nutrients such as Fe, Zn, Ca and Mg, reduce vitamin A deficiency and hence reduce child mortality rates by 23 to 30%.  CONCLUSION : The article highlights the significance of vitamin A for human nutrition, the effect of vitamin A deficiency, the different prevention methods and the potential of orange- fleshed sweet potato as a food crop to prevent vitamin A deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I439,I439)","v":24069582},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B439:D439)","v":1},2013,"Targeted therapy for breast cancer prevention.","den Hollander",24069582,"Targeted therapy for breast cancer prevention.    Abstract:   With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I440,I440)","v":23746772},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B440:D440)","v":1},2013,"Maternal and child undernutrition and overweight in low-income and middle-income countries.","Black",23746772,"Maternal and child undernutrition and overweight in low-income and middle-income countries.    Abstract:   Maternal and child malnutrition in low-income and middle-income countries encompasses both undernutrition and a growing problem with overweight and obesity. Low body-mass index, indicative of maternal undernutrition, has declined somewhat in the past two decades but continues to be prevalent in Asia and Africa. Prevalence of maternal overweight has had a steady increase since 1980 and exceeds that of underweight in all regions. Prevalence of stunting of linear growth of children younger than 5 years has decreased during the past two decades, but is higher in south Asia and sub-Saharan Africa than elsewhere and globally affected at least 165 million children in 2011; wasting affected at least 52 million children. Deficiencies of vitamin A and zinc result in deaths; deficiencies of iodine and iron, together with stunting, can contribute to children not reaching their developmental potential. Maternal undernutrition contributes to fetal growth restriction, which increases the risk of neonatal deaths and, for survivors, of stunting by 2 years of age. Suboptimum breastfeeding results in an increased risk for mortality in the first 2 years of life. We estimate that undernutrition in the aggregate--including fetal growth restriction, stunting, wasting, and deficiencies of vitamin A and zinc along with suboptimum breastfeeding--is a cause of 3·1 million child deaths annually or 45% of all child deaths in 2011. Maternal overweight and obesity result in increased maternal morbidity and infant mortality. Childhood overweight is becoming an increasingly important contributor to adult obesity, diabetes, and non-communicable diseases. The high present and future disease burden caused by malnutrition in women of reproductive age, pregnancy, and children in the first 2 years of life should lead to interventions focused on these groups."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I441,I441)","v":23736028},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B441:D441)","v":1},2013,"Functional and cancer genomics of ASXL family members.","Katoh",23736028,"Functional and cancer genomics of ASXL family members.    Abstract:   Additional sex combs-like (ASXL)1, ASXL2 and ASXL3 are human homologues of the Drosophila Asx gene that are involved in the regulation or recruitment of the Polycomb-group repressor complex (PRC) and trithorax-group (trxG) activator complex. ASXL proteins consist of ASXN, ASXH, ASXM1, ASXM2 and PHD domains. ASXL1 directly interacts with BAP1, KDM1A (LSD1), NCOA1 and nuclear hormone receptors (NHRs), such as retinoic acid receptors, oestrogen receptor and androgen receptor. ASXL family members are epigenetic scaffolding proteins that assemble epigenetic regulators and transcription factors to specific genomic loci with histone modifications. ASXL1 is involved in transcriptional repression through an interaction with PRC2 and also contributes to transcriptional regulation through interactions with BAP1 and/or NHR complexes. Germ-line mutations of human ASXL1 and ASXL3 occur in Bohring-Opitz and related syndromes. Amplification and overexpression of ASXL1 occur in cervical cancer. Truncation mutations of ASXL1 occur in colorectal cancers with microsatellite instability (MSI), malignant myeloid diseases, chronic lymphocytic leukaemia, head and neck squamous cell carcinoma, and liver, prostate and breast cancers; those of ASXL2 occur in prostate cancer, pancreatic cancer and breast cancer and those of ASXL3 are observed in melanoma. EPC1-ASXL2 gene fusion occurs in adult T-cell leukaemia/lymphoma. The prognosis of myeloid malignancies with misregulating truncation mutations of ASXL1 is poor. ASXL family members are assumed to be tumour suppressive or oncogenic in a context-dependent manner."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I442,I442)","v":23728640},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B442:D442)","v":1},2013,"Vaccines for women to prevent neonatal tetanus.","Demicheli",23728640,"Vaccines for women to prevent neonatal tetanus.    Abstract:    BACKGROUND : Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin.  OBJECTIVES : To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus.  SEARCH METHODS : We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (31 October 2012), The Cochrane Library (2012, Issue 10), PubMed (1966 to 31 October 2012), EMBASE (1974 to 31 October 2012). We also used the results from handsearching and consultations with manufacturers and authors.  SELECTION CRITERIA : Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths.  DATA COLLECTION AND ANALYSIS : Three review authors independently assessed trials for inclusion and trial quality, and extracted data.  MAIN RESULTS : Two trials (10,560 infants) were included. It should be noted that these trials are very old,1966 and 1980 respectively, and one trial randomised exclusively non-pregnant women. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. One study (1919 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. After a single dose, the risk ratio (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two- or three-dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at four to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%).  AUTHORS CONCLUSIONS : Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I443,I443)","v":23565653},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B443:D443)","v":1},2013,"The biology of the peroxisome proliferator-activated receptor system in the female reproductive tract.","Vélez",23565653,"The biology of the peroxisome proliferator-activated receptor system in the female reproductive tract.    Abstract:   Fuel sensors such as glucose, insulin or leptin, are known to be directly involved in the regulation of fertility at each level of the hypothalamic-pituitary-gonadal axis. The discovery of the peroxisome proliferator-activated receptor (PPAR) family of transcription factors has revealed the link between lipid/glucose availability and long-term metabolic adaptation. By binding to specific regions of DNA in heterodimers with the retinoid X receptors (RXRs), the members of the PPAR family (α, β/δ, γ) are able to regulate the gene expressions of several key regulators of energy homeostasis including several glucose regulators (glucose transporters, insulin receptor, substrate insulin receptor, etc), and also metabolic and endocrine pathways like lipogenesis, steroidogenesis, ovulation, oocyte maturation, maintenance of the corpus luteum, nitric oxide system, several proteases and plasminogen activator among others. All the three PPAR isoforms are expressed in different tissues of the female reproductive tract and regulate gametogenesis, ovulation, corpus luteum regression and the implantation process among others. The present review discusses the mechanisms involved in PPAR activation focusing on endogenous and synthetic ligands of PPAR not only in physiological but also in pathological conditions (such as polycystic ovary syndrome, pathologies of implantation process, chronic anovulation, etc)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I444,I444)","v":23540474},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B444:D444)","v":1},2013,"No evidence for topical preparations in preventing stretch marks in pregnancy.","McAvoy",23540474,"No evidence for topical preparations in preventing stretch marks in pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I445,I445)","v":23500006},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B445:D445)","v":1},2013,"Effects of probiotic administration on zebrafish development and reproduction.","Carnevali",23500006,"Effects of probiotic administration on zebrafish development and reproduction.    Abstract:   As the consumption of probiotics increases worldwide, scientists focus on identifying bacterial strains able to improve human life quality and evidence the biological pathways affected by probiotic treatment. In this review, some recent observations on the effects of changes of microbiota on zebrafish metabolism were discussed. In addition, the effects of Lactobacillus rhamnosus - a component of the human gut microflora - as a diet supplement on Danio rerio were presented. When administered chronically, L. rhamnosus may affect larval development and the physiology of reproductive system in the zebrafish model. It was hypothesized exogenous L. rhamnosus accelerates larval growth and backbone development by acting on insulin-like growth factors-I (igfI) and -II (igfII), peroxisome proliferator activated receptors-α and -β, (pparα,β) vitamin D receptor-α (vdrα) and retinoic acid receptor-γ (rarγ). Gonadal differentiation was anticipated at 6weeks together with a higher expression of gnrh3 at the larval stage when L. rhamnosus was administered throughout development. Moreover, brood stock alimented with a L. rhamnosus-supplemented diet showed better reproductive performances as per follicles development, ovulated oocytes quantification and embryos quality. A plausible involvement of factors such as leptin, and kiss1 and 2 in the improvements was concluded. The observations made on the physiology of female reproduction were correlated with the gene expression of a gigantic number of factors as the aromatase cytochrome p 19 (cyp19a), the vitellogenin (vtg) and the α isoform of the E2 receptor (erα), luteinizing hormone receptor (lhr), 20-β hydroxysteroid dehydrogenase (20β-hsd), membrane progesterone receptors α and β, cyclin B, activinβA1, smad2, transforming growth factor β1 (tgfβ1), growth differentiation factor9 (gdf9) and bone morphogenetic protein15 (bmp15.) A model in which the exogenous L. rhamnosus in the digestive tract of zebrafish from the first days of life through sexual maturation positively influences the physiological performances of zebrafish was evidenced and a number of pathways that might be influenced by the presence of this human probiotic strain were proposed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I446,I446)","v":23417400},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B446:D446)","v":1},2012,"Regulation of germ cell meiosis in the fetal ovary.","Spiller",23417400,"Regulation of germ cell meiosis in the fetal ovary.    Abstract:   Fertility depends on correct regulation of meiosis, the special form of cell division that gives rise to haploid gametes. In female mammals, germ cells enter meiosis during fetal ovarian development, while germ cells in males avoid entering meiosis until puberty. Decades of research have shown that meiotic entry, and germ cell sex determination, are not initiated intrinsically within the germ cells. Instead, meiosis is induced by signals produced by the surrounding somatic cells. More recently, retinoic acid (RA), the active derivative of vitamin A, has been implicated in meiotic induction during fetal XX and postnatal XY germ cell development. Evidence for an intricate system of RA synthesis and degradation in the fetal ovary and testis has emerged, explaining past observations of infertility in vitamin A-deficient rodents. Here we review how meiosis is triggered in fetal ovarian germ cells, paying special attention to the role of RA in this process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I447,I447)","v":23413096},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B447:D447)","v":1},2013,"Pregnane X receptor and human malignancy.","Koutsounas",23413096,"Pregnane X receptor and human malignancy.    Abstract:   Pregnane X Receptor (PXR) is a member of the nuclear receptor superfamily, expressed in liver, intestine and other tissues. PXR exerts transcriptional regulation by binding to its DNA response elements as an heterodimer with Retinoid X Receptor (RXR). This nuclear receptor is implicated in the homeostasis of numerous endobiotics, such as glucose, lipids, steroids and bile acids. Additionally, the activation of PXR induces expression of drug metabolizing enzymes (DMEs) and transporters, including multidrug resistance protein 1 (MDR1), leading to regulation of xenobiotic metabolism and drug-drug interactions. New roles for PXR have been established in inflammatory bowel disease, bone homeostasis, liver steatosis, antifibrogenesis and oxidative stress. PXR has, additionally, a multifactorial impact on cancer, either by directly affecting cell proliferation and apoptosis or by inducing chemotherapy resistance, in colon, breast, prostate, and endometrial cancer, and in osteosarcoma. PXR polymorphisms may also have clinical significance in certain types of cancer and their treatment. Further studies are needed in order to clarify the mechanisms involved in PXR-regulated carcinogenesis. PXR down-regulation could be considered as a novel therapeutic approach to overcome chemoresistance, while future research should be mainly focused on modulating PXR status in order to increase chemotherapy effectiveness and finally improve cancer patient prognosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I448,I448)","v":23343622},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B448:D448)","v":1},2013,"Non-pro-vitamin A and pro-vitamin A carotenoids in atopy development.","Rühl",23343622,"Non-pro-vitamin A and pro-vitamin A carotenoids in atopy development.    Abstract:   Carotenoids are important derivatives of the human diet and occur in high concentrations in the human organism. Various carotenoids are also present in human breast milk and are transferred to breast-fed children. The alternative to breastfeeding is supplementation with an infant milk formula, but these formulas contain only a limited variety of carotenoids. Our question is: What is the function of various carotenoids in human nutrition with a special emphasis on child development and the development of atopy? In this review, the mechanisms of action of the most important non-pro-vitamin A and pro-vitamin A carotenoids: α-carotene, β-carotene, β-cryptoxanthin, lutein, zeaxanthin, lycopene and retinoids are discussed. In summary, the combination of carotenoids, especially lycopene, seems to be of great importance, and exclusive usage of β-carotene in infant formula may yield in an increased atopy prevalence mediated in various target organs like the skin, lungs and immune competent cells. We conclude that the determination of novel bioactive metabolites of various carotenoids, at various stages in different organs during atopy development, might be the key to understanding the potential importance of carotenoids on atopy development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I449,I449)","v":23329078},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B449:D449)","v":1},2013,"Diagnosis and treatment of lichen sclerosus: an update.","Fistarol",23329078,"Diagnosis and treatment of lichen sclerosus: an update.    Abstract:   Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin. LS is a debilitating disease, causing itch, pain, dysuria and restriction of micturition, dyspareunia, and significant sexual dysfunction in women and men. Many findings obtained in recent years point more and more towards an autoimmune-induced disease in genetically predisposed patients and further away from an important impact of hormonal factors. Preceding infections may play a provocative part. The role for Borrelia is still controversial. Trauma and an occlusive moist environment may act as precipitating factors. Potent and ultrapotent topical corticosteroids still head the therapeutic armamentarium. Topical calcineurin inhibitors are discussed as alternatives in the treatment of LS in patients who have failed therapy with ultrapotent corticosteroids, or who have a contraindication for the use of corticosteroids. Topical and systemic retinoids may be useful in selected cases. Phototherapy for extragenital LS and photodynamic therapy for genital LS may be therapeutic options in rare cases refractory to the already mentioned treatment. Surgery is restricted to scarring processes leading to functional impairment. In men, circumcision is effective in the majority of cases, but recurrences are well described. Anogenital LS is associated with an increased risk for squamous cell carcinoma of the vulva or penis. This review updates the epidemiology, clinical presentation, histopathology, pathogenesis, and management of LS of the female and male genitals and extragenital LS in adults and children."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I450,I450)","v":23053550},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B450:D450)","v":1},2012,"The role of lycopene and its derivatives in the regulation of transcription systems: implications for cancer prevention.","Sharoni",23053550,"The role of lycopene and its derivatives in the regulation of transcription systems: implications for cancer prevention.    Abstract:   Evidence from epidemiologic studies has suggested that carotenoids, and lycopene in particular, decrease the risk of cancer: however, not all studies support this view. To gain insight into the molecular mechanisms whereby lycopene and other carotenoids may exert their chemoprotective effects, we and others performed a series of studies that used a large panel of cancer cell lines of different lineages and animal models of human cancer. In this review we address some of the mechanisms proposed for the cancer-preventive activity of tomato lycopene, focusing on the induction of the antioxidant response element transcription system and the inhibition of the transcriptional activity of sex hormones, such as estrogens and androgens, and the activity of growth factors, such as insulin-like growth factor. We also considered the modulation by lycopene of the transcription factors peroxisome proliferator-activated receptor, retinoid X receptor, liver X receptor, and activating protein-1. The ligands and the phytonutrient regulators of these transcription systems contain electrophilic active groups, whereas lycopene and nonxanthophylic carotenoids are devoid of them. Thus, we suggest that at least some of the cellular effects of carotenoids are mediated through their derivatives formed either by chemical oxidation or by enzymatic cleavage inside the cells. This review highlights findings that pertain to this exciting avenue of research, which is currently under intense scrutiny in several laboratories worldwide."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I451,I451)","v":22947624},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B451:D451)","v":1},2013,"Precious cargo: regulation of sex-specific germ cell development in mice.","Bowles",22947624,"Precious cargo: regulation of sex-specific germ cell development in mice.    Abstract:   Although mammalian sex determination is normally specified genetically by an XX or XY chromosome complement, germ cells develop as sperm or oocytes in response to molecular cues provided by the gonadal somatic cells. In an ovary, germ cells enter meiosis during fetal life, thereby committing to oogenesis. In a testis, germ cells do not enter meiosis until after birth, at puberty. Recent findings indicate that, in mice, the sex-specific timing of entry into meiosis is governed by the balance between 2 secreted signalling molecules, retinoic acid (RA), which promotes entry into meiosis, and fibroblast growth factor 9 (FGF9), which counteracts RA. The combined action of these 2 molecular regulators provides a safety mechanism to guard against germ cell dysregulation that can lead to infertility or germ cell cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I452,I452)","v":22845480},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B452:D452)","v":1},2012,"Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing.","Ong",22845480,"Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing.    Abstract:   In the field of oncology, clinical molecular diagnostics and biomarker discoveries are constantly advancing as the intricate molecular mechanisms that transform a normal cell into an aberrant state in concert with the dysregulation of alternative complementary pathways are increasingly understood. Progress in biomarker technology, coupled with the companion clinical diagnostic laboratory tests, continue to advance this field, where individualized and customized treatment appropriate for each individual patient define the standard of care. Here, we discuss the current commonly used predictive pharmacogenetic biomarkers in clinical oncology molecular testing: BRAF V600E for vemurafenib in melanoma; EML4-ALK for crizotinib and EGFR for erlotinib and gefitinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; ERBB2 (HER2/neu) for trastuzumab in breast cancer; BCR-ABL for tyrosine kinase inhibitors in chronic myeloid leukemia; and PML/RARα for all-trans-retinoic acid and arsenic trioxide treatment for acute promyelocytic leukemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I453,I453)","v":22750642},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B453:D453)","v":1},2012,"The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.","Kogai",22750642,"The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.    Abstract:   Expression of the sodium iodide symporter (NIS) is required for efficient iodide uptake in thyroid and lactating breast. Since most differentiated thyroid cancer expresses NIS, β-emitting radioactive iodide is routinely utilized to target remnant thyroid cancer and metastasis after total thyroidectomy. Stimulation of NIS expression by high levels of thyroid-stimulating hormone is necessary to achieve radioiodide uptake into thyroid cancer that is sufficient for therapy. The majority of breast cancer also expresses NIS, but at a low level insufficient for radioiodine therapy. Retinoic acid is a potent NIS inducer in some breast cancer cells. NIS is also modestly expressed in some non-thyroidal tissues, including salivary glands, lacrimal glands and stomach. Selective induction of iodide uptake is required to target tumors with radioiodide. Iodide uptake in mammalian cells is dependent on the level of NIS gene expression, but also successful translocation of NIS to the cell membrane and correct insertion. The regulatory mechanisms of NIS expression and membrane insertion are regulated by signal transduction pathways that differ by tissue. Differential regulation of NIS confers selective induction of functional NIS in thyroid cancer cells, as well as some breast cancer cells, leading to more efficient radioiodide therapy for thyroid cancer and a new strategy for breast cancer therapy. The potential for systemic radioiodide treatment of a range of other cancers, that do not express endogenous NIS, has been demonstrated in models with tumor-selective introduction of exogenous NIS."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I454,I454)","v":22513004},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B454:D454)","v":1},2012,"The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer.","Chakraborty",22513004,"The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer.    Abstract:   Neutrophil gelatinase associated lipocalin (NGAL), also known as oncogene 24p3, uterocalin, siderocalin or lipocalin 2, is a 24kDa secreted glycoprotein originally purified from a culture of mouse kidney cells infected with simian virus 40 (SV-40). Subsequent investigations have revealed that it is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. Since then, NGAL expression has been reported in several normal tissues where it serves to provide protection against bacterial infection and modulate oxidative stress. Its expression is also dysregulated in several benign and malignant diseases. Its small size, secreted nature and relative stability have led to it being investigated as a diagnostic and prognostic biomarker in numerous diseases including inflammation and cancer. Functional studies, conducted primarily on lipocalin 2 (Lcn2), the mouse homologue of human NGAL have revealed that Lcn2 has a strong affinity for iron complexed to both bacterial siderophores (iron-binding proteins) and certain human proteins like norepinephrine. By sequestering iron-laden siderophores, Lcn2 deprives bacteria of a vital nutrient and thus inhibits their growth (bacteriostatic effect). In malignant cells, its proposed functions range from inhibiting apoptosis (in thyroid cancer cells), invasion and angiogenesis (in pancreatic cancer) to increasing proliferation and metastasis (in breast and colon cancer). Ectopic expression of Lcn2 also promotes BCR-ABL induced chronic myelogenous leukemia in murine models. By transporting iron into and out of the cell, NGAL also regulates iron responsive genes. Further, it stabilizes the proteolytic enzyme matrix metalloprotease-9 (MMP-9) by forming a complex with it, and thereby prevents its autodegradation. The factors regulating NGAL expression are numerous and range from pro-inflammatory cytokines like interleukins, tumor necrosis factor-α and interferons to vitamins like retinoic acid. The purpose of this review article is to examine the expression, structure, regulation and biological role of NGAL and critically assess its potential as a novel diagnostic and prognostic marker in both benign and malignant human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I455,I455)","v":22459019},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B455:D455)","v":1},2012,"Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012.","Seitz",22459019,"Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012.    Abstract:    AIMS : To update epidemiological data on alcohol and breast cancer, with special emphasis on light alcohol consumption, and to review mechanisms of alcohol mediated mammary carcinogenesis.  METHODS : For epidemiological data, in November 2011 we performed a literature search in various bibliographic databases, and we conducted a meta-analysis of data on light alcohol drinking. Relevant mechanistic studies were also reviewed to November 2011.  RESULTS : A significant increase of the order of 4% in the risk of breast cancer is already present at intakes of up to one alcoholic drink/day. Heavy alcohol consumption, defined as three or more drinks/day, is associated with an increased risk by 40-50%. This translates into up to 5% of breast cancers attributable to alcohol in northern Europe and North America for a total of approximately 50,000 alcohol-attributable cases of breast cancer worldwide. Up to 1-2% of breast cancers in Europe and North America are attributable to light drinking alone, given its larger prevalence in most female populations when compared with heavy drinking. Alcohol increases estrogen levels, and estrogens may exert its carcinogenic effect on breast tissue either via the ER or directly. Other mechanisms may include acetaldehyde, oxidative stress, epigenetic changes due to a disturbed methyl transfer and decreased retinoic acid concentrations associated with an altered cell cycle.  CONCLUSIONS : Women should not exceed one drink/day, and women at elevated risk for breast cancer should avoid alcohol or consume alcohol occasionally only."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I456,I456)","v":22325302},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B456:D456)","v":1},2012,"Vitamin A: too much of a good thing?","Duerbeck",22325302,"Vitamin A: too much of a good thing?    Abstract:    UNLABELLEDVitamin A has the unique distinction of being readily available over the counter, yet conferring significant toxic and teratogenic potential. Although vitamin A deficiency is relatively rare in the United States, globally it is the most common cause of blindness. The following is a review of the various forms and derivatives of vitamin A and their associations with potential adverse perinatal outcomes.  TARGET AUDIENCE : Obstetricians amp; Gynecologists, Family Physicians.  LEARNING OBJECTIVES : After participating in this CME activity, physicians should be better able to identify sources of Vitamin A, distinguish between toxic and non toxic forms of Vitamin A and counsel patients regarding the dosages of Vitamin A that are tolerable during pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I457,I457)","v":22270214},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B457:D457)","v":1},2012,"Paclitaxel-associated subungual pyogenic granuloma: report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail.","Paul",22270214,"Paclitaxel-associated subungual pyogenic granuloma: report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail.    Abstract:   Subungual and periungual pyogenic granuloma occur in association with certain systemic medications. Paclitaxel is an antitumor drug of the taxane family used in the management of breast cancer. Taxanes have many associated nail changes that may occur in patients receiving either docetaxel or paclitaxel for systemic chemotherapy. The nail changes in a 68-year-old woman with metastatic breast cancer who presented for nail changes after receiving 12 cycles of weekly paclitaxel are described herein: nail plate red-brown discoloration, onycholysis with leukonychia, proximal subungual hemorrhage, and subungual pyogenic granuloma. The literature on systemic medications associated with the development of subungual and periungual pyogenic granulomas is reviewed; drugs associated with the development of pyogenic granuloma at the locations include antineoplastics, antiretrovirals, epidermal growth factor receptor inhibitors, immunosuppressants and retinoids. In conclusion, subungual pyogenic granuloma can occur not only in patients receiving docetaxel, but also in patients treated with paclitaxel. And, paclitaxel should be included in the list of drugs associated with the occurrence of subungual pyogenic granuloma."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I458,I458)","v":22232934},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B458:D458)","v":1},2011,"[The mammalian gonocytes fate: oogenesis or spermatogenesis].","Kozhuhar",22232934,"[The mammalian gonocytes fate: oogenesis or spermatogenesis].    Abstract:   Germ line cells become gonocytes after the completion of migration and colonization of gonadal anlages. After the contact with the somatic cells of genital ridges the reprogramming of gonocytes takes place. Upon entry the embryonic gonads germ cells undergo the most complete demethylation during germ line development, their chromatin tends to have an open conformation for a short period. This event promotes the susceptibility to meiosis-inducing factors signaling. The choice of the further path of gonocytes development just after the gonadal sex differentiation, mitotic arrest and meiotic entry are discussed. Analisis of the action mechanisms of meiosis-inducing and meiosis-preventing factors, especially retinoic acid and enzymes of its degradation and synthesis, was performed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I459,I459)","v":25825298},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B459:D459)","v":1},2012,"Vitamin A supplementation, infectious disease and child mortality: a summary of the evidence.","Thorne-Lyman",25825298,"Vitamin A supplementation, infectious disease and child mortality: a summary of the evidence.    Abstract:   This manuscript reviews the evidence related to the effects of vitamin A (VA) supplementation of women and children on child health and mortality. VA supplementation of children aged 6-59 months has been well studied, and meta-analyses have consistently demonstrated effects on all-cause mortality, yet its mechanisms and the reasons for heterogeneous effects on mortality across trials continue to be debated. Recent meta-analysis of cause-specific mortality suggests beneficial effects on diarrheal mortality, with null but potentially beneficial effects also present for mortality from measles, lower respiratory infection, and meningitis. Some evidence suggests that pneumonia severity may increase with VA supplementation in this age group, particularly among well-nourished children. Maternal supplementation with VA during pregnancy has not shown benefits on neonatal mortality in large trials. A recent meta-analysis suggested that high-dose supplementation of lactating women immediately following delivery did not affect child survival. There is still uncertainty around the benefits of neonatal VA supplementation that should be resolved once the findings of ongoing trials are reported."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I460,I460)","v":22111835},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B460:D460)","v":1},2012,"Nuclear hormone receptor signals as new therapeutic targets for urothelial carcinoma.","Miyamoto",22111835,"Nuclear hormone receptor signals as new therapeutic targets for urothelial carcinoma.    Abstract:   Unlike prostate and breast cancers, urothelial carcinoma of the urinary bladder is not yet considered as an endocrine-related neoplasm, and hormonal therapy for bladder cancer remains experimental. Nonetheless, there is increasing evidence indicating that nuclear hormone receptor signals are implicated in the development and progression of bladder cancer. Androgen-mediated androgen receptor (AR) signals have been convincingly shown to induce bladder tumorigenesis. Androgens also promote the growth of AR-positive bladder cancer cells, although it is controversial whether AR plays a dominant role in bladder cancer progression. Both stimulatory and inhibitory functions of estrogen receptor signals in bladder cancer have been reported. Various studies have also demonstrated the involvement of other nuclear receptors, including progesterone receptor, glucocorticoid receptor, vitamin D receptor, and retinoid receptors, as well as some orphan receptors, in bladder cancer. This review summarizes and discusses available data suggesting the modulation of bladder carcinogenesis and cancer progression via nuclear hormone receptor signaling pathways. These pathways have the potential to be an extremely important area of bladder cancer research, leading to the development of effective chemopreventive/therapeutic approaches, using hormonal manipulation. Considerable uncertainty remains regarding the selection of patients who are likely to benefit from hormonal therapy and optimal options for the treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I461,I461)","v":22015291},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B461:D461)","v":1},2011,"The science behind vitamins and natural compounds for breast cancer prevention. Getting the most prevention out of it.","Lazzeroni",22015291,"The science behind vitamins and natural compounds for breast cancer prevention. Getting the most prevention out of it.    Abstract:   This review highlights the role of vitamins and natural compounds in breast cancer prevention, with a particular focus on Vitamin D. In the last decades, both encouraging and discouraging results about the association between antioxidant supplementation and cancer have been reported to public and scientific community. Their safe and favorable toxicity profile makes them suitable to be investigated in a preventive setting. However, a recent large meta-analysis showed that treatment with beta carotene, vitamin A, and vitamin E may increase mortality, whereas the potential roles of vitamin C and selenium on mortality need further study. Likewise, folate levels were not associated with reduced breast cancer risk in a recent meta-analysis. Several studies have shown that a high proportion of women at-risk for breast cancer or affected by the disease have deficient vitamin D levels, i.e., 250 H-D lt;20 ng/ml or 50 nmol/L. While the association between Vitamin D levels and breast cancer risk/prognosis is still controversial, the U-shaped relationship between 250 H-D levels observed in different studies suggests the need to avoid both deficient and too high levels. Further trials using an optimal dose range are needed to assess the preventive and therapeutic effect of vitamin D. Finally, Fenretinide, a pro-apoptotic and pro-oxidant vitamin A derivative, has shown promise in several trials and its preventive potential is being assessed in young women at very high risk for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I462,I462)","v":23362027},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B462:D462)","v":1},2011,"Prenatal exposures associated with neurodevelopmental delay and disabilities.","Diav-Citrin",23362027,"Prenatal exposures associated with neurodevelopmental delay and disabilities.    Abstract:   Neurobehavioral teratology refers to the study of the abnormal development of the structure and the behavioral functions of the central nervous system, which result from exposure to exogenous agents during prenatal development. The focus of this review is the effects of various prenatal exposures on human neurodevelopment. Studies that deal with the adverse effects of infectious agents (rubella, cytomegalovirus, and toxoplasma), teratogenic drugs (e.g., antiepileptic drugs such as phenytoin, valproate, and carbamazepine, coumarin derivatives, and retinoids), alcohol, and other substances of abuse will be reviewed. Additionally, prenatal exposure to industrial or environmental chemicals (e.g., lead, methylmercury, and polycarbonated biphenyls) as well as exposure of the embryo or fetus to high amounts of ionizing radiation will be addressed. Possible mechanisms of selected neurobehavioral teratogens will also be discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I463,I463)","v":21693195},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B463:D463)","v":1},2011,"Vitamin A: a multifunctional tool for development.","Gutierrez-Mazariegos",21693195,"Vitamin A: a multifunctional tool for development.    Abstract:   Extensive research carried out over the last 100 years has established that the fat-soluble organic compound vitamin A plays crucial roles in early development, organogenesis, cell proliferation, differentiation and apoptosis as well as in tissue homeostasis. Given its importance during development, the delivery of vitamin A to the embryo is very tightly regulated with perturbations leading to severe malformations. This review discusses the roles of vitamin A during human development and the molecular mechanisms controlling its biological effects, hence bridging the gap between human development and molecular genetic work carried out in animal models. Vitamin A delivery during pregnancy and its developmental teratology in humans are thus discussed alongside work on model organisms, such as chicken or mice, revealing the molecular layout and functions of vitamin A metabolism and signaling. We conclude that, during development, vitamin A-derived signals are very tightly controlled in time and space and that this complex regulation is achieved by elaborate autoregulatory loops and by sophisticated interactions with other signaling cascades."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I464,I464)","v":21549902},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B464:D464)","v":1},2011,"[Congenital diaphragmatic hernia - mechanisms of pulmonary hypoplasia].","Labbé",21549902,"[Congenital diaphragmatic hernia - mechanisms of pulmonary hypoplasia].    Abstract:   Congenital diaphragmatic hernia (CDH) is a common cause of severe neonatal respiratory distress. Mortality and morbidity are determined by the amount of pulmonary hypoplasia (PH) that occurs and by the development of therapy-resistant pulmonary hypertension. The pathogenesis and aetiology of CDH and its associated anomalies are still largely unknown despite all research efforts. The pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. PH, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Our understanding of CDH has also been aided by basic research with the use of dietary, teratogen-induced, and knockout models of CDH. These studies indicate that lung hypoplasia may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. Recent data reveal the role of disruption of a retinoid-signalling pathway in the pathogenesis of CDH. Although multifactorial inheritance may best explain most cases of CDH in humans, much has been learned about the genetic factors that play a role in the development of CDH by studies of patients with CDH caused by specific genetic syndromes and chromosome anomalies. More research is warranted to improve our understanding of normal and abnormal lung development in relation to CDH. Such investigations will help in the design of new treatment strategies to improve the natural course or even to prevent this anomaly."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I465,I465)","v":21441069},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B465:D465)","v":1},2011,"Preventive therapy for breast cancer: a consensus statement.","Cuzick",21441069,"Preventive therapy for breast cancer: a consensus statement.    Abstract:   In March, 2010, a group of breast cancer experts met to develop a consensus statement on breast cancer prevention, with a focus on medical and therapeutic interventions. We present the conclusions in this Review. First we agreed that the term chemoprevention is inappropriate and suggested that the term preventive therapy better represents this feature of management. Two selective oestrogen-receptor modulators--tamoxifen and raloxifene--are so far the only medical options approved by the US Food and Drug Administration for preventive therapy. Of these tamoxifen has greater efficacy and can be used in premenopausal women, but raloxifene has fewer side-effects. Two newer drugs in this class, lasofoxifene and arzoxifene, also show efficacy and possibly a better overall risk-benefit profile, but need further assessment. Aromatase inhibitors might be more efficacious, and results of prevention trials are eagerly awaited. Newer agents, notably bisphosphonates and metformin, have shown promise in observational studies and need to be assessed in randomised prevention trials. Other agents, such as aspirin, other non-steroidal anti-inflammatory drugs, COX-2 inhibitors, retinoids, rexinoids, and dietary components have limited effects or are in the early phases of investigation. New contralateral tumours in women with breast cancer might be generally useful as a model for prevention, as has been seen for tamoxifen. If valid such a model would facilitate the design of simpler, cheaper, and better-focused trials for assessing new agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I466,I466)","v":21415736},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B466:D466)","v":1},2011,"Evidence-based prevention of childhood malnutrition.","Imdad",21415736,"Evidence-based prevention of childhood malnutrition.    Abstract:    PURPOSE OF REVIEW : Childhood malnutrition is prevalent in developing countries and contributes to one-third of all deaths in these countries. There have been advances in prevention of childhood malnutrition and the purpose of this article was to review the current evidence in the field.  RECENT FINDINGS : Multiple micronutrient (MMN) supplements during pregnancy reduce the incidence of maternal anemia and small for gestational-age babies. Recent evidence suggest that combined supplementation of MMNs with protein energy supplement is more effective than MMN supplementation alone. It is now recommended that HIV-infected mothers can exclusively breast-feed their infants for 6 months when the mother or infant is on effective antiretroviral therapy. Home fortification of complementary foods reduces the prevalence of anemia in infancy and combined supplementation of MMNs with lipid-based supplements improves growth in young children. Ready-to-use therapeutic foods have been successfully used to manage severe acute malnutrition in the community. Zinc supplementation is associated with a reduction in diarrhea and respiratory disease morbidity and improves linear growth. Vitamin A supplementation decreases the incidence of diarrhea and measles. Water supply, sanitation, and hygiene are important for the prevention of malnutrition because of their direct impact on infectious disease.  SUMMARY : There is clear evidence on the causes and consequences of malnutrition as well as effective interventions to prevent undernutrition. The next step is to implement these packages of interventions at large scale. A global effort is required that should entail unified and compelling advocacy among governments, lead organizations, and institutions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I467,I467)","v":21399881},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B467:D467)","v":1},2011,"Preclinical in vitro models from genetically engineered mice for breast and colon cancer (Review).","Telang",21399881,"Preclinical in vitro models from genetically engineered mice for breast and colon cancer (Review).    Abstract:   Genetically engineered mice with targeted alterations in clinically relevant oncogenes, tumor suppressor genes or DNA mismatch repair genes provide unique predictive animal models for human carcinogenesis, and cancer prevention/therapy. However, some of the genetically engineered mouse models lack target organ specificity for colon carcinogenesis. We have established, characterized and validated stable epithelial cell lines from normal and genetically predisposed target organs that offer innovative and mechanistic approaches, complementing in vivo studies on existing animal models for clinical breast and colon cancer. Epithelial cell lines with up- regulated Ras or myc oncogene, mutated Apc tumor suppressor gene and Mlh1 DNA mismatch repair gene provide facile experimental systems for organ site carcinogenesis and cancer prevention. Altered expression of cancer specific biomarkers and their modulation by several synthetic pharmacological agents such as retinoids, selective estrogen receptor modulators, non-steroidal anti-inflammatory drugs and specific enzyme inhibitors have been reported from our laboratory. Oncogene expressing MMEC-Ras and MMEC-myc mammary epithelial cells, Apc mutant 850Min COL and 1638N COL, and DNA mismatch repair/Apc mutant Mlh1/1638N COL colon epithelial cells exhibit aberrant cell cycle progression, down-regulated apoptosis and enhanced carcinogenic risk in vitro and tumor formation in vivo. We have reported that relative to the parental normal non-neoplastic cells, genetically altered pre-neoplastic cells exhibit enhanced sensitivity for growth arrest by multiple mechanistically distinct pharmacological agents. Comparative experiments on isogenic normal and genetically altered target cell lines facilitate cancer selective efficacy and identification of susceptible mechanistic pathways. Treatment of these genetically altered pre-neoplastic cells with low dose combination of mechanistically distinct pharmacological agents as well as naturally occurring phytochemicals induce cytostatic growth arrest, alter cell cycle progression and reduce carcinogenic risk. The availability of validated technology for model development, and for mechanism based biomarker assays now establishes a novel platform to rapidly test carcinogenicity and preventive/therapeutic efficacy of novel pharmacological agents as well as naturally occurring phytochemicals. Thus, these data permit rational prioritization of efficacious lead compounds for preclinical testing and future clinical trials for prevention/therapy of breast and colon cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I468,I468)","v":21249656},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B468:D468)","v":1},2011,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.","Wiysonge",21249656,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : Observational studies of pregnant women in sub-Saharan Africa have shown that low serum vitamin A levels are associated with an increased risk of mother-to-child transmission (MTCT) of HIV. Vitamin A is cheap and easily provided through existing health services in low-income settings. It is thus important to determine the effect of routine supplementation of HIV positive pregnant or breastfeeding women with this vitamin on the risk of MTCT of HIV, which currently results in more than 1000 new HIV infections each day world-wide.  OBJECTIVES : We aimed to assess the effect of antenatal and or postpartum vitamin A supplementation on the risk of MTCT of HIV as well as infant and maternal mortality and morbidity.  SEARCH STRATEGY : In June 2010 we searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, AIDS Education Global Information System, and WHO International Clinical Trials Registry Platform; and checked reference lists of identified articles for any studies published after the earlier version of this review was updated in 2008.  SELECTION CRITERIA : We selected randomised controlled trials conducted in any setting that compared vitamin A supplementation with placebo in known HIV-infected pregnant or breastfeeding women.  DATA COLLECTION AND ANALYSIS : At least two authors independently assessed trial eligibility and quality and extracted data. We calculated relative risks (RR) or mean differences (MD), with their 95% confidence intervals (CI) for each study. We conducted meta-analysis using a fixed-effects method (when there was no significant heterogeneity between study results, i.e. Pgt;0.1) or the random-effects method (when there was significant heterogeneity), and report the Higgins statistic for all pooled effect measures.  MAIN RESULTS : Five randomised controlled trials which enrolled 7,528 HIV-infected women (either during pregnancy or the immediate postpartum period) met our inclusion criteria. These trials were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005. We combined the results of these trials and found no evidence that vitamin A supplementation has an effect on the risk of MTCT of HIV (4 trials, 6517 women: RR 1.04, 95% CI 0.87 to 1.24; I(2)=68%). However, antenatal vitamin A supplementation significantly improved birth weight (3 trials, 1809 women: MD 89.78, 95%CI 84.73 to 94.83; I(2)=33.0%), but there was no evidence of an effect on preterm births (3 trials, 2110 women: RR 0.88, 95%CI 0.65 to 1.19; I(2)=58.1%), stillbirths (4 trials, 2855 women: RR 0.99, 95%CI 0.68 to 1.43; I(2)=0%), deaths by 24 months (2 trials, 1635 women: RR 1.03, 95%CI 0.88 to 1.20; I(2)=0%), postpartum CD4 levels (1 trial, 727 women: MD -4.00, 95% CI -51.06 to 43.06), and maternal death ( 1 trial, 728 women: RR 0.49, 95%CI 0.04 to 5.37).  AUTHORS CONCLUSIONS : Current best evidence shows that antenatal or postpartum vitamin A supplementation probably has little or no effect on mother-to-child transmission of HIV. According to the GRADE classification, the quality of this evidence is moderate; implying that the true effect of vitamin A supplementation on the risk of mother-to-child transmission of HIV is likely to be close to the findings of this review, but that there is also a possibility that it is substantially different."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I469,I469)","v":21185068},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B469:D469)","v":1},2011,"Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis.","Nurmatov",21185068,"Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis.    Abstract:    BACKGROUND : Epidemiologic studies suggest that deficiencies of the nutrients selenium; zinc; vitamins A, C, D, and E; and low fruit and vegetable intake may be associated with the development of asthma and allergic disorders.  OBJECTIVES : To investigate the evidence that nutrient and food intake modifies the risk of children developing allergy.  METHODS : We systematically searched 11 databases. Studies were critically appraised, and meta-analyses were undertaken.  RESULTS : We identified 62 eligible reports. There were no randomized controlled trials. Studies used cohort (n = 21), case-control (n = 15), or cross-sectional (n = 26) designs. All studies were judged to be at moderate to substantial risk of bias. Meta-analysis revealed that serum vitamin A was lower in children with asthma compared with controls (odds ratio [OR], 0.25; 95% CI, 0.10-0.40). Meta-analyses also showed that high maternal dietary vitamin D and E intakes during pregnancy were protective for the development of wheezing outcomes (OR, 0.56, 95% CI, 0.42-0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). Adherence to a Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08-0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Seventeen of 22 fruit and vegetable studies reported beneficial associations with asthma and allergic outcomes. Results were not supportive for other allergic outcomes for these vitamins or nutrients, or for any outcomes in relation to vitamin C and selenium.  CONCLUSION : The available epidemiologic evidence is weak but nonetheless supportive with respect to vitamins A, D, and E; zinc; fruits and vegetables; and a Mediterranean diet for the prevention of asthma. Experimental studies of these exposures are now warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I470,I470)","v":21154354},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B470:D470)","v":1},2010,"Micronutrient supplementation in children and adults with HIV infection.","Irlam",21154354,"Micronutrient supplementation in children and adults with HIV infection.    Abstract:    BACKGROUND : Micronutrient deficiencies are widespread and compound the effects of HIV disease; micronutrient supplements may be effective and safe in reducing this burden.  OBJECTIVES : To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in adults and children with HIV infection.  SEARCH STRATEGY : The CENTRAL, EMBASE, PubMed, and GATEWAY databases were searched for randomised controlled trials of micronutrient supplements using the search methods of the Cochrane HIV/AIDS Group.  SELECTION CRITERIA : Randomised controlled trials were selected that compared the effects of micronutrient supplements (vitamins, trace elements, and combinations of these) with other supplements, placebo or no treatment on mortality, morbidity, pregnancy outcomes, immunologic indicators, and anthropometric measures in HIV-infected adults and children. Any adverse effects of supplementation were recorded.  DATA COLLECTION AND ANALYSIS : Two reviewers independently selected trials, appraised trial quality for risk of bias using standardised criteria, and extracted data using standardised forms.  MAIN RESULTS : Sixteen additional trials are included in this update to the original Cochrane review (Irlam 2005). Overall, 30 trials involving 22 120 participants are reviewed: 20 trials of single supplements (vitamin A, vitamin D, zinc, selenium) and 10 of multiple micronutrients. Eight trials were undertaken in child populations.None of the six trials of vitamin A or beta-carotene supplementation in adults demonstrated any significant reduction in HIV disease progression. Vitamin A halved all-cause mortality in a meta-analysis of three trials in African children, had inconsistent impacts on diarrhoeal and respiratory morbidity, and improved short-term growth in one trial. No significant adverse effects of vitamin A in adults or children have been reported.Zinc supplements reduced diarrhoeal morbidity and had no adverse effects on disease progression in a single safety trial in South African children. No significant clinical benefits were found from zinc supplementation of pregnant Tanzanian women or Peruvian adults with persistent diarrhoea.Selenium reduced diarrhoeal morbidity in pregnant women in Tanzania, and reduced viral load in two separate small trials in American adults.Single trials of vitamin D supplements in adults, and in adolescents and children, demonstrated safety but no clinical benefits.Multiple micronutrient supplements conferred multiple clinical benefits to pregnant women and their offspring in a large Tanzanian trial. Supplementation in another Tanzanian trial reduced the recurrence of pulmonary TB and increased weight gain in co-infected patients. No significant adverse effects were reported.  AUTHORS CONCLUSIONS : Multiple micronutrient supplements reduced morbidity and mortality in HIV-infected pregnant women and their offspring and also improved early child growth in one large randomised controlled trial in Africa. Additional research is needed to determine if these are generalisable findings. Vitamin A supplementation is beneficial and safe in HIV-infected children, but further evidence is needed to establish if supplementation confers similar benefits in HIV-infected adults. Zinc is safe in HIV-infected adults and children. It may have similar benefits in HIV-infected children and adults, and uninfected children with diarrhoea, as it does in HIV-uninfected children.Further trials of single supplements (vitamin D, zinc, and selenium) are required to build the evidence base. The long-term clinical benefits, adverse effects, and optimal formulation of multiple micronutrient supplements require further investigation in individuals with diverse disease status. "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I471,I471)","v":21111773},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B471:D471)","v":1},2011,"Inhibition of estrogen actions in human gynecological malignancies: new aspects of endocrine therapy for endometrial cancer and ovarian cancer.","Ito",21111773,"Inhibition of estrogen actions in human gynecological malignancies: new aspects of endocrine therapy for endometrial cancer and ovarian cancer.    Abstract:   Endometrial carcinoma and possibly ovarian carcinoma are considered quot;estrogen-dependent tumorsquot; in human gynecological malignancies. In endometrial carcinoma, the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are different from those in human breast carcinoma, although both of them are considered quot;estrogen-dependent malignanciesquot;. Specific and effective endocrine treatment of endometrial carcinoma should be explored, although progestin agents have been widely used for a long time. Aromatase inhibitors, the most effective endocrine agents of breast carcinoma, retinoids, metabolites of vitamin A, and synthetic peroxisome proliferator-activated receptor (PPAR) gamma ligands, used for the treatment of insulin resistance in type II diabetes mellitus, may be the important candidates for possible endocrine treatment of endometrial carcinoma. In ovarian carcinoma, several clinical studies recently demonstrated that aromatase inhibitors had some therapeutic activity against recurrent ovarian carcinoma. However, at least at this juncture, further studies should be required to establish an aromatase inhibitor treatment as one form of endocrine therapy of ovarian carcinoma in future."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I472,I472)","v":20576803},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B472:D472)","v":1},2010,"Orphan nuclear receptors in breast cancer pathogenesis and therapeutic response.","Riggins",20576803,"Orphan nuclear receptors in breast cancer pathogenesis and therapeutic response.    Abstract:   Nuclear receptors comprise a large family of highly conserved transcription factors that regulate many key processes in normal and neoplastic tissues. Most nuclear receptors share a common, highly conserved domain structure that includes a carboxy-terminal ligand-binding domain. However, a subgroup of this gene family is known as the orphan nuclear receptors because to date there are no known natural ligands that regulate their activity. Many of the 25 nuclear receptors classified as orphan play critical roles in embryonic development, metabolism, and the regulation of circadian rhythm. Here, we review the emerging role(s) of orphan nuclear receptors in breast cancer, with a particular focus on two of the estrogen-related receptors (ERRalpha and ERRgamma) and several others implicated in clinical outcome and response or resistance to cytotoxic or endocrine therapies, including the chicken ovalbumin upstream promoter transcription factors, nerve growth factor-induced B, DAX-1, liver receptor homolog-1, and retinoic acid-related orphan receptor alpha. We also propose that a clearer understanding of the function of orphan nuclear receptors in mammary gland development and normal mammary tissues could significantly improve our ability to diagnose, treat, and prevent breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I473,I473)","v":20417372},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B473:D473)","v":1},2010,"[Alitretinoin: Toctino].","Berbis",20417372,"[Alitretinoin: Toctino].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I474,I474)","v":20395427},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B474:D474)","v":1},2010,"Sex determination in mammalian germ cells: extrinsic versus intrinsic factors.","Bowles",20395427,"Sex determination in mammalian germ cells: extrinsic versus intrinsic factors.    Abstract:   Mammalian germ cells do not determine their sexual fate based on their XX or XY chromosomal constitution. Instead, sexual fate is dependent on the gonadal environment in which they develop. In a fetal testis, germ cells commit to the spermatogenic programme of development during fetal life, although they do not enter meiosis until puberty. In a fetal ovary, germ cells commit to oogenesis by entering prophase of meiosis I. Although it was believed previously that germ cells are pre-programmed to enter meiosis unless they are actively prevented from doing so, recent results indicate that meiosis is triggered by a signaling molecule, retinoic acid (RA). Meiosis is avoided in the fetal testis because a male-specifically expressed enzyme actively degrades RA during the critical time period. Additional extrinsic factors are likely to influence sexual fate of the germ cells, and in particular, we postulate that an additional male-specific fate-determining factor or factors is involved. The full complement of intrinsic factors that underlie the competence of gonadal germ cells to respond to RA and other extrinsic factors is yet to be defined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I475,I475)","v":20388054},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B475:D475)","v":1},2011,"Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part II--vitamin D, vitamin A, iron, zinc, iodine, essential fatty acids.","Simpson",20388054,"Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part II--vitamin D, vitamin A, iron, zinc, iodine, essential fatty acids.    Abstract:   Part II of this review considers additional micronutrients. Vitamin D is a fat soluble vitamin found in foods of animal origins (fatty fish, liver oil) or fortified products (milk, cheese). Vitamin D deficiency is common in African-American women living in northern latitudes. Vitamin D supplementation may be needed to reach desired 25-(OH)D3 concentrations of gt;50 nmol/L. In foods of animal origin, preformed Vitamin A is present; in plants (fruits and vegetables) vitamin A precursors (β-carotenoids) are present. Vitamin A supplementation is usually not warranted, and in developing countries should not exceed 3000 μg (10,000 IU)/day. Iron in the form of haem-iron is found in meat, fish and poultry; non-haem (inorganic) iron is found in vegetables, fruits and grains. Iron supplementation may be necessary in the third trimester, earlier in pregnancy or in non-pregnant states if serum ferritin is lt;20 μg/L or haemoglobin lt;10.9 g/dL. Zinc is available in red meat, seafood including oysters and unpolished grains; supplementation is not necessary. To assure adequate iodine, food is fortified worldwide with iodated salt. If urinary iodine levels are low, supplementation is needed. Essential fatty acids requirements can be met by one to two portions of fish per week."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I476,I476)","v":20102286},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B476:D476)","v":1},2010,"Molecular aspects of azoles-induced teratogenesis.","Marotta",20102286,"Molecular aspects of azoles-induced teratogenesis.    Abstract:    IMPORTANCE OF THE FIELD : Antifungal azole compounds are widely used as antimycotics in plant, veterinary and human therapies. Their pharmacological action is based on the inhibition of the CYP450 enzyme catalyzing the synthesis of steroids required for the synthesis and integrity of fungal cell wall. Azoles are teratogenic in animal models and are under investigation for potential human developmental toxic effects. Rational approaches to prevent teratogenic effects require knowledge of the underlying mechanisms.  AREAS COVERED IN THIS REVIEW : This review highlights the current knowledge on the molecular mechanisms that are potentially involved in the teratogenic response to azoles.  WHAT THE READER WILL GAIN : A comprehensive review of the literature on this subject including experimental and clinical studies. Particular attention is focused on the mechanistic role played by CYP26 family inhibition.  TAKE HOME MESSAGE : Significant advancements have been made in the comprehension of molecular mechanisms underlying teratogenic effects mediated by azole derivatives. Increasing evidence is linking disruption of embryonic retinoic acid homeostasis as a crucial determinant of azole-mediated teratogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I477,I477)","v":20100636},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B477:D477)","v":1},2010,"17q12-21 - the pursuit of targeted therapy in breast cancer.","Glynn",20100636,"17q12-21 - the pursuit of targeted therapy in breast cancer.    Abstract:    PURPOSE : Identification of HER2/neu, and the subsequent development of targeted therapy for patients who over-express it, has revolutionized their management. Research has since focused on the area of chromosome 17 in which HER2/neu is located in order to identify other genes in the vicinity. The aims of this review are, firstly, to discuss current thinking in relation to the role of these genes in the pathogenesis of breast cancer and, secondly, to examine how this evidence may be assimilated such that new forms of targeted therapy can be developed.  EXPERIMENTAL DESIGN : This review discusses the evidence in relation to 4 genes located at the HER2/neu amplicon, namely TOP2A, GRB7, STARD3 and RARA.  RESULTS : TOP2A has aroused particular interest as over-expression of its protein has been shown to correlate, both with amplification of HER2/neu, and with response to anthracycline-based chemotherapeutic agents in breast cancer. GRB7 is included on Oncotype DXtm, and has recently been implicated in gastric and oesophageal cancer. STARD3 and RARA also hold clinical relevance, the former having been shown to function in steroidogenesis and therefore implicated in hormone-receptor-positive breast cancer. Finally, RARA may be the key to unlocking the problem of resistance to all-trans retinoic acid (ATRA) in breast cancer sufferers; this treatment has previously been demonstrated to induce remission in over 80% of patients with acute promyelocytic leukaemia (APML).  CONCLUSION : These genes hold potential as therapeutic targets, and warrant further investigation as we move towards our goal of individually tailored therapeutic strategies in breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I478,I478)","v":20080321},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B478:D478)","v":1},2010,"X-linked ichthyosis: an oculocutaneous genodermatosis.","Fernandes",20080321,"X-linked ichthyosis: an oculocutaneous genodermatosis.    Abstract:   X-linked ichthyosis (XLI) is an X-linked recessive disorder of cutaneous keratinization with possible extracutaneous manifestations. It was first described as a distinct type of ichthyosis in 1965. XLI is caused by a deficiency in steroid sulfatase activity, which results in abnormal desquamation and a retention hyperkeratosis. XLI is usually evident during the first few weeks of life as polygonal, loosely adherent translucent scales in a generalized distribution that desquamate widely. These are quickly replaced by large, dark brown, tightly adherent scales occurring primarily symmetrically on the extensor surfaces and the side of the trunk. In addition, extracutaneous manifestations such as corneal opacities, cryptorchidism, and abnormalities related to contiguous gene syndromes may be observed. Diagnosis of XLI is usually made clinically, as the histopathology is nonspecific, but confirmation may be obtained through either biochemical or genetic analysis. Treatment should focus on cutaneous hydration, lubrication, and keratolysis and includes topical moisturizers and topical retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I479,I479)","v":19818218},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B479:D479)","v":1},2009,"Vitamin D endocrine system and psoriasis vulgaris--review of the literature.","Rucević",19818218,"Vitamin D endocrine system and psoriasis vulgaris--review of the literature.    Abstract:   Vitamin D exerts its physiological functions on calcium and bone metabolism in humans through the active metabolite 1,25-dihydroxyvitamin D3(1,25(OH)2D3). The other spectrum of vitamin D activities includes important effects on cellular proliferation, differentiation and the immune system. These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex binds in the nucleus to the vitamin D responsive element on the gene. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including FokI in exon 2, BsmI and ApaI in intron 8 and TaqI in exon 9. Alterations in vitamin D-1,25 (OH)2D3 levels and polymorphisms of VDR gene have been shown to be associated with several malignant or autoimmune diseases such as sclerosis multiplex, breast cancer, diabetes mellitus, malignant melanoma, and psoriasis vulgaris. The effects of VDR gene polymorphisms including immunomodulation, stimulation of cellular differentiation and inhibition of proliferation make it a possible candidate for therapy of psoriasis as well as for the psoriasis gene modification. The objective of this article is to present the state-of-the-art in the VDR gene polymorphism research in psoriasis vulgaris."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I480,I480)","v":19522700},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B480:D480)","v":1},2009,"Aldo-keto reductase family 1 member B1 inhibitors: old drugs with new perspectives.","Liu",19522700,"Aldo-keto reductase family 1 member B1 inhibitors: old drugs with new perspectives.    Abstract:   Aldo-keto reductase 1 member B1 (AKR1B1) is pathogenically involved in diabetic complications by driving glucose flux through polyol pathway; a variety of AKR1B1 inhibitors has been developed for the treatment of diabetic complications and a body of invaluable preclinical and clinical data have been collected through decades efforts. Recent studies have shown that some AKR1B1 inhibitors demonstrate strong inhibitory activity to aldo-keto reductase family 1 member B10 (AKR1B10), a protein identical to AKR1B1, in vitro and in cancer cells. AKR1B1 and AKR1B10 are overexpressed in human tumors, such as liver, breast, and lung cancer, and may play a critical role in the development and progression of cancer through carbonyl detoxification, retinoic acid homeostatic regulation, and lipid metabolic control, as well as the activation of tobacco smoke carcinogens. Therefore, AKR1B1 inhibitors may represent a novel class of antitumor agents; and the clinical data assembled in diabetic clinics would greatly assist the transition of these inhibitors to cancer clinics. This article summaries the current understanding of the expression and function of AKR1B1 and AKR1B10 in human cancers and reviews the patents and papers of AKR1B1 inhibitors. Authors opinions concerning the current and future development of AKR1B1 and/or AKR1B10-specific inhibitors are discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I481,I481)","v":19519292},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B481:D481)","v":1},2009,"Actual and potential agents and biomarkers in the treatment of cancer.","Carrera",19519292,"Actual and potential agents and biomarkers in the treatment of cancer.    Abstract:   It is well known that cancer is defined as a group of diseases that differ both regarding the tissues they affect as well as their origin. For this reason, much effort is being made in the development of new drugs with the aim of increasing survival and patients quality of life. There is already a wide spectrum of anti-cancer agents that follow different mechanisms of action, such as the inhibitors of topoisomerases I and II and anti-mitotic chemicals, among others. Usually, these drugs are able to increase the patients survival, although their toxicity worsens the patients quality of life. Therefore, we should seriously consider alternative mechanisms, as well as the co-administration of these drugs with non-toxic compounds, such as melatonin or retinoic acid. This would increase the toxic effects of these drugs at low doses. Obviously, a better understanding of modified physiological systems during the development of these diseases would improve the diagnostic tools. This would be translated, in turn, into a higher survival index. The alteration of the proteolytic enzymes involved in the renin-angiotensin system and in the regulation of the gonadotrophins and TRH synthesis in breast cancer are examples of the above. These two proteins are regulated by the same enzyme, pyrrolidon carboxipeptidase, and both are directly involved in the initiation and development of breast cancer. Therefore, the aim of the present review is to revise the different options available at present to improve patients survival and to show alternative mechanisms that may be beneficial to patients well being."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I482,I482)","v":19502515},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B482:D482)","v":1},2009,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.","Diamanti-Kandarakis",19502515,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.    Abstract:   There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I483,I483)","v":19383165},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B483:D483)","v":1},2009,"New insights into the functions and regulation of the transcriptional corepressors SMRT and N-CoR.","Stanya",19383165,"New insights into the functions and regulation of the transcriptional corepressors SMRT and N-CoR.    Abstract:   Corepressors are large proteins that facilitate transcriptional repression through recruitment of histone-modifying enzymes. Two major corepressors, SMRT (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor corepressor), have been shown to mediate repression associated with nuclear receptors and a myriad of other transcription factors. This review will focus on recent studies on these proteins, including newly discovered physiological roles of the corepressors, their modes of regulation, their roles in antiestrogen-resistant breast cancer and their functions during the cell cycle."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I484,I484)","v":19239019},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B484:D484)","v":1},2008,"[Advance of study on vitamin A deficiency and excess associatied with congenital heart disease].","Xing",19239019,"[Advance of study on vitamin A deficiency and excess associatied with congenital heart disease].    Abstract:   It was demonstrated that Vitamin A may be crucial for heart morphogenesis during pregnancy. Both deficiency and excess of Vitamin A could induce certain congenital heart disease. In the gastrula stage, vitamin A could play a specific role in the process of heart development because of activating many gene regulations, in order to promote heart development. In this article, the advance of mechanism study on vitamin A associated with congenital heart disease were reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I485,I485)","v":19229271},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B485:D485)","v":1},2009,"Ocular teratogens: old acquaintances and new dangers.","Tandon",19229271,"Ocular teratogens: old acquaintances and new dangers.    Abstract:   Recent research into animal studies has contributed significantly to understanding the pathophysiology of some well-known teratogens, such as alcohol. Techniques, such as positron emission tomography (PET) and retinal synaptogenesis studies, have helped determine the specific areas in the developing brain and ocular structures, which are targeted by various teratogens. In this article, we also highlight a few newer agents, such as benzodiazepines, with potential for ocular malformation and morbidity in the developing foetus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I486,I486)","v":19213564},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B486:D486)","v":1},2009,"Prevention of ER-negative breast cancer.","Li",19213564,"Prevention of ER-negative breast cancer.    Abstract:   The successful demonstration that the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of breast cancer has stimulated great interest in using drugs to prevent breast cancer in high-risk women. In addition, recent results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective at preventing breast cancer than are SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many estrogen-receptor (ER)-positive breast cancers, these drugs do not prevent the development of ER-negative breast cancer. Thus, there is an urgent need to identify agents that can prevent ER-negative breast cancer. We have studied the cancer preventative activity of several classes of drugs for their ability to prevent ER-negative breast cancer in preclinical models. Results from these studies demonstrate that rexinoids (analogs of retinoids that bind and activate RXR receptors), tyrosine kinase inhibitors (such as EGFR inhibitors and dual kinase inhibitors that block EGFR and HER2/neu signaling), and cyclo-oxygenase 2 (COX-2) inhibitors all prevent ER-negative breast cancer in transgenic mice that develop ER-negative breast cancer. Other promising agents now under investigation include vitamin D and vitamin D analogs, drugs that activate PPAR-gamma nuclear receptors, and statins. Many of these agents are now being tested in early phase cancer prevention clinical trials to determine whether they will show activity in breast tissue and whether they are safe for use in high-risk women without breast cancer. The current status of these studies will be reviewed. It is anticipated that in the future, drugs that effectively prevent ER-negative breast cancer will be used in combination with hormonal agents such SERMs or aromatase inhibitors to prevent all forms of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I487,I487)","v":18926534},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B487:D487)","v":1},2009,"A systematic review of randomized controlled trials of prenatal and postnatal vitamin A supplementation of HIV-infected women.","Kongnyuy",18926534,"A systematic review of randomized controlled trials of prenatal and postnatal vitamin A supplementation of HIV-infected women.    Abstract:   We searched the Cochrane Library, MEDLINE, EMBASE, AIDSearch, and Gateway to assess the effect of prenatal and/or postnatal vitamin A supplementation on the risk of mother-to-child transmission (MTCT) of HIV and other pregnancy outcomes. We included 5 trials totaling 7528 women (4 trials of prenatal and 1 trial of postnatal supplementation). Overall, there was no evidence of an effect of prenatal and/or postnatal vitamin A supplementation on the risk of MTCT of HIV (Relative Risk [RR] 1.06, 95% Confidence Interval [CI] 0.89-1.26). However, prenatal vitamin A supplementation significantly improved birth weight (weighted mean difference 89.78; 95% CI, 84.73-94.83), but there was no evidence of an effect on stillbirths (RR 0.99; 95% CI, 0.68-1.43), preterm births (RR 0.88; 95% CI, 0.65-1.19), death before 24 months among live births (RR 1.08; 95% CI, 0.91-1.29), and maternal death (RR 0.83; 95% CI, 0.59-1.17). The available evidence does not support vitamin A supplementation of HIV-infected pregnant and lactating women, despite improvement in birth weight."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I488,I488)","v":18812465},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B488:D488)","v":1},2009,"Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.","Sanz",18812465,"Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.    Abstract:   The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence- and expert opinion-based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I489,I489)","v":18806735},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B489:D489)","v":1},2008,"[Selected mechanisms of the therapeutic effect of arsenic trioxide in cancer treatment].","Izdebska",18806735,"[Selected mechanisms of the therapeutic effect of arsenic trioxide in cancer treatment].    Abstract:   The properties of arsenic trioxide (arsenic) have been known for centuries. This compound has been used, among others, in the industrial production of paints and glass and also for the conservation of leather and wood. Although arsenic trioxide is highly toxic, this compound was shown to have a therapeutic potential as early as the fifteenth century. The period between the seventeenth and nineteenth centuries resulted in the development of new arsenic-based drugs which were applied for the treatment of skin diseases and acute promyelocytic leukemia. The mechanism of action of arsenic trioxide is mainly related to the induction of apoptosis (programmed cell death) in cancer cells. In particular it involves effects on the activities of JNK kinases, NF-kB transcription factor, glutathione, caspases, as well as pro- and anti-apoptotic proteins. Experiments investigating the effect of arsenic trioxide on cell lines such as glioma and prostate, breast, stomach, liver, and ovarian cancer are in progress. There are also clinical trials underway aimed at the use of arsenic trioxide with ascorbic acid, retinoid acid, and growth factors in combined therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I490,I490)","v":18752475},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B490:D490)","v":1},2008,"Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts?","Kraemer",18752475,"Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts?    Abstract:   Vitamin A deficiency (VAD) is a major health problem, particularly in low-resource countries, putting an estimated 125-130 million preschool-aged children at increased risk of morbidity and mortality from infectious diseases. Vitamin A supplementation reduces VAD and increases child survival; it is complemented by fortifying foods with vitamin A. Concern over increased risk of bone fracture associated with vitamin A intakes below the tolerable upper intake level (UL) among populations in affluent countries conflicts with the need to increase intakes in less developed countries, where populations are at greater risk of VAD and intakes are unlikely to reach the UL as diets include fewer foods containing retinol while vitamin A from carotenoids poses no risk of overdose. With the implementation of recently developed risk management tools, vitamin A can be used safely in food fortification, including point-of-use fortification in the context of supplementation among specific target groups in low-resource countries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I491,I491)","v":18670157},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B491:D491)","v":1},2008,"Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor.","Nakanishi",18670157,"Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor.    Abstract:   Organotin compounds have been widely used as antifouling biocides for ships and fishing nets, agricultural fungicides and rodent repellents. These widespread uses have resulted in the release of increasing amounts of organotins into the environment. In aquatic invertebrates, particularly marine gastropods, organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), induce irreversible sexual abnormality in females which is termed quot;imposexquot; at very low concentrations. Although it has been theorized that these compounds act as potential competitive inhibitors of aromatase, which converts androgen to estrogen, and then increase levels of unconverted androgens in gastropods, their effective concentrations for aromatase inhibition are high. In addition to wildlife, organotins may have various undesirable effects on human health. Contrary to the theory of organotin-induced aromatase inhibition in gastropods, in human choriocarcinoma cells, these compounds markedly enhance estradiol biosynthesis along with the increase of both aromatase activity and 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I) activity, which converts low-activity estrogen estrone to the biologically more active form estradiol, at the same low concentrations. Although there are many reports describing the potential toxicity of organotins in human and mammals, the critical target molecules for the toxicity of organotin compounds remain unclear. Recently, organotin compounds including TBT and TPT were identified as nanomolar agonists for retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) gamma, which are members of the nuclear receptor superfamily. Here, we review the potential genetics action and subsequent toxicity induced by organotins via these nuclear receptors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I492,I492)","v":18537536},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B492:D492)","v":1},2008,"Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands: role in health and disease and their therapeutic potential.","Zimber",18537536,"Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands: role in health and disease and their therapeutic potential.    Abstract:   Bile acids, their physiology and metabolism, their role in carcinogenesis and other major human diseases are recently undergoing significant progress. Starting in 1999 when the orphan nuclear receptor FXR was shown to be specifically activated by bile acids, these compounds became part of the arsenal of ligands of the steroid hormone superfamily of nuclear receptors, including receptors of Vitamin D3, retinoids (RAR, RXR), and thyroid hormone. Another decisive discovery pointed later that the pregnane X-receptor (PXR) is activated by the endogenous toxic lithocholic acid, as well as several xenobiotics and drugs. Bile acids have recently emerged as key regulators of their own metabolism, and of lipid and carbohydrate metabolism. They have important role as promoters of esophageal and colon cancers, cholangiocarcinoma, as well as new implications in breast cancer development and metastasis. This Review will emphasize novel aspects of bile acids, FXR and PXR as regulators of interfaces at cell proliferation and differentiation, cell death, survival, invasion, and metastasis during normal development and cancer progression. Signaling pathways controlled by bile acids will be presented and discussed in relation to their impact on gene expression. The biological and pharmacological significance of bile acids and their recently developed synthetic derivatives and conjugates, as well as new development in the design of FXR agonists and antagonists for clinical applications in cancer prevention and therapy, will be evaluated. This part includes advances in the utilization of bile acid transporters in drug resistance, therapeutic targeting and delivery of anticancer drugs, as well as therapeutic combinations using new bile acid derivatives, sequestrating agents and reabsorption inhibitors, and their limitations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I493,I493)","v":18430166},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B493:D493)","v":1},2008,"Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.","Saga",18430166,"Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.    Abstract:   Much research has been conducted in recent years to elucidate the mechanisms underlying the crucial developmental process of sex determination. It has now been shown that somatic sex is principally determined by the chromosomal sex and the molecular mechanisms involved in this process have become relatively well understood in both human and mouse. However, the pathways involved in the sex determination of the germ cells remain largely unknown except for the fact that the somatic cues surrounding these cells play a significant role. Moreover, which sexual pathway of the germ cells is induced or suppressed has long been a subject of some dispute. Recent findings indicate that the key molecule that influences this choice is retinoic acid. In addition, the Nanos protein has been shown to play a critical role in promoting male germ cell differentiation. In this review, the possible mechanisms underlying these events, which have been brought to light by recent findings, are summarized to provide a better and more precise understanding of our current knowledge of the sex determination and subsequent differentiation of germ cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I494,I494)","v":18410980},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B494:D494)","v":1},2008,"Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases.","Lam",18410980,"Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases.    Abstract:   In patients with psoriasis, there is an increased availability of drugs for treatment. However, there are important questions about drug safety for mothers with psoriasis and their fetuses. Currently, there are limited safety data for many of the medications used. In this article, we review current pregnancy risk information for medications commonly used in the treatment of psoriasis. In addition, a list of teratology information resources is included to help practicing clinicians find up-to-date information regarding the safety of the medications they prescribe."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I495,I495)","v":18206226},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B495:D495)","v":1},2008,"What works? Interventions for maternal and child undernutrition and survival.","Bhutta",18206226,"What works? Interventions for maternal and child undernutrition and survival.    Abstract:   We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of womens empowerment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I496,I496)","v":18084010},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B496:D496)","v":1},2008,"Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.","Jones",18084010,"Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.    Abstract:   Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Downs syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I497,I497)","v":18024835},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B497:D497)","v":1},2008,"Structure, evolution, and biology of the MUC4 mucin.","Chaturvedi",18024835,"Structure, evolution, and biology of the MUC4 mucin.    Abstract:   Mucins are high-molecular-weight glycoproteins and are implicated in diverse biological functions. MUC4, a member of transmembrane mucin family, is expressed in airway epithelial cells and body fluids like saliva, tear film, ear fluid, and breast milk. In addition to its normal expression, an aberrant expression of MUC4 has been reported in a variety of carcinomas. Among various potential domains of MUC4, epidermal growth factor (EGF) -like domains are hypothesized to interact with and activate the ErbB2 receptors, suggesting an intramembrane-growth factor function for MUC4. The heavily glycosylated tandem repeat domain provides the structural rigidity to the extended extracellular region. MUC4, by virtue of its extended structure, serves as a barrier for some cell-cell and cell-extracellular matrix interactions and as a potential reservoir for certain growth factors. An intricate relationship between MUC4 and growth factor signaling is also reflected in the transcriptional regulation of MUC4. The MUC4 promoter has binding sites for different transcription factors, which are responsible for the regulation of its expression in different tissues. The interferon-gamma, retinoic acid, and transforming growth factor-beta signaling pathways regulate MUC4 expression in a partially interdependent manner. Taken together, all of these features of MUC4 strongly support its role as a potential candidate for diagnostic and therapeutic applications in cancer and other diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I498,I498)","v":17785917},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B498:D498)","v":1},2007,"Biological roles of estrogen and progesterone in human endometrial carcinoma--new developments in potential endocrine therapy for endometrial cancer.","Ito",17785917,"Biological roles of estrogen and progesterone in human endometrial carcinoma--new developments in potential endocrine therapy for endometrial cancer.    Abstract:   Endometrial carcinoma is one of the most common female pelvic malignancies. It is well known that uterine endometrial cell proliferation is under the control of both estrogen and progesterone. In this review, results of the recent studies on the biosynthesis and action of estrogen and progestin in normal endometrium and its disorders will be summarized and the new aspects of hormonal therapies in the patients with endometrial carcinoma will be discussed including its future prospectives. We reported that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinoma, although both of them are considered quot;estrogen-dependent malignanciesquot;. In addition, the biological significance of Progesterone receptor (PR) isoforms is considered to differ between endometrial and breast carcinomas. Clinical data concerning Hormone replacement therapy (HRT) and estrogen-dependent cancer risk also support these findings. These basic and clinical findings help to understand the biology and provide the new knowledge for prevention, diagnosis and treatment of human endomerial carcinoma. Specific endocrine treatment of endometrial carcinoma should be explored in future, although aromatase inhibitors are the most effective endocrine treatments of estrogen-responsive breast carcinoma. Retinoid, metabolities of vitamin A, and synthetic peroxisome proliferator-activated receptor (PPAR) gamma ligands, which have been used for the treatment of insulin resistance in type II diabetes mellitus, may be the important candidates as drugs not only for prevention but also for possible endocrine treatment of endometrial carcinoma."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I499,I499)","v":17691927},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B499:D499)","v":1},2007,"Maternal nutrition and predisposition to later kidney disease.","Woods",17691927,"Maternal nutrition and predisposition to later kidney disease.    Abstract:   Although it is well-accepted that size at birth is inversely related to adult blood pressure and cardiovascular risk in humans, the majority of information available with regard to maternal nutrition, prenatal growth, and subsequent renal disease comes from animal models. Restriction of food or protein during specific windows of pregnancy leads to hypertension in adult offspring. Depending on the degree of maternal restriction, nephron number and renal function in the offspring may be reduced, and proteinuria and histological signs of renal disease are present. All of these abnormalities appear to worsen with age. Female gender is relatively protective against these prenatal insults, but with more severe maternal dietary restriction female offspring are also affected. In addition to macronutrients, roles for several micronutrients have been identified in fetal programming for hypertension and renal disease. Ongoing investigations into the roles of sex hormones, the renin-angiotensin system, and vitamin A in these developmental processes may lead to strategies for prevention of dietary programming for hypertension and renal disease in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I500,I500)","v":17646865},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B500:D500)","v":1},2007,"Molecular mechanisms of alcohol-mediated carcinogenesis.","Seitz",17646865,"Molecular mechanisms of alcohol-mediated carcinogenesis.    Abstract:   Approximately 3.6% of cancers worldwide derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, most recent research has focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Ethanol may also stimulate carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Alcohol-related carcinogenesis may interact with other factors such as smoking, diet and comorbidities, and depends on genetic susceptibility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I501,I501)","v":17589794},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B501:D501)","v":1},2007,"Androgenic regulation of novel genes in the epididymis.","Robaire",17589794,"Androgenic regulation of novel genes in the epididymis.    Abstract:   The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone (T) and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I502,I502)","v":17483773},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B502:D502)","v":1},2007,"[Nutritional deficiencies associated with bariatric surgery].","Folope",17483773,"[Nutritional deficiencies associated with bariatric surgery].    Abstract:   Morbidly obese patients often have nutritional deficiencies, particularly in fat-soluble vitamins, folic acid and zinc. After bariatric surgery, these deficiencies may increase and others can appear, especially because of the limitation of food intake in gastric reduction surgery and of malabsorption in by-pass procedures. The latter result in more important weight loss but also increase the risk of more severe deficiencies. The protein deficiency associated with a decrease in the fat-free mass has been described in both procedures. It can sometimes require an enteral or parenteral support. Anemia can be secondary to iron deficiency, folic acid deficiency and even to vitamin B12 deficiency. Neurological disorders such as Gayet-Wernicke encephalopathy due to thiamine deficiency, or peripheral neuropathies may also be observed. Malabsorption of fat-soluble vitamins and other nutrients, especially if diagnosed after by-pass surgery, rarely cause clinical symptoms. However, some complications have been reported such as bone demineralization due to vitamin D deficiency, hair loss secondary to zinc deficiency or hemeralopia from vitamin A deficiency. A careful nutritional follow-up should be performed during pregnancy after obesity surgery, because possible deficiencies can affect the health of both the mother and child. In conclusion, increased awareness of the risk of deficiency and the systematic dosage of micronutrients are needed in the pre- and postoperative period in obese patients undergoing bariatric surgery. The case by case correction of these deficiencies is mandatory, and their systematic prevention should be evaluated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I503,I503)","v":17434893},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B503:D503)","v":1},2007,"Targeted therapy in nuclear medicine--current status and future prospects.","Oyen",17434893,"Targeted therapy in nuclear medicine--current status and future prospects.    Abstract:   In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I504,I504)","v":17315247},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B504:D504)","v":1},2006,"Inhibition of histone deacetylase as a new mechanism of teratogenesis.","Menegola",17315247,"Inhibition of histone deacetylase as a new mechanism of teratogenesis.    Abstract:   Histone deacetylases (HDACs) are nuclear and cytoplasmic enzymes that deacetylate a number of substrates, of which histones are the best known and described in the literature. HDACs are present in eukaryotic and bacteria cells, and are fundamental for a number of cellular functions, including correct gene expression. Surprisingly, only up to 20% of the whole genome is controlled by HDACs, but key processes for survival, proliferation, and differentiation have been strictly linked to HDAC enzyme functioning. The use of HDAC inhibitors (HDACi) has been proposed for the treatment of neoplastic diseases. Their effectiveness has been suggested for a number of liquid and solid tumors, particularly acute promyelocytic leukemia (APL). The role of HDACs in embryo development is currently under investigation. Published data indicate knockout phenotype analysis to be of particular interest, in which a number of HDACs play a key role during development. Little data have been published on the effects of HDACi on embryonic development, although for valproic acid (VPA), literature from the 1980s described its teratogenic effects in experimental animals and humans. To date, all tested HDACi have shown teratogenic effects similar to those described for VPA when tested in zebrafish, Xenopus laevis, and mice. HDACs were also able to alter embryo development in invertebrates and plants. A model, similar to that proposed in APL, involving retinoic acid receptors (RAR) and tissue specific Hox gene expression, is suggested to explain the HDAC effects on embryo development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I505,I505)","v":17242785},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B505:D505)","v":1},2006,"[Current status of breast cancer chemoprevention].","Oliveira",17242785,"[Current status of breast cancer chemoprevention].    Abstract:   Chemoprevention is defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER)-positive breast cancers [selective estrogen receptor modulators (SERM), aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER-negative breast cancers [cyclooxygenase-2 (COX-2) inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR), which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83). It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I506,I506)","v":17168675},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B506:D506)","v":1},2006,"Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets.","Narayanan",17168675,"Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets.    Abstract:   Chemoprevention has the potential to be a major component of colon, breast, prostate and lung cancer control. Epidemiological, experimental, and clinical studies provide evidence that antioxidants, anti-inflammatory agents, n-3 polyunsaturated fatty acids and several other phytochemicals possess unique modes of action against cancer growth. However, the mode of action of several of these agents at the gene transcription level is not completely understood. Completion of the human genome sequence and the advent of DNA microarrays using cDNAs enhanced the detection and identification of hundreds of differentially expressed genes in response to anticancer drugs or chemopreventive agents. In this review, we are presenting an extensive analysis of the key findings from studies using potential chemopreventive agents on global gene expression patterns, which lead to the identification of cancer drug targets. The summary of the study reports discussed in this review explains the extent of gene alterations mediated by more than 20 compounds including antioxidants, fatty acids, NSAIDs, phytochemicals, retinoids, selenium, vitamins, aromatase inhibitor, lovastatin, oltipraz, salvicine, and zinc. The findings from these studies further reveal the utility of DNA microarray in characterizing and quantifying the differentially expressed genes that are possibly reprogrammed by the above agents against colon, breast, prostate, lung, liver, pancreatic and other cancer types. Phenolic antioxidant resveratrol found in berries and grapes inhibits the formation of prostate tumors by acting on the regulatory genes such as p53 while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D, DNA fragmentation factor 45. The group of genes significantly altered by selenium includes cyclin D1, cdk5, cdk4, cdk2, cdc25A and GADD 153. Vitamine D shows impact on p21(Waf1/Cip1) p27 cyclin B and cyclin A1. Genomic expression profile with vitamin D indicated differential expression of gene targets such as c-JUN, JUNB, JUND, FREAC-1/FoxF1, ZNF-44/KOX7, plectin, filamin, and keratin-13, involved in antiproliferative, differentiation pathways. The agent UBEIL has a remarkable effect on cyclin D1. Curcumin mediated NrF2 pathway significantly altered p21(Waf1/Cip1) levels. Aromatase inhibitors affected the expression of cyclin D1. Interestingly, few dietary compounds listed in this review also have effect on APC, cdk inhibitors p21(Waf1/Cip1) and p27. Tea polyphenol EGCG has a significant effect on TGF-beta expression, while several other earlier studies have shown its effect on cell cycle regulatory proteins. This review article reveals potential chemoprevention drug targets, which are mainly centered on cell cycle regulatory pathway genes in cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I507,I507)","v":17107283},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B507:D507)","v":1},2006,"Prevention of breast cancer: current state of the science and future opportunities.","Uray",17107283,"Prevention of breast cancer: current state of the science and future opportunities.    Abstract:   Despite significant progress in breast cancer treatment, mammary tumours still represent the second most frequent cause of cancer-related death in women in the US, with gt; 211,000 new cases in 2005; however, an expanding range of options for early diagnosis and more reliable risk assessment offers new alternatives for disease control by cancer prevention. Completed large studies with the classical selective estrogen receptor modulator (SERM) tamoxifen have demonstrated that preventing breast cancer pharmacologically is now possible. Novel SERMs, aromatase inhibitors and gonadotropin-releasing hormone agonists targeting hormonal pathways are being tested in clinical trials, revealing the potential for dramatic reductions in tumour incidence with minimal side effects; however, SERMs and aromatase inhibitors are effective only against estrogen receptor-positive tumours, thus chemopreventive drugs targeting other critical signalling pathways (such as retinoids, selective COX inhibitors and tyrosine kinase inhibitors) may provide a means to prevent estrogen receptor-negative breast cancer. In the future, hormonal and estrogen receptor-independent agents may be combined to prevent the development of all mammary tumours. This article reviews the current and novel strategies for breast cancer prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I508,I508)","v":17101024},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B508:D508)","v":1},2006,"Fetal alcohol syndrome and developing craniofacial and dental structures--a review.","SantAnna",17101024,"Fetal alcohol syndrome and developing craniofacial and dental structures--a review.    Abstract:    OBJECTIVES : Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in children exposed to alcohol in the prenatal period. It is characterized mainly by a distinct pattern of craniofacial malformations, physical and mental retardation. However, with the increased incidence of FAS, there is a great variation in the clinical features of FAS.  DESIGN : Narrative review.  RESULTS : This review describes data from clinical and experimental studies, and in vitro models. Experimental studies have shown that alcohol has a direct toxic effect on the ectodermal and mesodermal cells of the developing embryo, particularly in the cells destined to give rise to dentofacial structures (i.e. cranial neural crest cells). Other effects, such as, abnormal pattern of cranial and mandibular growth and altered odontogenesis are described in detail. The exact mechanism by which alcohol induces its teratogenic effects remains still unknown. The possible mechanisms are outlined here, with an emphasis on the developing face and tooth. Possible future research directions and treatment strategies are also discussed.  CONCLUSION : Early identification of children affected by prenatal alcohol exposure leads to interventions, services, and improved outcomes. FAS can be prevented with the elimination of alcohol consumption during pregnancy. We need to provide education, target high-risk groups, and make this issue a high priority in terms of public health."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I509,I509)","v":17076197},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B509:D509)","v":1},2006,"[The role of peroxisome proliferator-activated receptors (PPAR) in carcinogenesis].","Knapp",17076197,"[The role of peroxisome proliferator-activated receptors (PPAR) in carcinogenesis].    Abstract:   Peroxisome proliferators-activated receptors are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPAR-alpha, PPAR-sigma (NUC-1 or beta) and PPAR-gamma. PPARs regulate gene expression by binding, as heterodimers with retinoid X receptors (RXR), to specific response elements (PPREs) in the promoter regions of target genes. The prostaglandin 12 especially, all arachidonic acid metabolites and polyunsaturated fatty acids are naturally occuring PPAR ligands. Synthetic PPAR ligands are thiazolidinediones (TZDs--rosiglitazone, pioglitazone, troglitazone). Activation of nuclear hormone receptors has been identified as an approach to induce differentiation and inhibit proliferation of cancer lines. The anti-proliferative, pro-differentiation effects of PPAR activators (TZDs) suggest that these compounds might be useful in slowing the proliferation of un-differentiated tumour cells. TZDs inhibit proliferation of human breast, prostate and colon cancers, both in vitro and in tumours derived from these cells implanted into rodents. Furthermore, recent studies show that PPAR-gamma ligands are potent inhibitors of angiogenesis, a process essential for solid-tumour growth and metastasis. In conclusion, the evidence to date suggests that activation of PPAR should suppress tumour growth and development. This represents an exciting novel therapeutic application of TZDs. In present paper, structural features of PPARs, their gene transcription mechanisms and recent developments in the discovery of their biological functions are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I510,I510)","v":16954431},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B510:D510)","v":1},2006,"Enhancement of sodium/iodide symporter expression in thyroid and breast cancer.","Kogai",16954431,"Enhancement of sodium/iodide symporter expression in thyroid and breast cancer.    Abstract:   The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a cold or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize beta-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10-20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of differentiation agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in scan-negative thyroid cancer and some breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I511,I511)","v":16950593},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B511:D511)","v":1},2006,"Metastatic breast cancer: an updating.","Nicolini",16950593,"Metastatic breast cancer: an updating.    Abstract:    UNLABELLEDThis article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined.  DETECTION NlmCategory=UNASSIGNEDUnlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with dynamic evaluation of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations.  PROGNOSIS AND THERAPY PREDICTORS NlmCategory=UNASSIGNEDDisease-free interval (DFI)lt;or=24 months, adjuvant chemotherapy, liver and distant soft tissue involvement or DFIgt;24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents.  THERAPY : Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called tailored or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called oligometastatic and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that biological therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I512,I512)","v":16936300},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B512:D512)","v":1},2006,"Genomic and post-genomic approaches to polycystic ovary syndrome--progress so far: Mini Review.","Hughes",16936300,"Genomic and post-genomic approaches to polycystic ovary syndrome--progress so far: Mini Review.    Abstract:   Genomic studies in polycystic ovary syndrome (PCOS) have focused on ovarian tissues and gene expression changes related to the gynaecological manifestations of PCOS. These studies have revealed a variety of altered genes that fall into many functional categories. Of these, the genes involved in steroidogenesis, including genes related to retinoic acid biosynthesis and LH-stimulated gene pathways, are generally up-regulated in PCOS samples. Genes involved in the Wnt signalling pathway appear down-regulated. Immune response genes and those involved in apoptosis are altered, but the net effect of these alterations is unclear at present. However, these altered gene expression patterns are yet to produce a defined aetiological basis or diagnostic biomarker for PCOS. The use of proteomic technologies for the study of the PCOS proteome is in its infancy; however, a few pilot studies have been published and the data are reviewed. Proteomics looks directly at the functional units within a cell, the proteins. This approach should thus serve to validate some of the gene expression changes identified and then build on the genomic results collected to date."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I513,I513)","v":16886664},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B513:D513)","v":1},2006,"Epigenetic corruption of VDR signalling in malignancy.","Abedin",16886664,"Epigenetic corruption of VDR signalling in malignancy.    Abstract:    BACKGROUND : The ligand-mediated switch from binding co-repressor to co-activator complexes is central to the transcriptional actions of the vitamin D receptor (VDR) and other nuclear receptors. The capacity of deregulated co-repressors to attenuate the responsiveness of VDR signalling in cancer models was examined.  MATERIALS AND METHODS : Proliferation and gene regulation studies were undertaken in non-malignant and malignant cell line and primary models.  RESULTS : Both primary tissue models and cancer cell lines displayed a spectrum of suppressed responsiveness towards 1alpha, 25 hydroxy vitamin D3 (1alpha25(OH)2D3) which correlated with elevated co-repressor content: specifically, elevated silencing mediator of retinoid and thyroid hormone receptors/nuclear co-repressor 2 (NCoR2/SMRT) in prostate cancer cell lines and primary tumour cultures, and elevated nuclear receptor co-repressor 1 (NCoR1) in breast cancer cell lines. Interestingly, whilst the cancer cell lines frequently also displayed reduced VDR content, the primary tumour material retained and/or elevated VDR mRNA, correlated with co-repressor content. Functional approaches towards NCoR2/SMRT (siRNA) in prostate cancer cells or NCoR1 (overexpression) in non-malignant breast epithelial cells confirmed a role in suppressing VDR transcriptional and cellular actions. Targeted co-treatments of 1alpha25(OH)2D3 plus HDAC inhibitors (TSA, NaB) resulted in re-expression of antiproliferative target genes (e.g., GADD45alpha, p21(waf1/cip1)) and synergistic inhibition of proliferation.  CONCLUSION : These data suggest that VDR actions in solid tumours are retained, but were skewed by epigenetic mechanisms to suppress selectively antiproliferative target gene promoter responses. This molecular lesion provides a novel chemotherapy target for acceptable doses of 1alpha25(OH)2D3 plus HDAC inhibitors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I514,I514)","v":16886661},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B514:D514)","v":1},2006,"Vitamin D compounds: activity against microbes and cancer.","Gombart",16886661,"Vitamin D compounds: activity against microbes and cancer.    Abstract:   Vitamin D3 is produced in skin and is sequentially metabolized by the liver and kidney to the biologically active form 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is a seco-steroid hormone that regulates calcium homeostasis within the body. The genomic actions of 1,25(OH)2D3 are modulated through the vitamin D receptor (VDR). VDR belongs to a superfamily of nuclear receptors that transduce hormonal signals from the immediate environment and transactivate genes in response to these signals. Target genes contain hormone response elements (VDREs) in their promoters to which heterodimers of VDR and retinoid X receptors (RXR) can bind and transactivate expression of the target genes. The VDR is expressed in at least 30 different target tissues including bone, kidney, blood, breast, prostate, gut, activated B- and T- lymphocytes, monocytes and keratinocytes). Most dividing cell types, normal and malignant, can express VDR and respond to 1,25(OH)2D3. Although 1,25(OH)2D3 and its analogs (termed deltanoids) are important regulators of calcium and bone metabolism, their non-calciotropic activities that include inhibition of cell proliferation, promotion of cell differentiation and modulation of immune cell function have spurred interest in therapeutic applications in a wide variety of diseases. In this report, the anticancer and newly discovered antimicrobial actions of 1,25(OH)2D3 and deltanoids are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I515,I515)","v":16858170},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B515:D515)","v":1},2006,"Chemoprevention of breast cancer: tamoxifen, raloxifene, and beyond.","Bao",16858170,"Chemoprevention of breast cancer: tamoxifen, raloxifene, and beyond.    Abstract:   Breast cancer is the most common cancer and the second most common cause of cancer death among women in the United States. While nonrandomized studies have reported that prophylactic mastectomy or oophorectomy can significantly reduce the risk of breast cancer, these approaches are unacceptable to the majority of women. Chemoprevention, which is defined as the prevention of cancer by pharmacological agents that inhibit or reverse the process of carcinogenesis, has thus increasingly become the focus of breast cancer prevention efforts. The first-generation selective estrogen receptor modulator (SERM) tamoxifen is the only US Food and Drug Administration- approved drug for breast cancer prevention and reduces the risk of breast cancer by as much as 50% in high-risk women. Raloxifene, a second-generation SERM, also has demonstrated efficacy for breast cancer prevention and is being compared with tamoxifen in a large randomized trial that has recently completed accrual. The aromatase inhibitors (AIs) decrease the incidence of contralateral breast cancer when used in the adjuvant setting and are being evaluated in ongoing primary prevention studies. In addition, a number of novel agents, including antiinflammatory drugs and retinoid derivatives, which appear to be of promise based on preclinical and epidemiological data, are under investigation. Several important challenges remain, including determination of the appropriate dose and duration of treatment when used in the primary prevention setting and development of new research models using surrogate end points for breast cancer incidence and mortality to permit more rapid clinical application of promising new agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I516,I516)","v":16850277},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B516:D516)","v":1},2006,"Ensuring the safe and effective use of medications during pregnancy: planning and prevention through preconception care.","Cragan",16850277,"Ensuring the safe and effective use of medications during pregnancy: planning and prevention through preconception care.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I517,I517)","v":16724326},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B517:D517)","v":1},2006,"The long and short of it: somite formation in mice.","Gridley",16724326,"The long and short of it: somite formation in mice.    Abstract:   A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior-posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I518,I518)","v":16721130},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B518:D518)","v":1},2006,"Targeting angiogenesis for the treatment of sarcoma.","Balasubramanian",16721130,"Targeting angiogenesis for the treatment of sarcoma.    Abstract:    PURPOSE OF REVIEW : More therapeutic options are needed for bone and soft tissue sarcomas, especially for patients with metastatic disease. Recent randomized clinical trials conducted in colon, breast and lung cancer have shown the anti-vascular endothelial growth factor agent, bevacizumab, alone or in combination with chemotherapy, improves response and survival. Preclinical studies have demonstrated the anti-tumor effects of varied anti-angiogenic agents in sarcoma cell lines and tumor models.  RECENT FINDINGS : Preclinical studies in sarcomas have evaluated the role of targeted agents including platelet-derived growth factor, matrix metalloproteinases, urokinase receptor and varied small-molecule tyrosine kinase inhibitors. Novel angiogenesis inhibitors are being studied in the treatment of sarcoma, including monoclonal antibodies against vascular endothelial growth factor, cis- and trans-retinoic acids, thalidomide, and tyrosine kinase inhibitors. Phase I, II and III clinical trials continue to evaluate these agents alone, in combinations together and combined with standard chemotherapy. We review herein the preclinical rationale and clinical trial results of anti-angiogenesis therapy in the treatment of soft tissue and bone sarcoma.  SUMMARY : Preclinical mechanistic study and clinical trials are continuing in order to evaluate the therapeutic role and ultimately validate the efficacy of the varied anti-angiogenesis agents in soft tissue and bone sarcoma."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I519,I519)","v":16720311},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B519:D519)","v":1},2006,"Chemoprevention of breast cancer: current status and future prospects.","Zhao",16720311,"Chemoprevention of breast cancer: current status and future prospects.    Abstract:   Chemoprevention plays an important role in the prevention of cancer. Due to being an estrogen-dependent cancer, breast carcinomas are ideal candidate for chemoprevention. The two main approaches to chemoprevention of breast cancer are to attain a balance in estrogen or to eliminate all estrogens by selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). A series of clinical trials have proven tamoxifene quite useful as a preventive strategy for women at high risk of breast cancer. The third-generation, AIs, hold a great promise in chemoprevention of breast cancer. In this review, the mechanisms, side effects and main clinical trials of SERMs and AIs are discussed. The use of other drugs including CoQ10, retinoids, cyclooxygenase (COX)-2 inhibitors, vitamin E, soy isoflavones, tea polyphenols and statins in chemoprevention is introduced. Since most studies on these drugs were conducted on animal models or cell culture, further studies are needed to determine the efficacy of these drugs in chemoprevention of human cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I520,I520)","v":16632680},{"$f":"(LEN($J520) - LEN(SUBSTITUTE(LOWER($J520),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J520) - LEN(SUBSTITUTE(LOWER($J520),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J520) - LEN(SUBSTITUTE(LOWER($J520),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B520:D520)","v":1},2006,"Endocrine regulation of HOX genes.","Daftary",16632680,"Endocrine regulation of HOX genes.    Abstract:   Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I521,I521)","v":16454047},{"$f":"(LEN($J521) - LEN(SUBSTITUTE(LOWER($J521),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J521) - LEN(SUBSTITUTE(LOWER($J521),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J521) - LEN(SUBSTITUTE(LOWER($J521),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B521:D521)","v":1},2005,"[Study of nutritional factors related to breast cancer prevention. Importance of animal models approaches].","García-Solís",16454047,"[Study of nutritional factors related to breast cancer prevention. Importance of animal models approaches].    Abstract:   Breast cancer is the most common worldwide neoplasia in women. The totality of etiology factors of breast cancer is unknown and thus an effective preventive strategy has not been developed. Risk factors associated to breast cancer can be grouped into three broad categories: a) family history (hereditary) factors, b) endocrine and reproductive factors and c) environmental and life-style factors including diet. Animal models of chemical induced mammary carcinogenesis with 7, 12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea have been useful in the study of biology, treatment and prevention of breast cancer. In this review we show the usefulness and advantages of animal models in the study of nutritional factors associated with breast cancer in order to propose new prevention strategies. We review briefly different experimental approaches as well as some physiologic effects and mechanisms of some nutritional factors studied with animal models of mammary carcinogenesis. Nutritional factors reviewed were: a) energy restriction and high-fat intake, b) soy and phytoestrogens, c) retinoids and carotenoids, d) conjugated linoleic acid, and e) brown seaweed and iodine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I522,I522)","v":16430309},{"$f":"(LEN($J522) - LEN(SUBSTITUTE(LOWER($J522),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J522) - LEN(SUBSTITUTE(LOWER($J522),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J522) - LEN(SUBSTITUTE(LOWER($J522),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B522:D522)","v":1},2006,"Significance of the minor cytochrome P450 3A isoforms.","Daly",16430309,"Significance of the minor cytochrome P450 3A isoforms.    Abstract:   Cytochrome P450 (CYP) 3A4 is responsible for most CYP3A-mediated drug metabolism but the minor isoforms CYP3A5, CYP3A7 and CYP3A43 also contribute. CYP3A5 is the best studied of the minor CYP3A isoforms. It is well established that only approximately 20% of livers express CYP3A5. The most common reason for the absence of expression is a splice site mutation. The frequency of variant alleles shows interethnic differences, with the wild-type CYP3A5*1 allele more common in Africans than Caucasians and Asians. In individuals who express CYP3A5, the percentage contributed to total hepatic CYP3A by this isoform is still unclear, with estimates ranging from 17% to 50%. CYP3A5 is also expressed in a range of extrahepatic tissues. Only limited information is available on the regulation of CYP3A5 expression but it appears to be inducible via the glucocorticoid receptor, pregnane X receptor and constitutive androstane receptor-beta, as for CYP3A4. Although information on the substrate specificity of CYP3A5 is limited compared with CYP3A4, there have been a number of recent pharmacokinetic studies on a small range of substrates in individuals of known genotype to investigate the contribution of CYP3A5. In the case of midazolam, ciclosporin, nifedipine and docetaxel, clearance by individuals with a CYP3A5-expressing genotype did not differ from that for nonexpressors, but in the case of tacrolimus, eight independent studies have demonstrated faster clearance by those carrying one or two CYP3A5*1 alleles. This may reflect faster turnover of tacrolimus by CYP3A5 than the other substrates. CYP3A5 genotype may affect cancer susceptibility. Certain combined CYP3A4/CYP3A5 haplotypes show differential susceptibility to prostate cancer and there is a nonsignificant increase in the risk of small-cell lung cancer for a CYP3A5*1/*1 genotype. Females positive for CYP3A5*1 appear to reach puberty earlier, which may affect breast cancer risk. CYP3A5*1 homozygotes may have higher systolic blood pressure.CYP3A7 is predominantly expressed in fetal liver but is also found in some adult livers and extrahepatically. The molecular basis for expression in adult liver relates to upstream polymorphisms, which appear to increase homology to CYP3A4 and make regulation of expression more similar. CYP3A7 has a specific role in hydroxylation of retinoic acid and 16alpha-hydroxylation of steroids, and is therefore of relevance both to normal development and carcinogenesis.CYP3A43 is the most recently discovered CYP3A isoform. In addition to a low level of expression in liver, it is expressed in prostate and testis. Its substrate specificity is currently unclear. Polymorphisms predicting absence of active enzyme have been identified."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I523,I523)","v":16285276},{"$f":"(LEN($J523) - LEN(SUBSTITUTE(LOWER($J523),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J523) - LEN(SUBSTITUTE(LOWER($J523),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J523) - LEN(SUBSTITUTE(LOWER($J523),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B523:D523)","v":1},2003,"[Systemic treatment of cutaneous lupus erythematosus].","Wenzel",16285276,"[Systemic treatment of cutaneous lupus erythematosus].    Abstract:   The treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic challenge. In many cases, systemic treatment of the disease is necessary, especially in cases resistant to topical treatment or with internal organ involvement. Even though many different agents can be employed in this situation, most are not approved in Germany for the treatment of CLE. We give an overview of the agents used in the systemic treatment of CLE and review their mechanisms of action, indications and their practical use in cutaneous LE based on literature results and our own experience. We discuss corticosteroids, antimalarials, dapsone, azathioprine, cyclophosphamide, methotrexate, retinoids, cyclosporine A, mycophenolate mofetil, sulfasalazine, thalidomide, clofazimine, tacrolimus, immunoglobulins, monoclonal antibodies, plasmapheresis, etanercept, infliximab, feflunomid, gold and interferon-alpha."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I524,I524)","v":16235333},{"$f":"(LEN($J524) - LEN(SUBSTITUTE(LOWER($J524),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J524) - LEN(SUBSTITUTE(LOWER($J524),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J524) - LEN(SUBSTITUTE(LOWER($J524),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B524:D524)","v":1},2005,"Micronutrient supplementation in children and adults with HIV infection.","Irlam",16235333,"Micronutrient supplementation in children and adults with HIV infection.    Abstract:    BACKGROUND : The scale and impact of the HIV/AIDS pandemic has made the search for simple, affordable, safe, and effective public health interventions all the more urgent. Micronutrient supplements hold the promise of meeting these criteria, but their widespread use needs to be based on sound scientific evidence of effectiveness and safety.  OBJECTIVES : To assess whether micronutrient supplements are effective in reducing morbidity and mortality in adults and children with HIV infection.  SEARCH STRATEGY : The Cochrane Library (CENTRAL), EMBASE, MEDLINE, AIDSearch, CINAHL, and conference proceedings were searched, and pharmaceutical manufacturers and researchers in the field were contacted to locate any ongoing or unpublished trials.  SELECTION CRITERIA : Randomised controlled trials comparing the effects of micronutrient supplements (vitamins, trace elements, and combinations of these) with placebo or no treatment on mortality and morbidity in HIV-infected individuals.  DATA COLLECTION AND ANALYSIS : Two reviewers independently appraised trial quality and extracted data. Study authors were contacted for additional data where necessary. A meta-analysis was not deemed appropriate due to significant heterogeneity between trials.  MAIN RESULTS : Fifteen trials were included. Six trials comparing vitamin A/beta-carotene with placebo in adults failed to show any effects on mortality, morbidity, CD4 and CD8 counts, or on viral load. Four trials of other micronutrients in adults did not affect overall mortality, although there was a reduction in mortality in a low CD4 subgroup. In a large Tanzanian trial in pregnant and lactating women, daily multivitamin supplementation was associated with a number of benefits to both mothers and children: a reduction in maternal mortality from AIDS-related causes; a reduced risk of progression to stage four disease; fewer adverse pregnancy outcomes; less diarrhoeal morbidity; and a reduction in early-child mortality among immunologically- and nutritionally-compromised women. Vitamin A alone reduced all-cause mortality and improved growth in a small sub-group of HIV-infected children in one hospital-based trial, and reduced diarrhoea-associated morbidity in a small HIV-infected sub-group of infants in another trial.  AUTHORS CONCLUSIONS : There is no conclusive evidence at present to show that micronutrient supplementation effectively reduces morbidity and mortality among HIV-infected adults. It is reasonable to support the current WHO recommendations to promote and support adequate dietary intake of micronutrients at RDA levels wherever possible. There is evidence of benefit of vitamin A supplementation in children. The long-term clinical benefits, adverse effects, and optimal formulation of micronutrient supplements require further investigation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I525,I525)","v":16235332},{"$f":"(LEN($J525) - LEN(SUBSTITUTE(LOWER($J525),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J525) - LEN(SUBSTITUTE(LOWER($J525),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J525) - LEN(SUBSTITUTE(LOWER($J525),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B525:D525)","v":1},2005,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.","Wiysonge",16235332,"Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : Mother-to-child transmission (MTCT) of HIV is the dominant mode of acquisition of HIV infection for children, currently resulting in more than 2000 new paediatric HIV infections each day worldwide.  OBJECTIVES : To assess the effects of antenatal and intrapartum vitamin A supplementation on the risk of MTCT of HIV infection and infant and maternal mortality and morbidity, and the tolerability of vitamin A supplementation.  SEARCH STRATEGY : We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, AIDSLINE, LILACS, AIDSTRIALS, and AIDSDRUGS, using standardised methodological filters for identifying trials. We also searched reference lists of identified articles, relevant editorials, expert opinions and letters to journal editors, and abstracts or proceedings of relevant conferences; and contacted subject experts, agencies, organisations, academic centres, and pharmaceutical companies. There were no language restrictions.  SELECTION CRITERIA : Randomised trials comparing vitamin A supplementation with no vitamin A supplementation in known HIV infected pregnant women. Trials had to include an estimate of the effect of vitamin A supplementation on MTCT of HIV and or any other adverse pregnancy outcome to be included.  DATA COLLECTION AND ANALYSIS : Two authors independently assessed trial eligibility and quality and extracted data. Effect measures (odds ratio [OR] for binary variables and weighted mean difference [WMD] for continuous variables) with their 95% confidence intervals (CI) were estimated for each study and combined using the fixed effect (Mantel-Haenszel) method, by intention to treat. Heterogeneity between studies was examined by graphical inspection of results followed by a chi-square test of homogeneity.  MAIN RESULTS : Four trials, which enrolled 3,033 HIV-infected pregnant women, are included in this review. There was no evidence of an effect of vitamin A supplementation on MTCT of HIV infection (OR 1.14, 95% CI 0.93 to 1.38). There was evidence of heterogeneity between the three trials with information on MTCT of HIV (I(2) =75.7%, P=0.02). While the trials conducted in South Africa (OR 0.98, 95% CI 0.67 to 1.42 at three months) and Malawi (OR 0.78, 95% CI 0.53 to 1.15 at 24 months) did not find evidence that the effect of Vitamin A supplementation was different from that of placebo, the trial in Tanzania did find evidence that vitamin A supplementation increased the risk of MTCT of HIV (OR 1.53, 95% CI 1.15 to 2.04 at 24 months). Vitamin A supplementation significantly improved birth weight (WMD 89.78, 95% CI 84.73 to 94.83), but there was no evidence of an effect of vitamin A supplementation on stillbirths (OR 0.99, 95% CI 0.67 to 1.46), preterm births (OR 0.89, 95% CI 0.71 to 1.11), death by 24 months among live births (OR 1.11, 95% CI 0.88 to 1.40), postpartum CD4 levels (WMD -4.00, 95% CI -51.06 to 43.06), and maternal death (OR 0.49, 95%CI 0.04 to 5.40).  AUTHORS CONCLUSIONS : /                <AbstractText IMPLICATIONS FOR PRACTICE : Currently available evidence do not support the use of vitamin A supplementation of HIV-infected pregnant women to reduce MTCT of HIV, though there is an indication that vitamin A supplementation improves birth weight.  IMPLICATIONS FOR RESEARCH : The awaited publication of data from a large trial involving 4,495 HIV infected pregnant women in Harare (Zimbabwe Vitamin A for Mothers and Babies Project), will further clarify the effect of vitamin A supplementation on MTCT of HIV. The current review will be updated as soon as the trial is published."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I526,I526)","v":16235306},{"$f":"(LEN($J526) - LEN(SUBSTITUTE(LOWER($J526),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J526) - LEN(SUBSTITUTE(LOWER($J526),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J526) - LEN(SUBSTITUTE(LOWER($J526),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B526:D526)","v":1},2005,"Vaccines for women to prevent neonatal tetanus.","Demicheli",16235306,"Vaccines for women to prevent neonatal tetanus.    Abstract:    BACKGROUND : Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin.  OBJECTIVES : To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus.  SEARCH STRATEGY : We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors.  SELECTION CRITERIA : Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths.  DATA COLLECTION AND ANALYSIS : Three review authors independently assessed trials for inclusion, data extraction and trial quality.  MAIN RESULTS : Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%).  AUTHORS CONCLUSIONS : Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I527,I527)","v":16126938},{"$f":"(LEN($J527) - LEN(SUBSTITUTE(LOWER($J527),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J527) - LEN(SUBSTITUTE(LOWER($J527),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J527) - LEN(SUBSTITUTE(LOWER($J527),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B527:D527)","v":1},2005,"Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know?","Mulholland",16126938,"Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know?    Abstract:   The cross-regulation of Wnt/beta-catenin/Tcf ligands, kinases, and transcription factors with members of the nuclear receptor (NR) family has emerged as a clinically and developmentally important area of endocrine cell biology. Interactions between these signaling pathways result in a diverse array of cellular effects including altered cellular adhesion, tissue morphogenesis, and oncogenesis. Analyses of NR interactions with canonical Wnt signaling reveal two broad themes: Wnt/beta-catenin modulation of NRs (theme I), and ligand-dependent NR inhibition of the Wnt/beta-catenin/Tcf cascade (theme II). Beta-catenin, a promiscuous Wnt signaling member, has been studied intensively in relation to the androgen receptor (AR). Beta-catenin acts as a coactivator of AR transcription and is also involved in co-trafficking, increasing cell proliferation, and prostate pathogenesis. T cell factor, a transcriptional mediator of beta-catenin and AR, engages in a dynamic reciprocity of nuclear beta-catenin, p300/CREB binding protein, and transcriptional initiation factor 2/GC receptor-interaction protein, thereby facilitating hormone-dependent coactivation and transrepression. Beta-catenin responds in an equally dynamic manner with other NRs, including the retinoic acid (RA) receptor (RAR), vitamin D receptor (VDR), glucocorticoid receptor (GR), progesterone receptor, thyroid receptor (TR), estrogen receptor (ER), and peroxisome proliferator-activated receptor (PPAR). The NR ligands, vitamin D(3), trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/beta-catenin/Tcf activity. Wnt signaling regulates, directly or indirectly, developmental processes such as ductal branching and adipogenesis, two processes dependent on NR function. Beta-catenin has been intensively studied in colorectal cancer; however, it is now evident that beta-catenin may be important in cancers of the breast, prostate, and thyroid. This review will focus on the cross-regulation of AR and Wnt/beta-catenin/Tcf but will also consider the dynamic manner in which RAR/RXR, GR, TR, VDR, ER, and PPAR modulate canonical Wnt signaling. Although many commonalities exist by which NRs interact with the Wnt/beta-catenin signaling pathway, striking cell line and tissue-specific differences require deciphering and application to endocrine pathology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I528,I528)","v":15940119},{"$f":"(LEN($J528) - LEN(SUBSTITUTE(LOWER($J528),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J528) - LEN(SUBSTITUTE(LOWER($J528),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J528) - LEN(SUBSTITUTE(LOWER($J528),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B528:D528)","v":1},2005,"Diet as a risk factor for atopy and asthma.","Devereux",15940119,"Diet as a risk factor for atopy and asthma.    Abstract:   It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I529,I529)","v":15925444},{"$f":"(LEN($J529) - LEN(SUBSTITUTE(LOWER($J529),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J529) - LEN(SUBSTITUTE(LOWER($J529),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J529) - LEN(SUBSTITUTE(LOWER($J529),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B529:D529)","v":1},2005,"Wnt-5a gene expression in malignant human neuroblasts.","Blanc",15925444,"Wnt-5a gene expression in malignant human neuroblasts.    Abstract:   Neuroblastoma (NB), an embryonal malignancy, poses a major challenge in pediatric oncology for the treatment of disseminated forms. Here, we report the decrease of Wnt-5a gene expression in high-risk NB (HR-NB) as well as in cultured metastatic neuroblasts. Wnt-5a is a member of the Wnt signaling pathway which is mainly associated with patterning decisions in the embryonic nervous system. Moreover, Wnt-5a has been involved in metastatic melanoma progression and invasive ductal breast cancer via adhesion and migration alterations. As retinoic acid (RA) plays a major role in the neural crest induction and differentiation, we showed that RA reverses the aberrant negative regulation of Wnt-5a in metastatic neuroblasts. While beta-catenin expression remained unchanged, PKC-theta, a protein kinase C isoform, was evidenced to increase and parallel Wnt-5a level. For the first time, the involvement of Wnt-5a through the Wnt/calcium signaling is highlighted in the pathogenesis of a pediatric embryonal malignancy, NB."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I530,I530)","v":15903013},{"$f":"(LEN($J530) - LEN(SUBSTITUTE(LOWER($J530),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J530) - LEN(SUBSTITUTE(LOWER($J530),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J530) - LEN(SUBSTITUTE(LOWER($J530),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B530:D530)","v":1},2005,"[The treatment of acne].","Dréno",15903013,"[The treatment of acne].    Abstract:   The treatment of acne is based on local and systemic treatments. It must be adapted to the type of acne and take some prognostic factors into account. Because of the possibility of drug resistance, systemic and local antibiotics should be used for only limited periods and preferably as part of combined treatments. Prescription of isotretinoin to women must follow strict rules. Some new-generation contraceptive pills are an interesting alternative for acne treatment in women. Zinc, which basically targets inflammatory acne, is a possible option for pregnant women and during the summer. Cosmetic care is also a fundamental part of acne treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I531,I531)","v":15705628},{"$f":"(LEN($J531) - LEN(SUBSTITUTE(LOWER($J531),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J531) - LEN(SUBSTITUTE(LOWER($J531),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J531) - LEN(SUBSTITUTE(LOWER($J531),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B531:D531)","v":1},2005,"Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review.","Arslan",15705628,"Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review.    Abstract:    BACKGROUND : Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development.  METHODS : Using Affymetrix U133A GeneChip we analysed expression profiles of 22,283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations.  RESULTS : We detected 80 genes with average differences of gt; or = 2-fold and false discovery rates of lt; 5% (14 overexpressed and 66 underexpressed). A comparative analysis including eight previous gene expression studies revealed eight prominent genes (ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies.  CONCLUSIONS : Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-beta signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I532,I532)","v":15481440},{"$f":"(LEN($J532) - LEN(SUBSTITUTE(LOWER($J532),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J532) - LEN(SUBSTITUTE(LOWER($J532),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J532) - LEN(SUBSTITUTE(LOWER($J532),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B532:D532)","v":1},2004,"DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia.","Rüter",15481440,"DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia.    Abstract:   DNA methylation provides a major epigenetic code (besides histone modification) of the lineage- and development-specific genes (such as regulators of differentiation in the hematopoietic lineages) that control expression of normal cells. However, DNA methylation is also involved in malignancies because aberrant methylating gene activity occurs during leukemic transformation. Thus, genes such as tumor suppressor genes, growth-regulatory genes, and adhesion molecules are often silenced in various hematopoietic malignancies by epigenetic inactivation via DNA hypermethylation. This inactivation is frequently seen not only in transformed cell lines but also in primary leukemia cells. Because this defect is amenable to reversion by pharmacologic means, agents that inhibit DNA methylation have been developed to specifically target this hypermethylation defect in leukemia and preleukemia cases. The most clinically advanced agents, the azanucleosides 5-azacytidine and 5-aza-2-deoxycytidine (decitabine), were discovered more than 25 years ago, when their methylation-inhibitory activities, even at low concentrations, became apparent. Although both of these agents, like cytarabine, had been clinically used until then at high doses, the redevelopment of these agents for low-dose schedules has revealed very interesting clinical activities for treating myelodysplasia (MDS) and acute myeloid leukemia (AML). Because these diseases occur mostly in patients over 60 years of age, low-dose schedules with these compounds provide a very promising approach in such patient groups by virtue of their low nonhematologic toxicity profiles. In the present review, we describe the development of treatments that target DNA hypermethylation in MDS and AML, and clinical results are presented. In addition, pharmacologic DNA demethylation may be viewed as a platform for biological modification of malignant cells to become sensitized (or resensitized) to secondary signals, such as differentiating signals (retinoids, vitamin D3) and hormonal signals (eg, estrogen receptor in breast cancer cells, androgen receptor in prostate cancer cells). Finally, an in vitro synergism between the reactivating potency of demethylating agents and inhibitors of histone deacetylation has been tested in several pilot studies of AML and MDS treatment. Finally, gene reactivation by either group of compounds results in therapeutically meaningful reactivation of fetal hemoglobin in patients with severe hemoglobinopathies, extending the therapeutic range of derepressive epigenetic agents to nonmalignant hematopoietic disorders."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I533,I533)","v":15379633},{"$f":"(LEN($J533) - LEN(SUBSTITUTE(LOWER($J533),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J533) - LEN(SUBSTITUTE(LOWER($J533),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J533) - LEN(SUBSTITUTE(LOWER($J533),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B533:D533)","v":1},2004,"Heparin affin regulatory peptide: a new target for tumour therapy?","Papadimitriou",15379633,"Heparin affin regulatory peptide: a new target for tumour therapy?    Abstract:   Heparin affin regulatory peptide (HARP), also known as pleiotrophin or heparin-binding growth-associated molecule, is an 18-kDa growth factor that has a high affinity for heparin. It constitutes with midkine and retinoic acid heparin-binding protein, a family of structurally related heparin-binding growth factors. A growing body of evidence indicates that HARP is involved in the control of cellular proliferation, migration and differentiation and plays a significant role in tumor growth and angiogenesis. HARP has a well described role in physiological as well as tumor angiogenesis, and is detected in various carcinomas, such as human breast and prostate cancer, neuroblastomas, gliomas, benign meningiomas, small cell lung cancer and mammary tumors, exhibiting a proto-oncogene function. It is also constitutively expressed in tumour cell lines and is involved in tumour growth and metastasis. Therefore, HARP appears to be a potential new target for the treatment or/and diagnosis of several types of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I534,I534)","v":15320743},{"$f":"(LEN($J534) - LEN(SUBSTITUTE(LOWER($J534),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J534) - LEN(SUBSTITUTE(LOWER($J534),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J534) - LEN(SUBSTITUTE(LOWER($J534),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B534:D534)","v":1},2004,"Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.","Takano",15320743,"Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs isoforms have been isolated and termed alpha, beta (or delta), and gamma. Although PPAR gamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPAR gamma is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D(2) (PGD(2)) metabolite, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPAR gamma. After it has been reported that activation of PPAR gamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPAR gamma have grown and a huge research effort has been concentrated. PPAR gamma, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimers disease. Moreover, PPAR gamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers. Recent studies suggest that TZDs not only ameliorate insulin sensitivity but also have pleiotropic effects on many tissues and cell types. Although activation of PPAR gamma seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPAR gamma ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPAR gamma field and the roles of PPAR gamma-dependent pathway in cardiovascular diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I535,I535)","v":15153892},{"$f":"(LEN($J535) - LEN(SUBSTITUTE(LOWER($J535),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J535) - LEN(SUBSTITUTE(LOWER($J535),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J535) - LEN(SUBSTITUTE(LOWER($J535),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B535:D535)","v":1},2004,"American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations.","Goldsmith",15153892,"American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I536,I536)","v":15125076},{"$f":"(LEN($J536) - LEN(SUBSTITUTE(LOWER($J536),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J536) - LEN(SUBSTITUTE(LOWER($J536),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J536) - LEN(SUBSTITUTE(LOWER($J536),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B536:D536)","v":1},2003,"[Vitamin A deficiency and clinical associations: a review].","El Beitune",15125076,"[Vitamin A deficiency and clinical associations: a review].    Abstract:   An important focus of attention in Public Health has been micronutrient deficiency in human being because of the enhanced vulnerability of individuals to the effects of micronutrient deficiency or imbalance. Among all micronutrients deficiencies, vitamin A has been one of the most important public health problems, affecting a large percentage of people in developing countries. Vitamin A is particularly important for its role in the process of organism defense against infections. This article reviews comprehensively vitamin A metabolism, it highlights hypovitaminosis A relationship with pregnancy and human imunodeficiency, showing its repercussions in several clinical conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I537,I537)","v":15070439},{"$f":"(LEN($J537) - LEN(SUBSTITUTE(LOWER($J537),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J537) - LEN(SUBSTITUTE(LOWER($J537),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J537) - LEN(SUBSTITUTE(LOWER($J537),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B537:D537)","v":1},2004,"Alcohol and cancer: genetic and nutritional aspects.","Pöschl",15070439,"Alcohol and cancer: genetic and nutritional aspects.    Abstract:   Chronic alcohol consumption is a major risk factor for cancer of upper aero-digestive tract (oro-pharynx, hypopharynx, larynx and oesophagus), the liver, the colo-rectum and the breast. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol-associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and protein, destroys the folate molecule and results in secondary cellular hyper-regeneration. Acetaldehyde is produced by mucosal and cellular alcohol dehydrogenase, cytochrome P450 2E1 and through bacterial oxidation. Its generation and/or its metabolism is modulated as a result of polymorphisms or mutations of the genes responsible for these enzymes. Acetaldehyde can also be produced by oral bacteria. Smoking, which changes the oral bacterial flora, also increases salivary acetaldehyde. Cigarette smoke and some alcoholic beverages, such as Calvados, contain acetaldehyde. In addition, chronic alcohol consumption induces cytochrome P450 2E1 enxyme activity in mucosal cells, resulting in an increased generation of reactive oxygen species and in an increased activation of various dietary and environmental carcinogens. Deficiencies of riboflavin, Zn, folate and possibly retinoic acid may further enhance alcohol-associated carcinogenesis. Finally, methyl deficiency as a result of multiple alcohol-induced changes leads to DNA hypomethylation. A depletion of lipotropes, including methionine, choline, betaine and S-adenosylmethionine, as well as folate, results in the hypomethylation of oncogenes and may lead to DNA strand breaks, all of which are associated with increased carcinogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I538,I538)","v":15024783},{"$f":"(LEN($J538) - LEN(SUBSTITUTE(LOWER($J538),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J538) - LEN(SUBSTITUTE(LOWER($J538),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J538) - LEN(SUBSTITUTE(LOWER($J538),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B538:D538)","v":1},2003,"Update on the prevalence of malnutrition among children in Asia.","Khor",15024783,"Update on the prevalence of malnutrition among children in Asia.    Abstract:   Approximately 70.0% of the worlds malnourished children live in Asia, resulting in the region having the highest concentration of childhood malnutrition. About half of the preschool children are malnourished ranging from 16.0% in the Peoples Republic of China to 64.0% in Bangladesh. Prevalence of stunting and underweight are high especially in South Asia where one in every two preschool children is stunted. Besides protein-energy malnutrition, Asian children also suffer from micronutrient deficiency. Iron deficiency anaemia affects 40.0-50.0% of preschool and primary school children. Nearly half of all vitamin A deficiency and xeropthalmia in the world occurs in South and Southeast Asia, with large numbers of cases in India (35.3 million), Indonesia (12.6 million) and China (11.4 million). Another major micronutrient problem in the region is iodine deficiency disorders, which result in high goiter rates as manifested in India, Pakistan and parts of Indonesia. While under-nutrition problem persists, overweight problem in children has emerged in Asia, including Taiwan, Singapore and urban China and Malaysia. The etiology of childhood malnutrition is complex involving interactions of multiple determinants that include biological, cultural and socio-economic influences. Protein-energy malnutrition and micronutrient deficiency leading to early growth failure often can be traced to poor maternal nutritional and health care before and during pregnancy, resulting in intrauterine growth retardation and children born with low birth weight. While significant progress has been achieved over the past 30 years in reducing the proportion of malnourished children in developing countries, nonetheless, malnutrition persists affecting large numbers of children. The socio-economic cost of the malnutrition burden to the individual, family and country is high resulting in lower cognitive outcomes in children and lower adult productivity. Interventions that are cost-effective and culturally appropriate for the elimination of childhood malnutrition deserve the support of all."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I539,I539)","v":14623515},{"$f":"(LEN($J539) - LEN(SUBSTITUTE(LOWER($J539),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J539) - LEN(SUBSTITUTE(LOWER($J539),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J539) - LEN(SUBSTITUTE(LOWER($J539),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B539:D539)","v":1},2003,"Sources of estrogen and their importance.","Simpson",14623515,"Sources of estrogen and their importance.    Abstract:   In premenopausal women, the ovaries are the principle source of estradiol, which functions as a circulating hormone to act on distal target tissues. However, in postmenopausal women when the ovaries cease to produce estrogen, and in men, this is no longer the case, because estradiol is no longer solely an endocrine factor. Instead, it is produced in a number of extragonadal sites and acts locally at these sites as a paracrine or even intracrine factor. These sites include the mesenchymal cells of adipose tissue including that of the breast, osteoblasts and chondrocytes of bone, the vascular endothelium and aortic smooth muscle cells, and numerous sites in the brain. Thus, circulating levels of estrogens in postmenopausal women and in men are not the drivers of estrogen action, they are reactive rather than proactive. This is because in these cases circulating estrogen originates in the extragonadal sites where it acts locally, and if it escapes local metabolism then it enters the circulation. Therefore, circulating levels reflect rather than direct estrogen action in postmenopausal women and in men. Tissue-specific regulation of CYP19 expression is achieved through the use of distinct promoters, each of which is regulated by different hormonal factors and second messenger signaling pathways. Thus, in the ovary, CYP19 expression is regulated by FSH which acts through cyclic AMP via the proximal promoter II, whereas in placenta the distal promoter I.1 regulates CYP19 expression in response to retinoids. In adipose tissue and bone by contrast, another distal promoter--promoter I.4--drives CYP19 expression under the control of glucocorticoids, class 1 cytokines and TNFalpha. The importance of this unique aspect of the tissue-specific regulation of aromatase expression lies in the fact that the low circulating levels of estrogens which are observed in postmenopausal women have little bearing on the concentrations of estrogen in, for example, a breast tumor, which can reach levels at least one order of magnitude greater than those present in the circulation, due to local synthesis within the breast. Thus, the estrogen which is responsible for breast cancer development, for the maintenance of bone mineralization and for the maintenance of cognitive function is not circulating estrogen but rather that which is produced locally at these specific sites within the breast, bone and brain. In breast adipose of breast cancer patients, aromatase activity and CYP19 expression are elevated. This occurs in response to tumor-derived factors such as prostaglandin E2 produced by breast tumor fibroblasts and epithelium as well as infiltrating macrophages. This increased CYP19 expression is associated with a switch in promoter usage from the normal adipose-specific promoter I.4 to the cyclic AMP responsive promoter, promoter II. Since these two promoters are regulated by different cohorts of transcription factors and coactivators, it follows that the differential regulation of CYP19 expression via alternative promoters in disease-free and cancerous breast adipose tissue may permit the development of selective aromatase modulators (SAMs) that target the aberrant overexpression of aromatase in cancerous breast, whilst sparing estrogen synthesis in other sites such as normal adipose tissue, bone and brain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I540,I540)","v":14587867},{"$f":"(LEN($J540) - LEN(SUBSTITUTE(LOWER($J540),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J540) - LEN(SUBSTITUTE(LOWER($J540),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J540) - LEN(SUBSTITUTE(LOWER($J540),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B540:D540)","v":1},2003,"Diet and breast cancer: can dietary factors influence survival?","Rock",14587867,"Diet and breast cancer: can dietary factors influence survival?    Abstract:   Breast cancer accounts for over one third of invasive cancers in women. Earlier detection and improved initial treatments have resulted in an increasing number of women who have completed standard treatments but who remain at risk for breast cancer recurrence or early death. Epidemiological studies have linked diet composition with prognosis, and many women attempt to modify their diets and improve nutritional status following diagnosis The hypothesis that dietary factors may reduce risk for secondary cancer events and increase survival in this population is currently under study in two large randomized clinical trials: the Womens Intervention Nutrition Study (WINS) and the Womens Healthy Eating and Living (WHEL) Study. The WHEL Study is testing the effect of a diet high in vegetables, fruit, and fiber, and low in fat, on disease-free survival in women with early stage breast cancer. Hypothesized mechanisms include effects of diet modification on gonadal hormones, retinoid-like activities of carotenoids, and other protective effects of biologically active dietary constituents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I541,I541)","v":14569515},{"$f":"(LEN($J541) - LEN(SUBSTITUTE(LOWER($J541),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J541) - LEN(SUBSTITUTE(LOWER($J541),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J541) - LEN(SUBSTITUTE(LOWER($J541),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B541:D541)","v":1},2003,"[Chemoprevention of breast cancer: a literature review and report on the current status in Germany].","Paepke",14569515,"[Chemoprevention of breast cancer: a literature review and report on the current status in Germany].    Abstract:   The prevention of breast cancer is increasingly of focus in health-politics policies and has gained a valid position in the area of medical intervention. Data from a current meta-analysis of all four randomised Tamoxifen prevention studies illustrate a reduction of 38 % (Odds ratio 0.62; 95 % CI 0.42-0.89) in the incidence of breast cancer. This observation lead to registration of this drug in the USA for the prevention of breast cancer in women with a calculated 5-year risk of gt; 1.66 %. In addition to Tamoxifen, further substances are currently being tested with the aim of improving the therapeutic index whilst reducing incidence and mortality rates. These are primarily substances which have proven efficacy in the treatment of breast cancer (other antioestrogens, aromatase inhibitors and GnRH-analogues) or those whose mechanism of action predict a preventative effect (retinoids, phytooestrogens, substitution preparations e. g. Tibolone). In Germany, chemoprevention is currently only to be recommended within study protocols, as to date no substance is approved in the indication prevention of breast cancer. A essential contribution to the accrual of valid data is the conduct of breast cancer prevention trials. The participation of women with high risk of breast cancer in Germany is, in contrast to comparable international studies, problematic. Data on the current knowledge and attitude of the female population towards such trials (gathered via a questionnaire of the DACH in 7 000 women) show that only 19.5 % of the women questioned during a consultation with a gynaecologist were aware of the possibility of active chemoprevention. However, 55.3 % stated that they would be prepared to take such a substance, were chemoprevention possible. Studies for both pre- and post-menopausal women with increased risk of breast cancer are currently active in Germany (GISS and IBIS-II of the study group GABG - German Adjuvant Breast cancer Group). An intensive information campaign to raise public awareness of breast cancer risk amongst women and their physicians is planned in conjunction with the IBIS-II study (www.brustkrebsvorbeugen.de). Latest literature recommendations for prevention of breast cancer (Chlebowski et al.) have been assessed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I542,I542)","v":12942384},{"$f":"(LEN($J542) - LEN(SUBSTITUTE(LOWER($J542),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J542) - LEN(SUBSTITUTE(LOWER($J542),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J542) - LEN(SUBSTITUTE(LOWER($J542),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B542:D542)","v":1},2003,"Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children.","Fawzi",12942384,"Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children.    Abstract:   The results of randomized trials among men and nonpregnant women have confirmed the potential benefits of vitamins B, C, and E supplements on the immune status of human immunodeficiency virus (HIV)-infected individuals. Larger trials are needed to ascertain whether these benefits are sustained and to examine the effect of supplementation on clinical outcomes. Among pregnant women, vitamin A supplements increase the risk of mother-to-child transmission. Supplementation with vitamins B, C, and E during prenatal and breastfeeding periods should be encouraged, in light of the protective effects on adverse pregnancy and child outcomes. In children aged gt;6 months, vitamin A supplements are beneficial for reducing morbidity and mortality in developing countries, including among HIV-infected children. There are no data on the relationships of other micronutrients and child health. For adults and children, more research is warranted on the role of selenium, zinc, and other trace elements on various measures of health among HIV-infected individuals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I543,I543)","v":12840216},{"$f":"(LEN($J543) - LEN(SUBSTITUTE(LOWER($J543),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J543) - LEN(SUBSTITUTE(LOWER($J543),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J543) - LEN(SUBSTITUTE(LOWER($J543),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B543:D543)","v":1},2003,"The use of genetically altered mice for breast cancer prevention studies.","Kavanaugh",12840216,"The use of genetically altered mice for breast cancer prevention studies.    Abstract:   Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive carcinoma formation, they may be particularly useful for determining cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/t-antigen transgenic mouse mammary cancer model has been utilized for chemopreventive research in which mammary tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary tumor development in this model, including retinoids, di-fluoromethylornithine (DFMO), dehydroepiandrosterone (DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human ductal carcinoma in situ (DCIS) to invasive carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I544,I544)","v":12622691},{"$f":"(LEN($J544) - LEN(SUBSTITUTE(LOWER($J544),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J544) - LEN(SUBSTITUTE(LOWER($J544),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J544) - LEN(SUBSTITUTE(LOWER($J544),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B544:D544)","v":1},2003,"Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues.","Bramley",12622691,"Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues.    Abstract:   In addition to their well-documented genomic effects, steroid hormones may also exert actions that are: (i) rapid, (ii) insensitive to inhibitors of transcription, (iii) mimicked by steroids coupled to cell membrane-impermeant molecules, and (iv) demonstrable in cells that do not express the classic genomic progesterone receptor (gPR). Such non-genomic effects have been described for all the major classes of steroids (progesterone, oestrogens, androgens and corticoids), as well as for thyroid hormones, retinoids and vitamin D(3). Rapid, membrane-mediated effects of progesterone have been studied most intensively in human spermatozoa and in the Xenopus oocyte. However, similar non-genomic actions of progesterone and other steroids have now been described in a wide variety of different tissues in many species. The first putative membrane steroid receptor to be cloned was that for the pig membrane progesterone receptor (mPR). Subsequently, similar genes were cloned from rats and cattle, and two related mPRs have been described in humans. Despite accumulating evidence for cell-surface membrane actions of steroids, a number of uncertainties remain as to the properties and identity of such receptors and their cellular actions. Furthermore, some rapid steroid effects may be mediated through membrane-associated classical steroid receptors, and steroid receptors may be capable of activating other signalling pathways non-classically. This review focuses on some of these unresolved issues, taking as its model the actions of progesterone in the mammalian ovary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I545,I545)","v":12572888},{"$f":"(LEN($J545) - LEN(SUBSTITUTE(LOWER($J545),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J545) - LEN(SUBSTITUTE(LOWER($J545),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J545) - LEN(SUBSTITUTE(LOWER($J545),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B545:D545)","v":1},2002,"Peroxisome proliferator-activated receptors (PPARs) in health and disease.","Ehrmann",12572888,"Peroxisome proliferator-activated receptors (PPARs) in health and disease.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) belong to the superfamily of steroid-thyroid-retinoid nuclear receptors. PPARs are transcription factors activated by specific ligands and play an important role during cell signalling. Intensive study of PPARs during recent years has revealed their importance in both normal physiology and in the pathology of various tissues. They participate in the regulation of lipid metabolism, inflammation and the development of atherosclerosis or diabetes. They also play a role in the regulation of growth and differentiation of cancer. It has been suggested that PPAR ligands may have potent anticancer effects and therefore may serve as potential anticancer drugs. In this review we focus on a role of PPARs in breast cancer and in glial tumors of the brain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I546,I546)","v":12548582},{"$f":"(LEN($J546) - LEN(SUBSTITUTE(LOWER($J546),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J546) - LEN(SUBSTITUTE(LOWER($J546),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J546) - LEN(SUBSTITUTE(LOWER($J546),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B546:D546)","v":1},2003,"The biology of breast carcinoma.","Keen",12548582,"The biology of breast carcinoma.    Abstract:   The biology of breast carcinoma is complex, with multiple factors contributing to its development and progression. The current review focuses on the role of several critical genes including estrogen receptor, progesterone receptor, retinoic acid receptor-beta, epidermal growth factor receptor family members, p53, BRCA1, and BRCA2 as risk factors for the development of disease, predictors of prognosis and response to therapy, and as therapeutic targets. Studies of the biology of these and other genes that contribute to the development and progression of breast carcinoma have had and will continue to have great impact on all aspects of disease management."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I547,I547)","v":12530669},{"$f":"(LEN($J547) - LEN(SUBSTITUTE(LOWER($J547),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J547) - LEN(SUBSTITUTE(LOWER($J547),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J547) - LEN(SUBSTITUTE(LOWER($J547),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B547:D547)","v":1},2002,"SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.","Beuschlein",12530669,"SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.    Abstract:   The formation of the adrenal cortex in humans is notable for the presence of two discrete zones, the fetal zone (FZ) which regresses soon after birth and the definitive zone (DZ) which gives rise to the classic steroidogenic zones of the adult cortex. Mice possess an analogous structure to the FZ referred to as the X-zone (XZ) which regresses at puberty in the male and during the first pregnancy in the female. Similar to the human FZ in X-linked Congenital Adrenal Hypoplasia caused by loss of function mutations in DAX-1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome), the mouse XZ does not regress when DAX-1 is mutated. Only in humans with DAX-1 mutations, however, is the DZ small and hypofunctional. Patients and mice with SF-1 mutations have complete adrenal aplasia with absence of both the DZ and FZ/XZ. Lastly, the phenotype of the Autosomal Recessive Adrenocortical Dysplasia (acd) mouse is strikingly similar to human Miniature Adult Congenital Adrenal Hypoplasia, lacking an XZ/FZ and possessing a dysfunctional DZ. Current work has addressed the regulation of SF-1 and DAX-1 dependent adrenocortical growth and steroidogenesis in vivo utilizing mouse models of simple and combined SF-1 and DAX-1 deficiency. In addition, the model of compensatory adrenal growth in SF-1 haplo-insufficient mice has been applied to evaluate the potential role of SF-1 in adrenocortical proliferation. Additional efforts aim to positionally clone the acd gene, predicated on the hypothesis that it is a critical component of the adrenal developmental cascade."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I548,I548)","v":12476934},{"$f":"(LEN($J548) - LEN(SUBSTITUTE(LOWER($J548),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J548) - LEN(SUBSTITUTE(LOWER($J548),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J548) - LEN(SUBSTITUTE(LOWER($J548),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B548:D548)","v":1},2002,"Role of steroid hormones and growth factors in breast cancer.","Lai",12476934,"Role of steroid hormones and growth factors in breast cancer.    Abstract:   Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I549,I549)","v":12415747},{"$f":"(LEN($J549) - LEN(SUBSTITUTE(LOWER($J549),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J549) - LEN(SUBSTITUTE(LOWER($J549),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J549) - LEN(SUBSTITUTE(LOWER($J549),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B549:D549)","v":1},2002,"Modulation of nuclear receptor dependent transcription.","Hart",12415747,"Modulation of nuclear receptor dependent transcription.    Abstract:   Nuclear receptors comprise a family of transcription factors that regulate gene expression in a ligand dependent manner. They can activate or repress target genes by binding directly to DNA response elements as homo- or hetero-dimers or by binding to other classes of DNA-bound transcription factors. These activities have been linked to the formation of complexes with molecules that appear to serve as coactivators or corepressors, causing local modification of chromatin structure in order to regulate expression of their target genes. Several members of nuclear receptor family are directly associated with human malignancies including breast cancer, prostate cancer and leukaemia. The pathogenesis of each of these diseases is underpinned by the activities of a member of the superfamily; estrogen receptor-alpha (ER alpha) in breast cancer, androgen receptor (AR) in prostate cancer, and retinoic acid receptor alpha (RAR alpha) in acute promyelocytic leukaemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I550,I550)","v":12408739},{"$f":"(LEN($J550) - LEN(SUBSTITUTE(LOWER($J550),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J550) - LEN(SUBSTITUTE(LOWER($J550),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J550) - LEN(SUBSTITUTE(LOWER($J550),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B550:D550)","v":1},2002,"Potential of interferon-alpha in solid tumours: part 2.","Santhanam",12408739,"Potential of interferon-alpha in solid tumours: part 2.    Abstract:   The second part of this review examines the use of recombinant interferon-alpha (rIFNalpha) in the following solid tumours: superficial bladder cancer, Kaposis sarcoma, head and neck cancer, gastrointestinal cancers, lung cancer, mesothelioma and ovarian, breast and cervical malignancies. In superficial bladder cancer, intravesical rIFNalpha has a promising role as second-line therapy in patients resistant or intolerant to intravesical bacille Calmette-Guérin (BCG). In HIV-associated Kaposis sarcoma, rIFNalpha is active as monotherapy and in combination with antiretroviral agents, especially in patients with CD4 counts gt;200/mm(3), no prior opportunistic infections and nonvisceral disease. rIFNalpha has shown encouraging results when used in combination with retinoids in the chemoprevention of head and neck squamous cell cancers. It is effective in the chemoprevention of hepatocellular cancer in hepatitis C-seropositive patients. In neuroendocrine tumours, including carcinoid tumour, low-dosage (lt;/=3 MU) or intermediate-dosage (5 to 10 MU) rIFNalpha is indicated as second-line treatment, either with octreotide or alone in patients resistant to somatostatin analogues. Intracavitary IFNalpha may be useful in malignant pleural effusions from mesothelioma. Similarly, intraperitoneal IFNalpha may have a role in the treatment of minimal residual disease in ovarian cancer. In breast cancer, the only possible role for IFNalpha appears to be intralesional administration for resistant disease. IFNalpha may have a role as a radiosensitising agent for the treatment of cervical cancer; however, this requires confirmation in randomised trials. On the basis of current evidence, the routine use of rIFNalpha is not recommended in the therapy of head and neck squamous cell cancers, upper gastrointestinal tract, colorectal and lung cancers, or mesothelioma. Pegylated IFNalpha (peginterferon-alpha) is an exciting development that offers theoretical advantages of increased efficacy, reduced toxicity and improved compliance. Further data from randomised studies in solid tumours are needed where rIFNalpha has activity, such as neuroendocrine tumours, minimal residual disease in ovarian cancer, and cervical cancer. A better understanding of the biological mechanisms that determine response to rIFNalpha is needed. Studies of IFNalpha-stimulated gene expression, which are now feasible, should help to identify molecular predictors of response and allow us to target therapy more selectively to patients with solid tumours responsive to IFNalpha."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I551,I551)","v":12202982},{"$f":"(LEN($J551) - LEN(SUBSTITUTE(LOWER($J551),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J551) - LEN(SUBSTITUTE(LOWER($J551),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J551) - LEN(SUBSTITUTE(LOWER($J551),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B551:D551)","v":1},2002,"Chromosome 3p and breast cancer.","Yang",12202982,"Chromosome 3p and breast cancer.    Abstract:   Solid tumors in humans are now believed to develop through a multistep process that activates oncogenes and inactivates tumor suppressor genes. Loss of heterozygosity at chromosomes 3p25, 3p22-24, 3p21.3, 3p21.2-21.3, 3p14.2, 3p14.3, and 3p12 has been reported in breast cancers. Retinoid acid receptor beta2 (3p24), thyroid hormone receptor beta1 (3p24.3), Ras association domain family 1A (3p21.3), and the fragile histidine triad gene (3p14.2) have been considered as tumor suppressor genes (TSGs) for breast cancers. Epigenetic change may play an important role for the inactivation of these TSGs. Screens for promoter hypermethylation may be able to identify other TSGs in chromosome 3p. Alternatively, use of an quot;epigenetic modifierquot; may enhance the response to another type of agent for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I552,I552)","v":12183893},{"$f":"(LEN($J552) - LEN(SUBSTITUTE(LOWER($J552),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J552) - LEN(SUBSTITUTE(LOWER($J552),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J552) - LEN(SUBSTITUTE(LOWER($J552),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B552:D552)","v":1},2002,"[Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus].","Velazquez Torres",12183893,"[Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus].    Abstract:   Activator protein-1 (AP1) is a dimeric protein, consisting either of homodimers between c-Jun, JunB, and JunD of by heterodimers with members of the Fos-family by physically interacting via a quot;leucine zipperquot; region. AP1 is an important transcription factor initially identified as a DNA binding protein that bound to enhancer sequences of the human metallothionein IIA gene. The protein components of AP1 are encoded by a set of genes known as quot;immediate-earlyquot; genes that can be activated by a variety of growth factors and mitogens through several different signaling pathways. Until recently, AP1 was considered a transcription factor expressed in most tissues to regulate cellular and viral genes now, it is becoming evident that AP1 can be involved in tissue-specific regulation of target genes due to the differential combination of the components of this important transcription factor. AP1 plays a crucial role during human papillomavirus (HPV) early gene expression, in particular of the expression of E6 and E7 oncoproteins. The HPV are a group of DNA viruses consisting of more than 80 different genotypes. Some of these HPV, know as high risk HPV, are important etiologic agents of uterine-cervical cancer (CaCu). Of the different types of cancer, CaCu is one of the most frequent among women worldwide, constituting the second death cause due to neoplasia. During cellular transformation, HPV infect basal cells in stratified epithelium; their DNA integrate into the host genome usually through the E2 gene; as these cells differentiate and migrate into the upper layer of the epithelium, viral oncogene are expressed blocking their differentiation. Mutagenesis in AP1 sites belonging to the HPV promoter region (LCR) completely abolished the HPV promoter activity in different cell lines; these results and biochemistry assays on this AP1 transcription factor, that includes protein-protein interactions between AP1 and another factors as E7 from HPV, and YY-1; the post-translattional modification and, the retinoic acid interaction; suggest a role for this AP1 factor in tissue-specific transcription of the human papillomavirus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I553,I553)","v":12163847},{"$f":"(LEN($J553) - LEN(SUBSTITUTE(LOWER($J553),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J553) - LEN(SUBSTITUTE(LOWER($J553),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J553) - LEN(SUBSTITUTE(LOWER($J553),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B553:D553)","v":1},2002,"Endocrine dismodulation and cancer.","Portier",12163847,"Endocrine dismodulation and cancer.    Abstract:    OBJECTIVE : Carcinogenesis has generally been viewed as a genomic disease resulting from genetic mutations occurring at critical locations in the genome in a particular sequence. In the last 10 years, scientists have increasingly identified changes in the levels, frequency and types of endocrine hormones as important contributors to the major cancers faced by western populations such as breast cancer (estrogen, progesterone, prolactin), prostate cancer (estrogen, testosterone), endometrial cancer (estrogen) and thyroid cancer (TSH, T3, T4). This manuscript summarizes cancer mechanisms linked to changes in endocrine function and discusses tools for analyzing and understanding the associated data.  DISCUSSION : A number of chemicals in the environment mimic the role of hormones to bind to receptors (e.g. phytoestrogens as estrogen mimics), alter signaling pathways (e.g. retinoids), inhibit steroid hormone synthesis (such as some fungicides) or alter steroid hormone metabolism (such as TCDD altering the metabolism of both estrogen and thyroid hormones). Genomic and non-genomic endocrine signaling pathways are extensively present in the body and function in a complicated fashion. In order to fully understand the basis for endocrine-induced cancers, one must simultaneously study the various receptors, ligands, enzymes, other proteins within different organs which all contribute to endocrine system function. Also, cross-talk between endocrine systems is common and is key to understanding a potential role of light-dark cycles on human cancer risks.  CONCLUSION : Mechanism-based mathematical models are the only analysis tool available to address all aspects of these complicated networks."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I554,I554)","v":12145573},{"$f":"(LEN($J554) - LEN(SUBSTITUTE(LOWER($J554),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J554) - LEN(SUBSTITUTE(LOWER($J554),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J554) - LEN(SUBSTITUTE(LOWER($J554),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B554:D554)","v":1},2002,"Biomarkers for breast cancer.","Beenken",12145573,"Biomarkers for breast cancer.    Abstract:   Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I555,I555)","v":12142230},{"$f":"(LEN($J555) - LEN(SUBSTITUTE(LOWER($J555),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J555) - LEN(SUBSTITUTE(LOWER($J555),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J555) - LEN(SUBSTITUTE(LOWER($J555),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B555:D555)","v":1},2002,"Colostral and milk insulin-like growth factors and related substances: mammary gland and neonatal (intestinal and systemic) targets.","Blum",12142230,"Colostral and milk insulin-like growth factors and related substances: mammary gland and neonatal (intestinal and systemic) targets.    Abstract:   The identification of hormones and regulatory factors in colostrum and milk has led to intensive investigations on their roles in the development and maintenance of the mammary and neonatal tissues. Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in transgenic mice influence mammary biology gland towards the end of lactation. In the bovine, IGFBP-3 is the major IGFBP in mammary secretions. In addition to binding IGFs, IGFBP-3 also binds to lactoferrin (Lf). Secreted IGFBP-3 re-enters mammary epithelial cells and with the presence of a nuclear localization sequence, IGFBP-3 and Lf enter the nucleus. Nuclear IGFBP-3 affects apoptotic signaling through the retinoic-x-receptors, while Lf affects apoptotic events through unknown mechanisms. Such interactions likely influence mammary development and involution. Furthermore, ingested colostral bioactive factors can exert regulatory functions in neonates. Intestinal receptors for IGFs and insulin are modified by age and/or diet. Feeding IGF-I had no effect, but colostrum extracts had small intestinal effects (stimulation of proliferation and villus size), suggesting that several factors, rather than one single bioactive factor were responsible. Systemic changes of metabolic and endocrine profiles in neonates depend on composition, amounts, time and duration of feeding colostrum. Early postnatal colostrum intake is not only important for the provision and absorption of immunoglobulins. Thus, in neonatal calves the lack of colostrum intake during the first 24h after birth results in a low immunoglobulin G, beta-carotene and Vitamin A status that persists for weeks and plasma patterns of fatty acids, essential amino acids and the glutamine/glutamate ratios are affected. In calves oral administration of IGF-I had no and feeding of colostrum whey extracts had only minor effects on metabolic and endocrine traits. Thus, mammary secretions influence regulatory functions of mammary and neonatal tissues."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I556,I556)","v":12139233},{"$f":"(LEN($J556) - LEN(SUBSTITUTE(LOWER($J556),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J556) - LEN(SUBSTITUTE(LOWER($J556),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J556) - LEN(SUBSTITUTE(LOWER($J556),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B556:D556)","v":1},2002,"Paradigms for primary prevention of ovarian carcinoma.","Barnes",12139233,"Paradigms for primary prevention of ovarian carcinoma.    Abstract:    OBJECTIVE : To provide the clinician with current concepts regarding prevention of ovarian cancer. Specifically, in this review, we provide a rationale for chemoprevention of ovarian cancer, a description of promising chemopreventive agents, and an overview of surgical strategies used in the prevention of ovarian cancer.  DATA SOURCES : A computerized search of articles published through December 2001 was performed using the MEDLINE database from the period of 1966 to present. Search terms utilized included ovarian neoplasms, primary prevention, chemoprevention, oral contraceptives, NSAIDs, retinoids, ovariectomy, and tubal sterilization. Additional sources were identified through cross-referencing.  METHODS OF STUDY SELECTION : All identified references relevant to prevention of ovarian carcinoma were reviewed.  TABULATION, INTEGRATION, AND RESULTS : Each reference was reviewed to determine the relevant contribution to the fundamental science of ovarian cancer prevention. Particular attention was paid to those studies that offered insight into the development of translational trials in ovarian cancer chemoprevention.  CONCLUSIONS : Investigation into chemoprevention for ovarian cancer represents a vastly underdeveloped area of research. Continued research efforts toward identification of novel compounds will accelerate the progress of clinical trials in this neglected area of investigation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I557,I557)","v":12133205},{"$f":"(LEN($J557) - LEN(SUBSTITUTE(LOWER($J557),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J557) - LEN(SUBSTITUTE(LOWER($J557),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J557) - LEN(SUBSTITUTE(LOWER($J557),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B557:D557)","v":1},2002,"Fortification strategies to meet micronutrient needs: successes and failures.","Darnton-Hill",12133205,"Fortification strategies to meet micronutrient needs: successes and failures.    Abstract:   Food fortification is likely to have played an important role in the current nutritional health and well-being of populations in industrialized countries. Starting in the early part of the 20th century, fortification was used to target specific health conditions: goitre with iodized salt; rickets with vitamin D-fortified milk; beriberi, pellagra and anaemia with B-vitamins and Fe-enriched cereals; more recently, in the USA, risk of pregnancy affected by neural-tube defects with folic acid-fortified cereals. A relative lack of appropriate centrally-processed food vehicles, less-developed commercial markets and relatively low consumer awareness and demand, means it has taken about another 50 years for fortification to be seen as a viable option for the less-developed countries. The present paper reviews selected fortification initiatives in developing countries to identify different factors that contributed to their successful implementation, as well as the challenges that continually threaten the future of these programmes. Ultimately, the long-term sustainability of fortification programmes is ensured when consumers are willing and able to bear the additional cost of fortified foods. There has been an enormous increase in fortification programmes over the last couple of decades in developing countries. Considerable progress has been made in reducing vitamin A and I deficiencies, although less so with Fe, even as Zn and folic acid deficiencies are emerging as important public health problems. Food fortification based on sound principles and supported by clear policies and regulations can play an increasingly large role in this progress towards prevention and control of micronutrient malnutrition."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I558,I558)","v":12069675},{"$f":"(LEN($J558) - LEN(SUBSTITUTE(LOWER($J558),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J558) - LEN(SUBSTITUTE(LOWER($J558),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J558) - LEN(SUBSTITUTE(LOWER($J558),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B558:D558)","v":1},2002,"Vitamins for chronic disease prevention in adults: scientific review.","Fairfield",12069675,"Vitamins for chronic disease prevention in adults: scientific review.    Abstract:    CONTEXT : Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.  OBJECTIVE : To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.  DATA SOURCES AND STUDY SELECTION : We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.  DATA EXTRACTION : We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.  DATA SYNTHESIS : Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.  CONCLUSIONS : Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I559,I559)","v":12026026},{"$f":"(LEN($J559) - LEN(SUBSTITUTE(LOWER($J559),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J559) - LEN(SUBSTITUTE(LOWER($J559),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J559) - LEN(SUBSTITUTE(LOWER($J559),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B559:D559)","v":1},2002,"Vitamin A and the nursing mother-infant dyad: evidence for intervention.","Stoltzfus",12026026,"Vitamin A and the nursing mother-infant dyad: evidence for intervention.    Abstract:   From the evidence at hand, interventions to reduce vitamin A deficiency in the breastfeeding mother and baby are likely to confer several health benefits. These include reduced puerperal morbidity, night blindness, and mortality in the mother, and reduced morbidity and mortality in the baby beginning around 6 months of age. Additional evidence is still needed to increase our confidence in these inferences, and to clarify the best interventions for achieving these outcomes. Current evidence about the effects of improved vitamin A status on early infant morbidity or mortality is mixed. There is accumulating evidence against the hypothesis that maternal vitamin A supplementation during pregnancy will reduce mother-to-child HIV transmission. There is so far no evidence about whether improved infant vitamin A status can prevent mother-to-child HIV transmission. In sum, the probable benefits of improving the vitamin A status of the breastfeeding mother and her baby are substantial, but to achieve these benefits, more aggressive interventions will be needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I560,I560)","v":12003090},{"$f":"(LEN($J560) - LEN(SUBSTITUTE(LOWER($J560),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J560) - LEN(SUBSTITUTE(LOWER($J560),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J560) - LEN(SUBSTITUTE(LOWER($J560),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B560:D560)","v":1},2001,"Vitamin A during pregnancy.","Reifen",12003090,"Vitamin A during pregnancy.    Abstract:   Vitamin A is an essential micronutrient throughout life. In areas of developing countries where vitamin A deficiency is endemic, an estimated 40% of the children are likely to be sub clinically deficient of the vitamin. Yet, the traditional view that preschool age children represent the main population at risk of vitamin A deficiency has been replaced by the growing awareness that sub clinical and even clinical vitamin A deficiency also occurs in women of reproductive age and infants less than 6 month of age. During the period of early foetal development the supply of vitamin A must be carefully managed to ensure that the developing foetus is exposed to neither too little not too much vitamin A because either condition can have teratogenic consequences. Towards the end of gestation, adequate maternal vitamin A status and dietary intakes are important to maximize the vitamin A transferred to the foetus in preparation for parturition and lactation. A review of the current knowledge and prospects for future research is presented."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I561,I561)","v":11932986},{"$f":"(LEN($J561) - LEN(SUBSTITUTE(LOWER($J561),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J561) - LEN(SUBSTITUTE(LOWER($J561),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J561) - LEN(SUBSTITUTE(LOWER($J561),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B561:D561)","v":1},2002,"Teratogenesis of holoprosencephaly.","Cohen",11932986,"Teratogenesis of holoprosencephaly.    Abstract:   Teratogenic causes of holoprosencephaly are critically assessed. A brief general review of holoprosencephaly is followed by four tables summarizing etiologic factors. Subjects evaluated here include: 1) maternal diabetes; 2) ethyl alcohol; 3) retinoic acid; 4) mutated genes and teratogens involving the sonic hedgehog signaling network and cholesterol biosynthesis; and 5) cholesterol trafficking, sterol adducts, target tissue response, and sterol sensing domain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I562,I562)","v":11885994},{"$f":"(LEN($J562) - LEN(SUBSTITUTE(LOWER($J562),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J562) - LEN(SUBSTITUTE(LOWER($J562),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J562) - LEN(SUBSTITUTE(LOWER($J562),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B562:D562)","v":1},2002,"Oestrogen/insulin-like growth factor-I receptor interaction in early breast cancer: clinical implications.","Stoll",11885994,"Oestrogen/insulin-like growth factor-I receptor interaction in early breast cancer: clinical implications.    Abstract:    UNLABELLEDThe expression of oestrogen receptor (ER) and that of the insulin-like growth factor-I receptor (IGF-IR) are positively correlated in breast cancer specimens. Their function is strongly linked in enhancing proliferative activity in normal and malignant human mammary epithelial cells in culture. This review examines the likely role of such a mechanism in the increased breast cancer risk reported in postmenopausal women with abdominal obesity. Precancerous breast lesions show an increased proportion of ER-positive cells with high proliferative activity, and recent studies suggest that genetic mutations or epigenetic variants in the ER alpha gene may increase the ERs sensitivity to oestrogen stimulation. Abdominal obesity in women is associated with higher concentrations both of free oestradiol and free IGF-I. Activation of their respective receptors may induce synergistic stimulation of mammary carcinogenesis. However, there is clinical evidence that progression in precancerous breast lesions may be delayed or reversed. Involution occurs spontaneously in a proportion of duct carcinoma in situ (DCIS) (intraductal) lesions as women approach the menopause, and antioestrogen therapy has been shown to reduce recurrence and progression of DCIS lesions.  CONCLUSIONS : Intervention trials in breast cancer prevention would greatly benefit from surrogate response markers which could predict long-term benefit. Changes in ER and IGF-IR expression apart from those in standardised cytomorphological criteria, might predict the likelihood of DCIS involution in cancer prevention trials. Future studies could involve examination of serial core biopsies from normal breast tissue during trials of antioestrogens, retinoids or weight-reduction interventions. Correlation of changes in these markers with changes in circulating IGF-I and oestradiol concentrations may help to clarify the roles of the markers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I563,I563)","v":11869564},{"$f":"(LEN($J563) - LEN(SUBSTITUTE(LOWER($J563),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J563) - LEN(SUBSTITUTE(LOWER($J563),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J563) - LEN(SUBSTITUTE(LOWER($J563),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B563:D563)","v":1},2002,"Interventions for reducing the risk of mother-to-child transmission of HIV infection.","Brocklehurst",11869564,"Interventions for reducing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : At the end of 1998 over 33 million people were infected with the human immunodeficiency virus (HIV) and over one million children had been infected from their mothers.  OBJECTIVES : The objective of this review was to assess what interventions may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.  SEARCH STRATEGY : The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched.  SELECTION CRITERIA : Randomised trials comparing any intervention aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with placebo or no treatment, or any two or more interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection.  DATA COLLECTION AND ANALYSIS : Trial quality assessments and data extraction were undertaken by the reviewer.  MAIN RESULTS : Zidovudine Four trials comparing zidovudine with placebo involving 1585 participants were included. Compared with placebo, there was a significant reduction in the risk of mother-to-child transmission with any zidovudine (relative risk (RR) 0.54, 95% confidence interval (CI) 0.42-0.69). There is no evidence that long course therapy is superior to short course therapy. Nevirapine One trial compared intrapartum and postnatal nevirapine with intrapartum and postnatal zidovudine in 626 women, the majority of whom breast fed their infants. Compared with zidovudine, there was a significant reduction in the risk of mother-to-child transmission of HIV with nevirapine (RR 0.58, 95% CI 0.40-0.83). No trials are available comparing nevirapine with placebo. Caesarean section One trial comparing elective caesarean section with anticipation of vaginal delivery involving 436 participants was included. Compared with vaginal delivery, there was a significant reduction in the risk of mother-to-child transmission of HIV infection with caesarean section (RR 0.17, 95% CI 0.05-0.55). Immunoglobulin One trial comparing hyperimmune immunoglobulin plus zidovudine with non-specific immunoglobulin plus zidovudine involving 501 participants was included. The addition of hyperimmune immunoglobulin to zidovudine does not appear to have any additional effect on the risk of mother-to-child transmission (RR 0.67, 95% CI 0.29-1.55).  REVIEWERS CONCLUSIONS : Zidovudine, nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I564,I564)","v":11818488},{"$f":"(LEN($J564) - LEN(SUBSTITUTE(LOWER($J564),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J564) - LEN(SUBSTITUTE(LOWER($J564),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J564) - LEN(SUBSTITUTE(LOWER($J564),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B564:D564)","v":1},2002,"Breast cancer risk reduction: strategies for women at increased risk.","Chlebowski",11818488,"Breast cancer risk reduction: strategies for women at increased risk.    Abstract:   Breast cancer risk reduction now represents an achievable medical objective. Current interventions include selective estrogen receptor modulators (SERMs), prophylactic surgery, and lifestyle change. For SERMs, current evidence supports tamoxifen use for breast cancer risk reduction whereas raloxifene requires further study. Prophylactic mastectomy and prophylactic oophorectomy, effective in retrospective clinical experiences, should be considered only for women at substantial risk willing to accept the irreversible consequences of these procedures. Although dietary fat intake is under clinical trial evaluation, lifestyle change, including weight loss, dietary change, and increased physical activity, can be recommended based on other health considerations. Use of any intervention requires careful breast cancer risk assessment, risk-benefit calculations, and informed decision making with full patient participation. Future breast cancer risk assessment may incorporate additional biologic measures of estrogen exposure and/or analyses of collected breast cells. Under active evaluation are novel SERMs, aromatase inhibitors/inactivators, gonadotrophin-releasing hormone agonists, retinoids, statins, and tyrosine kinase and cyclooxygenase-2 inhibitors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I565,I565)","v":11807170},{"$f":"(LEN($J565) - LEN(SUBSTITUTE(LOWER($J565),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J565) - LEN(SUBSTITUTE(LOWER($J565),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J565) - LEN(SUBSTITUTE(LOWER($J565),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B565:D565)","v":1},2002,"Molecular basis of environmentally induced birth defects.","Finnell",11807170,"Molecular basis of environmentally induced birth defects.    Abstract:   Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the introduction of new pharmacological agents and chemical compounds into the environment. This results in a concomitant need to more fully understand the relationship between in utero exposure to environmental teratogens and the risk of congenital malformations. The goal of this review is to provide a current perspective of the major concepts related to the molecular basis of environmentally induced birth defects. Starting with a discussion of commonly occurring birth defects, we consider important fundamental facets of embryonic development, teratology, and gene-environment interactions. The review then summarizes our current understanding of the molecular mechanisms involved in selected birth defects following exposure to pharmacological compounds, including thalidomide, retinoids, and valproic acid. Understanding these signaling pathways may lead to the development of safer pharmaceutical compounds and a reduction in the number of infants born with preventable birth defects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I566,I566)","v":11795443},{"$f":"(LEN($J566) - LEN(SUBSTITUTE(LOWER($J566),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J566) - LEN(SUBSTITUTE(LOWER($J566),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J566) - LEN(SUBSTITUTE(LOWER($J566),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B566:D566)","v":1},2001,"Beyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention.","Fabian",11795443,"Beyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention.    Abstract:   Although tamoxifen appears to markedly reduce breast cancer risk in women with a prior diagnosis of atypical hyperplasia or in situ carcinoma, it is not clear what other groups of women receive substantial benefit. Major breast chemoprevention priorities are to (1) develop new agents that (a) have fewer side effects, (b) are effective in ER--as well as tamoxifen-resistant precancerous tissue, and (c) are compatible with hormone therapy; and (2) develop efficient clinical strategies including prognostic and predictive morphologic and molecular biomarkers. Breast tissue may be repeatedly sampled for evidence of intraepithelial neoplasia by fine needle aspiration, ductal lavage, or needle biopsy to select candidates at highest short-term risk as well as to monitor response in small proof of principle studies prior to a large cancer incidence trial. Molecular marker expression may also be used to select a cohort most likely to respond to a particular agent. A large number of new agents are attractive as potential prevention agents and some are already in clinical prevention testing. Compounds which should be effective in ER + precancerous tissue but may have a better side-effect profile include new selective estrogen receptor modulators which lack uterine estrogen agonist activity, isoflavones, aromatase inactivators/inhibitors for postmenopausal women, and gonadotropin-releasing hormone regimens for premenopausal women. Retinoids, rexinoids, and deltanoids may be efficacious in ER+ tissue resistant to tamoxifen. Agents which should theoretically have activity in ER- or ER+ precancerous tissue include polyamine synthesis inhibitors, tyrosine kinase inhibitors, combined demethylating agents and histone deacetylase inhibitors, as well as metalloprotease and angiogenesis inhibitors. Sample Phase I and Phase II clinical trial designs are reviewed using modulation of molecular markers and breast intraepithelial neoplasia as the major endpoints."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I567,I567)","v":11739886},{"$f":"(LEN($J567) - LEN(SUBSTITUTE(LOWER($J567),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J567) - LEN(SUBSTITUTE(LOWER($J567),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J567) - LEN(SUBSTITUTE(LOWER($J567),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B567:D567)","v":1},2001,"Can lack of improvement in vitamin A status indicators be explained by little or no overall change in vitamin A status of humans?","Tanumihardjo",11739886,"Can lack of improvement in vitamin A status indicators be explained by little or no overall change in vitamin A status of humans?    Abstract:   Changes in vitamin A status using conventional indicators, i.e., serum and breast milk retinol concentrations and the modified relative dose response test, following a vitamin A intervention have not always been shown. A simplified model to predict calculated changes in vitamin A status after intervention is described. The model shows that changes in indicator values cannot be expected if the change in vitamin A status is only marginal. A critical review of several papers using vitamin A status assessment indicators was undertaken. Assumptions that included current knowledge concerning vitamin A absorption and metabolism were made and applied to the data. Based on current recommended daily allowances for women and children, one cannot necessarily expect a change in indicators if an overall change in vitamin A status was not achieved. Thus, when designing vitamin A intervention studies, the following parameters should be considered if applicable to the population to be enrolled in the study: average body weight, estimated liver weight, amount of vitamin A administered, estimated loss in breast milk and study duration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I568,I568)","v":11678873},{"$f":"(LEN($J568) - LEN(SUBSTITUTE(LOWER($J568),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J568) - LEN(SUBSTITUTE(LOWER($J568),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J568) - LEN(SUBSTITUTE(LOWER($J568),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B568:D568)","v":1},2001,"Morphoea of the breast in a young girl.","Weinberg",11678873,"Morphoea of the breast in a young girl.    Abstract:   Localized morphoea is an uncommon sclerosing skin disorder. Prognosis is usually good but it may lead to contractures, perturbed limb growth, atrophy, pigmentary changes and cosmetic disturbance. We describe a case of morphoea that developed in one breast in a 9-year-old white female. Treatment comprised topical ammonium lactate 12% cream and tretinoin 0.025% cream but no topical corticosteroids were prescribed. One year later she was noted to have bilateral symmetrical breast development and, although signs of morphoea were still present in one breast, the plaque had softened and there was no breast deformity. It is important to remember that most cases of morphoea improve spontaneously, although a number of possible therapeutic options may be indicated in some patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I569,I569)","v":11605727},{"$f":"(LEN($J569) - LEN(SUBSTITUTE(LOWER($J569),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J569) - LEN(SUBSTITUTE(LOWER($J569),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J569) - LEN(SUBSTITUTE(LOWER($J569),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B569:D569)","v":1},2001,"Role of coactivators and corepressors in steroid and nuclear receptor signaling: potential markers of tumor growth and drug sensitivity.","Cottone",11605727,"Role of coactivators and corepressors in steroid and nuclear receptor signaling: potential markers of tumor growth and drug sensitivity.    Abstract:   Nuclear receptors regulate target gene expression in response to steroid and thyroid hormones, retinoids, vitamin D and other ligands. These ligand-dependent transcription factors function by contacting various nuclear cooperating proteins, called coactivators and corepressors, which mediate local chromatin remodeling as well as communication with the basal transcriptional apparatus. Nuclear receptors and their coregulatory proteins play a role in cancer and other diseases, one leading example being the estrogen receptor pathway in breast cancer. Coregulators are often present in limiting amounts in cell nuclei and modifications of their level of expression and/or structure lead to alterations in nuclear receptor functioning, which may be as pronounced as a complete inversion of signaling, i.e. from stimulating to repressing certain genes in response to an identical stimulus. In addition, hemizygous knock-out of certain coactivator genes has been demonstrated to produce cancer-prone phenotypes in mice. Thus, assessment of coactivator and corepressor expression and structure in tumors may turn out to be essential to determine the role of nuclear receptors in cancer and to predict prognosis and response to therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I570,I570)","v":11594673},{"$f":"(LEN($J570) - LEN(SUBSTITUTE(LOWER($J570),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J570) - LEN(SUBSTITUTE(LOWER($J570),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J570) - LEN(SUBSTITUTE(LOWER($J570),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B570:D570)","v":1},2001,"Acne therapy: clinical pearls.","Stein",11594673,"Acne therapy: clinical pearls.    Abstract:   Several classes of medications successfully treat acne. Systemic and topical retinoids, systemic and topical antimicrobials, and systemic hormonal therapy are the major categories. Failure of therapy may result from drug interactions, antibiotic resistance, or coexisting conditions; therefore, a detailed history including these points should be used to decide which therapy is appropriate for each patient. Furthermore, one must consider the potential side effects of each treatment and make sure that (1) the benefits outweigh the risks of the treatment, (2) the side effects can be avoided by adding another agent, or (3) the side effects can be safely treated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I571,I571)","v":11501577},{"$f":"(LEN($J571) - LEN(SUBSTITUTE(LOWER($J571),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J571) - LEN(SUBSTITUTE(LOWER($J571),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J571) - LEN(SUBSTITUTE(LOWER($J571),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B571:D571)","v":1},2001,"Genes, chromatin, and breast cancer: an epigenetic tale.","Mielnicki",11501577,"Genes, chromatin, and breast cancer: an epigenetic tale.    Abstract:   The production of heritable changes in gene expression is the driving force in the development and progression of breast cancer. Such changes can result from mutations or from epigenetic events such as hypermethylation of DNA and hypoacetylation of histones. Histone acetylation and DNA methylation are major determinants of chromatin structure, and chromatin structure is a primary regulator of gene transcription. Cancer cells frequently contain both mutated genes and genes with altered expression due to one or more epigenetic mechanisms. This review describes the epigenetic changes that disrupt normal chromatin architecture and modify the expression of key genes in breast cancer cells. The structural integrity of the latter genes is usually intact, but their expression has been substantially altered due to methylation in their promoter region or deacetylation of histones that interact with their promoter region or both mechanisms. Genes affected by epigenetic changes in breast cancers include HoxA5, p21WAF, gelsolin, BRCA1, BRCA2, E-cadherin, steroid hormone receptors, and retinoic acid receptor II. Because these epigenetic modifications are usually reversible by treatment with certain drugs, they represent vulnerabilities in the cancer cell that can be exploited as novel targets for new prevention and therapeutic strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I572,I572)","v":11462638},{"$f":"(LEN($J572) - LEN(SUBSTITUTE(LOWER($J572),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J572) - LEN(SUBSTITUTE(LOWER($J572),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J572) - LEN(SUBSTITUTE(LOWER($J572),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B572:D572)","v":1},2001,"[Fetal retinoid syndrome].","Muto",11462638,"[Fetal retinoid syndrome].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I573,I573)","v":11376125},{"$f":"(LEN($J573) - LEN(SUBSTITUTE(LOWER($J573),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J573) - LEN(SUBSTITUTE(LOWER($J573),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J573) - LEN(SUBSTITUTE(LOWER($J573),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B573:D573)","v":1},2001,"Signalling pathways involved in antiproliferative effects of IGFBP-3: a review.","Baxter",11376125,"Signalling pathways involved in antiproliferative effects of IGFBP-3: a review.    Abstract:   Insulin-like growth factor binding protein-3 (IGFBP-3), the major circulating carrier protein for IGFs, is also active in the cellular environment as a potent antiproliferative agent. It appears to function both by cell cycle blockade and the induction of apoptosis. Transfection of p53 negative T47D breast cancer cells to express IGFBP-3 leads to induction of the apoptotic protein bax and an increase in sensitivity to ionising radiation. IGFBP-3 can be transported to the nucleus by an importin beta mediated mechanism, where it has been shown to interact with the retinoid X receptor alpha and possibly other nuclear elements. Expression of oncogenic ras is associated with resistance to exogenous IGFBP-3, the effect being reversible by inhibition of mitogen activated protein (MAP) kinase phosphorylation. IGFBP-3 antiproliferative signalling appears to require an active transforming growth factor beta (TGF-beta) signalling pathway, and IGFBP-3 stimulates phosphorylation of the TGF-beta signalling intermediates Smad2 and Smad3. These recent findings all point to a complex intracellular mode of action of IGFBP-3, which will need to be better understood if anti-cancer treatments are to take advantage of the antiproliferative activity of IGFBP-3."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I574,I574)","v":11345900},{"$f":"(LEN($J574) - LEN(SUBSTITUTE(LOWER($J574),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J574) - LEN(SUBSTITUTE(LOWER($J574),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J574) - LEN(SUBSTITUTE(LOWER($J574),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B574:D574)","v":1},2001,"Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions.","Safe",11345900,"Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions.    Abstract:   Estrogen receptor-alpha (ER alpha) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. The classic mechanism of ER alpha action is associated with estrogen-induced formation of a nuclear ER alpha homodimer, binding to 5-regulatory estrogen response elements (EREs) in target gene promoters, interaction with other nuclear proteins, and general transcription factors to activate gene expression. ER alpha also interacts with Sp1 protein to transactivate genes through binding Sp1(N)xERE or Sp1(N)xERE half-site (1/2) motifs where both ER alpha and Sp1 bind DNA elements. Activation through Sp1(N)xERE1/2 requires interactions of both proteins with their cognate DNA elements as well as additional nuclear factors to form a functional ER alpha/Sp1-DNA complex. Recent studies also show that ER alpha and Sp1 physically interact and ER alpha preferentially binds to the C-terminal DNA-binding domain of Sp1 protein. Moreover, ER alpha/Sp1 can activate transcription from a consensus GC-rich Sp1 binding site in transient transfection studies in MCF-7 human breast cancer cells, and this response is also observed with ER alpha variants that do not contain the DNA-binding domain. Several genes that are induced by estrogens in MCF-7 cells are activated through one or more GC-rich sites in their regulatory regions and these include the cathepsin D, E2F1, bcl-2, c-fos, adenosine deaminase, insulinlike growth factor binding protein 4, and retinoic acid receptor alpha 1 genes. ER alpha/Sp1 and ER beta/Sp1 action is dependent on ligand structure and cell context and ER beta/Sp1 is primarily associated with decreased ligand-dependent gene expression. ER alpha/Sp1, like ER alpha/AP1, represents a pathway for hormone activation of genes in which the receptor does not bind DNA, and results of ongoing studies suggest that ER alpha/Sp1 plays an important role in transcriptional activation of multiple growth regulatory genes in breast cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I575,I575)","v":11310425},{"$f":"(LEN($J575) - LEN(SUBSTITUTE(LOWER($J575),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J575) - LEN(SUBSTITUTE(LOWER($J575),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J575) - LEN(SUBSTITUTE(LOWER($J575),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B575:D575)","v":1},2001,"Nutrition-hormone receptor-gene interactions: implications for development and disease.","Dauncey",11310425,"Nutrition-hormone receptor-gene interactions: implications for development and disease.    Abstract:   Nutrition profoundly alters the phenotypic expression of a given genotype, particularly during fetal and postnatal development. Many hormones act as nutritional signals and their receptors play a key role in mediating the effects of nutrition on numerous genes involved in differentiation, growth and metabolism. Polypeptide hormones act on membrane-bound receptors to trigger gene transcription via complex intracellular signalling pathways. By contrast, nuclear receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid hormones (TH) directly regulate transcription via DNA binding and chromatin remodelling. Nuclear hormone receptors are members of a large superfamily of transcriptional regulators with the ability to activate or repress many genes involved in development and disease. Nutrition influences not only hormone synthesis and metabolism but also hormone receptors, and regulation is mediated either by specific nutrients or by energy status. Recent studies on the role of early environment on development have implicated GC and their receptors in the programming of adult disease. Intrauterine growth restriction and postnatal undernutrition also induce striking differences in TH-receptor isoforms in functionally-distinct muscles, with critical implications for gene transcription of myosin isoforms. glucose transporters, uncoupling proteins and cation pumps. Such findings highlight a mechanism by which nutritional status can influence normal development, and modify nutrient utilization. thermogenesis. peripheral sensitivity to insulin and optimal cardiac function. Diet and stage of development will also influence the transcriptional activity of drugs acting as ligands for nuclear receptors. Potential interactions between nuclear receptors, including those for retinoic acid and vitamin D, should not be overlooked in intervention programmes using I or vitamin A supplementation of young and adult human populations"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I576,I576)","v":11250754},{"$f":"(LEN($J576) - LEN(SUBSTITUTE(LOWER($J576),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J576) - LEN(SUBSTITUTE(LOWER($J576),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J576) - LEN(SUBSTITUTE(LOWER($J576),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B576:D576)","v":1},2001,"Breast cancer chemoprevention: beyond tamoxifen.","Fabian",11250754,"Breast cancer chemoprevention: beyond tamoxifen.    Abstract:   A large number of new potential chemoprevention agents are available that target molecular abnormalities found in estrogen receptor (ER)-negative and/or ER-positive precancerous breast tissue and have side effect profiles that differ from tamoxifen. Classes of agents currently undergoing evaluation in clinical prevention trials or those for which testing is planned in the near future include new selective ER modulators, aromatase inactivators/inhibitors, gonadotrophin-releasing hormone agonists, monoterpenes, isoflavones, retinoids, rexinoids, vitamin D derivatives, and inhibitors of tyrosine kinase, cyclooxygenase-2, and polyamine synthesis. New clinical testing models will use morphological and molecular biomarkers to select candidates at highest short-term risk, to predict the response to a particular class of agent, and to assess the response in phase II prevention trials. If validated, morphological and molecular markers could eventually replace cancer incidence as an indicator of efficacy in future phase III trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I577,I577)","v":11131740},{"$f":"(LEN($J577) - LEN(SUBSTITUTE(LOWER($J577),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J577) - LEN(SUBSTITUTE(LOWER($J577),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J577) - LEN(SUBSTITUTE(LOWER($J577),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B577:D577)","v":1},2000,"Nutritional factors and vertical transmission of HIV-1. Epidemiology and potential mechanisms.","Fawzi",11131740,"Nutritional factors and vertical transmission of HIV-1. Epidemiology and potential mechanisms.    Abstract:   Transmission of HIV from mothers to children may occur through the transplacental, intrapartum, or breastfeeding routes. Adequate nutritional status may reduce vertical transmission by affecting several maternal or fetal and child risk factors for transmission including enhancing systemic immune function in the mother or fetus/child; reducing the rate of clinical, immunological, or virological progression in the mother; reducing viral load or the risk of viral shedding in lower genital secretions or breast milk; reducing the risks of low birth weight or prematurity; or by maintaining the integrity of the fetus/child gastrointestinal integrity. In prospective observational studies, low plasma vitamin A levels were associated with higher risks of vertical transmission. However, findings from randomized, controlled trials suggest that supplements of vitamin A or other vitamins are unlikely to have an effect on vertical transmission during pregnancy or the intrapartum period. The effect of other nutrient supplements, such as zinc and selenium, is unknown. Similarly, whether nutrition supplements of mothers during the breastfeeding period has an effect on transmission is unknown. The potential benefits of direct supplementation of children born to HIV-infected women on transmission of HIV, as well as on the risk and severity of childhood infections and mortality, are also important to examine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I578,I578)","v":11057153},{"$f":"(LEN($J578) - LEN(SUBSTITUTE(LOWER($J578),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J578) - LEN(SUBSTITUTE(LOWER($J578),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J578) - LEN(SUBSTITUTE(LOWER($J578),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B578:D578)","v":1},2000,"[Retinoic acid embryopathy].","Harada",11057153,"[Retinoic acid embryopathy].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I579,I579)","v":10852835},{"$f":"(LEN($J579) - LEN(SUBSTITUTE(LOWER($J579),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J579) - LEN(SUBSTITUTE(LOWER($J579),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J579) - LEN(SUBSTITUTE(LOWER($J579),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B579:D579)","v":1},2000,"The environment as an etiologic factor in autism: a new direction for research.","London",10852835,"The environment as an etiologic factor in autism: a new direction for research.    Abstract:   Autism is one of a group of developmental disorders that have devastating lifelong effects on its victims. Despite the severity of the disease and the fact that it is relatively common (15 in 10,000), there is still little understanding of its etiology. Although believed to be highly genetic, no abnormal genes have been found. Recent findings in autism and in related disorders point to the possibility that the disease is caused by a gene-environment interaction. Epidemiologic studies indicate that the number of cases of autism is increasing dramatically each year. It is not clear whether this is due to a real increase in the disease or whether this is an artifact of ascertainment. A new theory regarding the etiology of autism suggests that it may be a disease of very early fetal development (approximately day 20-24 of gestation). This theory has initiated new lines of investigation into developmental genes. Environmental exposures during pregnancy could cause or contribute to autism based on the neurobiology of these genes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I580,I580)","v":10845115},{"$f":"(LEN($J580) - LEN(SUBSTITUTE(LOWER($J580),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J580) - LEN(SUBSTITUTE(LOWER($J580),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J580) - LEN(SUBSTITUTE(LOWER($J580),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B580:D580)","v":1},2000,"Role of transcription factors in fetal lung development and surfactant protein gene expression.","Mendelson",10845115,"Role of transcription factors in fetal lung development and surfactant protein gene expression.    Abstract:   Branching morphogenesis of the lung and differentiation of specialized cell populations is dependent upon reciprocal interactions between epithelial cells derived from endoderm of embryonic foregut and surrounding mesenchymal cells. These interactions are mediated by elaboration and concerted actions of a variety of growth and differentiation factors binding to specific receptors. Such factors include members of the fibroblast growth factor family, sonic hedgehog, members of the transforming growth factor-beta family, epidermal growth factor, and members of the platelet-derived growth factor family. Hormones that increase cyclic AMP formation, glucocorticoids, and retinoids also play important roles in branching morphogenesis, alveolar development, and cellular differentiation. Expression of the genes encoding these morphogens and their receptors is controlled by a variety of transcription factors that also are highly regulated. Several of these transcription factors serve dual roles as regulators of genes involved in early lung development and in specialized functions of differentiated cells. Targeted null mutations of genes encoding many of these morphogens and transcription factors have provided important insight into their function during lung development. In this chapter, the cellular and molecular mechanisms that control lung development are considered, as well as those that regulate expression of the genes encoding the surfactant proteins."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I581,I581)","v":10828183},{"$f":"(LEN($J581) - LEN(SUBSTITUTE(LOWER($J581),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J581) - LEN(SUBSTITUTE(LOWER($J581),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J581) - LEN(SUBSTITUTE(LOWER($J581),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B581:D581)","v":1},2000,"Malnutrition, morbidity and mortality in children and their mothers.","Tomkins",10828183,"Malnutrition, morbidity and mortality in children and their mothers.    Abstract:   While being underweight or stunted is recognized as an important risk factor for increased prevalence and severity of infection and high mortality rates, there is increasing evidence for an independent role for micronutrient deficiency. Improving vitamin A status reduces mortality among older infants and young children and reduces pregnancy-related mortality; it also reduces the prevalence of severe illness and clinic attendance among children. Improving Zn status reduces morbidity from diarrhoeal and respiratory infection. Treatment of established infection with vitamin A is effective in measles-associated complications, but is not as useful in the majority of diarrhoeal or respiratory syndromes. Zn supplements, however, have significant benefit on the clinical outcome of diarrhoeal and respiratory infections. Concerns that Fe supplements might increase morbidity if given in malarious populations appear to be decreasing, in the light of new studies on Fe supplements showing improved haemoglobin without an increase in morbidity. Breast-feeding, well known to protect against diarrhoea, is also important in protecting against respiratory infection, especially in the young infant. Transmission of human immunodeficiency virus (HIV) in breast milk is recognized, but new data showing reduced transmission in infants who receive exclusive breast-feeding rather than mixed feeding reinforces the importance of promoting this practice in areas where environmental contamination precludes the safe use of other infant feeding regimens. The presence of subclinical mastitis, now recognized to occur in approximately 20 % of mothers in several developing countries, has been shown to increase the concentration of HIV in breast milk. Preliminary findings suggest that the prevalence of subclinical mastitis is reduced by dietary supplements containing antioxidants. Governments and international agencies now have a strong scientific basis to be much more active and innovative in the introduction of focused nutrition interventions especially micronutrients, for the control of infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I582,I582)","v":10810532},{"$f":"(LEN($J582) - LEN(SUBSTITUTE(LOWER($J582),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J582) - LEN(SUBSTITUTE(LOWER($J582),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J582) - LEN(SUBSTITUTE(LOWER($J582),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B582:D582)","v":1},1999,"Melatonin synergizes with retinoic acid in the prevention and regression of breast cancer.","Hill",10810532,"Melatonin synergizes with retinoic acid in the prevention and regression of breast cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I583,I583)","v":10796128},{"$f":"(LEN($J583) - LEN(SUBSTITUTE(LOWER($J583),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J583) - LEN(SUBSTITUTE(LOWER($J583),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J583) - LEN(SUBSTITUTE(LOWER($J583),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B583:D583)","v":1},2000,"Interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection.","Brocklehurst",10796128,"Interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection.    Abstract:    BACKGROUND : At the end of 1998 over 33 million people were infected with the human immunodeficiency virus (HIV) and over one million children had been infected from their mothers.  OBJECTIVES : The objective of this review was to assess what interventions may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.  SEARCH STRATEGY : The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched.  SELECTION CRITERIA : Randomised trials comparing any intervention aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with placebo or no treatment, or any two or more interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection.  DATA COLLECTION AND ANALYSIS : Trial quality assessments and data extraction were undertaken by the reviewer.  MAIN RESULTS : Zidovudine Four trials comparing zidovudine with placebo involving 1585 participants were included. Compared with placebo, there was a significant reduction in the risk of mother-to-child transmission with any zidovudine (relative risk (RR) 0.54, 95% confidence interval (CI) 0.42-0.69). There is no evidence that long course therapy is superior to short course therapy. Nevirapine One trial compared intrapartum and postnatal nevirapine with intrapartum and postnatal zidovudine in 626 women, the majority of whom breast fed their infants. Compared with zidovudine, there was a significant reduction in the risk of mother-to-child transmission of HIV with nevirapine (RR 0.58, 95% CI 0.40-0.83). No trials are available comparing nevirapine with placebo. Caesarean section One trial comparing elective caesarean section with anticipation of vaginal delivery involving 436 participants was included. Compared with vaginal delivery, there was a significant reduction in the risk of mother-to-child transmission of HIV infection with caesarean section (RR 0.17, 95% CI 0.05-0.55). Immunoglobulin One trial comparing hyperimmune immunoglobulin plus zidovudine with non-specific immunoglobulin plus zidovudine involving 501 participants was included. The addition of hyperimmune immunoglobulin to zidovudine does not appear to have any additional effect on the risk of mother-to-child transmission (RR 0.67, 95% CI 0.29-1.55).  REVIEWERS CONCLUSIONS : Zidovudine, nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I584,I584)","v":10748547},{"$f":"(LEN($J584) - LEN(SUBSTITUTE(LOWER($J584),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J584) - LEN(SUBSTITUTE(LOWER($J584),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J584) - LEN(SUBSTITUTE(LOWER($J584),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B584:D584)","v":1},2000,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].","Bianchi",10748547,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].    Abstract:   The combined birth prevalence of cleft palate [CP] and cleft lip with or without cleft palate [CL(P)] in Europe is approximately one in 700 with characteristic regional variations. Orofacial clefting (OC) is therefore now one of the most frequent congenital anomalies, with a higher birth prevalence that Downs Syndrome or Neural Tube defects, but still lower than cardiovascular malformation. Babies with OC require a multidisciplinary medical approach, surgery and rehabilitative treatments over time. This means an important effort in terms of social organization as well as economical costs for the health care system. In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex and heterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role of genetics in producing susceptibility to the environment. Four categories of genes for which there are results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of the embryo or in a particular period of the palatine arch development, such as the transforming growth factors alpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to the OCs pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), the methylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes or locus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Several environmental factors have been implicated in the OC etiology; among those, the folic acid supplementation during the periconceptional period that was found effective in the prevention of neural tube defects. In fact, folic acid deficiency may be responsible for different malformations through a common mechanism that interferes with the embryonic development, depending on the maternal or embryo genotype. Further investigation is required to study in depth how the genotype would modify the role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seem to be able to give worthwhile information. Studies carried out in Europe on these issues are a few, particularly those on gene-environment interaction. Recent results obtained in molecular biology and the availability of wealth of data can allow to perform ad hoc investigations, being important not only for the basic research but also for their public health implications. For this objective a specific scientific network at the European level has been set by the European Science Foundation (ESF), whose first step will be to establish consistent case ascertainment and data collection across Europe and to develop standardized protocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative research will enable combined analysis and lead to the identification of genetic susceptibility to certain environmental factors, including nutrition. Such studies would inform the current debate about the efficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo. Subsequent public health measures targeted according to risk might reduce the prevalence of disorders such as orofacial clefting."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I585,I585)","v":10576759},{"$f":"(LEN($J585) - LEN(SUBSTITUTE(LOWER($J585),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J585) - LEN(SUBSTITUTE(LOWER($J585),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J585) - LEN(SUBSTITUTE(LOWER($J585),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B585:D585)","v":1},1999,"Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism.","Filetti",10576759,"Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism.    Abstract:   The recent cloning of the gene encoding the sodium/iodide symporter (NIS) has enabled better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to clarifying its role in thyroid diseases. Several studies, at both the mRNA and the protein expression levels, have demonstrated that TSH, the primary regulator of iodide uptake, upregulates NIS gene expression and NIS protein abundance, both in vitro and in vivo. However, other factors, including iodide, retinoic acid, transforming growth factor-beta, interleukin-1alpha and tumour necrosis factor alpha, may participate in the regulation of NIS expression. Investigation of NIS mRNA expression in different thyroid tissues has revealed increased levels of expression in Graves disease and toxic adenomas, whereas a reduction or loss of NIS transcript was detected in differentiated thyroid carcinomas, despite the expression of other specific thyroid markers. NIS mRNA was also detected in non-thyroid tissues able to concentrate radioiodine, including salivary glands, stomach, thymus and breast. The production of specific antibodies against the NIS has facilitated study of the expression of the symporter protein. Despite of the presence of high levels of human (h)NIS mRNA, normal thyroid glands exhibit a heterogeneous expression of NIS protein, limited to the basolateral membrane of the thyrocytes. By immunohistochemistry, staining of hNIS protein was stronger in Graves and toxic adenomas and reduced in thyroid carcinomas. Measurement of iodide uptake by thyroid cancer cells is the cornerstone of the follow-up and treatment of patients with thyroid cancer. However, radioiodide uptake is found only in about 67% of patients with persistent or recurrent disease. Several studies have demonstrated a decrease in or a loss of NIS expression in primary human thyroid carcinomas, and immunohistochemical studies have confirmed this considerably decreased expression of the NIS protein in thyroid cancer tissues, suggesting that the low expression of NIS may represent an early abnormality in the pathway of thyroid cell transformation, rather than being a consequence of cancer progression. The relationship between radioiodine uptake and NIS expression by thyroid cancer cells require further study. New strategies, based on manipulation of NIS expression, to obtain NIS gene reactivation or for use as NIS gene therapy in the treatment of radiosensitive cancer, are also being investigated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I586,I586)","v":10572559},{"$f":"(LEN($J586) - LEN(SUBSTITUTE(LOWER($J586),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J586) - LEN(SUBSTITUTE(LOWER($J586),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J586) - LEN(SUBSTITUTE(LOWER($J586),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B586:D586)","v":1},1999,"Chemoprevention of breast cancer.","Osborne",10572559,"Chemoprevention of breast cancer.    Abstract:   A critical question is, why do the European studies fail to confirm the US study? Clearly, the answers are complex and uncertain. Differences in power, age, risk, compliance, the use of ERT, and follow-up in the European studies may all be relevant. The efficacy of tamoxifen in BRCA 1 or 2 carriers is an important issue; recent data have shown a DNA repair defect in those with BRCA 1 gene alterations. This finding, coupled with the potential genotoxicity of tamoxifen, is of concern, but the NSABP study did show a significant reduction in breast cancer risk in those with first-degree relatives with breast cancer, including those likely to have a hereditary-predisposition gene. The issue will be clarified when the BRCA 1 or 2 status of these individuals is determined from the stored DNA samples of all participants in the NSABP study. The duration of use of an antiestrogen for prevention is uncertain; the adjuvant trial data for up to 5 years of tamoxifen use showed an effect on contralateral breast cancer prevention extending beyond 5 years, but experimental data show that stopping tamoxifen therapy results in the appearance of new tumors. The long-term use of tamoxifen for prevention carries significant risks. If raloxifene can be given long term, then continuing the prevention of tumors may be possible if raloxifene is proven safe. Should tamoxifen be used outside of a clinical trial? The FDA has approved its use to quot;delayquot; breast cancer so it can be prescribed for any patient at increased risk for breast cancer. The word prevention has been the subject of polemics. Every day that breast cancer is delayed is a day that it is prevented. Risk reduction is technically a more accurate phrase but lacks meaning to many women. Novel approaches to chemoprevention are being explored. Naturally occurring compounds or their analogues are being assessed. Based on experimental studies, the vitamin A analogue 4-hydroxyphenyl retinamide (4-HPR) was shown to delay and reduce carcinogen-induced breast cancer. A randomized clinical trial of 4-HPR is being tested in women in Italy to reduce contralateral breast cancer, but no results are available. New approaches using substances derived from plants, such as vegetables, are being pursued. Based on epidemiologic studies, investigators have proposed that an estrogen metabolite, C16 alpha-hydroxyesterone (16 alpha-OHE1), may have estrogen-stimulating and DNA-damaging properties of mammary epithelial cells. Strategies to reduce 16 alpha-OHE1 have been explored. Indole-3-carbinol, found in high concentration in cruciferous vegetables (i.e., cabbage, cauliflower, broccoli, rabe, brussels sprouts, kale, and bok choi), has been shown to reduce mammary cancer in rodent models and induces a metabolic pathway competing with 16 alpha-OHE1, which increases C-2 hydroxyesterone and thereby reduces substrate available for the 16 alpha-OHE1 pathway. Indole-3-carbinol has a good short-term safety profile. The minimum effective dose that favorably perturbs the ratio between 16 alpha-OHE1 and 2-OHE1 has been determined, and a pilot feasibility trial is in progress in women at risk for breast cancer at Strang Cancer Prevention Center. Future research will identify single or a combination of agents that may significantly reduce the risk for breast cancer without toxicity. A better understanding of the steps involved in the progression of normal breast cells toward cancer will permit the development of strategies to reduce the incidence of and mortality from breast cancer, with the ultimate goal of prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I587,I587)","v":10559659},{"$f":"(LEN($J587) - LEN(SUBSTITUTE(LOWER($J587),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J587) - LEN(SUBSTITUTE(LOWER($J587),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J587) - LEN(SUBSTITUTE(LOWER($J587),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B587:D587)","v":1},1999,"Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium.","Osteen",10559659,"Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium.    Abstract:   Endometrial expression of matrix metalloproteinase (MMP)-3, MMP-7 and MMP-11 occurs during menstrual breakdown and subsequent estrogen-mediated growth, but not during the secretory phase. These enzymes are suppressed by progesterone treatment. Paracrine factors, including transforming growth factor-beta (TGF-beta) and retinoic acid, are also critical for MMP regulation in the endometrium. In contrast, inflammatory cytokines such as interleukin-1alpha may block or interfere with steroid-mediated MMP regulation at ectopic sites of growth. Using in vitro models, our laboratory has investigated the complex interactions between progesterone and locally produced cytokines that may affect MMP expression during the development of endometriosis. Our results indicate that targeting the regulation of MMPs may represent an appropriate therapeutic strategy for the treatment of endometriosis. Copyrightz1999S. KargerAG,Basel"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I588,I588)","v":10436820},{"$f":"(LEN($J588) - LEN(SUBSTITUTE(LOWER($J588),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J588) - LEN(SUBSTITUTE(LOWER($J588),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J588) - LEN(SUBSTITUTE(LOWER($J588),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B588:D588)","v":1},1999,"An overview of preventive strategies for pancreatic cancer.","Levin",10436820,"An overview of preventive strategies for pancreatic cancer.    Abstract:   Cancer chemoprevention is defined as the use of specific chemical compounds to prevent, inhibit or reverse carcinogenesis. Chemopreventive intervention can occur throughout carcinogenesis. Many specific food components (e.g. calcium, selenium, folic acid) may also be suitable for chemopreventive use. Chemopreventive drugs are usually administered chronically and are expected to have low toxicity. A variety of mechanisms explain the actions of chemopreventive compounds including modification of carcinogen activation and cellular uptake, inhibition of aberrant signal transduction, induction of apoptosis and inhibition of angiogenesis. As our understanding of carcinogenesis has developed, more specific pharmacologic targets are being selected, e.g. retinoid receptors or cyclo-oxygenases. Definitive, large-scale placebo-controlled randomized trials are necessary to determine the clinical efficacy of chemopreventive compounds. Recent examples include the striking effectiveness of tamoxifen in reducing the risk of breast cancer in women at high risk. Conversely, beta carotene increased the risk of lung cancer in those who continued to smoke and/or who were exposed to asbestos. The future development of predictive risk models that take into account gene-environment interactions will be of considerable value in deciding on specific chemopreventive interventions in those at increased risk by virtue of life style or occupational exposures."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I589,I589)","v":10234899},{"$f":"(LEN($J589) - LEN(SUBSTITUTE(LOWER($J589),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J589) - LEN(SUBSTITUTE(LOWER($J589),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J589) - LEN(SUBSTITUTE(LOWER($J589),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B589:D589)","v":1},1999,"Insulin-like growth factors and cancer.","Yu",10234899,"Insulin-like growth factors and cancer.    Abstract:   Insulin-like growth factors (IGFs) regulate important cellular activities involving cell proliferation, differentiation, and apoptosis. Emerging evidence suggests that members of the IGF family, including IGF-1, IGF-2, the IGF-1 receptor (IGF-1R), and the IGF binding proteins (IGFBPs), play important roles in the development and progression of cancer. Both in vitro and in vivo studies show that IGFs are strong mitogens for a variety of cancer cells. IGF-1 also has an antiapoptotic action on cancer. IGF-1R, overexpressed in cancer cells, mediates the effects of IGFs and plays a role in cell transformation induced by tumor virus and oncogene products. IGFBPs inhibit the actions of IGFs and mediate the anti-proliferative effect of wild-type p53 protein, retinoic acid, vitamin D, and transforming growth factor-beta (TGF-beta). Findings from epidemiologic studies support the involvement of IGF in cancer etiology. Diet, nutrition, and other lifestyle features affect the expression and production of IGF-1 and other members of the IGF family. This may provide new approaches for cancer prevention. Growth hormone (GH) stimulates the production of IGF-1. Use of GH replacement therapy to improve physiological and psychological well-being and to prevent aging-related diseases has been recommended. Given the close relationship between GH and IGF-1, the long-term safety of GH treatment warrants a serious concern."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I590,I590)","v":10200043},{"$f":"(LEN($J590) - LEN(SUBSTITUTE(LOWER($J590),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J590) - LEN(SUBSTITUTE(LOWER($J590),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J590) - LEN(SUBSTITUTE(LOWER($J590),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B590:D590)","v":1},1999,"Potential risk of birth defects after acitretin discontinuation.","Maradit",10200043,"Potential risk of birth defects after acitretin discontinuation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I591,I591)","v":10023305},{"$f":"(LEN($J591) - LEN(SUBSTITUTE(LOWER($J591),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J591) - LEN(SUBSTITUTE(LOWER($J591),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J591) - LEN(SUBSTITUTE(LOWER($J591),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B591:D591)","v":1},1998,"Breast cancer and the western diet: role of fatty acids and antioxidant vitamins.","Stoll",10023305,"Breast cancer and the western diet: role of fatty acids and antioxidant vitamins.    Abstract:   Epidemiological reports are inconsistent on the association between breast cancer risk and the dietary intake of either individual fatty acids or of antioxidant vitamins. It is postulated here that the inconsistencies are in part due to interactions between the two classes of nutrients at the level of the cell membrane, affecting their potential role in mammary carcinogenesis. In this review, the effects of specific dietary fatty acids and antioxidant vitamins on experimental mammary cancer systems are compared with reported epidemiological associations of the same agents with breast cancer risk in humans. An increased ratio of n-3 to n-6 polyunsaturated fatty acids (PUFAs) in the diet inhibits the growth of the rat mammary cancer model. There is also evidence that members of the n-3 PUFA series can inhibit the growth of human breast cancer cells both in vitro and in explants. Clinical trials of supplementary n-3 PUFAs in conjunction with a reduced fat intake have been proposed for breast cancer prevention. It is postulated that further dietary supplementation with vitamin E and a retinoid is likely to increase the effectiveness of such a diet. A study of this type allows better control of specific dietary components than prospective trials of dietary fat reduction which are presently under evaluation. In particular, it is suggested that studies focusing on a single nutrient often fail to recognise interactions with other nutrients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I592,I592)","v":9932511},{"$f":"(LEN($J592) - LEN(SUBSTITUTE(LOWER($J592),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J592) - LEN(SUBSTITUTE(LOWER($J592),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J592) - LEN(SUBSTITUTE(LOWER($J592),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B592:D592)","v":1},1998,"The role of retinoids in developmental mechanisms in embryos.","Maden",9932511,"The role of retinoids in developmental mechanisms in embryos.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I593,I593)","v":9891229},{"$f":"(LEN($J593) - LEN(SUBSTITUTE(LOWER($J593),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J593) - LEN(SUBSTITUTE(LOWER($J593),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J593) - LEN(SUBSTITUTE(LOWER($J593),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B593:D593)","v":1},1998,"Current methods to prevent the development of breast cancer.","Cristofanilli",9891229,"Current methods to prevent the development of breast cancer.    Abstract:   Chemoprevention of breast cancer has long been an attractive goal. However, the women most likely to benefit from chemoprevention, women at high risk for breast cancer, have traditionally been difficult to identify. The increased incidence of proliferative breast disease (PBD), associated with an increased risk of developing breast cancer and the identification of the BRCA1 and BRCA2 breast cancer susceptibility genes have provided the opportunity for identification of high risk women. Recent chemopreventive randomized clinical trials have demonstrated that antiestrogens, in particular tamoxifen, and retinoids are among the most effective chemopreventive agents. Adjuvant dietary modifications have also been considered for investigation based on epidemiological and preclinical observations that links high-fat diet to mammary tumorigenesis. In future clinical trials, monitoring of molecular markers of genetic instability through novel laboratory techniques will provide sensitive surrogate endpoint biomarkers (SBEs) to evaluate efficacy of chemopreventive interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I594,I594)","v":9790574},{"$f":"(LEN($J594) - LEN(SUBSTITUTE(LOWER($J594),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J594) - LEN(SUBSTITUTE(LOWER($J594),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J594) - LEN(SUBSTITUTE(LOWER($J594),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B594:D594)","v":1},1998,"Current understanding of the molecular actions of vitamin D.","Jones",9790574,"Current understanding of the molecular actions of vitamin D.    Abstract:   The important reactions that occur to the vitamin D molecule and the important reactions involved in the expression of the final active form of vitamin D are reviewed in a critical manner. After an overview of the metabolism of vitamin D to its active form and to its metabolic degradation products, the molecular understanding of the 1alpha-hydroxylation reaction and the 24-hydroxylation reaction of the vitamin D hormone is presented. Furthermore, the role of vitamin D in maintenance of serum calcium is reviewed at the physiological level and at the molecular level whenever possible. Of particular importance is the regulation of the parathyroid gland by the vitamin D hormone. A third section describes the known molecular events involved in the action of 1alpha,25-dihydroxyvitamin D3 on its target cells. This includes reviewing what is now known concerning the overall mechanism of transcriptional regulation by vitamin D. It describes the vitamin D receptors that have been cloned and identified and describes the coactivators and retinoid X receptors required for the function of vitamin D in its genomic actions. The presence of receptor in previously uncharted target organs of vitamin D action has led to a study of the possible function of vitamin D in these organs. A good example of a new function described for 1alpha,25-dihydroxyvitamin D3 is that found in the parathyroid gland. This is also true for the role of vitamin D hormone in skin, the immune system, a possible role in the pancreas, i.e., in the islet cells, and a possible role in female reproduction. This review also raises the intriguing question of whether vitamin D plays an important role in embryonic development, since vitamin D deficiency does not prohibit development, nor does vitamin D receptor knockout. The final section reviews some interesting analogs of the vitamin D hormone and their possible uses. The review ends with possible ideas with regard to future directions of vitamin D drug design."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I595,I595)","v":9785241},{"$f":"(LEN($J595) - LEN(SUBSTITUTE(LOWER($J595),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J595) - LEN(SUBSTITUTE(LOWER($J595),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J595) - LEN(SUBSTITUTE(LOWER($J595),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B595:D595)","v":1},1998,"Requirements of fat-soluble vitamins for dairy cows: a review.","Weiss",9785241,"Requirements of fat-soluble vitamins for dairy cows: a review.    Abstract:   Knowledge about vitamins has evolved greatly since they were discovered lt; 100 yr ago, but the quantitative determination of the vitamin requirements of dairy cows has been difficult. Current requirements are based on data that are at least 20 yr old and, in some cases, gt; 50 years old. The response variables in those studies were the prevalence of overt signs of deficiency, level of milk production, reproductive performance, and vitamin concentrations in blood and tissues. Since those studies were conducted, milk production per cow has increased substantially, and the feeding and management of cows have changed (less pasture, less forage, and more total confinement). More refined measures of vitamin adequacy have been developed. Immunocompetence may be a useful tool for determining the requirements of some vitamins. Requirements that are based on measures of immune function are usually higher than those that are based on production or reproduction. The current requirements for vitamin D appear to be adequate, but the requirement for vitamin A should be increased by approximately 50% because of differences in bioavailability between beta-carotene and retinyl esters. Based on health data, the vitamin E requirement should be increased at least 500% and perhaps as much as 700% for dry cows and lactating cows."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I596,I596)","v":9709809},{"$f":"(LEN($J596) - LEN(SUBSTITUTE(LOWER($J596),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J596) - LEN(SUBSTITUTE(LOWER($J596),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J596) - LEN(SUBSTITUTE(LOWER($J596),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B596:D596)","v":1},1998,"Differentiation and cancer in the mammary gland: shedding light on an old dichotomy.","Petersen",9709809,"Differentiation and cancer in the mammary gland: shedding light on an old dichotomy.    Abstract:   In this brief review, the development of breast cancer is discussed from the vantage of phenotypic differentiation, similar to what has been considered over the years for leukemias and melanomas, both of which express easily visible differentiation markers (Hart and Easty, 1991; Clarke et al., 1995; Lynch, 1995; Sachs, 1996; Sledge, 1996). The review is divided into a theoretical background for human breast differentiation and a discussion of recent experimental results in our laboratories with differentiation of breast epithelial cells. In the theoretical background, in situ markers of differentiation of normal breast and carcinomas are discussed with emphasis on their possible implications for tumor therapy. So far, most of the emphasis regarding differentiation therapy of tumors has been focused on the possible action of soluble factors, such as colony-stimulating factors in leukemias and retinoic acids in solid tumors (Lotan, 1996; Sachs, 1996). However, an emerging and promising new avenue in this area appears to point to additional factors, such as the cellular form and extracellular matrix (ECM) (Bissel et al., 1982; Bissel and Barcellos-Hoff, 1987; Ingber, 1992). The recent interest in these parameters has evolved along with an increasing understanding of the molecular composition of the ECM, and of the molecular basis of the classical findings that normal cell--in contrast to tumor cells--are anchorage dependent for survival and growth (Folkman and Moscona, 1978; Hannigan et al., 1996). We now know that this is the case for epithelial as well as fibroblastic cells, and that interaction with ECM is crucial for such regulation. Indeed, ECM and integrins are emerging as the central regulators of differentiation, apoptosis, and cancer (Boudreau et al., 1995; Boudreau and Bissel, 1996; Werb et al., 1996; Bissell, 1997; Weaver, et al., 1997). In the experimental part, we elaborate on our own recent experiments with functional culture models of the human breast, with particular emphasis on how quot;normalquot; and cancer cells could be defined within a reconstituted ECM. Special attention is given to integrins, the prominent ECM receptors. We further discuss a number of recent experimental results, all of which point to the same conclusion: namely that phenotypic reversion toward a more normal state for epithelial tumors is no longer an elusive goal. Thus quot;therapy by differentiationquot; could be broadened to include not only blood-borne tumors, but also solid tumors of epithelial origin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I597,I597)","v":9597175},{"$f":"(LEN($J597) - LEN(SUBSTITUTE(LOWER($J597),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J597) - LEN(SUBSTITUTE(LOWER($J597),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J597) - LEN(SUBSTITUTE(LOWER($J597),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B597:D597)","v":1},1998,"Zinc metabolism during pregnancy--interactions with vitamin A.","Lönnerdal",9597175,"Zinc metabolism during pregnancy--interactions with vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I598,I598)","v":9563695},{"$f":"(LEN($J598) - LEN(SUBSTITUTE(LOWER($J598),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J598) - LEN(SUBSTITUTE(LOWER($J598),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J598) - LEN(SUBSTITUTE(LOWER($J598),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B598:D598)","v":1},1998,"Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.","Gardner",9563695,"Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.    Abstract:    BACKGROUND : The pre- and peri-natal drug exposures reported by women participating in a case-control study of children in Colorado were examined for association with infant craniosynostosis.  METHODS : Mothers of case and control children underwent a standardized telephone interview and obstetric and newborn medical record review. The interview included questions on the use of prescription and non-prescription drugs, nutritional supplements, recreational and drugs of abuse. The mothers obstetric record was abstracted for information about pharmacologic agents taken before and during the antepartum period.  RESULTS : There were no statistically significant risk ratios associating craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine. Mothers of four case children and one control child reported specific exposure to retinoic acid. There were no statistically significant increases in the odds ratio (OR) for any suture type among children exposed to hypoxigenic agents, sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI): 1.08) among children with sagittal/lambdoid suture synostosis who were exposed to nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin compared to controls.  CONCLUSIONS : Certain nitrosatable drugs may be associated with increased risk of infant sagittal/lambdoid craniosynostosis. A possible mechanism related to ischaemia/reperfusion injury is suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I599,I599)","v":9545362},{"$f":"(LEN($J599) - LEN(SUBSTITUTE(LOWER($J599),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J599) - LEN(SUBSTITUTE(LOWER($J599),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J599) - LEN(SUBSTITUTE(LOWER($J599),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B599:D599)","v":1},1998,"Drugs in pregnancy.","Koren",9545362,"Drugs in pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I600,I600)","v":9537645},{"$f":"(LEN($J600) - LEN(SUBSTITUTE(LOWER($J600),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J600) - LEN(SUBSTITUTE(LOWER($J600),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J600) - LEN(SUBSTITUTE(LOWER($J600),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B600:D600)","v":1},1998,"Melatonin: receptor-mediated events that may affect breast and other steroid hormone-dependent cancers.","Baldwin",9537645,"Melatonin: receptor-mediated events that may affect breast and other steroid hormone-dependent cancers.    Abstract:   Epidemiological studies have suggested a possible link between extremely low frequency electromagnetic fields (EMFs) and increased rates of certain cancers. One cancer that has been postulated to be associated with EMF exposure is breast cancer, for which increased rates have been reported among electricians. These cancer associations are weak, and the link to EMF exposures remains tenuous. Understanding the mechanisms by which EMFs could have biological effects will help in elucidating the risk, if any, from EMFs. One hypothesis that has received considerable attention involves reduction of melatonin levels by EMFs. This hypothesis suggests that loss of melatonin affects a variety of hormonal processes such as estrogen homeostasis and thereby may increase breast cancer rates. Since this theory was first presented, putative melatonin receptors have been cloned, providing new tools with which to examine melatonins mechanism of action and the melatonin hypothesis. These receptors are found in nuclear and membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are found both in the brain and in non-neural tissues, whereas the membrane-bound receptors are found primarily in neural tissue and have a higher affinity for melatonin. These receptors may control a variety of hormonal and immunological functions, including the release of gonadotropins from the hypothalamus and pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis briefly reviews our current knowledge of melatonin receptors and then provides theories on how the inactivation of melatonin receptors may cause cancer and suggests areas of research for addressing this question."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I601,I601)","v":9478268},{"$f":"(LEN($J601) - LEN(SUBSTITUTE(LOWER($J601),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J601) - LEN(SUBSTITUTE(LOWER($J601),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J601) - LEN(SUBSTITUTE(LOWER($J601),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B601:D601)","v":1},1997,"Animal models of breast cancer: experimental design and their use in nutrition and psychosocial research.","Clarke",9478268,"Animal models of breast cancer: experimental design and their use in nutrition and psychosocial research.    Abstract:   This is the second Special Issue addressing the diversity and use of animal models of breast cancer. The previous issue (Breast Cancer Res Treat 39:1-135, 1996), dealt with a variety of topics such as the characteristics of chemically- and virally-induced rodent models, immunobiologies of immunedeficient mice, transgenic mouse models, and models of metastasis. In the first part of this second Special Issue, the articles address animal models for studying life-style factors, including psychosocial, exercise, and nutritional research in breast cancer. In the second section, there is emphasis on the controversial area of dietary fat, with other authors addressing caloric restriction and dietary isoflavonoids, retinoids, and monoterpenes in the third part. In the final section, a series of authors provide suggestions for approaching various issues involving experimental design, including nutritional studies, drug screening models, statistical considerations, quantitation of tumor growth kinetics, and animal husbandry. These articles, and some additional issues raised during the previous Special Issue, are briefly discussed in this overview. They include a further evaluation of the relative merits of 7,12-dimethylbenz(a)anthracene and N-nitroso-N-methylurea as carcinogens, and of the use of the AIN76 and AIN93 semipurified diets in studies of mammary carcinogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I602,I602)","v":9516082},{"$f":"(LEN($J602) - LEN(SUBSTITUTE(LOWER($J602),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J602) - LEN(SUBSTITUTE(LOWER($J602),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J602) - LEN(SUBSTITUTE(LOWER($J602),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B602:D602)","v":1},1998,"IGF-independent regulation of breast cancer growth by IGF binding proteins.","Oh",9516082,"IGF-independent regulation of breast cancer growth by IGF binding proteins.    Abstract:   The human IGFBP family consists of at least seven proteins, designated as IGFBP-1, -2, -3, -4, -5, -6, and-7. IGFBPs 1-6 bind IGF-I and IGF-II with high affinity whereas IGFBP-7, a newly identified IGFBP, binds IGFs with lower affinity and constitutes a low-affinity member of the IGFBP family. IGFBPs serve to transport the IGFs, prolong their half-lives, and modulate their biological action. At the cellular level, IGFBPs can either potentiate or inhibit the mitogenic effects of IGFs, depending upon cell types and IGFBP species (IGF-dependent action of IGFBPs). However, recent studies have indicated that IGFBPs, especially IGFBP-3, potently inhibit breast cancer cell growth in an IGF-independent manner. The IGF-independent action of IGFBP-3 requires interaction with cell-surface association proteins, presumably putative IGFBP-3 specific receptors, and is responsible for growth inhibitory action of the known growth suppressing factors such as TGF-beta, retinoic acid, and antiestrogens in breast cancer cells. Thus, IGFBP-3 appears to be a major factor in a negative control system involved in regulating human breast cancer cell growth in vitro. IGFBP-7, representing a low affinity IGFBP, appears to function as an IGF-independent cell growth regulator in breast cancer cells. Overall structural similarity between IGFBP-7 and classical high affinity IGFBPs 1-6 suggests that the mechanisms of action and signaling pathways used by IGFBP-7 may provide insight into the IGF-independent actions of the high affinity IGFBPs. A fuller understanding of the IGF-independent action of IGFBPs will allow us to understand how the growth of neoplastic cells can be modulated by the IGF/IGFBP system, and how other growth factors or pharmacological agents can interface with this system."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I603,I603)","v":9504042},{"$f":"(LEN($J603) - LEN(SUBSTITUTE(LOWER($J603),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J603) - LEN(SUBSTITUTE(LOWER($J603),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J603) - LEN(SUBSTITUTE(LOWER($J603),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B603:D603)","v":1},1998,"What are the molecular mechanisms of neural tube defects?","Corcoran",9504042,"What are the molecular mechanisms of neural tube defects?    Abstract:   Neural tube defects (NTDs) are some of the most common human malformations. The vast majority of NTDs can be prevented by the administration of folic acid; however, to date there has been no effective treatment of folic acid-resistant NTDs. A recent paper has confirmed an earlier report that the administration of inositol to the curly tail mutant mouse, which is a model of folate-resistant NTDs, can cure such defects. The molecular pathway by which this is achieved is thought to occur by the up-regulation of the retinoic acid receptor beta in the underlying hindgut endoderm, correcting a proliferation defect. However, alternative explanations also may account for NTDs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I604,I604)","v":9436085},{"$f":"(LEN($J604) - LEN(SUBSTITUTE(LOWER($J604),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J604) - LEN(SUBSTITUTE(LOWER($J604),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J604) - LEN(SUBSTITUTE(LOWER($J604),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B604:D604)","v":1},1997,"Ethical and legal aspects of teratogenic medications: the case of isotretinoin.","Moskop",9436085,"Ethical and legal aspects of teratogenic medications: the case of isotretinoin.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I605,I605)","v":9313977},{"$f":"(LEN($J605) - LEN(SUBSTITUTE(LOWER($J605),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J605) - LEN(SUBSTITUTE(LOWER($J605),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J605) - LEN(SUBSTITUTE(LOWER($J605),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B605:D605)","v":1},1997,"Retinoids.","Gollnick",9313977,"Retinoids.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I606,I606)","v":9659415},{"$f":"(LEN($J606) - LEN(SUBSTITUTE(LOWER($J606),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J606) - LEN(SUBSTITUTE(LOWER($J606),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J606) - LEN(SUBSTITUTE(LOWER($J606),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B606:D606)","v":1},1997,"Micronutrient regulation in pregnant and lactating women from Rio de Janeiro.","Trugo",9659415,"Micronutrient regulation in pregnant and lactating women from Rio de Janeiro.    Abstract:   Studies with low-income pregnant and lactating women from the city of Rio de Janeiro, concerned mainly with the changes in micronutrient homeostasis during pregnancy and lactation in the absence of overt clinical deficiencies, are reported. These studies focused on folate, cobalamin, iron, zinc and vitamin A. Factors that may affect the maternal micronutrient state, such as dietary intakes, use of supplements and interrelationships of micronutrients have been considered, as well as the implications of these changes for maternal-fetal transfer and milk composition. Although these studies were not designed to evaluate the prevalence of sub-clinical micronutrient deficiencies in pregnant and lactating women, they indicate that high frequencies of sub-clinical deficiencies of folate, iron, zinc and vitamin A, especially in pregnant women, are expected to be found in Rio de Janeiro."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I607,I607)","v":9240869},{"$f":"(LEN($J607) - LEN(SUBSTITUTE(LOWER($J607),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J607) - LEN(SUBSTITUTE(LOWER($J607),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J607) - LEN(SUBSTITUTE(LOWER($J607),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B607:D607)","v":1},1997,"Overview of the potential role of vitamin A in mother-to-child transmission of HIV-1.","Semba",9240869,"Overview of the potential role of vitamin A in mother-to-child transmission of HIV-1.    Abstract:   Vitamin A is an essential micronutrient for normal immune function. Vitamin A deficiency is common among human immunodeficiency virus (HIV)-infected pregnant women and is associated with higher mother-to-child transmission of HIV-1 and increased infant mortality. The biological mechanisms by which vitamin A deficiency could influence mother-to-child transmission of HIV-1 include impairment of immune responses in both mother and infant, abnormal placental and vaginal pathology and increased HIV viral burden in breastmilk and blood. Clinical trials are currently in progress to determine whether daily micronutrient supplementation, including vitamin A, during pregnancy can reduce mother-to-child transmission of HIV-1."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I608,I608)","v":9206593},{"$f":"(LEN($J608) - LEN(SUBSTITUTE(LOWER($J608),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J608) - LEN(SUBSTITUTE(LOWER($J608),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J608) - LEN(SUBSTITUTE(LOWER($J608),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B608:D608)","v":1},1997,"[Intrauterine exposure to drugs].","Legido",9206593,"[Intrauterine exposure to drugs].    Abstract:   The development of the fetal central nervous system can be effected by drugs. In this paper we review the neurological consequences of intrauterine exposure to alcohol, cocaine, opiates and marijuana. Ethanol causes the fetal alcohol syndrome: mental retardation, intrauterine and postnatal growth retardation, and peculiar dysmorphic features. Is pathogenesis has been explained on the basis of maternal nutritional deficiencies or due to abnormalities in the conversion of ethanol to aldehyde, or abnormalities in the metabolism of prostaglandins or retinoic acid, the neurotransmitter systems, the neuronal excitotoxic activity, the development of the white matter, the production of gangliosides, and/or genetic regulation cell-cell adhesion. Cocaine has been related to congenital malformations, neurologic abnormalities during the neonatal period and psychomotor and cognitive development deficits. Characteristic dysmorphic features and a higher incidence of the sudden infant death syndrome (SIDS) have also been described. The following mechanisms have been implicated in the pathogenesis: vascular effects, superoxide formation, chelation of calcium ion channels, and abnormalities in the production of glycosphingolipids, the synthesis of DNA, the functioning of neurotransmitter systems, the neuronal growth and differentiation, the neuronal excitotoxic activity and/or the expression of early immediate genes. Opiates produce intrauterine and postnatal growth retardation, neonatal abstinence syndrome, and deficits of the psychomotor and cognitive development. They also increase the incidence of SIDS. The pathogenesis has been related to abnormalities in the sensitivity of the locus ceruleus, the functioning of the neurotransmitter systems, and/or the expression of early immediate genes. Marijuana has been associated with intrauterine growth retardation, dysmorphic features, and abnormalities of the behavior during the neonatal period, the psychomotor and cognitive development, and the sleep. The pathogenesis is thought to be due to an action upon specific receptors, or upon the neurotransmitter systems, and/or to an increase in the production of carbon monoxide. The best treatment of the syndrome of intrauterine exposure to drugs in the prophylaxis. The identification of emotional and drug addiction problems in the mother can avoid disastrous consequences. The care of these children is complex and requires a good pediatric follow-up and an early intervention program while the mother on the parents continue with the drug addiction therapy. The coordinations of all the necessary services with the active participation of social workers, physicians, educators and teachers is crucial for a successful treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I609,I609)","v":9159786},{"$f":"(LEN($J609) - LEN(SUBSTITUTE(LOWER($J609),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J609) - LEN(SUBSTITUTE(LOWER($J609),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J609) - LEN(SUBSTITUTE(LOWER($J609),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B609:D609)","v":1},1997,"Chemoprevention of cancer: review of the literature.","Swan",9159786,"Chemoprevention of cancer: review of the literature.    Abstract:    PURPOSE/OBJECTIVES : To explain the concept of cancer chemoprevention, describe chemoprevention trials, and discuss the agents currently under study to lower the incidence of oral premalignancy and head and neck, lung, breast, prostate, and colon cancers.  DATA SOURCES : Published journal articles, books, bulletins, monographs, protocols, and professional experience.  DATA SYNTHESIS : Chemoprevention is a promising approach to cancer control, and several key agents have been identified that may be able to block carcinogenesis. Phase III chemoprevention trials are being conducted to identify the role of agents (e.g., retinoids, tamoxifen, finasteride, aspirin) in cancer prevention.  CONCLUSION : Knowledge of the genetic and hormonal changes that occur during carcinogenesis continues to increase. Agents are being identified that block the development of cancer by arresting carcinogenesis. As more agents are identified and investigated, their importance in chemoprevention is increasing.  IMPLICATION FOR NURSING PRACTICE : The goal of nursing care for participants in prevention trials is to promote compliance with the study protocol while supporting optimum quality of life. Through proactive education of participants, family members, and the public and skillful management of side effects, nurses can play an integral part in the success of prevention trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I610,I610)","v":9033661},{"$f":"(LEN($J610) - LEN(SUBSTITUTE(LOWER($J610),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J610) - LEN(SUBSTITUTE(LOWER($J610),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J610) - LEN(SUBSTITUTE(LOWER($J610),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B610:D610)","v":1},1997,"Retinoid-interferon therapy of solid tumors.","Lippman",9033661,"Retinoid-interferon therapy of solid tumors.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I611,I611)","v":9040906},{"$f":"(LEN($J611) - LEN(SUBSTITUTE(LOWER($J611),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J611) - LEN(SUBSTITUTE(LOWER($J611),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J611) - LEN(SUBSTITUTE(LOWER($J611),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B611:D611)","v":1},1997,"How to ensure fetal safety when mothers use isotretinoin (Accutane).","Koren",9040906,"How to ensure fetal safety when mothers use isotretinoin (Accutane).    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I612,I612)","v":15706739},{"$f":"(LEN($J612) - LEN(SUBSTITUTE(LOWER($J612),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J612) - LEN(SUBSTITUTE(LOWER($J612),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J612) - LEN(SUBSTITUTE(LOWER($J612),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B612:D612)","v":1},1997,"Alcohol-induced cell death in the embryo.","Smith",15706739,"Alcohol-induced cell death in the embryo.    Abstract:   Exposure to alcohol during gestation can have profound consequences, but not all cells within the embryo are affected equally. Recent advances in molecular embryology have allowed an exploration of this variation. Much of this research has focused on the embryos vulnerability to the facial malformations characteristic of fetal alcohol syndrome. Studies using mice and chicks show that alcohol exposure at specific stages of early embryo development results in significant death among the cells destined to give rise to facial structures (i.e., cranial neural crest cells). This type of cell death is through activation of the cells own quot;self-destructquot; machinery (i.e., apoptosis). Researchers have advanced several theories to explain how alcohol triggers apoptosis in the neural crest cells. These theories include deficiency in a type of vitamin A compound, retinoic acid; reduced levels of antioxidant compounds (i.e., free radical scavengers) that protect against damage from toxic oxygen molecules (i.e., free radicals); and interference with the cells normal internal communication pathways."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I613,I613)","v":9561639},{"$f":"(LEN($J613) - LEN(SUBSTITUTE(LOWER($J613),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J613) - LEN(SUBSTITUTE(LOWER($J613),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J613) - LEN(SUBSTITUTE(LOWER($J613),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B613:D613)","v":1},1997,"Nutrition and development: other micronutrients effect on growth and cognition.","Wasantwisut",9561639,"Nutrition and development: other micronutrients effect on growth and cognition.    Abstract:   Previous studies have provided strong evidence that protein-energy malnutrition, deficiencies of iron and iodine early on in life led to compromised growth and cognitive functions in young children. Recently, a growing body of knowledge indicated that other micronutrients also play a role in young child development. Severe as well as marginal vitamin A efficiency were shown to lead to an increased risk of morbidity and mortality in children. A meta-analysis of vitamin A intervention trials indicated an overall reduction of 23% in all-cause mortality rate. Delayed growth, especially stunting, was reported in children with clinical signs of vitamin A deficiency. In addition, deficiency of zinc, which is essential for DNA and protein synthesis, leads to growth failure and delayed secondary sexual maturation in man and animals. Preterm infants appear to benefit from zinc administration in terms of growth and development. Supplementation studies in infants and older children revealed that those who manifested overt zinc deficiency through either clinical or biochemical indicators showed an improvement in linear growth and occasionally, an increase in weight gain. Zinc may also play a major role in brain function based on strong evidence from experimental animals. Zinc deficiency gestation in mice, rats, rhesus monkeys caused impaired learning, reduced attention and poor memory in their offspring. Data in humans are few and inconclusive. With respect to brain function alone, other nutrients such as docosahexaenoic acid (DHA, 22:6 n-3 fatty acid) improve visual acuity and mental development in small-for-gestational-age infants, folate supplementation during pregnancy prevents neural tube defect in infants, selenium deficiency in animals affects activities of brain enzymes necessary for brain development and function. Although evidence is accumulating that micronutrients other than iron and iodine may be important for physical growth and brain development in young children, more well-controlled studies in humans are needed. Critical issues to be considered include: single vs multiple limiting nutrients, critical period of deficiency, responsive indicators and variables that may affect the results as environmental, psychological and social factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I614,I614)","v":9238853},{"$f":"(LEN($J614) - LEN(SUBSTITUTE(LOWER($J614),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J614) - LEN(SUBSTITUTE(LOWER($J614),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J614) - LEN(SUBSTITUTE(LOWER($J614),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B614:D614)","v":1},1997,"Aromatase expression in health and disease.","Simpson",9238853,"Aromatase expression in health and disease.    Abstract:   Family 19 of the P450 superfamily is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization, since it involves conversion of the delta 4-3-one A-ring of the androgens to the corresponding phenolic A-ring characteristic of estrogens. Its members occur throughout the entire vertebrate phylum. The reaction mechanism of aromatase is very interesting from a chemical point of view and has been studied extensively; however, a detailed examination of structure-function relationships has not been possible due to lack of a crystal structure. Recent attempts to model the three-dimensional structure of aromatase have permitted a model that accounts for the reaction mechanism and predicts the location of aromatase inhibitors. The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, since there are a number of untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion, due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in ovary utilizes a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in placenta utilizes a distal promoter that is located at least 40 kb upstream of the start of transcription and that is regulated by retinoids. Other promoters are employed in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11 as well as TNF alpha are important regulatory factors. PGE2 is also an important regulator of aromatase expression in adipose mesenchymal cells via cAMP and PGE2 appears to be a major factor produced by breast tumors that stimulates estrogen biosynthesis in local mesenchymal sites. In all of the splicing events involved in the use of these various promoters, a common 3-splice junction is employed that is located upstream of the start of translation; thus, the coding regions of the transcripts- and hence the protein-are identical regardless of the tissue site of expression; what differ in a tissue-specific fashion are the 5-ends of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint as well as for the physiology and pathophysiology of estrogen formation. Recently, a number of mutations of the aromatase gene have been described, which give rise to complete estrogen deficiency. In females this results in virilization in utero and primary amenorrhea with hypergonadotropic hypogonadism at the time of puberty. In men the most striking feature is continued linear bone growth beyond the time of puberty, delayed bone age, and failure of epiphyseal closure, thus indicating an important role of estrogens in bone metabolism in men. In both sexes the symptoms can be alleviated by estrogen administration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I615,I615)","v":9238852},{"$f":"(LEN($J615) - LEN(SUBSTITUTE(LOWER($J615),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J615) - LEN(SUBSTITUTE(LOWER($J615),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J615) - LEN(SUBSTITUTE(LOWER($J615),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B615:D615)","v":1},1997,"Steroidogenic factor 1 plays multiple roles in endocrine development and function.","Wong",9238852,"Steroidogenic factor 1 plays multiple roles in endocrine development and function.    Abstract:   The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also contains members for which activating ligands have not been identified-the orphan nuclear receptors. One of these orphan nuclear receptors, steroidogenic factor 1 (SF-1), has emerged as an essential regulator of steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays important roles in reproduction at all three levels of the hypothalamic-pituitary-gonadal axis. First identified as a tissue-specific regulator of the transcription of the cytochrome P450 steroid hydroxylases, considerably broader roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal glands and gonads, male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels. Despite these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts its multiple effects remain to be determined. This review highlights experiments that have established SF-1 as a pivotal determinant of endocrine differentiation and function and identifies areas in which additional studies are needed to expand our understanding of SF-1 action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I616,I616)","v":9132131},{"$f":"(LEN($J616) - LEN(SUBSTITUTE(LOWER($J616),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J616) - LEN(SUBSTITUTE(LOWER($J616),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J616) - LEN(SUBSTITUTE(LOWER($J616),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B616:D616)","v":1},1997,"[The eye and pregnancy].","Funk",9132131,"[The eye and pregnancy].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I617,I617)","v":9034163},{"$f":"(LEN($J617) - LEN(SUBSTITUTE(LOWER($J617),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J617) - LEN(SUBSTITUTE(LOWER($J617),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J617) - LEN(SUBSTITUTE(LOWER($J617),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B617:D617)","v":1},1997,"Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage.","Simpson",9034163,"Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage.    Abstract:   Family 19 of the P450 super family is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization because it involves conversion of the delta4-3-one A-ring of the androgens to the corresponding phenolic A-ring characteristic of estrogens. The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, because there are numerous untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in the ovary uses a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in the placenta uses a distal promoter located at least 40 kb upstream of the start of transcription that is regulated by retinoids. Other promoters are used in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11, as well as TNF-alpha, are important regulatory factors. A common 3-splice junction located upstream of the start of translation is used in all of the splicing events involved in the use of these various promoters. Thus, the coding region of the transcripts, and hence the protein, are identical regardless of the tissue site of expression; what differs in a tissue-specific fashion is the 5-end of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint, as well as for the physiology and pathophysiology of estrogen formation, as will be discussed in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I618,I618)","v":8971464},{"$f":"(LEN($J618) - LEN(SUBSTITUTE(LOWER($J618),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J618) - LEN(SUBSTITUTE(LOWER($J618),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J618) - LEN(SUBSTITUTE(LOWER($J618),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B618:D618)","v":1},1996,"Epidemiology, prevention, and early detection of breast cancer.","Daudt",8971464,"Epidemiology, prevention, and early detection of breast cancer.    Abstract:   Breast cancer is the most common cancer among women worldwide. Genetic, environmental, and gene-environment interactions are discussed in relation to breast cancer etiology. A major advance in the study of inherited forms of breast cancer occurred with the identification of two genes, BRCA1 and BRCA2, that may account for a majority of inherited forms of breast cancer cases. Hypotheses have been formulated concerning the importance of timing of exposures to environmental agents and a possible role of quot;xenogeneticsquot; in relation to breast cancer risk. With respect to early detection, regular mammography screening for women aged 50 years and older is clearly associated with a significant reduction in breast cancer mortality, but mammography among women aged 40 to 49 remains controversial. Concerning chemoprevention, the risks and benefits of tamoxifen continue to be clarified, retinoids hold promise, and monoterpenes have emerged as a possible chemopreventive agent."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I619,I619)","v":8861920},{"$f":"(LEN($J619) - LEN(SUBSTITUTE(LOWER($J619),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J619) - LEN(SUBSTITUTE(LOWER($J619),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J619) - LEN(SUBSTITUTE(LOWER($J619),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B619:D619)","v":1},1996,"Overview of perinatal HIV infection.","Fowler",8861920,"Overview of perinatal HIV infection.    Abstract:   The global HIV epidemic is having a profound impact on the health and survival of children. As of 1994, it is estimated that about 2 million children worldwide (WHO, 1994) and 12 thousand children in the United States are HIV infected (Davis et al. 1995). Almost all HIV infection among infants and young children are from mother-to-infant transmission. By the year 2000, HIV is projected to infect 40 million men, women, and children unless effective prevention strategies are developed. Perinatal HIV transmission rates currently vary from 14-40% with the lowest rates being seen in Europe and highest rates in Africa. Known risk factors for perinatal transmission include advanced maternal HIV disease, lower CD4+ counts, and increased viral burden during pregnancy. Observational cohort data suggest that prenatal vitamin A levels, maternal drug use, and duration of membrane rupture during labor also are related to risk of transmission. The United States clinical trial utilizing an antiretroviral (zidovudine [AZT]) prenatally, intrapartum, and for 6 weeks to the infant demonstrated that perinatal HIV transmission was reduced by two-thirds. This dramatic result gives strong encouragement that simpler perinatal prevention strategies applicable to developing countries may also be successful. A number of international studies are underway or planned including perinatal vitamin A and micronutrient trials in Africa."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I620,I620)","v":8943783},{"$f":"(LEN($J620) - LEN(SUBSTITUTE(LOWER($J620),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J620) - LEN(SUBSTITUTE(LOWER($J620),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J620) - LEN(SUBSTITUTE(LOWER($J620),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B620:D620)","v":1},1996,"Expression and regulation of 17 beta-hydroxysteroid dehydrogenase type 1.","Peltoketo",8943783,"Expression and regulation of 17 beta-hydroxysteroid dehydrogenase type 1.    Abstract:   The current data indicate that during a womans reproductive years, 17 beta-hydroxysteroid dehydrogenase type 1 is the major 17 beta-hydroxysteroid dehydrogenase (17HSD) involved in glandular oestradiol biosynthesis. The type 1 enzyme catalyses reduction from low-activity oestrone to high-activity oestradiol in ovarian granulosa cells and placental syncytiotrophoblasts, in which it is abundantly expressed. In addition to steroidogenic cells, 17HSD type 1 is present in certain peripheral tissues in which it reduces circulating oestrone, thus regulating the intracellular ligand supply for oestrogen receptors. Several factors and second messenger pathways are involved in the cell-specific expression of 17HSD type 1. In ovarian granulosa cells, 17HSD type 1 expression is strictly regulated by pituitary gonadotrophins, steroid hormones and growth factors, while in peripheral tissues progestins and retinoic acids, at least, affect 17HSD type 1 concentrations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I621,I621)","v":9118615},{"$f":"(LEN($J621) - LEN(SUBSTITUTE(LOWER($J621),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J621) - LEN(SUBSTITUTE(LOWER($J621),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J621) - LEN(SUBSTITUTE(LOWER($J621),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B621:D621)","v":1},1996,"[Clinical use of interferon].","Lauta",9118615,"[Clinical use of interferon].    Abstract:   It has been thought that there is a particular balance between interferon and humoral immunity in the specific antiviral activity exerted by these systems. A possible relationship has been observed between some interferon-related proteins and the interferon serum level and a predictive significance can be assigned to MxA protein regarding the progression of some haematological malignancies. Both natural and recombinant interferon have been shown to be effective in the treatment of T-cell cutaneous lymphoma and the myeloma cell expression of Bcl-2 oncoprotein correlates to the response to interferon therapy in multiple myeloma patients. It has been thought that the combined therapy including interferon and cis-retinoic acid might be effective in the therapy of metastatic melanoma and breast cancer, whereas the combination of interferon with other chemotherapeutic agents appears to be effective in the treatment of hepatocellular cancer. It has been confirmed that interferon-alpha is useful in the therapy of chronic hepatitis C and a better knowledge regarding the mechanism of action of beta interferon in the therapy of multiple sclerosis has been acquired. Finally, a remarkable report regards the effectiveness of interferon in the therapy of idiopatic dilated cardiomiopathy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I622,I622)","v":8801165},{"$f":"(LEN($J622) - LEN(SUBSTITUTE(LOWER($J622),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J622) - LEN(SUBSTITUTE(LOWER($J622),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J622) - LEN(SUBSTITUTE(LOWER($J622),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B622:D622)","v":1},1996,"The contribution of vitamin A to public health.","Underwood",8801165,"The contribution of vitamin A to public health.    Abstract:   Vitamin A deficiency among children in developing countries remains the leading cause of preventable severe visual impairment and blindness, and is a significant contributor to severe infections and death, particularly from diarrhea and measles. Vitamin A deficiency is also likely to increase vulnerability to other illnesses in both women and children, such as iron-deficiency anemia, and may be an important factor contributing to poor maternal performance during pregnancy and lactation and to growth deficits in children. Benefits to public health can be expected by improving the vitamin A status of deficient populations through an appropriate mix of acceptable, affordable, and available programs including promotion of breast-feeding, control of infections, dietary diversification, food fortification, and supplementation. Benefits include not only improved health and welfare for individuals and their families, but also improved chances of survival for an estimated 254 million children."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I623,I623)","v":8784884},{"$f":"(LEN($J623) - LEN(SUBSTITUTE(LOWER($J623),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J623) - LEN(SUBSTITUTE(LOWER($J623),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J623) - LEN(SUBSTITUTE(LOWER($J623),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B623:D623)","v":1},1996,"Vaginal intraepithelial neoplasia and vaginal cancer.","Wharton",8784884,"Vaginal intraepithelial neoplasia and vaginal cancer.    Abstract:   Vaginal cancer is infrequent, but the morbidity associated with treatment is high. Delays in diagnosis account for presentations in advanced stages. Screening is probably not warranted given the low incidence, but inspection of the vagina should be performed at the time of Pap smear screening. No molecular markers are currently promising. Chemoprevention with retinoids may be feasible."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I624,I624)","v":8643218},{"$f":"(LEN($J624) - LEN(SUBSTITUTE(LOWER($J624),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J624) - LEN(SUBSTITUTE(LOWER($J624),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J624) - LEN(SUBSTITUTE(LOWER($J624),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B624:D624)","v":1},1996,"Breast cancer chemoprevention: clinical trials and research.","Noguchi",8643218,"Breast cancer chemoprevention: clinical trials and research.    Abstract:   We have reviewed the literature regarding the chemoprevention of breast cancer. Several clinical trials using retinoid, tamoxifen, or low-fat dietary intervention for the prevention of breast cancer are ongoing. In the next few years, the implementation of these clinical chemoprevention trials will take place. Moreover, combinations of such chemopreventive agents, as well as the development of new chemopreventive compounds, will require testing in clinical settings. Even though there is probably a substantial delay before such chemopreventive approaches have a significant effect, it is clear that chemoprevention will complement other approaches in controlling breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I625,I625)","v":8935219},{"$f":"(LEN($J625) - LEN(SUBSTITUTE(LOWER($J625),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J625) - LEN(SUBSTITUTE(LOWER($J625),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J625) - LEN(SUBSTITUTE(LOWER($J625),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B625:D625)","v":1},1996,"Plant sources of vitamin A and human nutrition: renewed strategies.","Solomons",8935219,"Plant sources of vitamin A and human nutrition: renewed strategies.    Abstract:   The ability of a supplement of local, cooked green leaves to support vitamin A nutriture of anemic, lactating rural Indonesian women was tested using increments in carotenoid and retinol content in plasma and breast milk as indices of bioavailability and bioconversion, respectively. While beta-carotene provided in a simple matrix of a fortified cracker produced substantial improvements in both vitamin A and carotenoid status, an equivalent amount from stir-fried vegetables had a negligible effect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I626,I626)","v":8677058},{"$f":"(LEN($J626) - LEN(SUBSTITUTE(LOWER($J626),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J626) - LEN(SUBSTITUTE(LOWER($J626),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J626) - LEN(SUBSTITUTE(LOWER($J626),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B626:D626)","v":1},1996,"Surgical treatment of vulvar lichen sclerosus: a review.","Abramov",8677058,"Surgical treatment of vulvar lichen sclerosus: a review.    Abstract:   Surgical therapy of lichen sclerosus of the vulva consists of three main operations: vulvectomy (with or without a skin graft), cryosurgery, and laser ablation. It is indicated in two conditions, either when malignant transformation is present or is likely to occur, or when medical treatment has failed. The overall risk for malignant transformation of vulvar lichen sclerosus is low, ranging between 0 and 9 percent. However, specific histological criteria, such as mixed dystrophy, have recently been associated with higher malignancy rates. Vulvectomy is indicated only when these criteria are met. Both skinning and simple vulvectomies are associated with recurrence rates as high as 50 percent. However, better sexual function and cosmetic results have been reported in the former, especially with concomitant split skin grafting. Cryosurgery also has high recurrence rates, although short-term results are favorable. Although only small series have been reported, laser therapy seems to carry better long-term results than other modes of treatment. Convalescence is complete within 6 weeks posttreatment, and remission rates are as high as 85 percent at 3 years of follow-up. The high recurrence rate of all surgical modalities makes surgical treatment suitable only for patients who failed to respond to multiple medical treatments such as topical high potent steroid ointments, testosterone, and retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I627,I627)","v":9216791},{"$f":"(LEN($J627) - LEN(SUBSTITUTE(LOWER($J627),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J627) - LEN(SUBSTITUTE(LOWER($J627),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J627) - LEN(SUBSTITUTE(LOWER($J627),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B627:D627)","v":1},1996,"Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview.","Santamaria",9216791,"Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview.    Abstract:   In 1980, two carotenoids, beta-carotene (BC) and canthaxanthine (CX) with and without pro-vitamin A activity, respectively, were orally administered to female Swiss albino mice and were found to substantially prevent skin carcinogenesis induced by benzo(a)pyrene (BP). This preventive effect was observed in darkness by means of photocarcinogenic enhancement (PCE) following UV (300 to 400 nm) irradiation. In 1984, the same experiment produced antitumorigenic activity when applied to breast carcinogenesis induced in mice by 8-methoxypsoralen (8-MOP) plus UV-A light and, in 1985, when directed toward gastric carcinogenesis induced in rats by N-methyl-N-nitro-N-nitrosoguanidine (MNNG). These data suggested a rationale for human intervention to prevent, by carotenoid supplementation, a second primary malignancy after the primary malignancy has been radically excised. In the 1980s, a pilot clinical study (15 cases) showed a longer than expected disease-free interval in all surviving patients. It was also subsequently found that, if treated daily with 20 mg of BC and intermittently with retinol 150 to 300,000 IU daily for seven days just prior to menses, women suffering from cyclical mastalgia were relieved from pain, without any toxic side effects. When BC was given in high daily doses (60 mg) to 60 drug addicts suffering from AIDS-related complex (ARC), they recovered from their objective and subjective symptoms (but not from lymphadenopathy) with improvement in their general health and increased performance status. At higher doses, BC (with or without hyperthermia) was effective even in patients in advanced stages of AIDS. A debate has arisen concerning a recent statement by the U.S. Government that quot;beta-carotene supplements do not protect Americans against cancer or heart disease, and may actually increase the risk of deadly lung tumors in smokersquot;."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I628,I628)","v":9027595},{"$f":"(LEN($J628) - LEN(SUBSTITUTE(LOWER($J628),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J628) - LEN(SUBSTITUTE(LOWER($J628),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J628) - LEN(SUBSTITUTE(LOWER($J628),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B628:D628)","v":1},1996,"Cancer risk factors for selecting cohorts for large-scale chemoprevention trials.","Greenwald",9027595,"Cancer risk factors for selecting cohorts for large-scale chemoprevention trials.    Abstract:   Many anticipate that application of findings in molecular genetics will help to achieve greater precision in defining high-risk populations that may benefit from chemopreventive interventions. We must recognize, however, that genetic susceptibility, environmental factors, and complex gene-environment interactions are all likely to be risk determinants for most cancers. Cohort studies of twins and cancer indicate that having quot;identicalquot; genes is generally not a very accurate predictor of cancer incidence. Data from twin studies support the suggestion that environmental factors such as tobacco use significantly influence cancer risk. The complexities of the genetic contribution to disease risk are exemplified by the development of Duchenne muscular dystrophy in only one of monozygotic twin girls, hypothesized to be the result of X chromosome inactivation, with the distribution patterns of the X chromosome being skewed to the female X in the manifesting twin and to the male X in the normal twin. Evidence from transgenic and genetic-environmental studies in animals support the possibility of genetic-environmental interactions. Calorie restriction modifies tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D diet increases prepolyp hyperplasia formation in Apc-mutated mice; and calorie restriction early in life influences development of obesity in the genetically obese Zucker rat (fafa). Such environmental modulation of gene expression suggests that chemoprevention has the potential to reduce risk for both environmentally and genetically determined cancers. In view of the growing research efforts in chemoprevention, the NCI has developed a Prevention Trials Decision Network (PTDN) to formalize the evaluation and approval process for large-scale chemoprevention trials. The PTDN addresses large trial prioritization and the associated issues of minority recruitment and retention; identification and validation of biomarkers as intermediate endpoints for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDNs decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scale testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I629,I629)","v":8791119},{"$f":"(LEN($J629) - LEN(SUBSTITUTE(LOWER($J629),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J629) - LEN(SUBSTITUTE(LOWER($J629),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J629) - LEN(SUBSTITUTE(LOWER($J629),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B629:D629)","v":1},1996,"Chemoprevention of breast cancer with fenretinide.","Veronesi",8791119,"Chemoprevention of breast cancer with fenretinide.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I630,I630)","v":8734332},{"$f":"(LEN($J630) - LEN(SUBSTITUTE(LOWER($J630),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J630) - LEN(SUBSTITUTE(LOWER($J630),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J630) - LEN(SUBSTITUTE(LOWER($J630),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B630:D630)","v":1},1996,"[Current therapeutic methods in onco-hematology].","Madelaine-Chambrin",8734332,"[Current therapeutic methods in onco-hematology].    Abstract:   These next years, many anticancer drugs will be available with new mechanism of action. The taxoïd compounds: Taxol and Taxotere have been judged efficous in the treatment of advanced ovary and breast cancers. Also, DNA-Topoisomerase I inhibitors, a new enzyme molecular target, will expand solid tumors therapeutic strategies. The adenosine analogs represent the xnewest advances in hematology: fludarabine becomes the second line treatment for chronic lymphoïd leukemia, cladribine the reference treatment for hairy cell leukemia. At least, all-trans retinoïc acid has changed acute promyelocytic leukemia pronostic by differentiating tumor cells, and open a very new way of cancer treatment. All these agents are the first compounds available, others are still in development. They, all, are benefit of a productive research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I631,I631)","v":8623511},{"$f":"(LEN($J631) - LEN(SUBSTITUTE(LOWER($J631),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J631) - LEN(SUBSTITUTE(LOWER($J631),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J631) - LEN(SUBSTITUTE(LOWER($J631),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B631:D631)","v":1},1996,"Biochemical characteristics and recent biological knowledge on prostate-specific antigen.","Seregni",8623511,"Biochemical characteristics and recent biological knowledge on prostate-specific antigen.    Abstract:   Since its identification in seminal fluid in 1971, much new information has been obtained about the biology and expression of prostate-specific antigen (PSA). PSA is a glycoprotein composed of 93% amino acids and 7% carbohydrates, with a molecular weight of about 30,000 Da. Functionally and structurally PSA is a kallikrein-like serine protease, and its physiologic role is degradation of the major proteins of seminal coagulum (semenogelin I and II, fibronectin), which leads to semen liquefaction. The PSA gene is located on the 13q region of chromosome 19, and it has a high degree of homology (more than 80%) with genes of the human glandular kallikrein (hKGK1). PSA production and expression are preferentially but not exclusively associated to the normal, benign hyperplastic and cancerous tissues of the prostate. In fact, it has been demonstrated that PSA is also present in accessory male sex glands and breast cancer. It was recently reported that PSA was also present in milk of lactating women. Many factors may influence PSA synthesis and production, and among them the most important are androgen, retinoic acid and growth factor stimulation. Significant advances have been recently made as regards the molecular isoforms of PSA. In the seminal fluid PSA seems partially bound to a serpine (protein C inhibitor), whereas in serum it is predominantly associated to alpha-1-antichymotrypsin and in a small quantity to alpha-2-macroglobulin. These new findings will have implications for the clinical application of PSA as a tumor marker for prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I632,I632)","v":12290880},{"$f":"(LEN($J632) - LEN(SUBSTITUTE(LOWER($J632),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J632) - LEN(SUBSTITUTE(LOWER($J632),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J632) - LEN(SUBSTITUTE(LOWER($J632),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B632:D632)","v":1},1995,"Breast milk transmission of HIV-1.","Nduati",12290880,"Breast milk transmission of HIV-1.    Abstract:   Breast milk provides infants and children immunologic, nutritional, and child spacing benefits. Yet it also transmits some viruses, for example, HIV-1. The World Health Organization recommends that, in conditions with poor access to breast milk substitutes, HIV-positive women should still breast feed due to the nutritional and infectious risk of artificial feeding. It appears that breast fed infants experience a slower progression of AIDS and death. Vertical transmission of HIV-1 may occur during pregnancy, at delivery, or through breast milk. The HIV-1 transmission rate via breast milk from acutely infected women is estimated to be 29-36%. A meta-analysis of case reports and small case series of women with chronic HIV-1 infection indicated a breast feeding transmission rate of 14%. Studies suggest that the likelihood of HIV-1 transmission via breast milk increases as duration of breast feeding increases. Infants with detectable HIV-1 DNA tend to have mothers whose absolute CD4 counts are less than 400 and have severe vitamin A deficiency. Breast milk has HIV-1 specific immunoglobulins (IgG, IgA, and IgM). It appears that HIV-1 elicits a local immune response. Breast milk of HIV-1 positive mothers with non-infected children tends to still have IgM and IgA until 18 months. Potential risk factors for breast milk transmission of HIV-1 include cracked nipples and mastitis in the mother; oral thrush, malnutrition, inflammation of the lips, and mucosal compromise in the infant; and vigorous suction of the neonate and use of the wrong equipment for suctioning. Inhibiting factors of HIV-1 in breast milk are bovine and human lactoferrin and a membrane associated protein that attaches to the CD4 receptor and thus prevents attachment of the HIV antigen gp120 to the CD4 receptor on T-cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I633,I633)","v":7495240},{"$f":"(LEN($J633) - LEN(SUBSTITUTE(LOWER($J633),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J633) - LEN(SUBSTITUTE(LOWER($J633),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J633) - LEN(SUBSTITUTE(LOWER($J633),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B633:D633)","v":1},1995,"Prevention of cervical intraepithelial neoplasia and cervical cancer.","Meyskens",7495240,"Prevention of cervical intraepithelial neoplasia and cervical cancer.    Abstract:   We review the current status of prevention trials in the management of cervical intraepithelial neoplasia (CIN) and cervical cancer. Two large, randomized controlled trials have shown that folic acid is inactive in reversing low to moderate grade CIN. A large randomized trial of locally applied beta-trans retinoic acid showed that the agent was effective in reversing moderate but not severe CIN. Results from a pilot trial involving 30 patients with CIN I (mild dysplasia) and CIN II (moderate dysplasia) indicate that beta-carotene can suppress CIN; a large ongoing randomized trial will answer the question more definitively."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I634,I634)","v":8547408},{"$f":"(LEN($J634) - LEN(SUBSTITUTE(LOWER($J634),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J634) - LEN(SUBSTITUTE(LOWER($J634),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J634) - LEN(SUBSTITUTE(LOWER($J634),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B634:D634)","v":1},1995,"Recent advances in hormonal therapy for cancer.","Traynor",8547408,"Recent advances in hormonal therapy for cancer.    Abstract:   Hormonal manipulation of cancer is no longer confined to the use of effective antiestrogen therapy for breast cancer or surgical or hormonal castration for prostate cancer. A broader acknowledgment of the potential of different hormonal ligands to evoke cell cycle arrest to prevent the progress of neoplastic transformation, and even to elicit active cell death, has expanded the concept of hormonal therapy. The use of retinoids and deltanoids in conjunction with antiestrogens and antiandrogens is progressing into clinical trials. The use of glucocorticoids in conjunction with cyclic AMP may enhance apotosis induction. The use of antiandrogens in conjunction with cytotoxic therapy may diminish the risk of bcl-2-mediated resistance in prostate cancer. Innovative use of sequential and synergistic hormonal manipulations based on an expanding understanding of transcriptional regulation promises to advance this science."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I635,I635)","v":7791922},{"$f":"(LEN($J635) - LEN(SUBSTITUTE(LOWER($J635),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J635) - LEN(SUBSTITUTE(LOWER($J635),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J635) - LEN(SUBSTITUTE(LOWER($J635),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B635:D635)","v":1},1995,"[Local treatment of dermatoses in pregnancy].","Arnold",7791922,"[Local treatment of dermatoses in pregnancy].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I636,I636)","v":7627281},{"$f":"(LEN($J636) - LEN(SUBSTITUTE(LOWER($J636),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J636) - LEN(SUBSTITUTE(LOWER($J636),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J636) - LEN(SUBSTITUTE(LOWER($J636),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B636:D636)","v":1},1995,"[Prevention of breast cancer: what are the other possibilities under study besides tamoxifen chemoprevention?].","Espie",7627281,"[Prevention of breast cancer: what are the other possibilities under study besides tamoxifen chemoprevention?].    Abstract:   Tamoxifen and retinoids are actually studied for breast cancer chemoprevention. The role of fat intake, vitamins, selenium, alcohol consumption and progestins are reviewed in view of prevention trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I637,I637)","v":8817695},{"$f":"(LEN($J637) - LEN(SUBSTITUTE(LOWER($J637),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J637) - LEN(SUBSTITUTE(LOWER($J637),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J637) - LEN(SUBSTITUTE(LOWER($J637),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B637:D637)","v":1},1995,"Antiproliferative actions of insulin-like growth factor binding protein (IGFBP)-3 in human breast cancer cells.","Oh",8817695,"Antiproliferative actions of insulin-like growth factor binding protein (IGFBP)-3 in human breast cancer cells.    Abstract:   A number of lines of evidence suggest that IGFs are important mitogens in human breast cancer: (1) IGFs are the most potent growth factor in human breast cancer cells; (2) estrogen stimulates expression of IGF-II and the type 1 IGF receptor; and (3) stromal cells express IGFs, which may act in a paracrine manner. Numerous studies have demonstrated that IGFBPs modulate the mitogenic effects of IGFs in the local environment. In particular, we have recently demonstrated that IGFBP-3 inhibits the growth of Hs578T and MDA-MB-231 human breast cancer cells in an IGF-independent manner. Further studies revealed the existence of cell surface-associated IGFBP-3 receptors. Receptor binding and the subsequent antiproliferative action of IGFBP-3 was inhibited by IGFs, owing to the formation of an IGF-IGFBP-3 complex that prevents the binding of IGFBP-3 to its receptors. In addition, exogeneously added soluble heparin or heparan sulfate inhibited the binding of IGFBP-3 to the cell surface in a dose-dependent manner. However, when heparin and heparan sulfate linkages of glycosaminoglycans on the cell surface were enzymatically remove, IGFBP-3 binding was only minimally affected. These data suggest that soluble heparin or heparan sulfate forms a complex with IGFBP-3, thereby inhibiting receptor binding of IGFBP-3, rather than competing with cell-surface glycosaminoglycans for binding of IGFBP-3. Additionally, the role of IGFBP-3 in the antiproliferative effects of transforming growth factor (TGF)-beta and retinoic acid (RA) is supported by our observations that: (1) inhibition of IGFBP-3 gene expression using an IGFNBP-3 antisense oligodeoxynucleotide not only blocks TGF-beta and RA simulation of IGFBP-3 production by up to 90%m but also inhibits their antiproliferative effects by 40-60%; and (2) treatment with IGF-II and IGF-II analogs diminish TGF-beta effects by blocking TGF-beta induced binding of IGFBP-3 to the cell surface. Taken together, our results support the hypothesis that IGFBP-3 is an important antiproliferative factor in human breast cancer, acting in an IGF-independent manner in addition to its ability to modulate the binding of IGF peptides to IGF receptors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I638,I638)","v":8747383},{"$f":"(LEN($J638) - LEN(SUBSTITUTE(LOWER($J638),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J638) - LEN(SUBSTITUTE(LOWER($J638),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J638) - LEN(SUBSTITUTE(LOWER($J638),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B638:D638)","v":1},1995,"Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias and cancer.","Romney",8747383,"Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias and cancer.    Abstract:   The role of nutritional factors in biochemical interactions that are part of an oncogenic process or inhibit free radical proliferation have attracted considerable interest in relation to molecular mechanism(s) and the natural history of human cancer. Epidemiologic and experimental studies have drawn attention to the association between dietary micronutrient deficiencies and the incidence of neoplastic and malignant lesions. In the last two decades, the role(s) of retinoids, carotenoids, tocopherols and water-soluble antioxidant vitamins, and allegations of anti-tumor properties in the daily dietary consumption of fresh fruits and green leafy vegetables, have captured the attention of an increasingly sensitive diet- and health care-conscious public, the biochemical community, and industrial food producers. Moreover, recent epidemiologic and compelling advances in molecular biology have linked the presence of restricted human papillomavirus (HPV) subtypes to cervical carcinoma and precursor lesions. In the present report, we identify and review measurable effects of dietary deficiencies of selected antioxidant micronutrients (i.e., beta-carotene and vitamins A, C, and E) and their association with known cervix cancer risk factors in the pathogenesis and potential prevention of cervix dysplasias, presumed to be the precursor lesions of cervix cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I639,I639)","v":8538187},{"$f":"(LEN($J639) - LEN(SUBSTITUTE(LOWER($J639),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J639) - LEN(SUBSTITUTE(LOWER($J639),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J639) - LEN(SUBSTITUTE(LOWER($J639),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B639:D639)","v":1},1995,"Controlled clinical trials with fenretinide in breast cancer, basal cell carcinoma and oral leukoplakia.","Jungi",8538187,"Controlled clinical trials with fenretinide in breast cancer, basal cell carcinoma and oral leukoplakia.    Abstract:   We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here. The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I640,I640)","v":7652224},{"$f":"(LEN($J640) - LEN(SUBSTITUTE(LOWER($J640),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J640) - LEN(SUBSTITUTE(LOWER($J640),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J640) - LEN(SUBSTITUTE(LOWER($J640),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B640:D640)","v":1},1995,"[Chemotherapy and systemic treatments of cervical cancer].","Zylberait",7652224,"[Chemotherapy and systemic treatments of cervical cancer].    Abstract:   The prognosis of cervical cancer depends on nodal status and tumoral volume. Among patients with risk factors, chemotherapy seems promising, particularly with concomitant chemoradiation or neo adjuvant chemotherapy before surgery. The advent of treatments with combination of alpha interferon and 13 cis retinoid acid probably leads to a new therapeutic generation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I641,I641)","v":7731635},{"$f":"(LEN($J641) - LEN(SUBSTITUTE(LOWER($J641),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J641) - LEN(SUBSTITUTE(LOWER($J641),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J641) - LEN(SUBSTITUTE(LOWER($J641),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B641:D641)","v":1},1994,"Risk factors.","Marchant",7731635,"Risk factors.    Abstract:   Risk factors for breast cancer whose modification would be culturally acceptable have not been established. Nearly all women in the United States are at a substantial risk for the development of breast cancer. The majority of women, however, in whom breast cancer will be diagnosed will live out their lives without recurrence of the disease. Newer strategies include prevention and the development of effective chemopreventive programs. Phase III clinical trials are underway to assess the value of retinoids and tamoxifen. Phase I and II studies are underway to assess the potential of more specific treatments to inhibit growth factors important in maintaining the malignant phenotype. Obviously, more studies are needed to address this major public health problem."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I642,I642)","v":7827159},{"$f":"(LEN($J642) - LEN(SUBSTITUTE(LOWER($J642),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J642) - LEN(SUBSTITUTE(LOWER($J642),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J642) - LEN(SUBSTITUTE(LOWER($J642),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B642:D642)","v":1},1994,"Advances in the chemotherapy of gynecologic cancer.","Neijt",7827159,"Advances in the chemotherapy of gynecologic cancer.    Abstract:   By combining paclitaxel and cisplatin in treatment schedules for the initial treatment of advanced ovarian cancer, new hope has been engendered that we can further improve survival. With premedication, paclitaxel can be administered safely as a short infusion. The combination of paclitaxel and carboplatin is recognized as an alternative to the combination of cisplatin and paclitaxel, and is now under study to define its role in future treatment programs. Other new drugs have been recognized as active in platinum-resistant disease, including docetaxel and gemcitabine. Renewed interest arose for a chronic low dose of oral etoposide in platinum-refractory ovarian cancer. The results obtained with chemotherapy in cervical cancer have always been modest, and no combinations have been shown to result in improved survival rates as compared with single drugs. The novel biologic regimen, using retinoids and interferon, was confirmed to be active in locally advanced cervical cancer. In trophoblastic disease, the Charing Cross scoring system is a relevant pretreatment scoring system compared with the International Federation of Gynecology of Obstetrics staging. Careful recognition of prognostic subgroups can prevent under- or overtreatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I643,I643)","v":8064405},{"$f":"(LEN($J643) - LEN(SUBSTITUTE(LOWER($J643),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J643) - LEN(SUBSTITUTE(LOWER($J643),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J643) - LEN(SUBSTITUTE(LOWER($J643),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B643:D643)","v":1},1994,"Hypovitaminosis A: international programmatic issues.","Underwood",8064405,"Hypovitaminosis A: international programmatic issues.    Abstract:   The virtual elimination of vitamin A deficiency and all its consequences is high on the political agenda as a solvable public health problem by the end of the decade. Five to six times more children in the developing world are likely to be subclinically than clinically deficient. Subclinical deficiency can be detected by newer methodological approaches. Subclinically deficient children are at increased risk of severe and fatal infections. The problem at a population level is avoidable by the appropriate selection and application of a mix of available interventions. Countries are challenged to assess, analyze and take actions to incorporate nutrition concerns into development planning to attain end-of-decade goals. This article is based on a presentation given at a nutritional symposium at the Experimental Biology 93 Conference. The author describes the worldwide problem of vitamin A deficiency. Children of developing countries are particularly affected and may develop keratomalacia. Keratomalacia remains the major cause of preventable childhood blindness in developing countries. In 1987 WHO identified 37 developing countries that exhibited an increased risk for eye disease because of a deficiency of vitamin A. Vitamin A deficient populations may be identified by classic xerophthalmia (clinical symptoms) or by using 1-2 biological measurements. No single biological measurement of a subclinical deficiency was considered best. Subclinical indicators might include: plasma and/or breast milk retinol levels, dose-response testing, and functional tests measuring night blindness and eye conjunctival impression cytology. Treatment is immediate and given in 3 doses of vitamin A at concentrations related to the childs age. Children 1 year old and older are given 200,000 international units (IU), infants aged 6-12 months are given 100,000 IU, and for those aged under 6 months 50,000 IU are recommended. Intervention efforts should be customized to fit the country. WHO recommends that any strategy include the following: public awareness, infectious disease control, improved agricultural and horticultural programs, nutritional and health education programs, breast feeding promotion, vitamin A supplemental programs, and world health leaders conferences."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I644,I644)","v":7913662},{"$f":"(LEN($J644) - LEN(SUBSTITUTE(LOWER($J644),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J644) - LEN(SUBSTITUTE(LOWER($J644),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J644) - LEN(SUBSTITUTE(LOWER($J644),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B644:D644)","v":1},1994,"New chemotherapeutic agents for breast cancer.","Abrams",7913662,"New chemotherapeutic agents for breast cancer.    Abstract:   The drug discovery programs of the National Cancer Institute and the pharmaceutical industry recently have provided oncologists with a wide array of new chemotherapeutic agents that have considerable potential for breast cancer treatment. Foremost among these new agents are the taxanes, of which paclitaxel and docetaxel, the only members of this class currently in clinical use, have been associated with impressive response rates in patients with metastatic disease. Importantly, they display some evidence clinically of not being cross-resistant with the anthracyclines. Efforts now are being directed toward optimizing dose and schedule in the metastatic setting while integrating these agents into standard adjuvant regimens. Other agents that have undergone Phase II testing in breast cancer include vinorelbine, edatrexate, and losoxantrone. It remains to be determined, however, whether these drugs possess substantial advantages over other members of their class. Newer compounds, such as pyrazoloacridine, ICI D1694, topoisomerase-I inhibitors, temozolomide, penclomidine, fumagillin (TNP-470), and differentiators like the retinoids, hold substantial promise because of their unique mechanisms of action; however, Phase II testing of these agents is just beginning. Although alternative approaches to treatment, such as gene therapies, monoclonal antibodies, and growth factor inhibitors, are likely to have a positive impact, it is probable that progress will best be made by combining these strategies with chemotherapy. Therefore, continuation of the search for more effective chemotherapeutic agents should remain a high priority."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I645,I645)","v":8005001},{"$f":"(LEN($J645) - LEN(SUBSTITUTE(LOWER($J645),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J645) - LEN(SUBSTITUTE(LOWER($J645),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J645) - LEN(SUBSTITUTE(LOWER($J645),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B645:D645)","v":1},1994,"Chemoprevention of cancer.","Szarka",8005001,"Chemoprevention of cancer.    Abstract:   Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I646,I646)","v":7569034},{"$f":"(LEN($J646) - LEN(SUBSTITUTE(LOWER($J646),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J646) - LEN(SUBSTITUTE(LOWER($J646),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J646) - LEN(SUBSTITUTE(LOWER($J646),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B646:D646)","v":1},1994,"Development and validation of swine embryonic stem cells: a review.","Wheeler",7569034,"Development and validation of swine embryonic stem cells: a review.    Abstract:   The establishment of embryonic cell lines from swine should be useful for studies of cell differentiation, developmental gene regulation and the production of transgenics. This paper summarizes the establishment of porcine (Sus scrofa) embryonic stem (ES) cell lines from preimplantation blastocysts and their ability to develop into normal chimaeras. ES cells can spontaneously differentiate into cystic embryoid bodies with ectodermal, endodermal, and mesodermal cell types. Further, culture of ES cells to confluence or induction of differentiation with retinoic acid or dimethylsulfoxide results in morphological differentiation into fibroblasts, adipocytes, and epithelial, neuronal, and muscle cells. These ES cells have a normal diploid complement of 38 chromosomes. Scanning electron microscopy of the ES cells reveals a rounded or polygonal, epithelial-like cell with numerous microvilli. The differentiation of these embryonic cell lines into several cell types indicates a pluripotent cell. Furthermore, chimaeric swine have been successfully produced using such ES cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I647,I647)","v":8242570},{"$f":"(LEN($J647) - LEN(SUBSTITUTE(LOWER($J647),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J647) - LEN(SUBSTITUTE(LOWER($J647),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J647) - LEN(SUBSTITUTE(LOWER($J647),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B647:D647)","v":1},1993,"Cancer chemoprevention.","Itri",8242570,"Cancer chemoprevention.    Abstract:   Encouraging results from several recent trials have increased interest in the potential of chemoprevention in reducing the incidence of cancer. Treatment with 13-cis-retinoic acid has reversed oral leukoplakia, a premalignant lesion, and prevented the development of second primary carcinomas of the head and neck. Tamoxifen has proven effective in preventing both the recurrence of breast cancer and the development of new tumors in the contralateral breast, and is being tested in high-risk patients who have not yet developed disease. The results of the Physicians Health Study, which demonstrated the effectiveness of aspirin in reducing heart attacks, already have been incorporated into health care practice, while the component investigating the effect of beta carotene on the incidence of cancer still is underway. These studies demonstrate the importance of careful design if chemoprevention trials are to yield convincing data."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I648,I648)","v":8193278},{"$f":"(LEN($J648) - LEN(SUBSTITUTE(LOWER($J648),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J648) - LEN(SUBSTITUTE(LOWER($J648),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J648) - LEN(SUBSTITUTE(LOWER($J648),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B648:D648)","v":1},1993,"Chemoprevention of breast cancer.","De Palo",8193278,"Chemoprevention of breast cancer.    Abstract:   Chemoprevention of cancer is a new branch of the medical science and represents a topic of increasing concern in public health. Over the last decade chemoprevention has been extensively studied from many points of view, and topics in the field of chemoprevention have expanded considerably. Breast cancer, the most common malignant neoplasm in women, is one of the areas of clinical interest for chemoprevention. In this paper the authors synthesized the quot;status of artquot; in chemoprevention of breast cancer with retinoids and antiestrogens."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I649,I649)","v":8105975},{"$f":"(LEN($J649) - LEN(SUBSTITUTE(LOWER($J649),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J649) - LEN(SUBSTITUTE(LOWER($J649),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J649) - LEN(SUBSTITUTE(LOWER($J649),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B649:D649)","v":1},1993,"Systemic therapy for gynecologic cancer.","Kavanagh",8105975,"Systemic therapy for gynecologic cancer.    Abstract:   Several provocative studies in gynecologic cancer were recently presented. Long-term follow-up of ovarian cancer patients has confirmed the clinical impression of a low survival. Novel classes of active chemotherapeutics are the second-generation topoisomerase I inhibitors, irinotecan (CPT-11) and topotecan, and the taxanes, Taxol (Bristol-Meyers, Wallingford, CT) and Taxotere (Rhone-Poulenc Rorer, Antony, France). Dose intensity remains an intriguing issue. Biologic agents, including monoclonal antibodies, are being developed for palliation of ascites. In cervical cancer, use of retinoids and interferons has opened up a new avenue of investigation. Use of the World Health Organization sophisticated scoring criteria has improved the primary treatment of trophoblastic disease. Advances in salvage therapy have been noted. Progress in the treatment of advanced endometrial cancer and uterine sarcomas is beginning."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I650,I650)","v":8409102},{"$f":"(LEN($J650) - LEN(SUBSTITUTE(LOWER($J650),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J650) - LEN(SUBSTITUTE(LOWER($J650),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J650) - LEN(SUBSTITUTE(LOWER($J650),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B650:D650)","v":1},1993,"Antioxidant micronutrients and breast cancer.","Garland",8409102,"Antioxidant micronutrients and breast cancer.    Abstract:   We reviewed epidemiologic evidence on the relationship between four antioxidant micronutrients (vitamin A, vitamin C, vitamin E, and selenium) and breast cancer risk. Available data support a modest protective effect of vitamin A, although more studies are needed to examine further this association and to assess the relative contributions of preformed vitamin A (retinol) and carotenoids. In addition, the possibility that some other component of vitamin A-rich foods may account for this observed association should be explored. Data on the relationship between vitamins C and E and breast cancer risk are limited and inconsistent, and further information is necessary. A substantial body of evidence indicates a lack of any appreciable effect of selenium intake on breast cancer risk, at least within the range of human diets. Future observational studies should ideally be prospective in design, as prospective studies are less prone to selection and recall bias than are case-control studies, and should address methodologic issues such as confounding by other micronutrients and appropriate storage conditions of blood specimens. Although hypotheses relating micronutrient intake to risk of breast cancer should be tested in randomized trials, ethical and logistical constraints make these studies difficult to perform."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I651,I651)","v":8334674},{"$f":"(LEN($J651) - LEN(SUBSTITUTE(LOWER($J651),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J651) - LEN(SUBSTITUTE(LOWER($J651),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J651) - LEN(SUBSTITUTE(LOWER($J651),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B651:D651)","v":1},1993,"Chemoprevention. Strategies for the control of cancer.","Lippman",8334674,"Chemoprevention. Strategies for the control of cancer.    Abstract:   High incidence and low survival rates of many epithelial cancers remain beyond the control of established preventive and therapeutic modalities. Chemoprevention is a new approach under study that involves the intervention within the premalignant process with specific chemical agents to reverse carcinogenesis and prevent the development of invasive cancer. The two biologic concepts that underlie this research are multistep carcinogenesis and field carcinogenesis. Major clinical issues include trial design and drug development in head and neck, lung, and breast cancer chemoprevention. Within the area of trial design, intermediate end point biomarkers will become very important for providing biologic insights in the short term and greater trial efficiencies in the long term. Drugs that are under the strongest investigation include retinoids and beta-carotene in the head and neck and lung, calcium in the colon, and tamoxifen in the breast. This new field has the potential to make an important contribution toward increasing our control over many deadly epithelial cancers Cancer 1993; 72:984-90."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I652,I652)","v":8499668},{"$f":"(LEN($J652) - LEN(SUBSTITUTE(LOWER($J652),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J652) - LEN(SUBSTITUTE(LOWER($J652),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J652) - LEN(SUBSTITUTE(LOWER($J652),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B652:D652)","v":1},1993,"Neurobehavioral teratology of isotretinoin.","Adams",8499668,"Neurobehavioral teratology of isotretinoin.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I653,I653)","v":8466478},{"$f":"(LEN($J653) - LEN(SUBSTITUTE(LOWER($J653),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J653) - LEN(SUBSTITUTE(LOWER($J653),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J653) - LEN(SUBSTITUTE(LOWER($J653),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B653:D653)","v":1},1993,"The pharmacological manipulation of members of the transforming growth factor beta family in the chemoprevention of breast cancer.","Dickens",8466478,"The pharmacological manipulation of members of the transforming growth factor beta family in the chemoprevention of breast cancer.    Abstract:   The transforming growth factors beta are a family of peptides which are involved in the regulation of cell growth and differentiation. It has been suggested that the loss of sensitivity to growth inhibition by endogenous TGF-beta may contribute to the process of carcinogenesis in epithelial systems. However, many breast cancer cells remain sensitive to the growth inhibitory effects of these peptides, suggesting that the local induction of TGF-beta could provide a pharmacological approach to chemoprevention. Triphenylethylene anti-oestrogens, synthetic progestins and retinoids all offer potential as chemopreventative agents. A common feature of their mechanism of action is the ability to locally increase the production of the transforming growth factors beta."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I654,I654)","v":1445597},{"$f":"(LEN($J654) - LEN(SUBSTITUTE(LOWER($J654),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J654) - LEN(SUBSTITUTE(LOWER($J654),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J654) - LEN(SUBSTITUTE(LOWER($J654),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B654:D654)","v":1},1992,"Clinical breast cancer, new developments in selection and endocrine treatment of patients.","Klijn",1445597,"Clinical breast cancer, new developments in selection and endocrine treatment of patients.    Abstract:   Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I655,I655)","v":1352038},{"$f":"(LEN($J655) - LEN(SUBSTITUTE(LOWER($J655),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J655) - LEN(SUBSTITUTE(LOWER($J655),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J655) - LEN(SUBSTITUTE(LOWER($J655),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B655:D655)","v":1},1992,"[Developmental disorders of man. Part 2].","Opitz",1352038,"[Developmental disorders of man. Part 2].    Abstract:   At the beginning of this century genetics arose out of developmental history (Entwicklungsgeschichte) as the science of the causal understanding of development. After Spemanns epochal discovery (justifiably rewarded with the Nobel Prize in 1935) of the organizer and the beginning of the experimental analysis of developmental fields, little or no progress was made until the last few years when a virtual revolution occurred in developmental biology. If nothing else, this revolution has re-inspired in medicine an enormous respect for developmental animal models which are homologous to the human condition in the strict sense of the term, both in formal (formalgenetischer) and causal (kausalgenetischer) respects. Thus, the earliest stages of development in the primary field (during gastrulation) and in the later mosaic of secondary, epimorphic fields, represents the harmonically coordinated and epigenetically regulated effects of many genes which (with of without imprinting) code for cellular adhesion molecules, the peptide regulatory factors, homeobox genes, retinoic acid receptors and many other genes. Some of these genes act as regulators of DNA transcription, and, until recently no clinically identifiable developmental attribute to their function was known in humans. However, just in the last few weeks we have witnessed the identification of a gene on 11p13 in humans which is a paired box- and homeobox-containing gene as the cause of human aniridia, with the identical (homologous) mutation in the mouse Pax-6 gene producing the Sey phenotype (small eye).(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I656,I656)","v":1605903},{"$f":"(LEN($J656) - LEN(SUBSTITUTE(LOWER($J656),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J656) - LEN(SUBSTITUTE(LOWER($J656),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J656) - LEN(SUBSTITUTE(LOWER($J656),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B656:D656)","v":1},1992,"Oral retinoids. What should the prescriber known about their teratogenic hazards among women of child-bearing potential?","Mitchell",1605903,"Oral retinoids. What should the prescriber known about their teratogenic hazards among women of child-bearing potential?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I657,I657)","v":1469896},{"$f":"(LEN($J657) - LEN(SUBSTITUTE(LOWER($J657),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J657) - LEN(SUBSTITUTE(LOWER($J657),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J657) - LEN(SUBSTITUTE(LOWER($J657),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B657:D657)","v":1},1992,"Molecular and endocrine biomarkers in non-involved breast: relevance to cancer chemoprevention.","Telang",1469896,"Molecular and endocrine biomarkers in non-involved breast: relevance to cancer chemoprevention.    Abstract:   The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro- and micronutrients. In the initiation/promotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistent Ras p21-GTP binding, altered C16 alpha/C2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypic chemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotype is suggestive of their potential clinical application in chemopreventive intervention for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I658,I658)","v":1335261},{"$f":"(LEN($J658) - LEN(SUBSTITUTE(LOWER($J658),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J658) - LEN(SUBSTITUTE(LOWER($J658),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J658) - LEN(SUBSTITUTE(LOWER($J658),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B658:D658)","v":1},1992,"Retinoic acid and development.","Morriss-Kay",1335261,"Retinoic acid and development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I659,I659)","v":1297764},{"$f":"(LEN($J659) - LEN(SUBSTITUTE(LOWER($J659),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J659) - LEN(SUBSTITUTE(LOWER($J659),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J659) - LEN(SUBSTITUTE(LOWER($J659),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B659:D659)","v":1},1992,"Carotenoids in cancer chemoprevention and therapeutic interventions.","Santamaria",1297764,"Carotenoids in cancer chemoprevention and therapeutic interventions.    Abstract:   Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I660,I660)","v":1877744},{"$f":"(LEN($J660) - LEN(SUBSTITUTE(LOWER($J660),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J660) - LEN(SUBSTITUTE(LOWER($J660),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J660) - LEN(SUBSTITUTE(LOWER($J660),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B660:D660)","v":1},1991,"Inhibition of retinoic acid synthesis and its implications in fetal alcohol syndrome.","Keir",1877744,"Inhibition of retinoic acid synthesis and its implications in fetal alcohol syndrome.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I661,I661)","v":1912609},{"$f":"(LEN($J661) - LEN(SUBSTITUTE(LOWER($J661),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J661) - LEN(SUBSTITUTE(LOWER($J661),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J661) - LEN(SUBSTITUTE(LOWER($J661),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B661:D661)","v":1},1991,"13th San Antonio Breast Cancer Symposium--Plenary Lecture. Steroid hormone receptors as transactivators of gene expression.","OMalley",1912609,"13th San Antonio Breast Cancer Symposium--Plenary Lecture. Steroid hormone receptors as transactivators of gene expression.    Abstract:   In the two decades since the discovery of the steroid hormone receptors, a great deal has been learned about their structure, their relationships with each other, and the target sequences (response elements) at which they regulate expression of specific genes. Analysis of receptor sequences has confirmed the existence of several domains with distinct functions in each receptor molecule, and has also indicated that the steroid receptors are members of a superfamily which also includes receptors for vitamin D, retinoic acid, thyroid hormone and its related oncogene v-erbA, and a substantial number of receptors whose ligands are still unidentified. The response element sequences are also closely related, and we are beginning to understand the interaction of the receptors with these response elements and with proteins bound nearby such as transcription factors. Certain naturally occurring genetic diseases have been identified with specific receptor mutations. The future promises greater understanding not only of the detailed action of the receptors of this superfamily, but of their precise role in fertility, development, and disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I662,I662)","v":1879897},{"$f":"(LEN($J662) - LEN(SUBSTITUTE(LOWER($J662),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J662) - LEN(SUBSTITUTE(LOWER($J662),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J662) - LEN(SUBSTITUTE(LOWER($J662),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B662:D662)","v":1},1991,"Vitamin A during pregnancy in India: how much is safe for the fetus?","Raman",1879897,"Vitamin A during pregnancy in India: how much is safe for the fetus?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I663,I663)","v":2060847},{"$f":"(LEN($J663) - LEN(SUBSTITUTE(LOWER($J663),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J663) - LEN(SUBSTITUTE(LOWER($J663),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J663) - LEN(SUBSTITUTE(LOWER($J663),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B663:D663)","v":1},1991,"Prevention of cancer by agents that suppress oxygen radical formation.","Troll",2060847,"Prevention of cancer by agents that suppress oxygen radical formation.    Abstract:   The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIs). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIs also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H2O2 formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one, including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I664,I664)","v":1677274},{"$f":"(LEN($J664) - LEN(SUBSTITUTE(LOWER($J664),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J664) - LEN(SUBSTITUTE(LOWER($J664),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J664) - LEN(SUBSTITUTE(LOWER($J664),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B664:D664)","v":1},1991,"Modulation of EGF receptor protooncogene expression by growth factors and hormones in human breast carcinoma cells.","Fernandez-Pol",1677274,"Modulation of EGF receptor protooncogene expression by growth factors and hormones in human breast carcinoma cells.    Abstract:   In this review I summarize the experimental data in favor of the notion that control of epidermal growth factor (EGF) receptor (R) and/or c-erbB-2 protooncogene expression by specific autocrine growth factors and certain classical endocrine hormones serves as a transducer of extracellular signals that ultimately lead to growth responses in breast carcinoma cells. I summarize some new results on the role of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and TGF beta in the control of EGF-R protooncogene expression in human breast carcinoma cells. Furthermore, the data embracing the hypothesis that the growth actions of hormone receptors that are homologous to the v-erbA oncogene (estrogens, progesterone, thyroid hormones, retinoic acid, and vitamin D) are mediated, in part, by modulating EGF-R and/or c-erbB-2 protooncogene transcription are reviewed. Finally, I develop the theme that cooperation of certain c-erb-A-related, c-erbB-2 and/or EGF-R gene products contribute to the uncontrolled growth of human mammary carcinoma cells. From the evidence reviewed, one can infer that elucidation of the molecular control of EGF-R/c-erbB-2 gene expression by c-erbA-related gene products may lead to both a better understanding of breast carcinogenesis and a new therapeutic approach directed at controlling the transcriptional responses of EGF-R/c-erbB-2 genes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I665,I665)","v":2285590},{"$f":"(LEN($J665) - LEN(SUBSTITUTE(LOWER($J665),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J665) - LEN(SUBSTITUTE(LOWER($J665),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J665) - LEN(SUBSTITUTE(LOWER($J665),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B665:D665)","v":1},1990,"Anti-steroidal and anti-growth factor activities of anti-estrogens.","Freiss",2285590,"Anti-steroidal and anti-growth factor activities of anti-estrogens.    Abstract:   Both steroid hormones, such as estrogens and progestins acting via nuclear receptors, and growth factors, such as EGF, IGF-I and IGF-II acting via transmembrane receptors, are able to modulate the growth of human breast cancer cells. In addition to its anti-estrogenic action requiring estrogen receptor (ER) and leading to growth arrest, we have previously shown that the anti-hormone tamoxifen (Tam) is able to block EGF, insulin and IGF-I mitogenic activities in total absence of estrogens (BBRC, 146,1502,1987). This anti-growth factor activity is observed exclusively in ER + cells and is rescued by estradiol addition, thus suggesting that it is mediated by accessible ER sites. In the same culture conditions, progestins and anti-progestins do not display such an inhibition, whereas retinoic acid does, thus indicating that this anti-growth factor effect is not restricted to ER ligands. To progress in the understanding of this inhibition, we first analyzed how Tam could affect EGF and IGF-I binding in responsive cells. We have shown that Tam neither affects EGF and IGF-I binding to their respective receptors by direct competition nor modulates their affinities. However, our recent data suggest that Tam pretreatment (6 days) of MCF7 cells, which similarly prevents EGF and IGF-I mitogenic activities, results in opposite effects on the concentrations of their binding sites. In conclusion, we propose that some steroid antagonists can inhibit not only the action of agonist ligands of the receptors they are binding to, but can also modulate the action of growth factors by decreasing their receptor concentrations or altering their functionalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I666,I666)","v":2110956},{"$f":"(LEN($J666) - LEN(SUBSTITUTE(LOWER($J666),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J666) - LEN(SUBSTITUTE(LOWER($J666),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J666) - LEN(SUBSTITUTE(LOWER($J666),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B666:D666)","v":1},1990,"Syndromology: an updated conceptual overview. VII. Aspects of teratogenesis.","Cohen",2110956,"Syndromology: an updated conceptual overview. VII. Aspects of teratogenesis.    Abstract:   Principles of teratogenesis are reviewed, including adverse environmental factors and the genotype, timing of exposure, mechanisms and pathogenesis, the nature of teratogenic agents, manifestations of deviant development, and dosage. Human teratogenic conditions are summarized with special emphasis on the fetal alcohol syndrome, fetal hydantoin syndrome, fetal trimethadione syndrome, fetal valproate syndrome, warfarin embryopathy, retinoic acid embryopathy, congenital rubella syndrome, radiation effects, and diabetic embryopathy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I667,I667)","v":3288575},{"$f":"(LEN($J667) - LEN(SUBSTITUTE(LOWER($J667),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J667) - LEN(SUBSTITUTE(LOWER($J667),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J667) - LEN(SUBSTITUTE(LOWER($J667),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B667:D667)","v":1},1988,"[Drug prescriptions in pregnancy. Current status].","Neubert",3288575,"[Drug prescriptions in pregnancy. Current status].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I668,I668)","v":2951855},{"$f":"(LEN($J668) - LEN(SUBSTITUTE(LOWER($J668),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J668) - LEN(SUBSTITUTE(LOWER($J668),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J668) - LEN(SUBSTITUTE(LOWER($J668),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B668:D668)","v":1},1987,"Isotretinoin.","Millan",2951855,"Isotretinoin.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I669,I669)","v":3327234},{"$f":"(LEN($J669) - LEN(SUBSTITUTE(LOWER($J669),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J669) - LEN(SUBSTITUTE(LOWER($J669),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J669) - LEN(SUBSTITUTE(LOWER($J669),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B669:D669)","v":1},1987,"Nutrient utilization during pregnancy.","King",3327234,"Nutrient utilization during pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I670,I670)","v":3036386},{"$f":"(LEN($J670) - LEN(SUBSTITUTE(LOWER($J670),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J670) - LEN(SUBSTITUTE(LOWER($J670),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J670) - LEN(SUBSTITUTE(LOWER($J670),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B670:D670)","v":1},1987,"Stem cells and the development of mammary cancers in experimental rats and in humans.","Rudland",3036386,"Stem cells and the development of mammary cancers in experimental rats and in humans.    Abstract:   Evidence based on immunocytochemical staining and ultrastructure suggests that morphological gradations between epithelial and myoepithelial cells, and possibly between epithelial cells and alveolar-like cells occur in terminal ductal structures of rat and human mammary glands. The benign carcinogen-induced rat and benign human mammary tumors can contain epithelial, myoepithelial-like and alveolar-like cells, whereas the malignant counterparts mainly contain only epithelial-like cells. Clonal epithelial cell lines from normal rat mammary glands, benign tumors, and SV40-transformed human mammary glands can differentiate to either myoepithelial-like or alveolar-like cells. In those of the rat, the differentiation processes occur in steps: intermediate cells along the myoepithelial-like pathway resemble intermediates in terminal ductal structures in vivo, and can also generate certain well-differentiated mesenchymal elements of the original tumours. Differentiation of the benign rat cells to alveolar-like cells with mammatrophic hormones and retinoids in vitro leads to a reduction in their tumor-forming ability in vivo. Cell lines from malignant rat mammary tumors of increasing metastatic potential and from human ductal carcinomas largely fail to yield myoepithelial-like or alveolar-like cells and are relatively slow-growing. Growth of the rat mammary epithelial cells in culture is stimulated by a pituitary-derived mammatrophic growth factor (PMGF), prostaglandin E2, and alpha-transforming growth factor; the response of the malignant cell lines to PMGF is reduced. It is suggested that stem cells exist in the rat and human glands that are capable of differentiating to the other major cell types of the mammary parenchyma, and that during the carcinogenic process they generate genetically unstable cells which lose their ability to differentiate and attempt to maximise their intrinsically slow growth rate."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I671,I671)","v":3537865},{"$f":"(LEN($J671) - LEN(SUBSTITUTE(LOWER($J671),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J671) - LEN(SUBSTITUTE(LOWER($J671),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J671) - LEN(SUBSTITUTE(LOWER($J671),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B671:D671)","v":1},1986,"Isotretinoin and human teratogenicity.","Corson",3537865,"Isotretinoin and human teratogenicity.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I672,I672)","v":3524949},{"$f":"(LEN($J672) - LEN(SUBSTITUTE(LOWER($J672),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J672) - LEN(SUBSTITUTE(LOWER($J672),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J672) - LEN(SUBSTITUTE(LOWER($J672),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B672:D672)","v":1},1986,"Prescribing in pregnancy. Mineral and vitamin supplements.","Drife",3524949,"Prescribing in pregnancy. Mineral and vitamin supplements.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I673,I673)","v":3524948},{"$f":"(LEN($J673) - LEN(SUBSTITUTE(LOWER($J673),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J673) - LEN(SUBSTITUTE(LOWER($J673),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J673) - LEN(SUBSTITUTE(LOWER($J673),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B673:D673)","v":1},1986,"Adverse effects of drugs in the first trimester of pregnancy.","Beeley",3524948,"Adverse effects of drugs in the first trimester of pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I674,I674)","v":3541761},{"$f":"(LEN($J674) - LEN(SUBSTITUTE(LOWER($J674),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J674) - LEN(SUBSTITUTE(LOWER($J674),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J674) - LEN(SUBSTITUTE(LOWER($J674),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B674:D674)","v":1},1986,"[Side-effects of retinoids].","Auffret",3541761,"[Side-effects of retinoids].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I675,I675)","v":3146293},{"$f":"(LEN($J675) - LEN(SUBSTITUTE(LOWER($J675),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J675) - LEN(SUBSTITUTE(LOWER($J675),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J675) - LEN(SUBSTITUTE(LOWER($J675),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B675:D675)","v":1},1986,"Fibular a/hypoplasia: review and documentation of the fibular developmental field.","Lewin",3146293,"Fibular a/hypoplasia: review and documentation of the fibular developmental field.    Abstract:   Fibular aplasia and/or hypoplasia is documented as a developmental field defect and the extent of the fibular developmental field is delineated. The term fibular a/hypoplasia denotes the clinical spectrum of fibular deficiency in different patients and also implies that aplasia can be present in one limb and hypoplasia in the other. Causal heterogeneity of fibular a/hypoplasia is demonstrated, thereby defining it as a developmental field defect. Most cases of fibular a/hypoplasia are isolated, sporadic events. An autosomal dominant form of isolated fibular a/hypoplasia with ankle joint anomaly is reviewed. Fibular a/hypoplasia may be part of more complex sporadic dysostoses; sporadic syndromes, an aneuploidy syndrome; several autosomal dominant and autosomal recessive conditions. Fibular a/hypoplasia is also postulated to occur as a result of disruption or teratogenic insult; in animals, fibular development can be disturbed by radiation, busulfan, and retinoic acid. Clinical data allow evaluation of the extent of the fibular developmental field of the lower limb. This appears to include the pubic portion of the pelvis, proximal femur (distal half being apparent tibial developmental territory), patella, anterior cruciate ligament, and lateral and/or axial foot rays (but quot;neverquot; the hallux and almost never associated with polydactyly). The rare cases of fibuloulnar dimelia allow confirmation of the well known homology of mesomelic limb segments responsible for concordant ulnar and fibular (and radial and tibial) defect, if both upper and lower limbs are involved in a given condition. Because fibular a/hypoplasia is the commonest of the mesomelic paraxial hemimelias, is usually nonsyndromal, and in most cases is apparently nongenetic (ie, with negligible recurrence risk), we propose that in humans, as in several other tetrapods, the fibula is undergoing regressive evolution and hence is developmentally especially labile."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I676,I676)","v":6375195},{"$f":"(LEN($J676) - LEN(SUBSTITUTE(LOWER($J676),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J676) - LEN(SUBSTITUTE(LOWER($J676),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J676) - LEN(SUBSTITUTE(LOWER($J676),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B676:D676)","v":1},1984,"[Aromatic retinoids in the therapy of dermatoses].","Shakhtmeĭster",6375195,"[Aromatic retinoids in the therapy of dermatoses].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I677,I677)","v":6226083},{"$f":"(LEN($J677) - LEN(SUBSTITUTE(LOWER($J677),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J677) - LEN(SUBSTITUTE(LOWER($J677),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J677) - LEN(SUBSTITUTE(LOWER($J677),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B677:D677)","v":1},1983,"[Indications and limits for retinoid treatments in dermatology].","Puissant",6226083,"[Indications and limits for retinoid treatments in dermatology].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I678,I678)","v":6369942},{"$f":"(LEN($J678) - LEN(SUBSTITUTE(LOWER($J678),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J678) - LEN(SUBSTITUTE(LOWER($J678),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J678) - LEN(SUBSTITUTE(LOWER($J678),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B678:D678)","v":1},1983,"Nutritional physiology in pregnancy and lactation.","Nichols",6369942,"Nutritional physiology in pregnancy and lactation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I679,I679)","v":6356585},{"$f":"(LEN($J679) - LEN(SUBSTITUTE(LOWER($J679),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J679) - LEN(SUBSTITUTE(LOWER($J679),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J679) - LEN(SUBSTITUTE(LOWER($J679),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B679:D679)","v":1},1983,"[Vitamin A, retinoids and tumor development].","Nozdrin",6356585,"[Vitamin A, retinoids and tumor development].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I680,I680)","v":6340124},{"$f":"(LEN($J680) - LEN(SUBSTITUTE(LOWER($J680),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J680) - LEN(SUBSTITUTE(LOWER($J680),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J680) - LEN(SUBSTITUTE(LOWER($J680),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B680:D680)","v":1},1983,"Vitamin A in pregnancy and lactation.","Bates",6340124,"Vitamin A in pregnancy and lactation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I681,I681)","v":6315467},{"$f":"(LEN($J681) - LEN(SUBSTITUTE(LOWER($J681),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J681) - LEN(SUBSTITUTE(LOWER($J681),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J681) - LEN(SUBSTITUTE(LOWER($J681),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B681:D681)","v":1},1983,"Toward a dietary prevention of cancer.","Graham",6315467,"Toward a dietary prevention of cancer.    Abstract:   I have attempted to address in brief fashion the question as to whether we can recommend a dietary prevention of cancer. This same question was explored in hundreds of pages recently by the large number of advisors assembled by the National Academy of Sciences to assess the animal, cell culture, and human data with regard to diet and cancer (52). My brief assessment has resulted in recommendations to the scientific community not unlike those of the National Academy, but without their clear-cut recommendation against dietary fat. It is obvious that we need a great deal more research on the factors evaluated here, that is, fiber, ascorbic acid, retinoids, the cruciferae, nitrates, alcohol, coffee, saccharine, alpha-tocopherol, aflatoxins, selenium, and saturated and polyunsaturated fats. These factors need assessment not only as they might affect the incidence of any single cancer, but also in relationship to at least the incidence of the cancers that frequently occur in humans. The human epidemiologic inquires have barely begun. We have a few studies of cancer of the colon and of cancer of the lung, and only one or two studies of such important sites as cancer of the larynx, oropharynx, stomach, and breast. Not only have the studies of specific sites been lamentably too few, but only a small number of nutrients have been evaluated. To make matters worse, we have little notion as to the competing risk of different cancers and of other diseases associated with various nutrients. There may be factors that enhance the risk of some diseases at the same time they reduce the risk of others. It is not outside the realm of possibility that the relationship discovered to date with regard to serum cholesterol, heart disease, and cancer may continue to be replicated and may be found related to ingestion of dietary fats. If such should be the case, and the potential is there, we would need to weigh the risks associated with reducing dietary fats for cancer as well as for coronary disease. Questions will need to be answered. For example, what is the optimum level of serum cholesterol to lower the risk of heart disease and at the same time not to enhance the risk of cancer. The same may be said for the association of alcohol with the risk of coronary disease compared to the risk of cancer of the upper alimentary tract.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I682,I682)","v":6177111},{"$f":"(LEN($J682) - LEN(SUBSTITUTE(LOWER($J682),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J682) - LEN(SUBSTITUTE(LOWER($J682),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J682) - LEN(SUBSTITUTE(LOWER($J682),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B682:D682)","v":1},1981,"[Recent findings on the importance of vitamin A and its metabolism in man and laboratory animals].","Kolb",6177111,"[Recent findings on the importance of vitamin A and its metabolism in man and laboratory animals].    Abstract:   A survey is given concerning recent realizations of importance and metabolism of vitamin A in man and experimental animals. The transport of vitamin A from the small intestine takes place in form of esters by inclusion in chylomicrons and lipoproteins. A higher content in the blood plasma over a longer period evokes toxic effects. In the liver one part of the vitamin A in form of an ester with binding to lipoproteins is accumulated, one part is - according to the need - associated with a vitamin-A-binding protein, which forms complexes with prealbumin molecules and transports the vitamin to the various places of effect. With the help of the receptor proteins the vitamin A is included in the cells, in which it is effective and is transported into the vitamin-A-aldehyde and the vitamin-A-acid. The vitamin A and the vitamin-A-acid are transported into the cell nuclei with the help of receptor-proteins and play a role in the differentiation of the tissues and in the regulation of the synthesis of RNA. When a deficit or an abundance of vitamin A is present in the early phase of pregnancy malformations in the fetuses appear. The vitamin A and structure-similar connections have an inhibiting effect on the development of tumours."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I683,I683)","v":7031803},{"$f":"(LEN($J683) - LEN(SUBSTITUTE(LOWER($J683),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J683) - LEN(SUBSTITUTE(LOWER($J683),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J683) - LEN(SUBSTITUTE(LOWER($J683),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B683:D683)","v":1},1981,"[Possible use of retinoids in the prevention and therapy of epithelial tumors].","Fantoli",7031803,"[Possible use of retinoids in the prevention and therapy of epithelial tumors].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I684,I684)","v":6810319},{"$f":"(LEN($J684) - LEN(SUBSTITUTE(LOWER($J684),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J684) - LEN(SUBSTITUTE(LOWER($J684),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J684) - LEN(SUBSTITUTE(LOWER($J684),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B684:D684)","v":1},1981,"Influence of diet on mammary cancer.","Carroll",6810319,"Influence of diet on mammary cancer.    Abstract:   Analysis of epidemiological data and experiments with animals have provided evidence that dietary fat has an important influence on mammary cancer. Further epidemiological studies should be carried out to examine this relationship more fully, and additional experimental work is required to determine the mechanisms by which dietary fat influences mammary cancer in animals. Dietary carbohydrate and minor dietary components, such as retinoids and certain trace elements, have also been shown to influence mammary cancer in animals. Decreasing the fat content of the diet may offer a practical means of reducing mortality from breast cancer, which continues to be a major cause of death in many parts of the world."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I685,I685)","v":6989103},{"$f":"(LEN($J685) - LEN(SUBSTITUTE(LOWER($J685),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J685) - LEN(SUBSTITUTE(LOWER($J685),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J685) - LEN(SUBSTITUTE(LOWER($J685),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B685:D685)","v":1},1980,"[Vitamin A transport mechanism: retinol cell reception and the intracellular proteins that bind vitamin A (a review)].","Kon",6989103,"[Vitamin A transport mechanism: retinol cell reception and the intracellular proteins that bind vitamin A (a review)].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I686,I686)","v":389569},{"$f":"(LEN($J686) - LEN(SUBSTITUTE(LOWER($J686),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J686) - LEN(SUBSTITUTE(LOWER($J686),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J686) - LEN(SUBSTITUTE(LOWER($J686),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B686:D686)","v":1},1979,"Hypervitaminosis A induced teratogenesis.","Geelen",389569,"Hypervitaminosis A induced teratogenesis.    Abstract:   In the past decade, the toxicology of reproduction has become increasingly important. This branch of toxicology focuses on mutagenic and embryotoxic effects. The study of embryotoxicity requires an extensive knowledge of the interaction of drugs and embryonic tissues, normal and abnormal developmental processes, and the susceptible stages during prenatal development. Hypervitaminosis A is one of the most extensively studied teratogens. It produces defects in almost all organ systems. Therefore, this article will first of all review the vitamin A-induced malformations in several organ systems. Moreover, it will discuss their morphogenesis and the susceptible developmental stages. Thus, the first ten chapters will cover the following subjects: malformations of the nervous system, ocular malformations, malformations of the ear, craniofacial malformations, cleft palate, defects of the circulatory system, defects of the respiratory systems, defects of the digestive tract, urogenital defects, skeletal malformations, and abnormal postnatal development. Since in general little is known about the mechanisms involved in the induction of congenital defects, we think it is of great value to review the knowledge and experience that have been gathered by the experimental work with hypervitaminosis A. Therefore, the next chapters will discuss the following subjects: teratogenic effects in different species, minimum effective dose, interaction with other agents, influence of chemical form, solvent, and route of administration, pathophysiology of vitamin A embryotoxicity, and hypervitaminosis A and human pregnancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I687,I687)","v":343567},{"$f":"(LEN($J687) - LEN(SUBSTITUTE(LOWER($J687),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J687) - LEN(SUBSTITUTE(LOWER($J687),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J687) - LEN(SUBSTITUTE(LOWER($J687),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B687:D687)","v":1},1978,"The volume and composition of human milk in poorly nourished communities. A review.","Jelliffe",343567,"The volume and composition of human milk in poorly nourished communities. A review.    Abstract:   A review of various studies on breast milk suggests the need for more coordinated comparative studies into all aspects of human lactation in well-nourished and poorly nourished communities using similar sampling methods and analytic techniques. The following generalizations were also drawn from the review for practical action: 1) unsupplemented human milk is all that is required to nourish babies of well-nourished mothers for the 1st 6 months of life; 2) although the volume and composition of human milk in poorly nourished women is surprisingly good, it is often suboptimal in quantity and quality with lower values of fat, H20 soluble vitamins, vitamin A, and somewhat lower calcium and protein; 3) limited studies with supplementary feeding of poorly nourished lactating women (and common sense probabilities) have suggested the feasibility of improvement in volume of output and in nutritional quality of breast milk; 4) adequacy of breast milk as sole food for the baby is related to the mothers diet in pregnancy, to maternal puerperal calorie reserves, to fetal stores, to birthweight, and to iron obtained from placental transfusion. Breast milk produced in the so-called quot;late lactation (e.g., 7 months to 2 years or more) is insufficient by itself for the rising nutrient needs (and declining stores) or the rapidly growing infant. The 2 main forms of interference with lactation performance (maternal reflexes and maternal nutrition) are also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I688,I688)","v":138998},{"$f":"(LEN($J688) - LEN(SUBSTITUTE(LOWER($J688),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J688) - LEN(SUBSTITUTE(LOWER($J688),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J688) - LEN(SUBSTITUTE(LOWER($J688),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B688:D688)","v":1},1977,"[Vitamin A acid (tretinoin)].","Christiansen",138998,"[Vitamin A acid (tretinoin)].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I689,I689)","v":1102220},{"$f":"(LEN($J689) - LEN(SUBSTITUTE(LOWER($J689),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J689) - LEN(SUBSTITUTE(LOWER($J689),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J689) - LEN(SUBSTITUTE(LOWER($J689),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B689:D689)","v":1},1975,"Vitamins and minerals in pregnancy.","Pitkin",1102220,"Vitamins and minerals in pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I690,I690)","v":27378094},{"$f":"(LEN($J690) - LEN(SUBSTITUTE(LOWER($J690),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J690) - LEN(SUBSTITUTE(LOWER($J690),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J690) - LEN(SUBSTITUTE(LOWER($J690),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B690:D690)","v":0},2016,"Integrated management of childhood illness (IMCI) strategy for children under five.","Gera",27378094,"Integrated management of childhood illness (IMCI) strategy for children under five.    Abstract:    BACKGROUND : More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community.  OBJECTIVES : To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries.  SEARCH METHODS : We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library amp; Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies.  SELECTION CRITERIA : We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI.  DATA COLLECTION AND ANALYSIS : Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence.  MAIN RESULTS : Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period.One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low-certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants).One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence).We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence).Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low-certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results.Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low.For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate-certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI.Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this.All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding.No studies reported on the satisfaction of mothers and service users.  AUTHORS CONCLUSIONS : The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I691,I691)","v":27022437},{"$f":"(LEN($J691) - LEN(SUBSTITUTE(LOWER($J691),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J691) - LEN(SUBSTITUTE(LOWER($J691),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J691) - LEN(SUBSTITUTE(LOWER($J691),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B691:D691)","v":0},2016,"Role of nuclear receptors in breast cancer stem cells.","Papi",27022437,"Role of nuclear receptors in breast cancer stem cells.    Abstract:   The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells, capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and pro-inflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the anti-inflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I692,I692)","v":26970129},{"$f":"(LEN($J692) - LEN(SUBSTITUTE(LOWER($J692),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J692) - LEN(SUBSTITUTE(LOWER($J692),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J692) - LEN(SUBSTITUTE(LOWER($J692),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B692:D692)","v":0},2016,"Novel routes for administering chemoprevention: local transdermal therapy to the breasts.","Lee",26970129,"Novel routes for administering chemoprevention: local transdermal therapy to the breasts.    Abstract:   Breast cancer prevention with pharmacologic agents requires that the breast be exposed to an effective drug; systemic exposure is unnecessary, and its harms lead many eligible women to decline preventive therapy. Local transdermal therapy (LTT) to the breast involves the application of active drugs to the breast skin, resulting in high concentrations in the breast but low systemic exposure. It is non-invasive, self-delivered, and not dependent on hepatic metabolism. Existing data on LTT include investigations demonstrating relief of mastalgia with topical 4-hydroxytamoxifen (4-OHT, an active tamoxifen metabolite). Two presurgical window trials in women with invasive breast cancer, and ductal carcinoma in situ (DCIS) demonstrate that LTT decreases proliferation of invasive and non-invasive cancer cells to a similar degree as oral tamoxifen, with low systemic levels, and no effect on coagulation proteins. These data are promising regarding the use of LTT for the primary prevention of breast cancer, and for therapy of DCIS, since systemic exposure is not required for either of these purposes. They also suggest that an LTT approach could be developed for any small, lipophilic molecule with good dermal permeation, thus greatly expanding the menu of drugs that could be tested for breast cancer prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I693,I693)","v":26693639},{"$f":"(LEN($J693) - LEN(SUBSTITUTE(LOWER($J693),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J693) - LEN(SUBSTITUTE(LOWER($J693),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J693) - LEN(SUBSTITUTE(LOWER($J693),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B693:D693)","v":0},2015,"Residentscorner October 2015. Editorial: Whats new this month ?","Kuonen",26693639,"Residentscorner October 2015. Editorial: Whats new this month ?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I694,I694)","v":26637438},{"$f":"(LEN($J694) - LEN(SUBSTITUTE(LOWER($J694),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J694) - LEN(SUBSTITUTE(LOWER($J694),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J694) - LEN(SUBSTITUTE(LOWER($J694),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B694:D694)","v":0},2015,"p53 as an Effector or Inhibitor of Therapy Response.","Ablain",26637438,"p53 as an Effector or Inhibitor of Therapy Response.    Abstract:   Although integrity of the p53 signaling pathway in a given tumor was expected to be a critical determinant of response to therapies, most clinical studies failed to link p53 status and treatment outcome. Here, we present two opposite situations: one in which p53 is an essential effector of cure by targeted leukemia therapies and another one in advanced breast cancers in which p53 inactivation is required for the clinical efficacy of dose-dense chemotherapy. If p53 promotes or blocks therapy response, therapies must be tailored on its status in individual tumors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I695,I695)","v":26454096},{"$f":"(LEN($J695) - LEN(SUBSTITUTE(LOWER($J695),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J695) - LEN(SUBSTITUTE(LOWER($J695),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J695) - LEN(SUBSTITUTE(LOWER($J695),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B695:D695)","v":0},2015,"Molecular events and signalling pathways of male germ cell differentiation in mouse.","Rossitto",26454096,"Molecular events and signalling pathways of male germ cell differentiation in mouse.    Abstract:   Germ cells, the precursors of gametes, represent a unique cell lineage that is able to differentiate into spermatozoa or oocytes depending on the chromosomal sex of the organism. In the mammalian embryonic gonad, commitment to oogenesis involves pre-meiotic DNA replication and entry into the first meiotic division; whereas, commitment to spermatogenesis involves inhibition of meiotic initiation, suppression of pluripotency, mitotic arrest and expression of specific markers that will control the development of the male germ cells. The crucial decision made by the germ line to commit to either a male or a female fate has been partially explained by genetic and ex vivo studies in mice which have implicated a complex network of regulatory genes, numerous factors and pathways. Besides the reproductive failure that may follow a deregulation of this complex network, the germ cells may, in view of their proliferative and pluripotent nature, act as precursors of potential malignant transformation and as putative targets for exogenous environmental compounds. Our review summarizes and discusses recent developments that have improved our understanding on how germ cell precursors are committed to a male or a female cell fate in the mouse gonad."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I696,I696)","v":26370648},{"$f":"(LEN($J696) - LEN(SUBSTITUTE(LOWER($J696),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J696) - LEN(SUBSTITUTE(LOWER($J696),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J696) - LEN(SUBSTITUTE(LOWER($J696),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B696:D696)","v":0},2015,"Alopecias due to drugs and other skin and systemic disorders.","Guzmán-Sánchez",26370648,"Alopecias due to drugs and other skin and systemic disorders.    Abstract:   In this chapter, we will discuss the most common alopecias due to drugs and other skin and systemic disorders. The following hair disorders will be analyzed: telogen effluvium (acute and chronic); anagen effluvium; folliculotropic mycosis fungoides; and folliculitis due to bacteria, fungi, parasites, human immunodeficiency virus disease, lupus erythematosus, and sarcoidosis. We will cover topics including the epidemiology, etiology, clinical picture, and diagnosis of and current treatments for each disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I697,I697)","v":26297705},{"$f":"(LEN($J697) - LEN(SUBSTITUTE(LOWER($J697),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J697) - LEN(SUBSTITUTE(LOWER($J697),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J697) - LEN(SUBSTITUTE(LOWER($J697),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B697:D697)","v":0},2015,"Inclusion of Small Indigenous Fish Improves Nutritional Quality During the First 1000 Days.","Bogard",26297705,"Inclusion of Small Indigenous Fish Improves Nutritional Quality During the First 1000 Days.    Abstract:    BACKGROUND : Within food-based approaches to improve nutrition during the first 1000 days of life, improved formulations of food products and the use of animal source foods, such as fish, are 2 widely cited strategies; however, there are few examples where the 2 strategies are combined. Furthermore, although small indigenous fish are highly nutritious and available to the poor in many regions of the world, their importance is often overlooked.  OBJECTIVE : To document the development of 2 nutritious fish-based food products in Bangladesh: a chutney for pregnant and lactating women (PLW) and a complementary food (CF) for infants and young children (6-23 months), including potential contributions to recommended or desirable nutrient intakes in the first 1000 days, processing methods, and nutrient composition.  METHODS : Local nutrient-rich ingredients and simple processing methods based on traditional knowledge (for the chutney), and a literature review (for the CF), were selected and trial batches produced. Products were analyzed for nutrient composition using standard analytical procedures and results compared with recommended or desirable nutrient intakes for women and children.  RESULTS : Both products could contribute significantly to micronutrient intakes of PLW (24% of iron and 35% of calcium recommended intakes) and macro- and micronutrient intake of infants and young children (≥ 65% of vitamin A, ≥ 61% of zinc, and 41% of iron desirable intakes) when consumed in the proposed serving size.  CONCLUSION : Inclusion of small indigenous fish as an underutilized animal source food in combination with other local nutrient-rich ingredients in food products represents a promising food-based strategy to improve nutrition, with many additional potential benefits for communities involved in production, and therefore warrants further investigation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I698,I698)","v":25791730},{"$f":"(LEN($J698) - LEN(SUBSTITUTE(LOWER($J698),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J698) - LEN(SUBSTITUTE(LOWER($J698),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J698) - LEN(SUBSTITUTE(LOWER($J698),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B698:D698)","v":0},2015,"Sex determination in mammalian germ cells.","Spiller",25791730,"Sex determination in mammalian germ cells.    Abstract:   Germ cells are the precursors of the sperm and oocytes and hence are critical for survival of the species. In mammals, they are specified during fetal life, migrate to the developing gonads and then undergo a critical period during which they are instructed, by the soma, to adopt the appropriate sexual fate. In a fetal ovary, germ cells enter meiosis and commit to oogenesis, whereas in a fetal testis, they avoid entry into meiosis and instead undergo mitotic arrest and mature toward spermatogenesis. Here, we discuss what we know so far about the regulation of sex-specific differentiation of germ cells, considering extrinsic molecular cues produced by somatic cells, as well as critical intrinsic changes within the germ cells. This review focuses almost exclusively on our understanding of these events in the mouse model."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I699,I699)","v":25666708},{"$f":"(LEN($J699) - LEN(SUBSTITUTE(LOWER($J699),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J699) - LEN(SUBSTITUTE(LOWER($J699),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J699) - LEN(SUBSTITUTE(LOWER($J699),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B699:D699)","v":0},2015,"Mucosal Immune Development in Early Life: Setting the Stage.","Brugman",25666708,"Mucosal Immune Development in Early Life: Setting the Stage.    Abstract:   Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system. The mucosal immune system is composed of a single epithelial cell layer protected by a mucus layer. Different immune cells monitor the baso-lateral side of the epithelial cells and dispersed secondary lymphoid organs, such as Peyers patches and isolated lymphoid follicles are equipped with immune cells able to mount appropriate and specific responses. This review will focus on the current knowledge on host, dietary and bacterial-derived factors that shape the mucosal immune system before and after birth. We will discuss current knowledge on fetal immunity (both responsiveness and lymphoid organ development) as well as the impact of diet and microbial colonization on neonatal immunity and disease susceptibility. Lastly, inflammatory bowel disease will be discussed as an example of how the composition of the microbiota might predispose to disease later in life. A fundamental understanding of the mechanisms involved in mucosal immune development and tolerance will aid nutritional intervention strategies to improve health in neonatal and adult life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I700,I700)","v":25639141},{"$f":"(LEN($J700) - LEN(SUBSTITUTE(LOWER($J700),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J700) - LEN(SUBSTITUTE(LOWER($J700),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J700) - LEN(SUBSTITUTE(LOWER($J700),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B700:D700)","v":0},2014,"Context for food-based approaches for improved feeding of infants and children in Ethiopia.","Stoecker",25639141,"Context for food-based approaches for improved feeding of infants and children in Ethiopia.    Abstract:    BACKGROUND : Regardless of efforts by the health sector and partner organizations, maternal and child malnutrition is still a challenge in Ethiopia.  OBJECTIVE : To describe the context of current infant and child feeding patterns in Ethiopia.  METHODS : Feeding patterns, diet content and quality, and nutritional outcomes and feeding practices of mothers of young children are described from literature review of a number of field studies.  RESULTS : Protein and energy deficiencies and multiple micronutrient deficiencies are common. Breastfeeding is often prolonged until 2 years of age, with introduction of small amounts of poor-quality complementary foods. Vitamin A and iodine deficiencies have also been problems. Focus group discussions showed that mothers did not believe that animal-source foods are needed.by young children or schoolchildren. However, the Health Extension Program led by the Federal Ministry of Health promotes optimal child feeding as one of the health extension packages.  CONCLUSIONS : Continued use of germination and fermentation of cereals should be encouraged to increase bioavailability of trace elements. Use of fat in the diet would increase energy density. To improve the situation, extension education, including nutrition and agricultural expertise delivered in aformat understandable to mothers about appropriate complementary feeding, including animal-source foods, is urgently needed, with expansion of governmental and nongovernmental resources."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I701,I701)","v":25456754},{"$f":"(LEN($J701) - LEN(SUBSTITUTE(LOWER($J701),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J701) - LEN(SUBSTITUTE(LOWER($J701),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J701) - LEN(SUBSTITUTE(LOWER($J701),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B701:D701)","v":0},2014,"Novel non-surgical prenatal approaches to treating congenital diaphragmatic hernia.","Jeanty",25456754,"Novel non-surgical prenatal approaches to treating congenital diaphragmatic hernia.    Abstract:   This review focuses on the emerging field of non-surgical in-utero therapies in the management of fetal pulmonary hypoplasia and pulmonary hypertension associated with congenital diaphragmatic hernia (CDH). These experimental approaches include pharmacologic as well as stem-cell-based strategies. Current barriers of non-surgical therapies toward clinical translation are emphasized. As the severity of CDH will likely influence the efficacy of any in-utero therapy, the current status of prenatal imaging and the role of novel biomarkers, especially those related to fetal inflammation, are also reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I702,I702)","v":25405717},{"$f":"(LEN($J702) - LEN(SUBSTITUTE(LOWER($J702),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J702) - LEN(SUBSTITUTE(LOWER($J702),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J702) - LEN(SUBSTITUTE(LOWER($J702),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B702:D702)","v":0},2015,"Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?","Justus",25405717,"Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?    Abstract:    BACKGROUND : The long-term outcomes of antenatal glucocorticoids (GCs) vary between reports, and have generated controversy in terms of repeated and single-course events, causing irreversible effects on endocrine set points.  AIM : This study aimed to assess the effects of alternative therapeutic agents other than synthetic glucocorticoid GC administration for fetal lung maturation.  METHODS : A review of literature from PubMed, EMBASE, Cochrane Library, and Google Scholar was conducted to assess the use of alternative therapies to synthetic GCs using recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). End points included the rates of respiratory distress syndrome (RDS), mRNA expression for pneumocyte type II, concentration of surfactant proteins in alveolar lavage, morphological differences, histological proof of lung maturation, and angiogenesis or quantification of the surfactant pool.  RESULTS : In all 41 studies examined, we found that ambroxol showed positive effects on lung maturation, but it has yet to be analyzed with sufficient significance in humans. Interleukins and TNF-alpha produce accelerated lung maturation, but have only been evaluated in basic research/experimental studies. Growth factors promote structural and functional growth in all phases of lung maturation, but little is known about their reciprocal effects and exact mechanisms as therapeutics. Thyroid releasing hormone or vitamin A cause detrimental side effects or were less effective for lung maturation.  CONCLUSIONS : The efficacy and safety of these alternative agents are differentiated and none up to now can be recommended as an alternative to GCs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I703,I703)","v":25398731},{"$f":"(LEN($J703) - LEN(SUBSTITUTE(LOWER($J703),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J703) - LEN(SUBSTITUTE(LOWER($J703),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J703) - LEN(SUBSTITUTE(LOWER($J703),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B703:D703)","v":0},2014,"Nutrition implications for fetal alcohol spectrum disorder.","Young",25398731,"Nutrition implications for fetal alcohol spectrum disorder.    Abstract:   Prenatal alcohol exposure produces a multitude of detrimental alcohol-induced defects in children collectively known as fetal alcohol spectrum disorder (FASD). Children with FASD often exhibit delayed or abnormal mental, neural, and physical growth. Socioeconomic status, race, genetics, parity, gravidity, age, smoking, and alcohol consumption patterns are all factors that may influence FASD. Optimal maternal nutritional status is of utmost importance for proper fetal development, yet is often altered with alcohol consumption. It is critical to determine a means to resolve and reduce the physical and neurological malformations that develop in the fetus as a result of prenatal alcohol exposure. Because there is a lack of information on the role of nutrients and prenatal nutrition interventions for FASD, the focus of this review is to provide an overview of nutrients (vitamin A, docosahexaenoic acid, folic acid, zinc, choline, vitamin E, and selenium) that may prevent or alleviate the development of FASD. Results from various nutrient supplementation studies in animal models and FASD-related research conducted in humans provide insight into the plausibility of prenatal nutrition interventions for FASD. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of multiple-nutrient supplementation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I704,I704)","v":25287557},{"$f":"(LEN($J704) - LEN(SUBSTITUTE(LOWER($J704),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J704) - LEN(SUBSTITUTE(LOWER($J704),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J704) - LEN(SUBSTITUTE(LOWER($J704),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B704:D704)","v":0},2015,"A decade of nutrition research in Africa: assessment of the evidence base and academic collaboration.","Lachat",25287557,"A decade of nutrition research in Africa: assessment of the evidence base and academic collaboration.    Abstract:    OBJECTIVE : Malnutrition in Africa has not improved compared with other regions in the world. Investment in the build-up of a strong African research workforce is essential to provide contextual solutions to the nutritional problems of Africa. To orientate this process, we reviewed nutrition research carried out in Africa and published during the last decade.  DESIGN : We assessed nutrition research from Africa published between 2000 and 2010 from MEDLINE and EMBASE and analysed the study design and type of intervention for studies indexed with major MeSH terms for vitamin A deficiency, protein-energy malnutrition, obesity, breast-feeding, nutritional status and food security. Affiliations of first authors were visualised as a network and power of affiliations was assessed using centrality metrics.  SETTING : Africa.  SUBJECTS : Africans, all age groups.  RESULTS : Most research on the topics was conducted in Southern (36%) and Western Africa (34%). The intervention studies (9%; n 95) mainly tested technological and curative approaches to the nutritional problems. Only for papers on protein-energy malnutrition and obesity did lead authorship from Africa exceed that from non-African affiliations. The 10% most powerfully connected affiliations were situated mainly outside Africa for publications on vitamin A deficiency, breast-feeding, nutritional status and food security.  CONCLUSIONS : The development of the evidence base for nutrition research in Africa is focused on treatment and the potential for cross-African networks to publish nutrition research from Africa remains grossly underutilised. Efforts to build capacity for effective nutrition action in Africa will require forging a true academic partnership between African and non-African research institutions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I705,I705)","v":25177974},{"$f":"(LEN($J705) - LEN(SUBSTITUTE(LOWER($J705),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J705) - LEN(SUBSTITUTE(LOWER($J705),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J705) - LEN(SUBSTITUTE(LOWER($J705),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B705:D705)","v":0},2014,"Essential interventions for child health.","Lassi",25177974,"Essential interventions for child health.    Abstract:   Child health is a growing concern at the global level, as infectious diseases and preventable conditions claim hundreds of lives of children under the age of five in low-income countries. Approximately 7.6 million children under five years of age died in 2011, calculating to about 19,000 children each day and almost 800 every hour. About 80 percent of the worlds under-five deaths in 2011 occurred in only 25 countries, and about half in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. The implications and burden of such statistics are huge and will have dire consequences if they are not corrected promptly. This paper reviews essential interventions for improving child health, which if implemented properly and according to guidelines have been found to improve child health outcomes, as well as reduce morbidity and mortality rates. It also includes caregivers and delivery strategies for each intervention. Interventions that have been associated with a decrease in mortality and disease rates include exclusive breastfeeding, complementary feeding strategies, routine immunizations and vaccinations for children, preventative zinc supplementation in children, and vitamin A supplementation in vitamin A deficient populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I706,I706)","v":25101554},{"$f":"(LEN($J706) - LEN(SUBSTITUTE(LOWER($J706),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J706) - LEN(SUBSTITUTE(LOWER($J706),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J706) - LEN(SUBSTITUTE(LOWER($J706),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B706:D706)","v":0},2014,"Global burden of childhood diarrhea and interventions.","Das",25101554,"Global burden of childhood diarrhea and interventions.    Abstract:    PURPOSE OF REVIEW : Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions.  RECENT FINDINGS : There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the Lives Saved tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted.  SUMMARY : The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I707,I707)","v":24856991},{"$f":"(LEN($J707) - LEN(SUBSTITUTE(LOWER($J707),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J707) - LEN(SUBSTITUTE(LOWER($J707),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J707) - LEN(SUBSTITUTE(LOWER($J707),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B707:D707)","v":0},2014,"Patterns and etiology of acute and chronic lung injury: insights from experimental evidence.","Hütten",24856991,"Patterns and etiology of acute and chronic lung injury: insights from experimental evidence.    Abstract:   Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I708,I708)","v":24660660},{"$f":"(LEN($J708) - LEN(SUBSTITUTE(LOWER($J708),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J708) - LEN(SUBSTITUTE(LOWER($J708),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J708) - LEN(SUBSTITUTE(LOWER($J708),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B708:D708)","v":0},2014,"A patent review on the development of human cytochrome P450 inhibitors.","Francis",24660660,"A patent review on the development of human cytochrome P450 inhibitors.    Abstract:    INTRODUCTION : CYP, a ubiquitous superfamily of enzymes expressed in major organs in humans, plays a key role in biosynthesis of steroids and metabolism of xenobiotics. Inhibitors of these vital enzymes provide, as tools, the opportunity to gain an insight to their role in a myriad of bioactivity and to intervene as therapeutics in disease.  AREAS COVERED : This article reviews granted patents for human CYP inhibitors from the US and European territories within the past decade.  EXPERT OPINION : Granted patents, albeit mostly embodying evidence from in vitro and limited preclinical trials, demonstrate good potential for use in industry and the clinic following future human trials. Indeed, only a handful is on the market or under clinical evaluation. Diagnostic monoclonal antibodies (mAbs) show high specificity for CYP families 1, 2, and 3, while potent inhibitors of CYPs 17, 19, 24, 26, 3A4 activities, in use with or without other drugs, display potential in treating prostate and breast cancers, dermatology, and improved retroviral therapy, although some may have challenges in delivery to target tissues. The involvement of this superfamily of enzymes in cellular functions, a multitude of disease states, and pharmacogenetics make them ideal candidates to better understand contemporary human health issues and identification of targeted, specific, and potent inhibitors is a useful strategy to employ, toward achieving that wider goal."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I709,I709)","v":24592582},{"$f":"(LEN($J709) - LEN(SUBSTITUTE(LOWER($J709),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J709) - LEN(SUBSTITUTE(LOWER($J709),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J709) - LEN(SUBSTITUTE(LOWER($J709),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B709:D709)","v":0},2013,"Prevalence of vitamin A deficiency in South Asia: causes, outcomes, and possible remedies.","Akhtar",24592582,"Prevalence of vitamin A deficiency in South Asia: causes, outcomes, and possible remedies.    Abstract:   Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitots spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stem efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I710,I710)","v":24564520},{"$f":"(LEN($J710) - LEN(SUBSTITUTE(LOWER($J710),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J710) - LEN(SUBSTITUTE(LOWER($J710),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J710) - LEN(SUBSTITUTE(LOWER($J710),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B710:D710)","v":0},2013,"Financial incentives and coverage of child health interventions: a systematic review and meta-analysis.","Bassani",24564520,"Financial incentives and coverage of child health interventions: a systematic review and meta-analysis.    Abstract:    BACKGROUND : Financial incentives are widely used strategies to alleviate poverty, foster development, and improve health. Cash transfer programs, microcredit, user fee removal policies and voucher schemes that provide direct or indirect monetary incentives to households have been used for decades in Latin America, Sub-Saharan Africa, and more recently in Southeast Asia. Until now, no systematic review of the impact of financial incentives on coverage and uptake of health interventions targeting children under 5 years of age has been conducted. The objective of this review is to provide estimates on the effect of six types of financial incentive programs: (i) Unconditional cash transfers (CT), (ii) Conditional cash transfers (CCT), (iii) Microcredit (MC), (iv) Conditional Microcredit (CMC), (v) Voucher schemes (VS) and (vi) User fee removal (UFR) on the uptake and coverage of health interventions targeting children under the age of five years.  METHODS : We conducted systematic searches of a series of databases until September 1st, 2012, to identify relevant studies reporting on the impact of financial incentives on coverage of health interventions and behaviors targeting children under 5 years of age. The quality of the studies was assessed using the CHERG criteria. Meta-analyses were undertaken to estimate the effect when multiple studies meeting our inclusion criteria were available.  RESULTS : Our searches resulted in 1671 titles identified 25 studies reporting on the impact of financial incentive programs on 5 groups of coverage indicators: breastfeeding practices (breastfeeding incidence, proportion of children receiving colostrum and early initiation of breastfeeding, exclusive breastfeeding for six months and duration of breastfeeding); vaccination (coverage of full immunization, partial immunization and specific antigens); health care use (seeking healthcare when child was ill, visits to health facilities for preventive reasons, visits to health facilities for any reason, visits for health check-up including growth control); management of diarrhoeal disease (ORS use during diarrhea episode, continued feeding during diarrhea, healthcare during diarrhea episode) and other preventive health interventions (iron supplementation, vitamin A, zinc supplementation, preventive deworming). The quality of evidence on the effect of financial incentives on breastfeeding practices was low but seems to indicate a potential positive impact on receiving colostrum, early initiation of breastfeeding, exclusive breastfeeding and mean duration of exclusive breastfeeding. There is no effect of financial incentives on immunization coverage although there was moderate quality evidence of conditional cash transfers leading to a small but non-significant increase in coverage of age-appropriate immunization. There was low quality evidence of impact of CCT on healthcare use by children under age 5 (Risk difference: 0.14 [95%CI: 0.03; 0.26]) as well as low quality evidence of an effect of user fee removal on use of curative health services (RD=0.62 [0.41; 0.82]).  CONCLUSIONS : Financial incentives may have potential to promote increased coverage of several important child health interventions, but the quality of evidence available is low. The more pronounced effects seem to be achieved by programs that directly removed user fees for access to health services. Some indication of effect were also observed for programs that conditioned financial incentives on participation in health education and attendance to health care visits. This finding suggest that the measured effect may be less a consequence of the financial incentive and more due to conditionalities addressing important informational barriers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I711,I711)","v":24171049},{"$f":"(LEN($J711) - LEN(SUBSTITUTE(LOWER($J711),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J711) - LEN(SUBSTITUTE(LOWER($J711),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J711) - LEN(SUBSTITUTE(LOWER($J711),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B711:D711)","v":0},2013,"Vitamin supplement consumption and breast cancer risk: a review.","Misotti",24171049,"Vitamin supplement consumption and breast cancer risk: a review.    Abstract:    BACKGROUND : Breast cancer is the most frequently diagnosed cancer globally, and studies provide contradictory results about the possible effects of vitamin supplementation to reduce cancer risk. Our aim was to conduct a review to better investigate whether vitamin supplements given orally modify breast cancer risk.  METHODS : We conducted a comprehensive, systematic bibliographic search of the medical literature to identify relevant studies. Case-control, cohort studies, and randomised controlled trials (RCTs) published up to August 2013 that reported cancer risk estimates for vitamin supplementation were included. For each study, we retrieved study characteristics, study population, exposure evaluation, and risk estimates.  RESULTS : We identified 26 studies (14 cohort, 11 case-control, and one RCT) and overall, we found 104 estimates. We grouped all the estimates into six supplementation categories: vitamin A and beta-carotene, B-group vitamins and folic acid, vitamin C, vitamin D, vitamin E, and multivitamins. Only a few studies showed a statistically significant association between the consumption of supplemental vitamins and the occurrence of breast cancer, and most of the significant estimates were found in case-control studies. The results found in prospective studies seem to be in the opposite direction.  CONCLUSION : The role of vitamin supplements in preventing breast cancer still remains unclear, considering our review. Although biologic mechanisms exist to support the anticancer effects of vitamins, there is no clear evidence for an effect in cancer prevention for vitamin supplements. Further investigations are warranted to elucidate the mechanisms by which vitamin supplementation can modify breast cancer development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I712,I712)","v":24142805},{"$f":"(LEN($J712) - LEN(SUBSTITUTE(LOWER($J712),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J712) - LEN(SUBSTITUTE(LOWER($J712),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J712) - LEN(SUBSTITUTE(LOWER($J712),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B712:D712)","v":0},2014,"Dietary intake and ovarian cancer risk: a systematic review.","Crane",24142805,"Dietary intake and ovarian cancer risk: a systematic review.    Abstract:   Ovarian cancer is a leading cause of gynecological cancer death. There is a need to identify modifiable dietary risk factors for this disease. To evaluate the role of diet in ovarian cancer risk, we performed a PRISMA-directed systematic review that included prospective cohort studies with gt;200 cases (n = 24). Higher risk for ovarian cancer was shown for total, animal, and dairy fat (five of nine studies), as well as total nitrate and possibly total vitamin C. No associations were demonstrated for red meat, fiber, vitamin A, vitamin E, β-carotene, or folate. Vegetables were associated with lower risk in one of three studies; fruit showed no association, although risk estimates were all greater than 1.0. Isoflavones and flavonoids were associated with modestly lower risk in two studies and tea intake was associated with lower risk in one of two studies. This review suggests that no specific dietary factors are consistently associated with ovarian cancer risk. Data by tumor subtypes are limited, but suggest that differential associations by tumor subtype may exist and should be evaluated. Studies of ample sample size, varied exposure, which can better control for dietary measurement error, are needed to fully define dietary recommendations for ovarian cancer prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I713,I713)","v":24101020},{"$f":"(LEN($J713) - LEN(SUBSTITUTE(LOWER($J713),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J713) - LEN(SUBSTITUTE(LOWER($J713),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J713) - LEN(SUBSTITUTE(LOWER($J713),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B713:D713)","v":0},2014,"Cost-effectiveness of surgery in low- and middle-income countries: a systematic review.","Grimes",24101020,"Cost-effectiveness of surgery in low- and middle-income countries: a systematic review.    Abstract:    BACKGROUND : There is increasing interest in provision of essential surgical care as part of public health policy in low- and middle-income countries (LMIC). Relatively simple interventions have been shown to prevent death and disability. We reviewed the published literature to examine the cost-effectiveness of simple surgical interventions which could be made available at any district hospital, and compared these to standard public health interventions.  METHODS : PubMed and EMBASE were searched using single and combinations of the search terms quot;disability adjusted life yearquot; (DALY), quot;quality adjusted life year,quot; quot;cost-effectiveness,quot; and quot;surgery.quot; Articles were included if they detailed the cost-effectiveness of a surgical intervention of relevance to a LMIC, which could be made available at any district hospital. Suitable articles with both cost and effectiveness data were identified and, where possible, data were extrapolated to enable comparison across studies.  RESULTS : Twenty-seven articles met our inclusion criteria, representing 64 LMIC over 16 years of study. Interventions that were found to be cost-effective included cataract surgery (cost/DALY averted range US$5.06-$106.00), elective inguinal hernia repair (cost/DALY averted range US$12.88-$78.18), male circumcision (cost/DALY averted range US$7.38-$319.29), emergency cesarean section (cost/DALY averted range US$18-$3,462.00), and cleft lip and palate repair (cost/DALY averted range US$15.44-$96.04). A small district hospital with basic surgical services was also found to be highly cost-effective (cost/DALY averted 1 US$0.93), as were larger hospitals offering emergency and trauma surgery (cost/DALY averted US$32.78-$223.00). This compares favorably with other standard public health interventions, such as oral rehydration therapy (US$1,062.00), vitamin A supplementation (US$6.00-$12.00), breast feeding promotion (US$930.00), and highly active anti-retroviral therapy for HIV (US$922.00).  CONCLUSIONS : Simple surgical interventions that are life-saving and disability-preventing should be considered as part of public health policy in LMIC. We recommend an investment in surgical care and its integration with other public health measures at the district hospital level, rather than investment in single disease strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I714,I714)","v":24049998},{"$f":"(LEN($J714) - LEN(SUBSTITUTE(LOWER($J714),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J714) - LEN(SUBSTITUTE(LOWER($J714),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J714) - LEN(SUBSTITUTE(LOWER($J714),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B714:D714)","v":0},2013,"Vitamin A--fortified vegetable oil exported from Malaysia and Indonesia can significantly contribute to vitamin A intake worldwide.","Laillou",24049998,"Vitamin A--fortified vegetable oil exported from Malaysia and Indonesia can significantly contribute to vitamin A intake worldwide.    Abstract:    BACKGROUND : Vitamin A deficiency is a public health problem worldwide, affecting approximately 190 million preschool-aged children and 19.1 million pregnant women. Fortification of vegetable oils with vitamin A is an effective, low-cost technology to improve vitamin A intake.  OBJECTIVE : To examine the potential contribution of fortification of vegetable oils with vitamin A in Indonesia and Malaysia to increasing vitamin A consumption in these two countries and in countries to which oil is exported.  METHODS : Detailed interviews were administered and a desk review was conducted. We also estimated potential vitamin A intakes from fortified vegetable oil.  RESULTS : Malaysia and Indonesia are two of the largest producers and exporters of vegetable oil. Fortification of vegetable oil in both countries has the potential to be used as a tool for control of vitamin A deficiency. Both countries have the capacity to export fortified vegetable oil. Vegetable oil fortified at a level of 45 IU/g could provide 18.8% of the Estimated Average Requirement (EAR) for an Ethiopian woman, 30.9% and 46.9% of the EAR for a Bangladeshi child and woman, respectively, and 17.5% of the EAR for a Cambodian woman. Although concerns about obesity are valid, fortification of existing vegetable oil supplies does not promote overconsumption of oil but rather promotes consumption of vegetable oil of higher nutrient quality.  CONCLUSIONS : Fortifying vegetable oil on a large scale in Malaysia and Indonesia can reach millions of people globally, including children less than 5 years old. The levels of fortification used are far from reaching the Tolerable Upper Intake Level (UL). Vegetable oil fortification has the potential to become a global public health intervention strategy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I715,I715)","v":24018211},{"$f":"(LEN($J715) - LEN(SUBSTITUTE(LOWER($J715),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J715) - LEN(SUBSTITUTE(LOWER($J715),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J715) - LEN(SUBSTITUTE(LOWER($J715),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B715:D715)","v":0},2013,"Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.","Puig",24018211,"Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.    Abstract:   Biologic therapy is a well-established strategy for managing moderate and severe psoriasis. Nevertheless, the high cost of such therapy, the relatively short span of clinical experience with biologics, and the abundance of literature now available on these agents have made evidence-based and consensus-based clinical guidelines necessary. The ideal goal of psoriasis treatment is to achieve complete or nearly complete clearing of lesions and to maintain it over time. Failing that ideal, the goal would be to reduce involvement to localized lesions that can be controlled with topical therapy. Although current evidence allows us to directly or indirectly compare the efficacy or risk of primary or secondary failure of available biologics based on objective outcomes, clinical trial findings cannot be directly translated to routine practice. As a result, the prescribing physician must tailor the treatment regimen to the individual patient. This update of the clinical practice guidelines issued by the Spanish Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis incorporates information from the most recent publications on this topic."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I716,I716)","v":23933151},{"$f":"(LEN($J716) - LEN(SUBSTITUTE(LOWER($J716),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J716) - LEN(SUBSTITUTE(LOWER($J716),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J716) - LEN(SUBSTITUTE(LOWER($J716),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B716:D716)","v":0},2014,"PELP1: a review of PELP1 interactions, signaling, and biology.","Girard",23933151,"PELP1: a review of PELP1 interactions, signaling, and biology.    Abstract:   Proline, glutamic acid, and leucine rich protein 1 (PELP1) is a large multi-domain protein that has been shown to modulate an increasing number of pathways and biological processes. The first reports describing the cloning and characterization of PELP1 showed that it was an estrogen receptor coactivator. PELP1 has now been shown to be a coregulator for a growing number of transcription factors. Furthermore, recent reports have shown that PELP1 is a member of chromatin remodeling complexes. In addition to PELP1 nuclear functions, it has been shown to have cytoplasmic signaling functions as well. In the cytoplasm PELP1 acts as a scaffold molecule and mediates rapid signaling from growth factor and hormone receptors. PELP1 signaling ultimately plays a role in cancer biology by increasing proliferation and metastasis, among other cellular processes. Here we will review (1) the cloning and characterization of PELP1 expression, (2) interacting proteins, (3) PELP1 signaling, and (4) PELP1-mediated biology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I717,I717)","v":23420126},{"$f":"(LEN($J717) - LEN(SUBSTITUTE(LOWER($J717),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J717) - LEN(SUBSTITUTE(LOWER($J717),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J717) - LEN(SUBSTITUTE(LOWER($J717),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B717:D717)","v":0},2013,"Bronchopulmonary dysplasia: a review.","Ali",23420126,"Bronchopulmonary dysplasia: a review.    Abstract:    INTRODUCTION : The prevalence of bronchopulmonary dysplasia (BPD), one of the most frequently occurring complications following preterm birth, is increasing due to increased survival of preterm infants.  METHODS : Systematic literature review.  CONCLUSION : The etiology is multifactorial, with prematurity being a prerequisite for the development of BPD. Over time, there have been many different and new treatment modalities, some of them have reduced the severity of the disease, but none of them have been able to impact upon the increasing incidence of BPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I718,I718)","v":23324902},{"$f":"(LEN($J718) - LEN(SUBSTITUTE(LOWER($J718),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J718) - LEN(SUBSTITUTE(LOWER($J718),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J718) - LEN(SUBSTITUTE(LOWER($J718),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B718:D718)","v":0},2013,"The prevention of food allergy in children.","Szajewska",23324902,"The prevention of food allergy in children.    Abstract:    PURPOSE OF REVIEW : This article reports recent advances in early nutritional strategies used in the prenatal/postnatal periods for preventing allergies in children.  RECENT FINDINGS : Exclusive breastfeeding for 6 months is a desirable goal; however, with regard to allergy, the results of studies are inconsistent, showing a protective effect, no effect, or even a predisposing effect. For infants with a documented hereditary risk of allergy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively, dietary products with confirmed reduced allergenicity are recommended. Currently, there is no convincing scientific evidence that the avoidance or delayed introduction of potentially allergenic foods beyond 4-6 months reduces allergies in infants considered to be at increased risk for the development of allergic diseases or in those not considered to be at increased risk. The timing of n-3 long-chain polyunsaturated fatty acid supplementation may play a role in preventing early childhood allergy. Weak evidence from observational trials suggests a role of vitamins A, D, and E; zinc; fruit and vegetables; and a Mediterranean diet in the prevention of atopic disease.  SUMMARY : Current evidence challenges earlier dogma. Thus, more research, preferentially from randomized controlled trials, is needed with regard to evaluating the efficacy and safety of all nutritional interventions for allergy prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I719,I719)","v":23252770},{"$f":"(LEN($J719) - LEN(SUBSTITUTE(LOWER($J719),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J719) - LEN(SUBSTITUTE(LOWER($J719),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J719) - LEN(SUBSTITUTE(LOWER($J719),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B719:D719)","v":0},2013,"The environment and the origins of islet autoimmunity and Type 1 diabetes.","Eringsmark Regnéll",23252770,"The environment and the origins of islet autoimmunity and Type 1 diabetes.    Abstract:   Type 1 diabetes involves the specific destruction of the pancreatic islet β-cells, eventually resulting in a complete dependency of exogenous insulin. The clinical onset of diabetes is preceded by the appearance of autoantibodies against β-cell antigens. The human leukocyte antigen (HLA) region is the single most important genetic determinant of Type 1 diabetes susceptibility, yet variability in the HLA region has been estimated to explain only approximately 60% of the genetic influence of the disease. Over 50 identified non-HLA genetic polymorphisms support the notion that genetics alone cannot explain Type 1 diabetes. Several lines of evidence indicate that environmental triggers may be integral in inducing the onset of islet autoimmunity in genetically susceptible individuals. The association between environmental factors and the clinical onset is complicated by observation that the rate of progression to clinical onset may be affected by environmental determinants. Hence, the environment may be aetiological as well as pathogenic. Putative inductive mechanisms include viral, microbial, diet-related, anthropometric and psychosocial factors. Ongoing observational cohort studies such as The Environmental Determinants of Diabetes in the Young (TEDDY) study aim to ascertain environmental determinants that may trigger islet autoimmunity and either speed up or slow down the progression to clinical onset in subjects with persistent islet autoimmunity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I720,I720)","v":23246696},{"$f":"(LEN($J720) - LEN(SUBSTITUTE(LOWER($J720),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J720) - LEN(SUBSTITUTE(LOWER($J720),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J720) - LEN(SUBSTITUTE(LOWER($J720),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B720:D720)","v":0},2013,"Regulation of the MIR155 host gene in physiological and pathological processes.","Elton",23246696,"Regulation of the MIR155 host gene in physiological and pathological processes.    Abstract:   MicroRNAs (miRNAs), a family of small nonprotein-coding RNAs, play a critical role in posttranscriptional gene regulation by acting as adaptors for the miRNA-induced silencing complex to inhibit gene expression by targeting mRNAs for translational repression and/or cleavage. miR-155-5p and miR-155-3p are processed from the B-cell Integration Cluster (BIC) gene (now designated, MIR155 host gene or MIR155HG). MiR-155-5p is highly expressed in both activated B- and T-cells and in monocytes/macrophages. MiR-155-5p is one of the best characterized miRNAs and recent data indicate that miR-155-5p plays a critical role in various physiological and pathological processes such as hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular disease, and Down syndrome. In this review we summarize the mechanisms by which MIR155HG expression can be regulated. Given that the pathologies mediated by miR-155-5p result from the over-expression of this miRNA it may be possible to therapeutically attenuate miR-155-5p levels in the treatment of several pathological processes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I721,I721)","v":23157584},{"$f":"(LEN($J721) - LEN(SUBSTITUTE(LOWER($J721),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J721) - LEN(SUBSTITUTE(LOWER($J721),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J721) - LEN(SUBSTITUTE(LOWER($J721),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B721:D721)","v":0},2012,"An evidence-based systematic review of vitamin A by the natural standard research collaboration.","Ulbricht",23157584,"An evidence-based systematic review of vitamin A by the natural standard research collaboration.    Abstract:   An evidence-based systematic review of vitamin A by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated and reproducible grading rationale. This paper includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I722,I722)","v":23053551},{"$f":"(LEN($J722) - LEN(SUBSTITUTE(LOWER($J722),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J722) - LEN(SUBSTITUTE(LOWER($J722),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J722) - LEN(SUBSTITUTE(LOWER($J722),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B722:D722)","v":0},2012,"A global clinical view on vitamin A and carotenoids.","Sommer",23053551,"A global clinical view on vitamin A and carotenoids.    Abstract:   The clinical importance of vitamin A as an essential nutrient has become increasingly clear. Adequate vitamin A is required for normal organogenesis, immune competence, tissue differentiation, and the visual cycle. Deficiency, which is widespread throughout the developing world, is responsible for a million or more instances of unnecessary death and blindness each year. β-Carotene is an important, but insufficient, source of vitamin A among poor populations, which accounts for the widespread nature of vitamin A deficiency. It has only recently become apparent that the bioconversion of traditional dietary sources of β-carotene to vitamin A is much less efficient than previously supposed. The other major carotenoids, particularly lycopene, lutein, and zeaxanthin, have been found to have important biological properties, including antioxidant and photoprotective activity, and high intake has been linked in observational studies with reduced risk of a number of chronic diseases. But, to date, no clinical trials have proven the clinical value of ingested carotenoids individually or in combination, in either physiologic or pharmacologic doses, with the excepton of the provitamin A activity of carotene. Indeed, several trials have suggested an increased risk of lung cancer among high-risk individuals (smokers and asbestos workers) who were given high doses of β-carotene alone or in combination with other antioxidants. Much more evidence is needed before commonly encountered claims of the value of ingesting high doses of non-provitamin A carotenoids are validated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I723,I723)","v":23034368},{"$f":"(LEN($J723) - LEN(SUBSTITUTE(LOWER($J723),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J723) - LEN(SUBSTITUTE(LOWER($J723),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J723) - LEN(SUBSTITUTE(LOWER($J723),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B723:D723)","v":0},2012,"Exploration and innovation in addressing maternal, infant and neonatal mortality.","Khanal",23034368,"Exploration and innovation in addressing maternal, infant and neonatal mortality.    Abstract:   The Government of Nepal has been remarkably progressive in introducing innovative community-based maternal newborn and child health interventions in an effort to address the major causes of maternal and child mortality in the country. This article describes the introduction of innovative interventions, including a review of the landmark research that precipitated the discussion and provided evidence of practical feasibility, the acceptance of the intervention concept and validity, the approval process and the introduction and results from the pilot interventions. These interventions, which include the use of misoprostol to prevent post partum haemorrhage during homebirths, Morang Innovative Neonatal Intervention, gentamicin in Uniject and for the management of neonatal sepsis and newborn vitamin A supplementation, are in various stages and demonstrate the responsiveness of the Government to new approaches that address the major causes of maternal and child mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I724,I724)","v":23008041},{"$f":"(LEN($J724) - LEN(SUBSTITUTE(LOWER($J724),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J724) - LEN(SUBSTITUTE(LOWER($J724),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J724) - LEN(SUBSTITUTE(LOWER($J724),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B724:D724)","v":0},2012,"Interaction of vitamin A and other micronutrients.","McLaren",23008041,"Interaction of vitamin A and other micronutrients.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I725,I725)","v":22524113},{"$f":"(LEN($J725) - LEN(SUBSTITUTE(LOWER($J725),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J725) - LEN(SUBSTITUTE(LOWER($J725),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J725) - LEN(SUBSTITUTE(LOWER($J725),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B725:D725)","v":0},2012,"Nutrition of children and women in Bangladesh: trends and directions for the future.","Ahmed",22524113,"Nutrition of children and women in Bangladesh: trends and directions for the future.    Abstract:   Although child and maternal malnutrition has been reduced in Bangladesh, the prevalence of underweight (weight-for-age z-score lt;-2) among children aged less than five years is still high (41%). Nearly one-third of women are undernourished with body mass index of lt;18.5 kg/m2. The prevalence of anaemia among young infants, adolescent girls, and pregnant women is still at unacceptable levels. Despite the successes in specific programmes, such as the Expanded Programme on Immunization and vitamin A supplementation, programmes for nutrition interventions are yet to be implemented at scale for reaching the entire population. Given the low annual rate of reduction in child undernutrition of 1.27 percentage points per year, it is unlikely that Bangladesh would be able to achieve the United Nations Millennium Development Goal to address undernutrition. This warrants that the policy-makers and programme managers think urgently about the ways to accelerate the progress. The Government, development partners, non-government organizations, and the academia have to work in concert to improve the coverage of basic and effective nutrition interventions, including exclusive breastfeeding, appropriate complementary feeding, supplementation of micronutrients to children, adolescent girls, pregnant and lactating women, management of severe acute malnutrition and deworming, and hygiene interventions, coupled with those that address more structural causes and indirectly improve nutrition. The entire health system needs to be revitalized to overcome the constraints that exist at the levels of policy, governance, and service-delivery, and also for the creation of demand for the services at the household level. In addition, management of nutrition in the aftermath of natural disasters and stabilization of prices of foods should also be prioritized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I726,I726)","v":22450279},{"$f":"(LEN($J726) - LEN(SUBSTITUTE(LOWER($J726),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J726) - LEN(SUBSTITUTE(LOWER($J726),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J726) - LEN(SUBSTITUTE(LOWER($J726),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B726:D726)","v":0},2012,"Nutritional factors that regulate ovulation of the dominant follicle during the first follicular wave postpartum in high-producing dairy cows.","Kawashima",22450279,"Nutritional factors that regulate ovulation of the dominant follicle during the first follicular wave postpartum in high-producing dairy cows.    Abstract:   During recent decades, milk production per cow has increased drastically due to improved management, nutrition, and genetic selection; however, the reproductive performance of high-producing dairy cows has been declining. One of the factors responsible for this low reproductive performance is negative energy balance (NEB). NEB affects the onset of first ovulation in early postpartum cows. It is generally accepted that early first ovulation positively relates to the resumption of normal ovarian function, first service, and conception rate in dairy cows. Hence, delayed first ovulation has a negative impact on subsequent fertility. The metabolic condition of cows in NEB shifts to catabolic metabolism, which in turn causes increased plasma growth hormone and non-esterified fatty acid concentrations and decreased plasma insulin-like growth factor-1, insulin, and glucose concentrations. On the other hand, plasma β-carotene concentrations decrease throughout the dry period and reach their nadir in about the first week postpartum, and this change reflects energy balance during the peripartum period. β-Carotene plays a role independently of vitamin A in the reproductive performance of dairy cows, and the positive relationship between supplemental β-carotene and reproductive function has been demonstrated in many studies during the past decades. However, β-carotene content in corn silage, which is a popular main feed in high-producing dairy cows, is very low. This review describes nutritional factors related to ovulation during the first follicular wave postpartum in dairy cows."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I727,I727)","v":22315388},{"$f":"(LEN($J727) - LEN(SUBSTITUTE(LOWER($J727),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J727) - LEN(SUBSTITUTE(LOWER($J727),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J727) - LEN(SUBSTITUTE(LOWER($J727),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B727:D727)","v":0},2012,"Experiences integrating delivery of maternal and child health services with childhood immunization programs: systematic review update.","Wallace",22315388,"Experiences integrating delivery of maternal and child health services with childhood immunization programs: systematic review update.    Abstract:    BACKGROUND : The World Health Organization and the United Nations Childrens Fund promote integration of maternal and child health (MCH) and immunization services as a strategy to strengthen immunization programs. We updated our previous review of integrated programs and reviewed reports of integration of MCH services with immunization programs at the service delivery level.  METHODS : Published and unpublished reports of interventions integrating MCH and immunization service delivery were reviewed by searching journal databases and Web sites and by contacting organizations.  RESULTS : Among 27 integrated activities, interventions included hearing screening, human immunodeficiency virus services, vitamin A supplementation, deworming tablet administration, malaria treatment, bednet distribution, family planning, growth monitoring, and health education. When reported, linked intervention coverage increased, though not to the level of the corresponding immunization coverage in all cases. Logistical difficulties, time-intensive interventions ill suited for campaign delivery, concern for harming existing services, inadequate overlap of target age groups, and low immunization coverage were identified as challenges.  CONCLUSIONS : Results of this review reinforce our 2005 review findings, including importance of intervention compatibility and focus on immunization program strength. Ensuring proper planning and awareness of compatibility of service delivery requirements were found to be important. The review revealed gaps in information about costs, comparison to vertical delivery, and impact on all integrated interventions that future studies should aim to address."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I728,I728)","v":22326691},{"$f":"(LEN($J728) - LEN(SUBSTITUTE(LOWER($J728),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J728) - LEN(SUBSTITUTE(LOWER($J728),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J728) - LEN(SUBSTITUTE(LOWER($J728),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B728:D728)","v":0},2012,"Epidemiology of vitamin A deficiency and xerophthalmia in at-risk populations.","Sherwin",22326691,"Epidemiology of vitamin A deficiency and xerophthalmia in at-risk populations.    Abstract:   Vitamin A deficiency (VAD) is an important public health problem worldwide that contributes significantly to the global burden of disease. Vitamin A deficiency disorders include xerophthalmia and increased risk of infectious diseases, both of which increase risk of mortality. Xerophthalmia is also a leading cause of preventable blindness. Areas with highly prevalent VAD often share common dietary and other environmental exposures, including poverty, infectious diseases, limited development and poor availability of vitamin A containing food. Globally, the prevalence of VAD has been declining, which may be due to widespread vitamin A supplementation in conjunction with measles immunisation in at-risk populations. Recent meta-analyses confirm that provision of vitamin A to children aged between 6 months and 5 years confers a significant mortality benefit. Further preventative measures for VAD comprise improving availability of vitamin A containing food, including foods biofortified with vitamin A. Ensuring vitamin A is available in any form in adequate quantities remains problematic, especially in areas affected by environmental catastrophes and conflict, and other areas where access to vitamin A containing foods and healthcare interventions is limited. Hence, it remains essential that maternal and child health workers remain vigilant for VAD in nutritionally vulnerable populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I729,I729)","v":22089440},{"$f":"(LEN($J729) - LEN(SUBSTITUTE(LOWER($J729),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J729) - LEN(SUBSTITUTE(LOWER($J729),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J729) - LEN(SUBSTITUTE(LOWER($J729),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B729:D729)","v":0},2011,"Micronutrients in HIV/AIDS: is there evidence to change the WHO 2003 recommendations?","Forrester",22089440,"Micronutrients in HIV/AIDS: is there evidence to change the WHO 2003 recommendations?    Abstract:   To establish whether there is new evidence to inform changes to WHO 2003 recommendations for micronutrient intake in persons with HIV/AIDS, we conducted a narrative review of the literature published from 2003 to 2010. Although the review focused on new randomized controlled trials of multiple micronutrients in HIV-infected adults, including pregnant and lactating women, we also considered randomized trials of single micronutrients. The review found that there are few published randomized controlled trials of micronutrients in HIV-infected persons and that most trials used high-dose multiple micronutrient supplementation. The trials were heterogeneous with respect to the composition and dose of micronutrients used and the target population studied. Despite this heterogeneity, 5 of 6 trials that used high-dose multiple micronutrients showed benefits in terms of either improved CD4 cell counts or survival. However, many of these trials were small and of short duration, and therefore the long-term risks and benefits of high-dose multiple micronutrients are not established. The current WHO recommendation for an intake of micronutrients at Recommended Dietary Allowance amounts continues to be a reasonable target for persons with clinically stable HIV infection. In light of new data that show adverse effects of high-dose vitamin A, the current recommendation for a single high dose of vitamin A in HIV-infected women within 6 wk of delivery should be reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I730,I730)","v":21975770},{"$f":"(LEN($J730) - LEN(SUBSTITUTE(LOWER($J730),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J730) - LEN(SUBSTITUTE(LOWER($J730),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J730) - LEN(SUBSTITUTE(LOWER($J730),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B730:D730)","v":0},2011,"Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less.","Gogia",21975770,"Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less.    Abstract:    BACKGROUND : Vitamin A deficiency is a significant public health problem in low and middle income countries. Vitamin A supplementation (VAS) provided to lactating postpartum mothers or to infants less than six months of age are two possible strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity.  OBJECTIVES : To evaluate the effect of:1. VAS in postpartum breast feeding mothers in low and middle income countries, irrespective of antenatal VAS status, on mortality, morbidity and adverse effects in their infants up until the age of one year.2. VAS initiated in the first half of infancy (lt; 6 months of age) in low and middle income countries, irrespective of maternal antenatal or postnatal VAS status, on mortality, morbidity and adverse effects up until the age of one year.  SEARCH STRATEGY : The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), EMBASE, MEDLINE, clinical trials websites, conference proceedings, donor agencies, experts and researchers (up to October 15, 2010).  SELECTION CRITERIA : Randomized or quasi-randomised, individually or cluster randomised, placebo controlled trials involving synthetic VAS provided to the postpartum mothers or their infants up to the age of six months were eligible.  DATA COLLECTION AND ANALYSIS : Two review authors assessed the studies for their risk of bias and collected data on outcomes.  MAIN RESULTS : Of the 18 included studies, eight provided information on maternal VAS and 15 on infant VAS.For maternal VAS, there was no evidence of a reduced risk of mortality of their babies during infancy (96,203 participants, seven studies, high quality evidence; random-effects model RR 1.00, 95% CI 0.94 to 1.06, P = 0.9; test of heterogeneity I(2) = 0%, P = 0.9) or in the neonatal period (moderate quality evidence); nor of morbidities (very low quality evidence).  For infant VAS, there was no evidence of a reduced risk of mortality during infancy (59,402 participants, nine studies, moderate quality evidence; random-effects model RR 0.97, 0.83 to 1.12, P = 0.65; test of heterogeneity I(2) = 49%, P = 0.05) or in the neonatal period, nor morbidities (low quality evidence), but an increased risk of bulging fontanelle (32,978 participants, 10 studies, low quality evidence; random-effects model RR 1.55, 1.05 to 2.28, P = 0.03; test of heterogeneity I(2) = 68%, P = 0.0009).  AUTHORS CONCLUSIONS : There is no convincing evidence that either maternal postpartum or infant vitamin A supplementation results in a reduction in infant mortality or morbidity in low and middle income countries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I731,I731)","v":21967161},{"$f":"(LEN($J731) - LEN(SUBSTITUTE(LOWER($J731),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J731) - LEN(SUBSTITUTE(LOWER($J731),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J731) - LEN(SUBSTITUTE(LOWER($J731),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B731:D731)","v":0},2011,"Vitamin A and clefting: putative biological mechanisms.","Ackermans",21967161,"Vitamin A and clefting: putative biological mechanisms.    Abstract:   Nutritional factors such as vitamin intake contribute to the etiology of cleft palate. Vitamin A is a regulator of embryonic development. Excess vitamin A can cause congenital malformations such as spina bifida and cleft palate. Therefore, preventive nutritional strategies are required. This review identifies putative biological mechanisms underlying the association between maternal vitamin A intake and cleft palate. Excessive vitamin A may disturb all three stages of palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and thus prevent tissue development; 2) it may prevent shelf elevation by affecting extracellular matrix composition and hydration; and 3) during shelf fusion, it may affect epithelial differentiation and apoptosis, which precludes the formation of a continuous palate. In general, high doses of vitamin A affect palatogenesis through interference with cell proliferation and growth factors such as transforming growth factor β and platelet-derived growth factor. The effects of lower doses of vitamin A need to be investigated in greater depth in order to improve public health recommendations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I732,I732)","v":21816150},{"$f":"(LEN($J732) - LEN(SUBSTITUTE(LOWER($J732),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J732) - LEN(SUBSTITUTE(LOWER($J732),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J732) - LEN(SUBSTITUTE(LOWER($J732),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B732:D732)","v":0},2011,"The gut as communicator between environment and host: immunological consequences.","Brandtzaeg",21816150,"The gut as communicator between environment and host: immunological consequences.    Abstract:   During human evolution, the mucosal immune system developed two anti-inflammatory mechanisms: immune exclusion by secretory antibodies (SIgA and SIgM) to control epithelial colonization of microorganisms and inhibit penetration of harmful substances; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens such as food proteins. The latter function is referred to as oral tolerance when induced via the gut. Similar mechanisms also control immunity to commensal bacteria. The development of immune homeostasis depends on quot;windows of opportunityquot; where adaptive and innate immunities are coordinated by antigen-presenting cells; their function is not only influenced by microbial products but also by dietary constituents, including vitamin A and lipids like polyunsaturated omega-3 fatty acids. These factors can in several ways exert beneficial effects on the immunophenotype of the infant. Also breast milk provides immune-modulating factors and SIgA antibodies - reinforcing the gut barrier. Mucosal immunity is most abundantly expressed in the gut, and the intestinal mucosa of an adult contains at least 80% of the bodys activated B cells - terminally differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric IgA which is exported by secretory epithelia expressing the polymeric Ig receptor (pIgR), also called membrane secretory component (SC). Immune exclusion is therefore performed mainly by SIgA. Notably, pIgR knockout mice which lack SIgs show increased uptake of food and microbial antigens and they have a hyper-reactive immune system with disposition for anaphylaxis; but this untoward development is counteracted by cognate oral tolerance induction as a homeostatic back-up mechanism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I733,I733)","v":21707575},{"$f":"(LEN($J733) - LEN(SUBSTITUTE(LOWER($J733),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J733) - LEN(SUBSTITUTE(LOWER($J733),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J733) - LEN(SUBSTITUTE(LOWER($J733),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B733:D733)","v":0},2011,"Severe acquired anaemia in Africa: new concepts.","van Hensbroek",21707575,"Severe acquired anaemia in Africa: new concepts.    Abstract:   Severe anaemia is common in Africa. It has a high mortality and particularly affects young children and pregnant women. Recent research provides new insights into the mechanisms and causes of severe acquired anaemia and overturns accepted dogma. Deficiencies of vitamin B12 and vitamin A, but not of iron or folic acid, are associated with severe anaemia. Bacterial infections and, in very young children, hookworm infections are also common in severe anaemia. Irrespective of the aetiology, the mechanism causing severe anaemia is often red cell production failure. Severe anaemia in Africa is therefore a complex multi-factorial syndrome, which, even in an individual patient, is unlikely to be amenable to a single intervention. Policies and practices concerning anaemia diagnosis, treatment and prevention need to be substantially revised if we are to make a significant impact on the huge burden of severe anaemia in Africa."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I734,I734)","v":21664474},{"$f":"(LEN($J734) - LEN(SUBSTITUTE(LOWER($J734),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J734) - LEN(SUBSTITUTE(LOWER($J734),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J734) - LEN(SUBSTITUTE(LOWER($J734),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B734:D734)","v":0},2011,"Pyridoxine supply in human development.","Bowling",21664474,"Pyridoxine supply in human development.    Abstract:   Vitamin B(6) has an important role in the function of the human nervous system. Experimental data are not generally available on the role in human development, but significant conclusions may be made from studies of the effect of disorders of B(6) vitamer metabolism. Vitamin B(6) comprises seven compounds - pyridoxal, pyridoxine, pyridoxamine and their respective 5 phosphates. The common active form in human tissue is the 5-phosphate form of pyridoxal (PLP) most of which is found in muscle bound to phosphorylase. Like many vitamins, B(6) can function both as a co-enzyme and as a chaperone. Pyridoxal-5-phosphate is the metabolically active form and is involved in 100 enzymatic reactions including carbohydrate, amino acid, and fatty acid metabolism. There is evidence that in some situations B(6) vitamers can function as antioxidants. The fetus is dependent on the placenta for supply of vitamin B(6) and the demand correlates with amino acid metabolism. Few reports are available on the role of B(6) in embryogenesis. Studies of human disorders where B(6) metabolism is blocked show a major role in neurotransmitter function with secondary cerebral and cerebellar hypoplasia. Pyridoxine potentiates vitamin A teratogenicity and an excess leads to peripheral nerve cell degeneration. The key role of vitamin B(6) in the developing human is in metabolism, especially of the neurotransmitters."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I735,I735)","v":21614468},{"$f":"(LEN($J735) - LEN(SUBSTITUTE(LOWER($J735),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J735) - LEN(SUBSTITUTE(LOWER($J735),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J735) - LEN(SUBSTITUTE(LOWER($J735),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B735:D735)","v":0},2012,"Advances in non-surgical treatments for urinary tract infections in children.","Yang",21614468,"Advances in non-surgical treatments for urinary tract infections in children.    Abstract:    OBJECTIVE : With growing antibiotics failure due to emerging resistance of bacteria, non-surgical management of pediatric UTI plays a more important role because of its non-invasive characteristics and little adverse effects.  METHODS : We searched the Pubmed for management of UTI in children other than surgical correction and antibiotics using terms: risk factor, prepuce/phimosis, steroid cream/steroid, behavioral therapy, urotherapy, biofeedback/pelvic floor exercise, adrenergic antagonist, anticholinergics, diet/dietary, dysfunctional voiding/dysfunctional elimination syndrome, constipation, dietary, clean intermittent catheterization, probiotics/lactobacillus, cranberry, vitamin supplement, breastfeeding, breast milk, with infant/child/children/pediatrics/pediatrics and urinary tract infection.  RESULTS : The proposed non-surgical management of pediatric UTI included behavioral modification (timed voiding and adequate fluids intake), topical steroid for phimosis, nutrient supplements (breast milk, cranberry, probiotics, and vitamin A), biofeedback training for dysfunctional voiding, anticholinergics for reducing intravesical pressure, alpha-blockers in dysfunctional voiding and neurogenic bladder, and intermittent catheterization for children with large PVR.  CONCLUSION : The published reports usually included small number of patients and were lacking of randomization and controlled group. Further well-designed studies are warranted to support the concepts of non-operative management for pediatric UTI."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I736,I736)","v":21470458},{"$f":"(LEN($J736) - LEN(SUBSTITUTE(LOWER($J736),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J736) - LEN(SUBSTITUTE(LOWER($J736),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J736) - LEN(SUBSTITUTE(LOWER($J736),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B736:D736)","v":0},2011,"Remaining questions about clinical variola major.","Lane",21470458,"Remaining questions about clinical variola major.    Abstract:   After the recent summary of World Health Organization-authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I737,I737)","v":21410888},{"$f":"(LEN($J737) - LEN(SUBSTITUTE(LOWER($J737),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J737) - LEN(SUBSTITUTE(LOWER($J737),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J737) - LEN(SUBSTITUTE(LOWER($J737),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B737:D737)","v":0},2011,"Accelerating improvements in nutritional and health status of young children in the Sahel region of Sub-Saharan Africa: review of international guidelines on infant and young child feeding and nutrition.","Wuehler",21410888,"Accelerating improvements in nutritional and health status of young children in the Sahel region of Sub-Saharan Africa: review of international guidelines on infant and young child feeding and nutrition.    Abstract:   The United Nations Convention on the Rights of the Child holds governments responsible to ensure childrens right to the highest attainable standard of health by providing breastfeeding support, and access to nutritious foods, appropriate health care, and clean drinking water. International experts have identified key child care practices and programmatic activities that are proven to be effective at reducing infant and young child undernutrition, morbidity, and mortality. Nevertheless, progress towards reducing the prevalence of undernutrition has been sporadic across countries of the Sahel sub-region of Sub-Saharan Africa. In view of this uneven progress, a working group of international agencies was convened to Reposition childrens right to adequate nutrition in the Sahel. The first step towards this goal was to organize a situational analysis of the legislative, research, and programmatic activities related to infant and young child nutrition (IYCN) in six countries of the sub-region: Burkina Faso, Chad, Mali, Mauritania, Niger, and Senegal. The purposes of this introductory paper are to review current information concerning the nutritional and health status of infants and young children in the Sahel and to summarize international guidelines on optimal IYCN practices. These guidelines were used in completing the above-mentioned situational analyses and encompass specific recommendations on: (i) breastfeeding (introduction within the first hour after birth, exclusivity to 6 months, continuation to at least 24 months); (ii) complementary feeding (introduction at 6 months, use of nutrient dense foods, adequate frequency and consistency, and responsive feeding); (iii) prevention and/or treatment of micronutrient deficiencies (vitamin A, zinc, iron and anaemia, and iodine); (iv) prevention and/or treatment of acute malnutrition; (v) feeding practices adapted to the maternal situation to reduce mother-to-child transmission of HIV; (vi) activities to ensure food security; and (vii) the promotion of hygienic practices concerning food preparation and storage and environmental sanitation. The following papers in this issue will present results of the situational analyses for the individual countries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I738,I738)","v":21398228},{"$f":"(LEN($J738) - LEN(SUBSTITUTE(LOWER($J738),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J738) - LEN(SUBSTITUTE(LOWER($J738),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J738) - LEN(SUBSTITUTE(LOWER($J738),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B738:D738)","v":0},2011,"Management of acne.","Kraft",21398228,"Management of acne.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I739,I739)","v":21310368},{"$f":"(LEN($J739) - LEN(SUBSTITUTE(LOWER($J739),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J739) - LEN(SUBSTITUTE(LOWER($J739),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J739) - LEN(SUBSTITUTE(LOWER($J739),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B739:D739)","v":0},2011,"[Narrowband UV-B, monochromatic excimer laser, and photodynamic therapy in psoriasis: a consensus statement of the Spanish Psoriasis Group].","Carrascosa",21310368,"[Narrowband UV-B, monochromatic excimer laser, and photodynamic therapy in psoriasis: a consensus statement of the Spanish Psoriasis Group].    Abstract:   Novel treatment strategies and new information concerning the management of moderate to severe psoriasis justify a reassessment of the role of the classic therapies in this setting. This consensus statement evaluates narrowband UV-B therapy, which is currently considered the phototherapy option of choice in psoriasis because of its risk-to-benefit ratio. The role of excimer laser and photodynamic therapies are also discussed. These targeted therapies are still only available in a small number of centers in Spain and are used principally in the treatment of localized and recalcitrant forms of psoriasis. We discuss the efficacy and safety of phototherapy as well as treatment regimens, combination therapy, and clinical considerations relating to the characteristics of the patient or the disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I740,I740)","v":21253797},{"$f":"(LEN($J740) - LEN(SUBSTITUTE(LOWER($J740),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J740) - LEN(SUBSTITUTE(LOWER($J740),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J740) - LEN(SUBSTITUTE(LOWER($J740),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B740:D740)","v":0},2011,"Chemoprevention of hormone receptor-negative breast cancer: new approaches needed.","Uray",21253797,"Chemoprevention of hormone receptor-negative breast cancer: new approaches needed.    Abstract:   Results from clinical trials have demonstrated that it is possible to prevent estrogen-responsive breast cancers by targeting the estrogen receptor with selective estrogen receptor modulators (SERMs) (tamoxifen, raloxifene, or lasofoxifene) or with aromatase inhibitors (AIs) (anastrozole, letrozole, or exemestene). Results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective in preventing breast cancer than SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many ER-positive breast cancers, these drugs do not prevent ER-negative breast cancer. These results show that new approaches are needed for the prevention of this aggressive form of breast cancer. Our laboratory and clinical efforts have been focused on identifying critical molecular pathways in breast cells that can be targeted for the prevention of ER-negative breast cancer. Our preclinical studies have demonstrated that other nuclear receptors, such as RXR receptors, vitamin D receptors, as well as others are critical for the growth of ER-negative breast cells and for the transformation of these cells into ER-negative cancers. Other studies show that growth factor pathways including those activated by EGFR, Her2, and IGFR, which are activated in many ER-negative breast cancers, can be targeted for the prevention of ER-negative breast cancer in mice. Clinical studies have also shown that PARP inhibitors are effective for the treatment of breast cancers arising in BRCA-1 or -2 mutation carriers, suggesting that targeting PARP may also be useful for the prevention of breast cancers arising in these high-risk individuals. Most recently, we have demonstrated that ER-negative breast cancers can be subdivided into four distinct groups based on the kinases that they express. These groups include ER-negative/Her-2-positive groups (the MAPK and immunomodulatory groups) and ER-negative/Her2-negative groups (the S6K and the cell cycle checkpoint groups). These groups of ER-negative breast cancers can be targeted with kinase inhibitors specific for each subgroup. These preclinical studies have supported the development of several clinical trials testing targeted agents for the prevention of breast cancer. The results of a completed Phase II cancer prevention trial using the RXR ligand bexarotene in women at high risk of breast cancer will be reviewed, and the current status of an ongoing Phase II trial using the EGFR and Her2 kinase inhibitor lapatinib for the treatment of women with DCIS breast cancer will be presented. It is anticipated that in the future these molecularly targeted drugs will be combined with hormonal agents such as SERMs or aromatase inhibitors to prevent all forms of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I741,I741)","v":21194406},{"$f":"(LEN($J741) - LEN(SUBSTITUTE(LOWER($J741),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J741) - LEN(SUBSTITUTE(LOWER($J741),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J741) - LEN(SUBSTITUTE(LOWER($J741),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B741:D741)","v":0},2011,"Immunologic impact of nutrient depletion in chronic obstructive pulmonary disease.","Herzog",21194406,"Immunologic impact of nutrient depletion in chronic obstructive pulmonary disease.    Abstract:   Chronic obstructive pulmonary disease (COPD) is characterized by small airways, alveolar and systemic inflammation and remodeling causing airflow limitation and parenchymal destruction. Mechanisms of oxidative stress include exposure to cigarette smoke and environmental stimuli that activate proinflammatory responses, stimulate alveolar neutrophils and macrophages and lead to apoptosis of endothelial and epithelial cells. COPD may have origins in fetal and neonatal factors that affect intrauterine growth of lungs and airways, lead to low birth weight and impair the development of immune response. Maternal smoking may diminish interferon response secondary to micronutrient deficiency, particularly of Vitamin A, and support persistence of Respiratory Syncytial Virus (RSV), normally a childhood pathogen, into adult life. Muscle wasting and cachexia are systemic features of COPD. Cachexia is associated with systemic inflammation and worsened by Vitamin D deficiency. Nutritional depletion is related to poor survival and is a rational target for therapeutic intervention in advanced and critically ill patients. Preliminary studies and suggest that supplementation with omega-3 polyunsaturated fatty acids and micronutrient repletion with Vitamin A, Vitamin D3, and zinc may have beneficial effects in COPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I742,I742)","v":20933522},{"$f":"(LEN($J742) - LEN(SUBSTITUTE(LOWER($J742),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J742) - LEN(SUBSTITUTE(LOWER($J742),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J742) - LEN(SUBSTITUTE(LOWER($J742),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B742:D742)","v":0},2011,"Mother-to-child transmission of HIV-1 in sub-Saharan Africa: past, present and future challenges.","Taha",20933522,"Mother-to-child transmission of HIV-1 in sub-Saharan Africa: past, present and future challenges.    Abstract:   HIV prevalence continues to be high among women of reproductive age in sub-Saharan Africa. In 2007 the HIV prevalence among pregnant women attending antenatal clinics was gt;20% in the southern African counties of Botswana, Swaziland, South Africa and Lesotho. Mother-to-child transmission (MTCT) of HIV can occur in-utero, intrapartum or postnatally. Without any preventive measure the overall rate of the MTCT of HIV in breastfeeding women could be 25-45%. Prior to the discovery of successful antiretroviral interventions to prevent the MTCT of HIV in sub-Saharan Africa (before 1999), innovative research determined the magnitude of the problem, the impact of the HIV epidemic on mothers and children, and the main risk factors associated with MTCT. Non-antiretroviral interventions conducted before 1999 such as washing the birth canal with antiseptics and antenatal supplementation with vitamin A did not reduce the MTCT of HIV. However, during the period 1999 to present, major successes were made in the prevention of the MTCT of HIV. The use of single-dose nevirapine prophylaxis to the mother and infant reduced the MTCT of HIV to ~12%. Subsequently, longer prophylaxis and combined antiretroviral regimens were shown to be highly effective and very low HIV transmission rates comparable to those in developed countries were reported in some clinical trial settings in sub-Saharan Africa. The future is promising but challenges remain. The current successful intervention modalities are entirely dependent on antiretrovirals and breastfeeding continues to be vital for the survival of the child in the African setting. Reviewing past and present achievements assists in focusing future research and development of prevention programs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I743,I743)","v":22296250},{"$f":"(LEN($J743) - LEN(SUBSTITUTE(LOWER($J743),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J743) - LEN(SUBSTITUTE(LOWER($J743),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J743) - LEN(SUBSTITUTE(LOWER($J743),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B743:D743)","v":0},2010,"Nutritional requirements during lactation. Towards European alignment of reference values: the EURRECA network.","Hall Moran",22296250,"Nutritional requirements during lactation. Towards European alignment of reference values: the EURRECA network.    Abstract:   There is considerable variation in reference values for micronutrient intake during lactation across Europe. The European Micronutrients Recommendations Aligned project aims to harmonize dietary recommendations throughout Europe. Recommended nutrient intakes during lactation are based on limited data and are often extrapolated from known secretion of the nutrient in milk with adjustments for bioavailability, so that differences between values can be partly ascribed to differences in methodological approaches and how these approaches were applied. Few studies have considered the impact of lactation on the mothers nutritional status. Rather, focus has been placed on the influence of maternal nutritional status on the composition of her breast milk. Most common nutritional deficits in breast milk are the result of maternal deficiencies of the water-soluble vitamins, thiamine, riboflavin and vitamins B6 and B12. Other than maternal vitamin A status, which to some extent is reflected in breast milk, concentrations of fat-soluble vitamins and most minerals in breast milk are less affected by maternal status. Factors relating to suboptimal maternal nutritional status during lactation include maternal age, diet and lifestyle factors and spacing of consecutive births. Recent research is providing new knowledge on the micronutrient requirements of lactating women. Identifying needs for research and improving understanding of the differences in values that have been derived by various committees and groups across Europe will enhance transparency and facilitate the application of dietary recommendations in policy-making decision and their translation into recommendations for lactating women. Given the wide variation in breastfeeding practices across Europe, making nutritional recommendations for lactating women is complex and challenging. Thus, it is crucial to first examine the cultural practices within and across European populations and to assess its relevance before making recommendations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I744,I744)","v":20864442},{"$f":"(LEN($J744) - LEN(SUBSTITUTE(LOWER($J744),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J744) - LEN(SUBSTITUTE(LOWER($J744),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J744) - LEN(SUBSTITUTE(LOWER($J744),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B744:D744)","v":0},2010,"Comment on: Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomised controlled trials.","Fisker",20864442,"Comment on: Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomised controlled trials.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I745,I745)","v":20606633},{"$f":"(LEN($J745) - LEN(SUBSTITUTE(LOWER($J745),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J745) - LEN(SUBSTITUTE(LOWER($J745),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J745) - LEN(SUBSTITUTE(LOWER($J745),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B745:D745)","v":0},2010,"Food allergy: separating the science from the mythology.","Brandtzaeg",20606633,"Food allergy: separating the science from the mythology.    Abstract:   Numerous genes are involved in innate and adaptive immunity and these have been modified over millions of years. During this evolution, the mucosal immune system has developed two anti-inflammatory strategies: immune exclusion by the use of secretory antibodies to control epithelial colonization of microorganisms and to inhibit the penetration of potentially harmful agents; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens, such as food proteins. The latter strategy is called oral tolerance when induced via the gut. Homeostatic mechanisms also dampen immune responses to commensal bacteria. The mucosal epithelial barrier and immunoregulatory network are poorly developed in newborns. The perinatal period is, therefore, critical with regard to the induction of food allergy. The development of immune homeostasis depends on windows of opportunity during which innate and adaptive immunity are coordinated by antigen-presenting cells. The function of these cells is not only orchestrated by microbial products but also by dietary constituents, including vitamin A and lipids, such as polyunsaturated omega-3 fatty acids. These factors may in various ways exert beneficial effects on the immunophenotype of the infant. The same is true for breast milk, which provides immune-inducing factors and secretory immunoglobulin A, which reinforces the gut epithelial barrier. It is not easy to dissect the immunoregulatory network and identify variables that lead to food allergy. This Review discusses efforts to this end and outlines the scientific basis for future food allergy prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I746,I746)","v":20580500},{"$f":"(LEN($J746) - LEN(SUBSTITUTE(LOWER($J746),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J746) - LEN(SUBSTITUTE(LOWER($J746),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J746) - LEN(SUBSTITUTE(LOWER($J746),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B746:D746)","v":0},2010,"A review of select vitamins and minerals used by postmenopausal women.","Dennehy",20580500,"A review of select vitamins and minerals used by postmenopausal women.    Abstract:    OBJECTIVES : The purpose of this review is to summarize the effectiveness of select vitamins, minerals and trace elements in postmenopausal women for their effects on bone health, cardiovascular health, breast cancer, cognition and vasomotor symptoms.  METHODS : Review of the relevant literature and results from recent clinical studies, as well as critical analyses of published systematic reviews and meta-analyses were obtained from PubMed and Cochrane Library of Reviews. Vitamin A, the B vitamins, vitamin C, calcium, vitamin D, vitamin E, vitamin K, magnesium, selenium and zinc were selected for review. In circumstances where the vitamin, mineral or trace element has not been studied for a given condition, no information was provided.  RESULTS AND DISCUSSION : All vitamins, minerals and trace elements play an important role in maintaining health and wellbeing among menopausal women. Adequate dietary intake is essential and supplementation should be considered in women with documented malabsorption syndromes or deficiencies. Based on a review of the literature, supplementation with vitamin C, D, K and calcium can also be recommended for proper maintenance of bone health. The only supplement studied for vasomotor symptoms was vitamin E and this vitamin lacked clinical support. Supplementation in healthy postmenopausal women with vitamins and minerals in diet or pill forms cannot be recommended currently for any other indications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I747,I747)","v":20556793},{"$f":"(LEN($J747) - LEN(SUBSTITUTE(LOWER($J747),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J747) - LEN(SUBSTITUTE(LOWER($J747),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J747) - LEN(SUBSTITUTE(LOWER($J747),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B747:D747)","v":0},2010,"Prevention of diarrhoea in children with HIV infection or exposure to maternal HIV infection.","Humphreys",20556793,"Prevention of diarrhoea in children with HIV infection or exposure to maternal HIV infection.    Abstract:    BACKGROUND : Diarrhoea is a major cause of morbidity and mortality among infants and children worldwide, especially in low- and middle-income countries. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a condition that similarly disproportionately affects low- and middle-income countries; of the nearly 2.1 million children under age 15 years living with HIV/AIDS, the large majority reside in sub-Saharan Africa. Infants and children with HIV infection have more frequent and more severe diarrhoea than children without HIV. Interventions including vitamin A, zinc and cotrimoxazole may contribute substantially to preventing diarrhoea in children with HIV infection or exposure to HIV.  OBJECTIVES : We perform a systematic review of randomised controlled trials and nonrandomised studies that examine the effectiveness of vitamin A, zinc and cotrimoxazole on mortality and morbidity from diarrhoea in HIV-infected and -exposed infants and children.  SEARCH STRATEGY : Electronic databases including Pubmed, Central and EMBASE were searched without limits to language from 1980 to April 2010. Conference database searches were performed, experts were contacted and bibliographies were handsearched.  SELECTION CRITERIA : Randomised controlled trials (RCTs) and nonrandomised studies (NRSs) that examined the effectiveness of the three interventions were included.  DATA COLLECTION AND ANALYSIS : Two reviewers independently assessed citations for eligibility and double-extracted included studies. Assessment of bias of individual studies was performed independently by both reviewers. Only two summary estimates were performed due to heterogeneity in study design and interventions.  MAIN RESULTS : Four RCTs were identified for vitamin A. One RCT was identified for zinc. One RCT and two NRSs were identified for cotrimoxazole. Vitamin A reduced mortality overall in children with HIV infection (four studies). A pooled estimate of three studies for reduction in mortality from vitamin A compared to placebo had a relative risk (DerSimonian and Laird method, random effects) of 0.50 (95% confidence interval (CI): 0.31 to 0.79) in 267 patients. Diarrheoa-specific mortality did not reach statistical significance and diarrhoeal morbidity outcomes were variable in three trials. Zinc supplementation reduced the number of physician visits for watery diarrhoea in one trial. Cotrimoxazole reduced mortality and hospitalisations compared to placebo in one RCT, although diarrhoea-specific morbidities were not significant.  AUTHORS CONCLUSIONS : Vitamin A shows benefits in reduction of mortality in HIV-infected children. The effect of vitamin A on children with HIV exposure is not clear and needs further review. Zinc and combination vitamin A, zinc and micronutrient supplementation did not show an effect compared to vitamin A alone in children with HIV infection. Cotrimoxazole reduced mortality and some morbidity in children with HIV infection. Further research may clarify the effects of these interventions on morbidity from diarrhoea and in the population of children with HIV exposure."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I748,I748)","v":20522482},{"$f":"(LEN($J748) - LEN(SUBSTITUTE(LOWER($J748),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J748) - LEN(SUBSTITUTE(LOWER($J748),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J748) - LEN(SUBSTITUTE(LOWER($J748),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B748:D748)","v":0},2010,"Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomized controlled trials.","Gogia",20522482,"Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomized controlled trials.    Abstract:    BACKGROUND : Maternal postpartum vitamin A supplementation (VAS) provides an opportunity to improve vitamin A nutriture of breast fed infants in developing countries and can possibly prevent infant mortality and morbidity attributable to vitamin A deficiency.  OBJECTIVE : To evaluate the effect of maternal postpartum VAS on infant mortality, morbidity and adverse effects.  DESIGN : Systematic review, meta-analysis and meta-regression of randomized controlled trials.  DATA SOURCES : Electronic databases and abstracts and proceedings of micronutrient conferences.  REVIEW METHODS : Randomized or quasi-randomized, placebo-controlled trials evaluating the effect of postpartum, maternal synthetic VAS on mortality or morbidity within infancy (lt;1 year), or adverse effects.  RESULTS : The seven included trials were from developing countries. There was no evidence of a reduced risk of mortality during infancy [relative risk (RR) 1.05, 95% confidence interval (CI) 0.92-1.20, P = 0.438; I² = 0%, P = 0.940]. No variable emerged as a significant predictor of mortality but data for high-risk groups (high maternal night blindness prevalence and low birth weights) was restricted. Neonatal mortality data was available from a single study, (RR 1.09, 95% CI 0.88-1.35; P = 0.422). In two trials, there was no evidence of a reduced risk of cause-specific mortality. In one trial, there was no evidence of a decrease in either diarrhoea or acute respiratory infection. No adverse effects were reported in the single relevant trial.  CONCLUSIONS : There is no evidence of a mortality or morbidity benefit to the infant following postpartum maternal VAS. Only prevention of infant morbidity or mortality would be sufficient justification for initiating this intervention in public health programmes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I749,I749)","v":20511062},{"$f":"(LEN($J749) - LEN(SUBSTITUTE(LOWER($J749),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J749) - LEN(SUBSTITUTE(LOWER($J749),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J749) - LEN(SUBSTITUTE(LOWER($J749),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B749:D749)","v":0},2010,"Vitamin D analogs.","Jones",20511062,"Vitamin D analogs.    Abstract:   Vitamin D has gone through a renaissance with the association of vitamin D deficiency with a wide array of common diseases including breast, colorectal and prostate cancers, cardio-vascular disease, autoimmune conditions and infections. Vitamin D analogs constitute a valuable group of compounds which can be used to regulate gene expression in functions as varied as calcium and phosphate homeostasis, as well as cell growth regulation and cell differentiation of a wide spectrum of cell types. This review will discuss the full range of vitamin D compounds currently available, some of their possible uses, and potential mechanisms of action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I750,I750)","v":22254046},{"$f":"(LEN($J750) - LEN(SUBSTITUTE(LOWER($J750),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J750) - LEN(SUBSTITUTE(LOWER($J750),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J750) - LEN(SUBSTITUTE(LOWER($J750),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B750:D750)","v":0},2010,"Micronutrients, N-acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression.","Hummelen",22254046,"Micronutrients, N-acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression.    Abstract:   Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I751,I751)","v":20478364},{"$f":"(LEN($J751) - LEN(SUBSTITUTE(LOWER($J751),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J751) - LEN(SUBSTITUTE(LOWER($J751),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J751) - LEN(SUBSTITUTE(LOWER($J751),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B751:D751)","v":0},2010,"Crosstalk and DC-SCRIPT: expanding nuclear receptor modulation.","Ansems",20478364,"Crosstalk and DC-SCRIPT: expanding nuclear receptor modulation.    Abstract:   Nuclear receptors (NR) are intracellular receptors that execute a transcriptional program upon binding to hormones, vitamins and metabolic products. They are key regulators of distinct physiological processes, including growth and differentiation, metabolism, and immunity. The impact of NR activation on a given cell can differ from proliferation induction to programmed cell death. NR malfunction is associated with different diseases, such as diabetes, chronic inflammatory diseases and cancer. Much progress has been made towards understanding the transcriptional regulation by individual NR at the molecular level. However, essentially every cell expresses multiple NR and will encounter complex mixtures of NR ligands during its life cycle. In this review, we will focus on novel insights in balancing NR activity via NR crosstalk and DC-SCRIPT/ZNF366, a bi-functional NR coregulator. The impact on breast cancer development and prognosis will be discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I752,I752)","v":20388388},{"$f":"(LEN($J752) - LEN(SUBSTITUTE(LOWER($J752),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J752) - LEN(SUBSTITUTE(LOWER($J752),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J752) - LEN(SUBSTITUTE(LOWER($J752),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B752:D752)","v":0},2010,"[Transcription factor Forkhead-box A1 and breast cancer].","Liu",20388388,"[Transcription factor Forkhead-box A1 and breast cancer].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I753,I753)","v":20095133},{"$f":"(LEN($J753) - LEN(SUBSTITUTE(LOWER($J753),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J753) - LEN(SUBSTITUTE(LOWER($J753),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J753) - LEN(SUBSTITUTE(LOWER($J753),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B753:D753)","v":0},2009,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.","Oguntibeju",20095133,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.    Abstract:   The link between dietary fats and cardiovascular disease has created a growing interest in dietary red palm oil research. Also, the link between nutrition and health, oxidative stress and the severity or progression of disease has stimulated further interest in the potential role of red palm oil (a natural antioxidant product) to improve oxidative status by reducing oxidative stress in patients with cardiovascular disease, cancer and other chronic diseases. In spite of its level of saturated fatty acid content (50%), red palm oil has not been found to promote atherosclerosis and/or arterial thrombosis. This is probably due to the ratio of its saturated fatty acid to unsaturated fatty acid content and its high concentration of antioxidants such as beta-carotene, tocotrienols, tocopherols and vitamin E. It has also been reported that the consumption of red palm oil reduces the level of endogenous cholesterol, and this seems to be due to the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of red palm oil to health include a reduction in the risk of arterial thrombosis and/or atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, a reduction in oxidative stress and a reduction in blood pressure. It has also been shown that dietary red palm oil, taken in moderation in animals and humans, promotes the efficient utilisation of nutrients, activates hepatic drug metabolising enzymes, facilitates the haemoglobinisation of red blood cells and improves immune function. This review provides a comprehensive overview of the nutritional, physiological and biochemical roles of red palm oil in improving wellbeing and quality of life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I754,I754)","v":20077417},{"$f":"(LEN($J754) - LEN(SUBSTITUTE(LOWER($J754),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J754) - LEN(SUBSTITUTE(LOWER($J754),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J754) - LEN(SUBSTITUTE(LOWER($J754),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B754:D754)","v":0},2010,"The influence of dietary status on the cognitive performance of children.","Benton",20077417,"The influence of dietary status on the cognitive performance of children.    Abstract:   The rapid rate of growth of the brain during the last third of gestation and the early postnatal stage makes it vulnerable to an inadequate diet, although brain development continues into adulthood and micronutrient status can influence functioning beyond infancy. Certain dietary deficiencies during the first 2 years of life, for example iodine and iron, create problems that are not reversed by a later adequate diet. It is important that the intake of micronutrients varies greatly between individuals as they are essential for metabolism in general and in particular cell division and hence growth. In developing countries, there is consistent evidence that the adequacy of diet has lasting implications for cognitive development. In particular, attention has been directed to protein-calorie malnutrition and more specifically the intake of iron, iodine and vitamin A, a deficiency of which damages eyesight. In industrialized countries variations in diet are less influential, although a few well-designed studies have reported that multivitamin and mineral supplementations influence anti-social behaviour and intelligence. In the short term, there is increasing evidence that the missing of breakfast has negative consequences late in the morning. A working hypothesis is that meals of a low rather than high glycaemic load are beneficial."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I755,I755)","v":19907408},{"$f":"(LEN($J755) - LEN(SUBSTITUTE(LOWER($J755),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J755) - LEN(SUBSTITUTE(LOWER($J755),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J755) - LEN(SUBSTITUTE(LOWER($J755),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B755:D755)","v":0},2009,"Treatment of moderate-to-severe plaque psoriasis.","Salgo",19907408,"Treatment of moderate-to-severe plaque psoriasis.    Abstract:   Psoriasis, a chronic common immune-mediated disease with frequent remitting/relapsing courses, has a high negative impact on the quality of life, especially in patients moderately or severely affected by the disease. It is also associated with various co-morbidities resulting in a decreased life expectancy and remarkable socioeconomic costs. At least one third of the patients who suffer from it has moderate or severe psoriasis and require continuous treatment to control disease activity. The therapeutic approach in daily practice is usually determined by the severity of the disease. Whether the definition of disease severity is not always clear, there is a considerable number of patients requiring systemic treatment to control the symptoms of psoriasis. The treatment options available for the management of moderate-severe psoriasis have dramatically increased over the past decade, and now range from phototherapy to traditional systemic treatments to biologics. Available data from clinical trials and growing number of patients treated with biologics shows that this new agent are effective and relatively safe to control psoriasis, and are coupled with improved tolerability, convenience and improvement in quality of life. This review shortly presents the characteristics, safety and efficacy profile of the conventional and newer systemic drugs used in moderate-to-severe psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I756,I756)","v":19775631},{"$f":"(LEN($J756) - LEN(SUBSTITUTE(LOWER($J756),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J756) - LEN(SUBSTITUTE(LOWER($J756),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J756) - LEN(SUBSTITUTE(LOWER($J756),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B756:D756)","v":0},2009,"The rationale and potential of cancer chemoprevention with special emphasis on breast cancer.","Puntoni",19775631,"The rationale and potential of cancer chemoprevention with special emphasis on breast cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I757,I757)","v":19618401},{"$f":"(LEN($J757) - LEN(SUBSTITUTE(LOWER($J757),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J757) - LEN(SUBSTITUTE(LOWER($J757),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J757) - LEN(SUBSTITUTE(LOWER($J757),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B757:D757)","v":0},2010,"Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluids.","Zhu",19618401,"Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluids.    Abstract:   The assessment of DNA had demonstrated altered methylation in malignant compared to benign breast tissue. The purpose of our study was to (i) confirm the predictive ability of methylation assessment in breast tissue, and (ii) use the genes found to be cancer predictive in tissue to evaluate the diagnostic potential of hypermethylation assessment in nipple aspirate fluid (NAF) and mammary ductoscopic (MD) samples. Quantitative methylation specific (qMS)-PCR was conducted on three specimen sets: 44 malignant (CA) and 34 normal (NL) tissue specimens, 18 matched CA, adjacent normal (ANL) tissue and NAF specimens, and 119 MD specimens. Training and validation tissue sets were analyzed to determine the optimal group of cancer predictive genes for NAF and MD analysis. NAF and MD cytologic review were also performed. Methylation of CCND-2, p16, RAR-beta and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. Receiver operating characteristic curve analysis demonstrated an area under the curve of 0.96. For the 18 matched CA, ANL and NAF specimens, the four predictive genes identified in cancer tissue contained increased methylation in CA vs. ANL tissue; NAF samples had higher methylation than ANL specimens. Methylation frequency was higher in MD specimens from breasts with cancer than benign samples for p16 and RASSF-1a. In summary, i) routine quantitative DNA methylation assessment in NAF and MD samples is possible, and ii) genes hypermethylated in malignant breast tissue are also altered in matched NAF and in MD samples, and may be useful to assist in early breast cancer detection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I758,I758)","v":19594962},{"$f":"(LEN($J758) - LEN(SUBSTITUTE(LOWER($J758),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J758) - LEN(SUBSTITUTE(LOWER($J758),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J758) - LEN(SUBSTITUTE(LOWER($J758),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B758:D758)","v":0},2009,"How is the adequacy of micronutrient intake assessed across Europe? A systematic literature review.","Tabacchi",19594962,"How is the adequacy of micronutrient intake assessed across Europe? A systematic literature review.    Abstract:   EURopean micronutrient RECommendations Aligned is a network of excellence funded by the European commission, and established to address the problem of differences between countries in micronutrient recommendations as well as to understand how nutritional information including requirements and adequacy of intake is processed among different population groups. The aims of the present paper were to review the methods used for the adequacy assessment of the intake of six micronutrients of public health concern (vitamin A, folate, vitamin B12, Fe, Zn and iodine) in non-European and European nutrition surveys carried out on the apparently healthy population and to compare in particular the adequacy across surveys for folate intake. A systematic literature review was conducted to identify nutrition surveys that assessed micronutrient intake adequacy. The search yielded 9049 records, out of which 337 were eligible for the selected micronutrients. The majority (83.9 %) of the European surveys compared the adequacy of the nutrient intake against the Recommended Dietary Allowances (RDA); only a few surveys (8.0 %) used the estimated average requirement cut-point method, while none of them used the probability approach. The comparison of folate inadequacy across eight countries revealed that about 25 % of the adult female population had inadequate intakes when judged against the different recommendations used by the respective investigators, but nearly 75 % had inadequate intakes when compared against the estimated average requirement cut-point value of 320 microg/d. The present review showed that different methods were applied across Europe to estimate the adequacy of micronutrient intake, which led to different prevalence estimates of micronutrient inadequacy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I759,I759)","v":19464395},{"$f":"(LEN($J759) - LEN(SUBSTITUTE(LOWER($J759),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J759) - LEN(SUBSTITUTE(LOWER($J759),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J759) - LEN(SUBSTITUTE(LOWER($J759),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B759:D759)","v":0},2009,"The etiology of congenital diaphragmatic hernia: still largely unknown?","Klaassens",19464395,"The etiology of congenital diaphragmatic hernia: still largely unknown?    Abstract:   Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by a defect in the diaphragm associated with pulmonary hypoplasia and postnatal pulmonary hypertension. Half of the cases present with other non-pulmonary congenital anomalies (so called non-isolated CDH) and in 5-10% of cases there is a chromosomal etiology. The clinical aspects of CDH are well documented but knowledge on the etiology of CDH is largely lacking. Worldwide many researchers have focused research efforts on CDH. Their findings have led to several hypotheses proposing roles for genetic and environmental factors. In this review we have combined these findings with our own research on the genetics of CDH in results from recent literature and propose a theory on the etiology of CDH. We also propose a protocol for the CDH patient that will help clinicians and researchers to obtain maximal success out of their collaborations that will eventually lead to unravelling the etiology of this intriguing birth defect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I760,I760)","v":19339773},{"$f":"(LEN($J760) - LEN(SUBSTITUTE(LOWER($J760),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J760) - LEN(SUBSTITUTE(LOWER($J760),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J760) - LEN(SUBSTITUTE(LOWER($J760),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B760:D760)","v":0},2009,"The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development.","Puddu",19339773,"The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development.    Abstract:   Modified embryonic-fetal development resulting in low birth weight may lead to a reduced nephron endowment, hypertension and renal diseases in adulthood. Regarding the involvement of genetic factors, several environmental conditions may also contribute towards reducing the number of nephrons in the fetus and infant, subsequently constituting a health burden in later life. To date no methods of investigation for the early detection of a reduced nephron reserve are available. However, more structured studies should be implemented to investigate the role of angiotensin-converting enzyme inhibitors in managing proteinurias and glomerulosclerosis in children with renal conditions characterized by reduce nephron number and glomerular hypertrophic changes. In view of the current lack of specific methods of investigation and management, close monitoring of children and young adults at risk of reduced renal reserve should be carried out to enhance the early detection of potential changes in renal function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I761,I761)","v":19237040},{"$f":"(LEN($J761) - LEN(SUBSTITUTE(LOWER($J761),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J761) - LEN(SUBSTITUTE(LOWER($J761),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J761) - LEN(SUBSTITUTE(LOWER($J761),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B761:D761)","v":0},2009,"Pathogenesis and prevention of chronic lung disease in the neonate.","Askin",19237040,"Pathogenesis and prevention of chronic lung disease in the neonate.    Abstract:   Often used interchangeably, chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) develops primarily in extremely low birth weight infants weighing lt;1000 g who receive prolonged oxygen therapy and or positive pressure ventilation. CLD, which occurs in as many as 30 percent of infants born weighing lt;1000 g, contributes significantly to the morbidity and mortality seen in very low birth weight infants. Despite extensive research aimed at identifying risk factors and devising preventative therapies, many questions about the etiology and pathogenesis of BPD remain. This article reviews the embryologic development of the lung and the pathogenesis of CLD or BPD. The authors discuss some of the measures that have been used in an attempt to both prevent and treat BPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I762,I762)","v":19160297},{"$f":"(LEN($J762) - LEN(SUBSTITUTE(LOWER($J762),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J762) - LEN(SUBSTITUTE(LOWER($J762),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J762) - LEN(SUBSTITUTE(LOWER($J762),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B762:D762)","v":0},2009,"Interventions for preventing late postnatal mother-to-child transmission of HIV.","Horvath",19160297,"Interventions for preventing late postnatal mother-to-child transmission of HIV.    Abstract:    BACKGROUND : Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection. Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented. However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission.  OBJECTIVES : The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival.  SEARCH STRATEGY : Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative.  SELECTION CRITERIA : Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis. Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality).  DATA COLLECTION AND ANALYSIS : Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies.  MAIN RESULTS : Six randomized clinical trials and one intervention cohort study were included in this review. Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids (hazard ratio = 10.87, p = 0.018) as well as higher 3-month mortality rates (hazard ratio = 2.06) among infants given non- breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. One trial found that breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as effective as formula feeding (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis and formula feeding had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis (10.6%) (p lt; 0.001). HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group.  AUTHORS CONCLUSIONS : Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2) chronic antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I763,I763)","v":18831224},{"$f":"(LEN($J763) - LEN(SUBSTITUTE(LOWER($J763),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J763) - LEN(SUBSTITUTE(LOWER($J763),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J763) - LEN(SUBSTITUTE(LOWER($J763),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B763:D763)","v":0},2008,"Child health and mortality.","El Arifeen",18831224,"Child health and mortality.    Abstract:   Bangladesh is currently one of the very few countries in the world, which is on target for achieving the Millennium Development Goal (MDG) 4 relating to child mortality. There have been very rapid reductions in mortality, especially in recent years and among children aged over one month. However, this rate of reduction may be difficult to sustain and may impede the achievement of MDG 4. Neonatal deaths now contribute substantially (57%) to overall mortality of children aged less than five years, and reductions in neonatal mortality are difficult to achieve and have been slow in Bangladesh. There are some interesting attributes of the mortality decline in Bangladesh. Mortality has declined faster among girls than among boys, but the poorest have not benefited from the reduction in mortality. There has also been a relative absence of a decline in mortality in urban areas. The age and cause of death pattern of under-five mortality indicate certain interventions that need to be scaled up rapidly and reach high coverage to achieve MDG 4 in Bangladesh. These include skilled attendance at delivery, postnatal care for the newborn, appropriate feeding of the young infant and child, and prevention and management of childhood infections. The latest (2007) Bangladesh Demographic and Health Survey shows that Bangladesh has made sustained and remarkable progress in many areas of child health. More than 80% of children are receiving all vaccines. The use of oral rehydration solution for diarrhoea is high, and the coverage of vitamin A among children aged 9-59 months has been consistently increasing. However, poor quality of care, misperceptions regarding the need for care, and other social barriers contribute to low levels of care-seeking for illnesses of the newborns and children. Improvements in the health system are essential for removing these barriers, as are effective strategies to reach families and communities with targeted messages and information. Finally, there are substantial health-system challenges relating to the design and implementation, at scale, of interventions to reduce neonatal mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I764,I764)","v":18683028},{"$f":"(LEN($J764) - LEN(SUBSTITUTE(LOWER($J764),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J764) - LEN(SUBSTITUTE(LOWER($J764),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J764) - LEN(SUBSTITUTE(LOWER($J764),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B764:D764)","v":0},2008,"Micronutrient status, cognition and behavioral problems in childhood.","Benton",18683028,"Micronutrient status, cognition and behavioral problems in childhood.    Abstract:   It is widely accepted that the rapid rate of growth of the brain during the last third of gestation and the early postnatal stage makes it vulnerable to an inadequate diet, although brain development continues into adulthood and micronutrient status can influence functioning beyond infancy. A deficiency of various micro-nutrients in developing countries has been found to have long-term implication for cognitive development. Vitamin A plays a critical role in visual perception and a deficiency is the leading cause of childhood blindness. A lack of iodine during a critical period in brain development is associated with reduced intellectual ability. Iron shortage is a widespread problem in the developing world but also in industrialized countries. There is evidence that iron deficiency in early life adversely effects brain development. In addition in industrialized countries a role for folate in the prevention of neural tube defects is well established and in a few individuals impaired cognitive functioning is associated with the inadequate provision of vitamin B(12. )The controversial suggestions that sub-clinical deficiencies of micronutrients may in industrialized societies influence anti-social behavior and intelligence are also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I765,I765)","v":18784430},{"$f":"(LEN($J765) - LEN(SUBSTITUTE(LOWER($J765),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J765) - LEN(SUBSTITUTE(LOWER($J765),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J765) - LEN(SUBSTITUTE(LOWER($J765),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B765:D765)","v":0},2008,"Maternal abetalipoproteinemia resulting in multiple fetal anomalies.","Seckeler",18784430,"Maternal abetalipoproteinemia resulting in multiple fetal anomalies.    Abstract:   Abetalipoproteinemia is a rare genetic condition that results in an inability of the body to absorb dietary fats, including fat-soluble vitamins. Deficiencies of these vitamins are known to cause a wide range of clinical effects ranging from blindness to coagulopathy and neuropathy. We present the case of a child with multisystem anomalies born to a mother with abetalipoproteinemia and provide a brief review of the literature about vitamin A and fetal development. Mothers at high risk for vitamin deficiencies should be screened and counseled on the potential benefits, and risks, of vitamin supplementation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I766,I766)","v":18655405},{"$f":"(LEN($J766) - LEN(SUBSTITUTE(LOWER($J766),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J766) - LEN(SUBSTITUTE(LOWER($J766),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J766) - LEN(SUBSTITUTE(LOWER($J766),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B766:D766)","v":0},2008,"Maternal postpartum vitamin A supplementation programme: is there a need in Pakistan?","Siddiqi",18655405,"Maternal postpartum vitamin A supplementation programme: is there a need in Pakistan?    Abstract:   Maternal postpartum vitamin A supplementation is a safe and effective practice to replenish maternal vitamin A stores after delivery and in addition to provide the breastfeeding newborn with sufficient vitamin A. This strategy has been implemented in many countries around the world where Vitamin A deficiency (VAD) is prevalent. Recently, this supplementation has also been suggested by the Ministry of Health, Pakistan. In the light of literature available to date on VAD, we have attempted to appraise the need for this supplementation in Pakistan."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I767,I767)","v":18626575},{"$f":"(LEN($J767) - LEN(SUBSTITUTE(LOWER($J767),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J767) - LEN(SUBSTITUTE(LOWER($J767),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J767) - LEN(SUBSTITUTE(LOWER($J767),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B767:D767)","v":0},2008,"FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity.","Zhou",18626575,"FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity.    Abstract:   Forkhead box protein P3 (FOXP3) contributes to a unique transcriptional signature and serves as a functional marker of CD4(+)CD25(+) natural regulatory T cells. Dysfunction of FOXP3 in human is associated with fatal autoimmune disease known as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) or X-linked autoimmunity-allergic disregulation syndrome (XLAAD). FOXP3 also can act as a breast tumor suppressor of the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog (avian)) (Her2/neu) gene. While the suppressive functions of FOXP3 in maintaining the immune balance between tolerance and autoimmunity are obvious, the underlying molecular mechanism remains almost entirely undefined. Recent studies indicate that FOXP3 may form a dynamic superamolecular complex with a variety of molecular partners including transcription factors and enzymatic proteins to regulate transcription. How the FOXP3 ensemble changes in response to T-cell receptor signals and/or proinflammatory signal remains unclear although work from this laboratory has revealed its complexity. Structural information on FOXP3 complex may offer novel functional insights, as well as facilitate the development of rational means to modulate regulatory T-cell function in various human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I768,I768)","v":18545738},{"$f":"(LEN($J768) - LEN(SUBSTITUTE(LOWER($J768),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J768) - LEN(SUBSTITUTE(LOWER($J768),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J768) - LEN(SUBSTITUTE(LOWER($J768),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B768:D768)","v":0},2008,"Acute lower respiratory infections in childhood: opportunities for reducing the global burden through nutritional interventions.","Roth",18545738,"Acute lower respiratory infections in childhood: opportunities for reducing the global burden through nutritional interventions.    Abstract:   Inadequate nutrition and acute lower respiratory infection (ALRI) are overlapping and interrelated health problems affecting children in developing countries. Based on a critical review of randomized trials of the effect of nutritional interventions on ALRI morbidity and mortality, we concluded that: (1) zinc supplementation in zinc-deficient populations prevents about one-quarter of episodes of ALRI, which may translate into a modest reduction in ALRI mortality; (2) breastfeeding promotion reduces ALRI morbidity; (3) iron supplementation alone does not reduce ALRI incidence; and (4) vitamin A supplementation beyond the neonatal period does not reduce ALRI incidence or mortality. There was insufficient evidence regarding other potentially beneficial nutritional interventions. For strategies with a strong theoretical rationale and probable operational feasibility, rigorous trials with active clinical case-finding and adequate sample sizes should be undertaken. At present, a reduction in the burden of ALRI can be expected from the continued promotion of breastfeeding and scale-up of zinc supplementation or fortification strategies in target populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I769,I769)","v":18417735},{"$f":"(LEN($J769) - LEN(SUBSTITUTE(LOWER($J769),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J769) - LEN(SUBSTITUTE(LOWER($J769),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J769) - LEN(SUBSTITUTE(LOWER($J769),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B769:D769)","v":0},2008,"Minireview: nuclear receptors and breast cancer.","Conzen",18417735,"Minireview: nuclear receptors and breast cancer.    Abstract:   Until recently, the study of nuclear receptor (NR) function in breast cancer biology has been largely limited to estrogen and progesterone receptors. The development of reliable gene expression arrays, real-time quantitative RT-PCR, and immunohistochemical techniques for studying NR superfamily members in primary human breast cancers has now revealed the presence and potential importance of several additional NRs in the biology of breast cancer. These include receptors for steroid hormones (including androgens and corticosteroids), fat-soluble vitamins A and D, fatty acids, and xenobiotic lipids derived from diet. It is now clear that after NR activation, both genomic and nongenomic NR pathways can coordinately activate growth factor signaling pathways. Advances in our understanding of both NR functional networks and epithelial cell growth factor signaling pathways have revealed a frequent interplay between NR and epithelial cell growth factor family signaling that is clinically relevant to breast cancer. Understanding how growth factor receptors and their downstream kinases are activated by NRs (and vice-versa) is a central goal for maximizing treatment opportunities in breast cancer. In addition to the estrogen receptor, it is predicted that modulating the activity of other NRs will soon provide novel prevention and treatment approaches for breast cancer patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I770,I770)","v":18246473},{"$f":"(LEN($J770) - LEN(SUBSTITUTE(LOWER($J770),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J770) - LEN(SUBSTITUTE(LOWER($J770),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J770) - LEN(SUBSTITUTE(LOWER($J770),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B770:D770)","v":0},2008,"Nutrition, child growth, and chronic disease prevention.","Uauy",18246473,"Nutrition, child growth, and chronic disease prevention.    Abstract:   Countries undergoing the nutrition transition are experiencing a progressive increase in obesity and nutrition-related chronic diseases (NRCDs). In transitional countries, stunting (shortness for age) and micronutrient deficiencies (iron, vitamin A, and zinc) in children coexist with obesity and NRCDs originating the double burden of nutritional disease. The causal web for obesity and NRCDs is complex and multifaceted; changes in diet and physical activity of the population are likely the main concurrent determinant factors. However, recent evidence suggests that specific patterns of prenatal and postnatal growth are also potential contributors. Evidence indicates that intervention strategies to prevent malnutrition should emphasize improvements in linear growth in the first 2-3 years of life rather than aim at gaining weight. Avoiding excessive weight gain relative to height gain (BMI) is especially relevant after the first 2 years of life. Routine assessment of child growth based on the new World Health Organization (WHO) standard, defining energy needs based on the recent Food and Agricultural Organization (FAO)/WHO norms, and providing critical micronutrients to support lean mass growth are critical to prevent obesity and NRCDs starting early in the life course. These actions should contribute in the prevention and control of obesity in childhood and thus help prevent NRCDs in future generations of adults."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I771,I771)","v":18058459},{"$f":"(LEN($J771) - LEN(SUBSTITUTE(LOWER($J771),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J771) - LEN(SUBSTITUTE(LOWER($J771),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J771) - LEN(SUBSTITUTE(LOWER($J771),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B771:D771)","v":0},2007,"Epigenetic regulation as a new target for breast cancer therapy.","Stearns",18058459,"Epigenetic regulation as a new target for breast cancer therapy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I772,I772)","v":17952249},{"$f":"(LEN($J772) - LEN(SUBSTITUTE(LOWER($J772),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J772) - LEN(SUBSTITUTE(LOWER($J772),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J772) - LEN(SUBSTITUTE(LOWER($J772),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B772:D772)","v":0},2007,"[Evidence of the impact of vitamin A supplementation on maternal and child health].","Oliveira",17952249,"[Evidence of the impact of vitamin A supplementation on maternal and child health].    Abstract:   The aim of this article was to collect the results of systematic reviews and meta-analyses that evaluated the effect of vitamin A supplementation on child growth and maternal, fetal, and child morbidity and mortality. A detailed search was performed in PubMed, Cochrane Library, LILACS, PAHO, CAPES, USP Digital Thesis Library, and UNIFESP Collection Database. A total of 14 studies published from 1993 to 2006 were included in the review. There is evidence that vitamin A supplementation in children is associated with a reduction of 23% to 30% in mortality risk and attenuation in the severity of measles and diarrhea. There is no evidence of the interventions impact on pneumonia incidence or mortality in children without measles. Vitamin A also appears to be protective in children and pregnant women with HIV/AIDS, with a positive effect on child morbidity and mortality and birth weight. There is no evidence that supplementation in pregnant and lactating women reduces infant morbidity and mortality, but there is an indication that vitamin A protects against maternal morbidity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I773,I773)","v":17947457},{"$f":"(LEN($J773) - LEN(SUBSTITUTE(LOWER($J773),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J773) - LEN(SUBSTITUTE(LOWER($J773),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J773) - LEN(SUBSTITUTE(LOWER($J773),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B773:D773)","v":0},2007,"Rexinoids and breast cancer prevention.","Howe",17947457,"Rexinoids and breast cancer prevention.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I774,I774)","v":17824853},{"$f":"(LEN($J774) - LEN(SUBSTITUTE(LOWER($J774),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J774) - LEN(SUBSTITUTE(LOWER($J774),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J774) - LEN(SUBSTITUTE(LOWER($J774),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B774:D774)","v":0},2007,"Food-based dietary guidelines and nutrition interventions for children at primary healthcare facilities in South Africa.","Hendricks",17824853,"Food-based dietary guidelines and nutrition interventions for children at primary healthcare facilities in South Africa.    Abstract:   Existing dietary recommendations and nutrition counselling provided to mothers/caregivers at primary healthcare (PHC) facilities are reviewed and analysed to be consistent with food-based dietary guidelines (FBDGs) that are being developed for preschool children. Recommendations provided by the Integrated Management of Childhood Illness and the provincial Paediatric Case Management Guidelines, which are currently implemented at PHC facilities were reviewed. For FBDGs to be consistent with nutrition counselling that is provided to mothers/caregivers at these facilities, various principles need to be promoted. These include among others, exclusive and on-demand breastfeeding in the HIV-negative mother; exclusive breastfeeding with abrupt cessation preferably at 6 months or exclusive, safe and adequate formula feeding in the HIV-infected mother; the introduction of complementary feeds in all infants at 6 months; the provision of energy-dense and micronutrient-enriched (particularly, iron, zinc, calcium and vitamin A) complementary feeds; frequent visits to the healthcare facility; and physical activity aimed at encouraging a healthy lifestyle and preventing overweight and obesity in childhood. The FBDGs should be incorporated into nutrition and child health programmes and be reviewed and modified regularly."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I775,I775)","v":17824851},{"$f":"(LEN($J775) - LEN(SUBSTITUTE(LOWER($J775),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J775) - LEN(SUBSTITUTE(LOWER($J775),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J775) - LEN(SUBSTITUTE(LOWER($J775),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B775:D775)","v":0},2007,"Addressing malnutrition in young children in South Africa. Setting the national context for paediatric food-based dietary guidelines.","Bourne",17824851,"Addressing malnutrition in young children in South Africa. Setting the national context for paediatric food-based dietary guidelines.    Abstract:   Despite various national nutrition and primary healthcare programmes being initiated in South Africa over the last decade, child health has deteriorated. This is seen by the rise in infant and child mortality rates, the high prevalence of preventable childhood diseases, e.g. diarrhoea and lower respiratory tract infections, and the coexistence of under-nutrition along with HIV/AIDS. Poor dietary intake, food insecurity and poor quality of basic services prevail within this precarious causal web. The national Integrated Nutrition Programme is a comprehensive nutrition strategy that focuses on children below 6 years old, at-risk pregnant and lactating women, and those affected by communicable and non-communicable diseases. Focus areas relevant to pre-school children include disease-specific nutrition treatment, support and counselling; growth monitoring and promotion (GMP); micronutrient malnutrition control; breastfeeding promotion, protection and support; contributions to household food security; nutrition interventions among HIV-infected children; and nutrition promotion, education and advocacy. Progress towards this includes the Baby-Friendly Hospital Initiative; mandatory fortification of maize meal and wheat flour with multiple micronutrients; vitamin A supplementation coverage and mandatory iodization of salt by legislation; the provision of free road-to-health charts for GMP; and the National School Nutrition Programme. Since 2003, the basis of the nutrition education strategy has been the locally developed food-based dietary guidelines (FBDGs), directed at adults and school-going children. This review sketches the backdrop to and motivation for the introduction of specifically targeted paediatric FBDGs, for mothers and caregivers of children from birth to age 7 years, as a national initiative."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I776,I776)","v":17664893},{"$f":"(LEN($J776) - LEN(SUBSTITUTE(LOWER($J776),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J776) - LEN(SUBSTITUTE(LOWER($J776),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J776) - LEN(SUBSTITUTE(LOWER($J776),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B776:D776)","v":0},2007,"Breastfeeding and complementary feeding of children up to 2 years of age.","Brown",17664893,"Breastfeeding and complementary feeding of children up to 2 years of age.    Abstract:   Appropriate breastfeeding and complementary feeding practices are fundamental to childrens nutrition, health, and survival during the first 2 years of life. The World Health Organization recommends exclusive breastfeeding until 6 months of age and continued breastfeeding for at least 2 years, along with the timely introduction of adequate amounts of complementary foods of suitable nutritional and microbiological quality. The amounts of energy and micronutrients required from complementary foods have been estimated as the difference between the total physiological requirements of these food components and the amounts transferred to the child in breast milk. Recommendations for the energy density of complementary foods and their frequency of feeding have also been proposed. Intakes of several micronutrients, including iron, zinc, calcium, selected B vitamins and (in some settings) vitamin A, remain problematic because commonly available, low-cost foods contain inadequate amounts of these nutrients to provide the shortfall in breast milk. Alternative strategies to provide these nutrients include adding animal source foods to the diet, providing fortified, processed complementary foods, administering micronutrient supplements, or offering some combination of these approaches. Advantages, disadvantages, and possible risks of these different strategies are discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I777,I777)","v":17544277},{"$f":"(LEN($J777) - LEN(SUBSTITUTE(LOWER($J777),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J777) - LEN(SUBSTITUTE(LOWER($J777),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J777) - LEN(SUBSTITUTE(LOWER($J777),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B777:D777)","v":0},2007,"Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development.","Bruno",17544277,"Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development.    Abstract:   Cytochrome P450s (CYPs) represent a large class of heme-containing enzymes that catalyze the metabolism of multitudes of substrates both endogenous and exogenous. Until recently, however, CYPs have been largely overlooked in cancer drug development, acknowledged only for their role in phase I metabolism of chemotherapeutics. The first successful strategy targeting CYP enzymes in cancer therapy was the development of potent inhibitors of CYP19 (aromatase) for the treatment of breast cancer. Aromatase inhibitors ushered in a new era in hormone ablation therapy for estrogen dependent cancers, and have paved the way for similar strategies (i.e., inhibition of CYP17) that combat androgen dependent prostate cancer. Identification of CYPs involved in the inactivation of anti-cancer metabolites of vitamin D(3) and vitamin A has triggered development of agents that target these enzymes as well. The discovery of the over-expression of exogenous metabolizing CYPs, such as CYP1B1, in cancer cells has roused interest in the development of inhibitors for chemoprevention and of prodrugs designed to be activated by CYPs only in cancer cells. Finally, the expression of CYPs within tumors has been utilized in the development of bioreductive molecules that are activated by CYPs only under hypoxic conditions. This review offers the first comprehensive analysis of strategies in drug development that either inhibit or exploit CYP enzymes for the treatment of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I778,I778)","v":17415091},{"$f":"(LEN($J778) - LEN(SUBSTITUTE(LOWER($J778),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J778) - LEN(SUBSTITUTE(LOWER($J778),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J778) - LEN(SUBSTITUTE(LOWER($J778),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B778:D778)","v":0},2007,"Translational approaches for the prevention of estrogen receptor-negative breast cancer.","Li",17415091,"Translational approaches for the prevention of estrogen receptor-negative breast cancer.    Abstract:   Breast cancer prevention has focused heavily on endocrine interventions using selective estrogen receptor modulators and aromatase inhibitors. Tamoxifen, the stereotypical selective estrogen receptor modulator, significantly reduces the breast cancer incidence in high-risk women. Selective estrogen receptor modulators and aromatase inhibitors, however, only prevent the development of estrogen receptor-positive breast cancer and have no effect in reducing the risk of estrogen receptor-negative breast cancer, which has poor prognosis. Thus, preventive therapies for estrogen receptor-negative breast cancer are clearly needed. Recently, a number of novel chemopreventive agents targeting nonendocrine pathways have been developed and shown to prevent estrogen receptor-negative mammary tumorigenesis in animal models. These agents include rexinoids, selective cyclooxygenase-2 inhibitors, tyrosine kinase inhibitors, and others. In this review, we discuss the effects of selective estrogen receptor modulators and aromatase inhibitors, as well as novel agents targeting nonendocrine pathways. We also discuss the promise of combining these agents for the effective prevention of all forms of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I779,I779)","v":17264286},{"$f":"(LEN($J779) - LEN(SUBSTITUTE(LOWER($J779),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J779) - LEN(SUBSTITUTE(LOWER($J779),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J779) - LEN(SUBSTITUTE(LOWER($J779),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B779:D779)","v":0},2007,"Vitamins for babies and young children.","Leaf",17264286,"Vitamins for babies and young children.    Abstract:   The Welfare Food Scheme has recently been reviewed, and, although changes are being made, free vitamin supplements for children lt;4 years old will remain an important part of the new quot;Healthy Startquot; scheme. Establishing precise daily requirements for vitamins is not easy, and there is considerable individual variation; however, achieving the reference nutrient intake (RNI) should be possible with a healthy balanced diet for all except vitamins K and D, which require additional physiological or metabolic processes. For vitamin K, there is a well-established neonatal supplementation programme, and clinical deficiency is extremely rare. For vitamin D, however, supplementation is inconsistent, and both clinical and subclinical deficiencies are not uncommon in young children in the UK, particularly infants of Asian and Afro-Caribbean ethnic origin, and those who have prolonged exclusive breast feeding and delayed weaning. Most vitamin supplements contain vitamins A, C and D, with or without some of the B group of vitamins. There is clinical and dietary evidence to support vitamin D supplementation and some evidence from dietary surveys that vitamin A intakes may be low; however, there is no evidence to support supplementation of diets of UK children with water-soluble vitamins. Future strategy should aim at education of the public and health professionals regarding dietary intake and physiological aspects of vitamin sufficiency, as well as increasing awareness and availability of supplements, particularly of vitamin D, for those at increased risk of deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I780,I780)","v":17073603},{"$f":"(LEN($J780) - LEN(SUBSTITUTE(LOWER($J780),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J780) - LEN(SUBSTITUTE(LOWER($J780),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J780) - LEN(SUBSTITUTE(LOWER($J780),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B780:D780)","v":0},2006,"Potential gene therapy strategies for cancer stem cells.","Sell",17073603,"Potential gene therapy strategies for cancer stem cells.    Abstract:   To be maximally effective, therapy of cancer must be directed against both the resting stem cells and the proliferating cells of the cancer. The cell populations of both normal and cancer tissues consist of resting stem cells, proliferating transit-amplifying cells, terminally differentiating cells and dying (apoptotic) cells. The difference between normal tissue renewal and growth of cancers is that some of the transit-amplifying cells in the cancer population do not mature into terminally differentiating cells, but instead continue to proliferate and do not die (maturation arrest). Because of this the number of cancer cells increase, whereas the cell population of normal tissues remains a relatively constant. Conventional radiation treatment and chemotherapy kill the actively proliferating transit- amplifying cells of the cancer. Differentiation therapy, using specific targeted inhibitors of activation, effectively induces differentiation of the proliferating transit-amplifying cancer cells. However, even if the proliferating cancer cells are completely inhibited or eliminated, the cancer stem cells may restore the transit-amplifying population, so that clinical remission is usually temporary. The hypothesis presented in this paper is that successful cancer therapy must be directed against both the resting stem cells and the proliferating cells of the cancer. This may be possible if specific stem cell signals are inhibited using gene therapy, while at the same time attacking proliferating cells by conventional radiation treatment or chemotherapy. With advances in approaches using specific inhibitory RNA, such combination therapy may now be possible, but critical problems in delivering the inhibitory effect specifically to the cancer stem cells have yet to be worked out."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I781,I781)","v":16894622},{"$f":"(LEN($J781) - LEN(SUBSTITUTE(LOWER($J781),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J781) - LEN(SUBSTITUTE(LOWER($J781),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J781) - LEN(SUBSTITUTE(LOWER($J781),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B781:D781)","v":0},2006,"Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.","Robert",16894622,"Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.    Abstract:   The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I782,I782)","v":16862939},{"$f":"(LEN($J782) - LEN(SUBSTITUTE(LOWER($J782),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J782) - LEN(SUBSTITUTE(LOWER($J782),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J782) - LEN(SUBSTITUTE(LOWER($J782),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B782:D782)","v":0},2004,"Zinc in human health.","Temple",16862939,"Zinc in human health.    Abstract:   Malnutrition is a contributing cause of about half of the 10 million deaths annually worldwide, and contributes to a substantial proportion of the infectious disease morbidity among children in developing countries. Recent epidemiological and clinical evidence has shown that in most developing countries deficiencies of specific micronutrients are partly responsible for the severity of infectious disease morbidity and mortality in malnourished children. Efforts to improve micronutrient status have focused on iron, vitamin A and iodine. Supplementation with iron and vitamin A significantly reduces child mortality, while implementation of the universal salt iodization strategy reduces the incidence of iodine deficiency disorders. These strategies are considered to be among the most cost-effective health interventions in developing countries. A number of recent zinc supplementation studies in developing countries suggest that greater priority should also be given to the correction of mild to moderate zinc deficiency in children, pregnant women and lactating mothers. Some of these studies showed that zinc supplementation reduces the duration of malaria, and the severity of diarrhoea and respiratory infections (including pneumonia), and improves immunocompetence in susceptible children. The results of these studies indicate that zinc may be another specific micronutrient in which there is widespread deficiency in developing countries and that great benefits can be achieved by its supplementation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I783,I783)","v":16632927},{"$f":"(LEN($J783) - LEN(SUBSTITUTE(LOWER($J783),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J783) - LEN(SUBSTITUTE(LOWER($J783),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J783) - LEN(SUBSTITUTE(LOWER($J783),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B783:D783)","v":0},2005,"Nutrient effects upon embryogenesis: folate, vitamin A and iodine.","Rosenquist",16632927,"Nutrient effects upon embryogenesis: folate, vitamin A and iodine.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I784,I784)","v":16452274},{"$f":"(LEN($J784) - LEN(SUBSTITUTE(LOWER($J784),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J784) - LEN(SUBSTITUTE(LOWER($J784),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J784) - LEN(SUBSTITUTE(LOWER($J784),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B784:D784)","v":0},2006,"Vitamins.","Sethuraman",16452274,"Vitamins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I785,I785)","v":16335761},{"$f":"(LEN($J785) - LEN(SUBSTITUTE(LOWER($J785),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J785) - LEN(SUBSTITUTE(LOWER($J785),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J785) - LEN(SUBSTITUTE(LOWER($J785),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B785:D785)","v":0},2004,"Iron deficiency anaemia--an old enemy.","Bagchi",16335761,"Iron deficiency anaemia--an old enemy.    Abstract:   Anaemia has remained a widespread public health problem in countries of the Eastern Mediterranean Region. Prevalence figures vary from a low of 17% to a high of over 70% among preschool children; from 14% to 42% among adolescents and from 11% to over 40% among women of childbearing age. Although the prevalence of anaemia has often been used as a proxy indicator for iron deficiency anaemia, this approach is not valid in settings where the etiology of anaemia is complex or unknown or where other micronutrient deficiencies of folate, vitamin B12 and vitamin A can co-exist. An integrated, multifactorial and multisectoral approach has to be adopted comprising targeted interventions to provide iron supplements to especially vulnerable segments of the population, in particular pregnant women; food-based approaches to increase iron intake through food fortification and dietary diversification; and other measures combined with iron interventions where other causes of anaemia are prevalent."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I786,I786)","v":16295146},{"$f":"(LEN($J786) - LEN(SUBSTITUTE(LOWER($J786),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J786) - LEN(SUBSTITUTE(LOWER($J786),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J786) - LEN(SUBSTITUTE(LOWER($J786),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B786:D786)","v":0},2005,"Vitamin A, mastitis, and mother-to-child transmission of HIV-1 through breast-feeding: current information and gaps in knowledge.","Dorosko",16295146,"Vitamin A, mastitis, and mother-to-child transmission of HIV-1 through breast-feeding: current information and gaps in knowledge.    Abstract:   Mastitis has been implicated as a risk factor for mother-to-child transmission (MTCT) of HIV-1 through breast-feeding. Maternal vitamin A deficiency is also associated with increased MTCT, as well as with episodes of mastitis in lactating animals. This review describes the complex interrelationship between vitamin A, mastitis, and MTCT of HIV-1 via mothers milk. Current gaps in knowledge, as well as recommendations for future research efforts, are also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I787,I787)","v":16258411},{"$f":"(LEN($J787) - LEN(SUBSTITUTE(LOWER($J787),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J787) - LEN(SUBSTITUTE(LOWER($J787),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J787) - LEN(SUBSTITUTE(LOWER($J787),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B787:D787)","v":0},2005,"[The action of oxidative stress induced by ethanol on the central nervous system (CNS)].","Augustyniak",16258411,"[The action of oxidative stress induced by ethanol on the central nervous system (CNS)].    Abstract:   The brain is an organ which metabolically consumes about 20% of the total oxygen received by the organism. This causes the generation of free radicals, especially in the presence of some xenobiotics, such as ethanol. In order to prevent free radical-induced cellular damage, the organism developed a defense mechanism, the antioxidative system. The content of both exogenous and endogenous antioxidants in the central nervous system (CNS) is very small in comparison with that of other tissues, which in relation to the high level of polyunsaturated fatty acids (PUFAs) makes the CNS exceptionally susceptible to free-radical damage. The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) are present in the CNS i.e. in the cortex, cerebellum, hypothalamus, striatum, and spinal cord, where they are responsible for the brains basic functions, both physical and cognitive. Moreover, the highest activity of these enzymes is observed in neurons and/or glial cells. The activity of antioxidant enzymes is significantly changed in the CNS of animals chronically intoxicated with ethanol. The decrease in these activity may indicate at oxidative modification of the enzymatic proteins caused by free radicals which are generated during ethanol and acetaldehyde metabolism. It may also be caused by the decrease in the synthesis rate of these enzymes. However, the increase in the activity of antioxidant enzymes may often be explained as an adaptive reaction to an excess production of free radicals. The catalase is an exception in this respect because the decrease in its activity is related to the enhancement of protein synthesis. Ethanol intoxication also caused a decrease in GSH concentration, especially in the cerebellum, striatum, and cortex. This may be explained by the increase in the concentration of acetaldehyde, which is removed from cells with the use of this antioxidant. The antioxidative abilities of the CNS also depend on exogenous antioxidants which are provided to the organism during food intake. The most important exogenous antioxidant in the CNS is vitamin E. The content of vitamin E as well as that of vitamin C in the CNS is decreased, whereas the content of vitamin A is increased after ethanol administration. The high vitamin A level may cause damage of the central nervous system, especially in young rats exposed to ethanol in the prenatal period."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I788,I788)","v":16205189},{"$f":"(LEN($J788) - LEN(SUBSTITUTE(LOWER($J788),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J788) - LEN(SUBSTITUTE(LOWER($J788),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J788) - LEN(SUBSTITUTE(LOWER($J788),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B788:D788)","v":0},2005,"Medical management of vulvar intraepithelial neoplasia.","Todd",16205189,"Medical management of vulvar intraepithelial neoplasia.    Abstract:    OBJECTIVE : To determine which nonsurgical treatments have been assessed for the treatment of vulvar intraepithelial neoplasia (VIN) and what the outcomes of such treatment might be.  MATERIALS AND METHODS : The English literature over the last 25 years was searched on Medline.  RESULTS : A wide variety of nonsurgical treatments was identified and the outcomes were very similar. These treatments showed responses rates varying between 10% and 60%. Responses were poorly defined, however, and few if any studies had large enough subject numbers or long enough follow-up to allow robust conclusions.  CONCLUSIONS : Although VIN is a condition in which there would seem to be a pressing need for nonsurgical interventions, none of the nonsurgical treatments reviewed resulted in optimal outcomes. No one treatment seemed to be superior. There is a need for consensus on how outcomes are measured and a move toward large well-constructed studies is recommended. Because VIN is uncommon, there is a strong case for establishing research collaboratives."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I789,I789)","v":16076825},{"$f":"(LEN($J789) - LEN(SUBSTITUTE(LOWER($J789),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J789) - LEN(SUBSTITUTE(LOWER($J789),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J789) - LEN(SUBSTITUTE(LOWER($J789),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B789:D789)","v":0},2005,"Malnutrition and health in developing countries.","Müller",16076825,"Malnutrition and health in developing countries.    Abstract:   Malnutrition, with its 2 constituents of protein-energy malnutrition and micronutrient deficiencies, continues to be a major health burden in developing countries. It is globally the most important risk factor for illness and death, with hundreds of millions of pregnant women and young children particularly affected. Apart from marasmus and kwashiorkor (the 2 forms of protein- energy malnutrition), deficiencies in iron, iodine, vitamin A and zinc are the main manifestations of malnutrition in developing countries. In these communities, a high prevalence of poor diet and infectious disease regularly unites into a vicious circle. Although treatment protocols for severe malnutrition have in recent years become more efficient, most patients (especially in rural areas) have little or no access to formal health services and are never seen in such settings. Interventions to prevent protein- energy malnutrition range from promoting breast-feeding to food supplementation schemes, whereas micronutrient deficiencies would best be addressed through food-based strategies such as dietary diversification through home gardens and small livestock. The fortification of salt with iodine has been a global success story, but other micronutrient supplementation schemes have yet to reach vulnerable populations sufficiently. To be effective, all such interventions require accompanying nutrition-education campaigns and health interventions. To achieve the hunger- and malnutrition-related Millennium Development Goals, we need to address poverty, which is clearly associated with the insecure supply of food and nutrition."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I790,I790)","v":16020684},{"$f":"(LEN($J790) - LEN(SUBSTITUTE(LOWER($J790),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J790) - LEN(SUBSTITUTE(LOWER($J790),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J790) - LEN(SUBSTITUTE(LOWER($J790),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B790:D790)","v":0},2005,"Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes.","Villamor",16020684,"Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes.    Abstract:   Vitamin A supplementation to preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are likely to be the result of the actions of vitamin A on immunity. Some of the immunomodulatory mechanisms of vitamin A have been described in clinical trials and can be correlated with clinical outcomes of supplementation. The effects on morbidity from measles are related to enhanced antibody production and lymphocyte proliferation. Benefits for severe diarrhea could be attributable to the functions of vitamin A in sustaining the integrity of mucosal epithelia in the gut, whereas positive effects among HIV-infected children could also be related to increased T-cell lymphopoiesis. There is no conclusive evidence for a direct effect of vitamin A supplementation on cytokine production or lymphocyte activation. Under certain circumstances, vitamin A supplementation to infants has the potential to improve the antibody response to some vaccines, including tetanus and diphtheria toxoids and measles. There is limited research on the effects of vitamin A supplementation to adults and the elderly on their immune function; currently available data provide no consistent evidence for beneficial effects. Additional studies with these age groups are needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I791,I791)","v":16020410},{"$f":"(LEN($J791) - LEN(SUBSTITUTE(LOWER($J791),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J791) - LEN(SUBSTITUTE(LOWER($J791),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J791) - LEN(SUBSTITUTE(LOWER($J791),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B791:D791)","v":0},2005,"Prevention of and therapies for nipple pain: a systematic review.","Morland-Schultz",16020410,"Prevention of and therapies for nipple pain: a systematic review.    Abstract:    OBJECTIVE : To review the literature on nipple pain and to delineate effective strategies for the prevention and treatment of nipple pain in breastfeeding mothers.  DATA SOURCES : Computerized searches on MEDLINE, Pre-MEDLINE, CINAHL, and the Cochrane Library.  STUDY SELECTION : Articles from indexed journals relevant to the objective were reviewed from January 1983 to April 2004. Preference was given to research-based studies in English.  DATA EXTRACTION : Data were extracted and organized under two headings: prevention of nipple pain or trauma and treatment of nipple pain or trauma. The Critical Appraisal Form by J. Briggs was used to extract the data from research-based articles.  DATA SYNTHESIS : The health benefits of breastfeeding for mother and infant are well documented; however, nipple pain is a common reason reported by women for the early termination of breastfeeding. Several studies have compared various treatments for either the prevention of or treatment for nipple pain. These treatments include warm water compresses, tea bag compresses, heat, application of expressed mothers milk, lanolin, vitamin A, collagenase, dexpanthenol, hydrogel therapy, glycerin gel therapy, moist occlusive dressing, education regarding proper latch-on and positioning, and no treatment.  CONCLUSIONS : No one topical agent showed superior results in the relief of nipple discomfort. The most important factor in decreasing the incidence of nipple pain is the provision of education in relation to proper breastfeeding technique and latch-on as well as anticipatory guidance regarding the high incidence of early postpartum nipple pain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I792,I792)","v":15964182},{"$f":"(LEN($J792) - LEN(SUBSTITUTE(LOWER($J792),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J792) - LEN(SUBSTITUTE(LOWER($J792),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J792) - LEN(SUBSTITUTE(LOWER($J792),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B792:D792)","v":0},2005,"SERMs in chemoprevention of breast cancer.","Gasco",15964182,"SERMs in chemoprevention of breast cancer.    Abstract:   Selective estrogen receptor modulators (SERMs) play a key role in breast cancer chemoprevention. Tamoxifen has been shown to reduce breast cancer incidence by 30-40% in at-risk subjects in large phase III trials. However, toxicity may be a limiting factor. Thus, different strategies are being pursued to improve the risk: benefit ratio of using these compounds in chemoprevention. Firstly, the second generation SERM raloxifene is currently undergoing evaluation in comparison with tamoxifen in a large phase III trial. Also, lower doses of tamoxifen are being assessed in phase II-III trials. In addition, the combination of hormone replacement therapy (HRT) or aromatase inhibitors and tamoxifen at low doses may reduce the risks while retaining the benefits of either agents. Finally, new agents that interfere with the onset of ER-negative breast cancer are being sought for combination chemoprevention since almost a third of breast cancers will not be sensitive to hormonal modulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I793,I793)","v":15876415},{"$f":"(LEN($J793) - LEN(SUBSTITUTE(LOWER($J793),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J793) - LEN(SUBSTITUTE(LOWER($J793),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J793) - LEN(SUBSTITUTE(LOWER($J793),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B793:D793)","v":0},2005,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?","Beck",15876415,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?    Abstract:   The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I794,I794)","v":15854063},{"$f":"(LEN($J794) - LEN(SUBSTITUTE(LOWER($J794),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J794) - LEN(SUBSTITUTE(LOWER($J794),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J794) - LEN(SUBSTITUTE(LOWER($J794),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B794:D794)","v":0},2005,"Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements.","Bartlett",15854063,"Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements.    Abstract:   The role of oxidation in the development of age-related eye disease has prompted interest in the use of nutritional supplementation for prevention of onset and progression. Our aim is to highlight possible contraindications and adverse reactions of isolated or high dose ocular nutritional supplements. Web of Science and PubMed database searches were carried out, followed by a manual search of the bibliographies of retrieved articles. Vitamin A should be avoided in women who may become pregnant, in those with liver disease, and in people who drink heavily. Relationships have been found between vitamin A and reduced bone mineral density, and beta-carotene and increased risk of lung cancer in smoking males. Vitamin E and Ginkgo biloba have anticoagulant and anti-platelet effects respectively, and high doses are contraindicated in those being treated for vascular disorders. Those patients with contraindications or who are considered at risk of adverse reactions should be advised to seek specialist dietary advice via their medical practitioner."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I795,I795)","v":15788108},{"$f":"(LEN($J795) - LEN(SUBSTITUTE(LOWER($J795),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J795) - LEN(SUBSTITUTE(LOWER($J795),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J795) - LEN(SUBSTITUTE(LOWER($J795),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B795:D795)","v":0},2005,"Vitamins A and E: metabolism, roles and transfer to offspring.","Debier",15788108,"Vitamins A and E: metabolism, roles and transfer to offspring.    Abstract:   Vitamins A and E are essential, naturally occurring, fat-soluble nutrients that are involved in several important biological processes such as immunity, protection against tissue damage, reproduction, growth and development. They are extremely important during the early stages of life and must be transferred adequately to the young during gestation and lactation. The present article presents an overview of their biological functions, metabolism and dynamics of transfer to offspring in mammals. Among other topics, the review focuses on the biochemical aspects of their intestinal absorption, blood transport, tissue uptake, storage and catabolism. It also describes their different roles as well as their use as preventive and therapeutic agents. Finally, the mechanisms involved in their transfer during gestation and lactation are discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I796,I796)","v":15763234},{"$f":"(LEN($J796) - LEN(SUBSTITUTE(LOWER($J796),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J796) - LEN(SUBSTITUTE(LOWER($J796),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J796) - LEN(SUBSTITUTE(LOWER($J796),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B796:D796)","v":0},2005,"Alcohol in hepatocellular cancer.","Voigt",15763234,"Alcohol in hepatocellular cancer.    Abstract:   Hepatocellular cancer accounts for almost half a million cancer deaths a year, with an escalating incidence in the Western world. Alcohol has long been recognized as a major risk factor for cancer of the liver and of other organs including oropharynx, larynx, esophagus, and possibly the breast and colon. There is compelling epidemiologic data confirming the increased risk of cancer associated with alcohol consumption, which is supported by animal experiments. Cancer of the liver associated with alcohol usually occurs in the setting of cirrhosis. Alcohol may act as a cocarcinogen, and has strong synergistic effects with other carcinogens including hepatitis B and C, aflatoxin, vinyl chloride, obesity, and diabetes mellitus. Acetaldehyde, the main metabolite of alcohol, causes hepatocellular injury, and is an important factor in causing increased oxidant stress, which damages DNA. Alcohol affects nutrition and vitamin metabolism, causing abnormalities of DNA methylation. Abnormalities of DNA methylation, a key pathway of epigenetic gene control, lead to cancer. Other nutritional and metabolic effects, for example on vitamin A metabolism, also play a key role in hepatocarcinogenesis. Alcohol enhances the effects of environmental carcinogens directly and by contributing to nutritional deficiency and impairing immunological tumor surveillance. This review summarizes the epidemiologic evidence for the role of alcohol in hepatocellular cancer, and discusses the mechanisms involved in the promotion of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I797,I797)","v":15613442},{"$f":"(LEN($J797) - LEN(SUBSTITUTE(LOWER($J797),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J797) - LEN(SUBSTITUTE(LOWER($J797),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J797) - LEN(SUBSTITUTE(LOWER($J797),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B797:D797)","v":0},2004,"Nutritional modulation of the cell cycle and breast cancer.","Hilakivi-Clarke",15613442,"Nutritional modulation of the cell cycle and breast cancer.    Abstract:   In the USA, breast cancer accounts for approximately 30% of all cancers diagnosed in women and is the second leading cause of cancer death in women. An understanding of the molecular genetic events governing breast cancer lead to both prevention and intervention strategies in an attempt to reduce mortality and morbidity from breast cancer. The last three decades of medical research examining the molecular pathogenesis of cancers have provided compelling evidence for the universal disruption of the cell cycle in human tumors. The importance of cell cycle control in human cancer was recognized by the recent award of the Nobel Prize to Drs Nurse and Hartwell for their discovery of the cyclins. More recent studies have demonstrated a critical interface between hormonal signaling and the cell cycle. In parallel, epidemiological studies have identified as being associated with breast cancer important dietary and environmental components that regulate hormonal signaling. This review describes the intersection of these two fields of study, which together imply a role for dietary prevention and intervention in human breast cancer perhaps through altering cell cycle components."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I798,I798)","v":15570043},{"$f":"(LEN($J798) - LEN(SUBSTITUTE(LOWER($J798),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J798) - LEN(SUBSTITUTE(LOWER($J798),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J798) - LEN(SUBSTITUTE(LOWER($J798),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B798:D798)","v":0},2004,"Review of the International Research Conference on Food, Nutrition, and Cancer, 2004.","Norman",15570043,"Review of the International Research Conference on Food, Nutrition, and Cancer, 2004.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I799,I799)","v":15464421},{"$f":"(LEN($J799) - LEN(SUBSTITUTE(LOWER($J799),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J799) - LEN(SUBSTITUTE(LOWER($J799),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J799) - LEN(SUBSTITUTE(LOWER($J799),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B799:D799)","v":0},2004,"Molecular mechanisms of DAX1 action.","Iyer",15464421,"Molecular mechanisms of DAX1 action.    Abstract:   DAX1 (dosage sensitive sex reversal (DSS), adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1) encoded by the gene NR0B1, is an unusual orphan nuclear receptor that when mutated causes AHC with associated hypogonadotropic hypogonadism (HH), and when duplicated causes DSS. DAX1 expression has been shown in all regions of the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis during development and in adult tissues, suggesting a critical role for DAX1 in the normal development and function of this axis. Steroidogenic factor 1 (SF1, NR5A1) knockout mice show similar developmental defects as AHC and HH patients, but paradoxically, DAX1 is a negative coregulator of SF1 transactivation. The function of DAX1 as an antagonist of SF1 in gonadal development is consistent with the fact that in humans, duplication of the region of the X chromosome containing DAX1 causes a similar phenotype as mutations in SF1. However, how disruption of DAX1 leads to adrenal, hypothalamic, and pituitary developmental defects similar to SF1 disruption remains to be clarified. The exact mechanism of DAX1 action in each of these tissues during adulthood and critical stages of development are not fully understood. Recent evidence suggests a broader functional role for DAX1 as a negative coregulator of estrogen receptor (ER, NR3A1-2), liver receptor homologue-1 (LRH-1, NR5A2), androgen receptor (AR, NR3C4), and progesterone receptor (PR, NR3C3), each by distinct repression mechanisms. DAX1 may have pleiotropic roles in addition to its function as a negative regulator of steroidogenesis during the development and adult function of the HPAG axis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I800,I800)","v":15289752},{"$f":"(LEN($J800) - LEN(SUBSTITUTE(LOWER($J800),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J800) - LEN(SUBSTITUTE(LOWER($J800),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J800) - LEN(SUBSTITUTE(LOWER($J800),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B800:D800)","v":0},2004,"[Celiac disease and its endocrine and nutritional implications on male reproduction].","Stazi",15289752,"[Celiac disease and its endocrine and nutritional implications on male reproduction].    Abstract:   The problem of the interference of celiac disease (CD) with the male reproductive system is made evident both by the recognized adverse effects on female reproduction and by the multifactorial nature of the disease. It is important to consider CD as a multifactorial condition since its diverse effects can be modulated, besides gluten, by different concurrent genetic and environmental factors. The male CD patient has a greater risk of infertility and other reproductive disturbances, as well as a greater incidence of hypoandrogenism. In this paper the problems of CD associated to endocrine disorders and to deficiencies of micronutrients are discussed. Affected males show a picture of tissue resistance to androgens. Moreover, attention should be paid to increases of FSH and prolactin; these are not associated to infertility and/or impotence, but they may indicate an imbalance at hypothalamus-pituitary level, with general effects on health: an example is the increased risk of male osteoporosis in CD patients. Hormone alterations are reversible upon start of the gluten-free diet, emphasizing the importance of early diagnosis; this should be performed in the case of clinical suspicion, e.g., unexplained hypoandrogenism. As regards nutritional aspects, the folic acid deficiency of CD can affect rapidly proliferating tissues, such as the embryo and the seminiferous epithelium. More attention should be paid to deficiencies of fat-soluble vitamins, such as A and E, observed in CD. Vitamin A is important for Sertoli cell function as well as for early spermatogenetic phases. Vitamin E supports the correct differentiation and function of epidydimal epithelium, spermatid maturation and secretion of proteins by the prostate. Therefore, CD male patients should be considered as vulnerable subjects; thus, the detection of early biomarkers of andrological or endocrinological dysfunctions should trigger timely strategies for prevention and treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I801,I801)","v":15222487},{"$f":"(LEN($J801) - LEN(SUBSTITUTE(LOWER($J801),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J801) - LEN(SUBSTITUTE(LOWER($J801),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J801) - LEN(SUBSTITUTE(LOWER($J801),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B801:D801)","v":0},2004,"Recombinant human lactoferrin treatment for global health issues: iron deficiency and acute diarrhea.","Bethell",15222487,"Recombinant human lactoferrin treatment for global health issues: iron deficiency and acute diarrhea.    Abstract:   Iron deficiency and diarrhea are two of the most significant issues for global health. Iron deficiency anemia is the most common nutritional deficiency in the world, affecting nearly 25% of the world population (UNICEF/WHO 1999). The prevalence of iron deficiency in developing countries is illustrated by comparison with other deficiencies: iron deficiency affects 3.5 billion people, while vitamin A and iodine deficiency affect 0.3 billion people and 0.8 billion people, respectively. The prevalence is highest among young children and women of childbearing age (particularly pregnant women). It is estimated that national productivity levels could be raised as much as 20% by correcting iron deficiency in developing countries. Recombinant human lactoferrin (rhLF), expressed and extracted from rice seed, is being evaluated by Ventria Bioscience for use as a dietary supplement to treat iron deficiency and/or iron deficiency anemia. Diarrhea is also a major world health issue. Sixty percent of children who die under age five die of pneumonia, diarrhea or measles. World Health Organization oral rehydration solution (WHO-ORS) is one of the major medical advances in the past 50 years, saving the lives of 1 to 2 million children annually. Many studies have demonstrated similar efficacy of rice-based ORS. There are studies documenting the reduced frequency of diarrhea in breast-fed children and this health improvement is attributed to the antimicrobial action of the human milk proteins lactoferrin and lysozyme. In vitro data document the growth inhibition of the diarrheal associated organisms: rotavirus, ETEC, cholera, salmonella, and shigella by human lactoferrin (hLF) and human lysozyme. Using Ventrias ExpressTec system, we have expressed human lactoferrin and human lysozyme in rice. In a rice-based ORS formulation, these proteins have the potential to provide not only the benefits of reduced stool volume and improved weight gain, but also shorten the course of diarrheal episodes via antimicrobial activity against the causative agent."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I802,I802)","v":15147854},{"$f":"(LEN($J802) - LEN(SUBSTITUTE(LOWER($J802),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J802) - LEN(SUBSTITUTE(LOWER($J802),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J802) - LEN(SUBSTITUTE(LOWER($J802),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B802:D802)","v":0},2004,"Puerperal sepsis and maternal mortality: what role can new technologies play?","Hussein",15147854,"Puerperal sepsis and maternal mortality: what role can new technologies play?    Abstract:    OBJECTIVE : To identify new and underutilized technologies to reduce maternal mortality related to puerperal sepsis in developing countries.  METHOD : Review of current medical literature.  RESULT : The literature indicates that infection-control protocols and evidence-based procedures--including prophylactic antibiotics for cesarean section or preterm rupture of membranes, and updated antibiotic regimens--should be widely adopted. Devices such as hand rubs, needle-disposal systems, and rapid microbiological diagnostic tests can improve compliance and efficiency. Operational research on promising developments like vaginal cleansing with antiseptics, vitamin A supplementation, and prophylactic antibiotics in high-risk women is needed.  CONCLUSION : Sepsis management continues to depend on good implementation of established technologies. Program-based approaches are required to improve uptake."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I803,I803)","v":15128003},{"$f":"(LEN($J803) - LEN(SUBSTITUTE(LOWER($J803),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J803) - LEN(SUBSTITUTE(LOWER($J803),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J803) - LEN(SUBSTITUTE(LOWER($J803),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B803:D803)","v":0},2004,"Role of vitamins in the risk, prevention, and treatment of breast cancer.","Zhang",15128003,"Role of vitamins in the risk, prevention, and treatment of breast cancer.    Abstract:    PURPOSE OF REVIEW : This article presents an overview of the role of vitamins in the risk, prevention, and treatment of breast cancer, with emphasis on current evidence from English-language articles published since 1 August 2002 and indexed in MEDLINE.  RECENT FINDINGS : Findings from epidemiologic studies that have evaluated vitamin A and carotenoids in relation to breast cancer risk have been inconclusive. The available data, especially from prospective studies, do not support an association between vitamins E and C and risk of breast cancer. Recent studies suggest that folate plays an important role in the prevention of breast cancer, particularly among women consuming alcohol. Limited data also support a potential role of vitamin D in the prevention of breast cancer.  SUMMARY : High intake of folate or adequate circulating levels of folate may reduce the risk of breast cancer. Adequate folate levels may be particularly important for women who are at higher risk of breast cancer because of high alcohol consumption. The inverse association between vitamin D and risk of breast cancer needs to be evaluated in more studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I804,I804)","v":15012972},{"$f":"(LEN($J804) - LEN(SUBSTITUTE(LOWER($J804),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J804) - LEN(SUBSTITUTE(LOWER($J804),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J804) - LEN(SUBSTITUTE(LOWER($J804),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B804:D804)","v":0},2004,"Progress in chemoprevention of breast cancer.","Serrano",15012972,"Progress in chemoprevention of breast cancer.    Abstract:   Primary prevention trials have shown that tamoxifen lowers breast cancer incidence by 30-40%. Because of the endometrial risk of tamoxifen and the pro-thrombotic effects of tamoxifen and raloxifene, different strategies are being pursued to improve the risk:benefit ratio of breast cancer chemoprevention. Thus, raloxifene is being compared with tamoxifen in a phase III trial, while the minimal active dose of tamoxifen is being assessed in phase I-II trials. Also, the combination of hormone replacement therapy (HRT) and tamoxifen may reduce the risks while retaining the benefits of either agent. Anastrozole holds promise as a preventive agent based on preliminary results on contralateral breast cancer. The identification of women at increased risk for estrogen receptor (ER)-positive breast cancer due to hormonal and reproductive factors may maximize the therapeutic index of hormonal agents. Finally, new targets that interfere with ER-negative breast carcinogenesis are being sought as one-third of breast cancers will not be preventable by hormonal interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I805,I805)","v":15000734},{"$f":"(LEN($J805) - LEN(SUBSTITUTE(LOWER($J805),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J805) - LEN(SUBSTITUTE(LOWER($J805),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J805) - LEN(SUBSTITUTE(LOWER($J805),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B805:D805)","v":0},2004,"Haematological profiles of the people of rural southern Malawi: an overview.","Brabin",15000734,"Haematological profiles of the people of rural southern Malawi: an overview.    Abstract:   An integrative review of the results of two published and two unpublished studies of anaemia in children, adolescent females, pregnant women and adults living in southern Malawi is presented. Anaemia was universally present in all age-groups, with the higher prevalences in infants (100%) and adolescent primigravidae (93.8%). Nutritional deficits of iron and vitamin A were major contributory factors but chronic malarial haemolysis also significantly contributed to the anaemia. Among boys, anaemia was more common among those with glucose-6-phosphate-dehydrogenase (G6PD) deficiency than in those without this deficiency (Plt;0.002). This enzymopathy, which occurred in 23.5% [95% confidence interval (CI)=16.7%-30.1%] of the male and 30% (CI=17.3%-42.7%) of the female infants examined, was also associated with neonatal jaundice. The overall prevalences of the-alpha(3.7)/alphaalpha and -alpha(3.7)/-alpha(3.7) thalassaemia genotypes were estimated at 41.0% (CI=28.3%-53.7%) and 8.7% (CI=1.5%-15.9%), respectively. Haemoglobin AS was present in 18.1% (CI=12.8%-23.4%) of the infants and haemoglobin SS in 2.5% (CI=1.4%-3.6%). As the prevalence of infection with Plasmodium falciparum was significantly higher in infants with haemoglobin AS than in those with AA (21.4% v. 6.7%; Plt;0.001), an increased risk of early-onset moderate parasitaemias in young infants probably stimulates the development of immunity, protecting older heterozygotes from severe malarial infection. Innovative community approaches are required to break the cycle of ill health that anaemia supports in those living in rural areas of southern Malawi. Interventions in adolescent girls could be of particular importance, as they could break the cycle in both pregnant women and their infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I806,I806)","v":14991556},{"$f":"(LEN($J806) - LEN(SUBSTITUTE(LOWER($J806),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J806) - LEN(SUBSTITUTE(LOWER($J806),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J806) - LEN(SUBSTITUTE(LOWER($J806),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B806:D806)","v":0},2004,"Recruitment and retention of economically underserved women to a cervical cancer prevention trial.","Bailey",14991556,"Recruitment and retention of economically underserved women to a cervical cancer prevention trial.    Abstract:   This review contrasts the planned and actual recruitment and retention efforts for a cervical cancer prevention study within a predominantly underserved population. Recruitment was a primary obstacle to trial progression and multiple strategies to improve recruitment were implemented to meet objectives. The actual recruitment strategies were expansion to five geographically distinct clinical sites, use of nurse practitioners focused primarily on patient issues, extremely flexible study hours and location, honorariums, support for transportation and child care, and creativity in maintaining contact with study participants. With these strategies, 90% of eligible patients consented to participate in the study."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I807,I807)","v":14659109},{"$f":"(LEN($J807) - LEN(SUBSTITUTE(LOWER($J807),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J807) - LEN(SUBSTITUTE(LOWER($J807),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J807) - LEN(SUBSTITUTE(LOWER($J807),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B807:D807)","v":0},2003,"Pharmacological prevention of breast cancer: quo vadis?","Serrano",14659109,"Pharmacological prevention of breast cancer: quo vadis?    Abstract:   Although tamoxifen reduces breast cancer incidence by 30-40% in at-risk subjects, its adverse events may be a limiting factor. Thus, different strategies are being pursued to improve the risk:benefit ratio of breast cancer chemoprevention intervention. Firstly, raloxifene is being compared with tamoxifen in a phase-III trial, whereas the minimal active dose of tamoxifen is being assessed in phase I-II trials. The combination of HRT and tamoxifen may also reduce the risks while retaining the benefits of either agent. Anastrozole holds promise as a preventive agent based on preliminary data on contralateral breast cancer. Another important area is the appropriate identification of women at increased risk for ER-positive breast cancer due to reproductive factors, which may maximize the therapeutic index of hormonal agents. Finally, new targets that interfere with the onset of ER-negative breast cancer are being sought since one-third of breast cancers will not be modulated by hormonal interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I808,I808)","v":14585302},{"$f":"(LEN($J808) - LEN(SUBSTITUTE(LOWER($J808),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J808) - LEN(SUBSTITUTE(LOWER($J808),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J808) - LEN(SUBSTITUTE(LOWER($J808),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B808:D808)","v":0},2003,"Human requirements for fat-soluble vitamins, and other things concerning these nutrients.","Krinsky",14585302,"Human requirements for fat-soluble vitamins, and other things concerning these nutrients.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I809,I809)","v":13677590},{"$f":"(LEN($J809) - LEN(SUBSTITUTE(LOWER($J809),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J809) - LEN(SUBSTITUTE(LOWER($J809),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J809) - LEN(SUBSTITUTE(LOWER($J809),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B809:D809)","v":0},2003,"Vitamin A, beta-carotene, and mother-to-child transmission of HIV.","Stephensen",13677590,"Vitamin A, beta-carotene, and mother-to-child transmission of HIV.    Abstract:   The role of maternal vitamin A supplements in decreasing the risk of mother-to-child HIV transmission has been examined in sub-Saharan Africa. Overall, there is no reduction in either mortality or HIV transmission in two recent studies. Contrary to expectations, one study reported an increased risk of transmission using vitamin A plus beta-carotene supplements."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I810,I810)","v":12949391},{"$f":"(LEN($J810) - LEN(SUBSTITUTE(LOWER($J810),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J810) - LEN(SUBSTITUTE(LOWER($J810),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J810) - LEN(SUBSTITUTE(LOWER($J810),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B810:D810)","v":0},2003,"Nutritional status of infants and young children and characteristics of their diets.","Lutter",12949391,"Nutritional status of infants and young children and characteristics of their diets.    Abstract:   Adoption of the recommended breast-feeding and complementary feeding behaviors and access to the appropriate quality and quantity of foods are essential components of optimal nutrition for infants and young children between ages 6 and 24 mo. Iron, zinc and vitamin B-6 are deficient in complementary food diets in Bangladesh, Ghana, Guatemala, Mexico and Peru. Low intakes of iron are consistent with a high prevalence of anemia seen in this age group. The adequacy of observed intakes for calcium, vitamin A, thiamin, folate and vitamin C depends on the age range in question and the set of requirements used in the assessment. The lipid content of many complementary food diets is low. In addition to providing essential fatty acids, lipids are needed for the absorption of fat-soluble vitamins and also enhance the texture, flavor and aroma of foods, which may lead to increased intake. The relative roles of palatability, micronutrient deficiency and morbidity-induced anorexia in the appetite of infants and young children are not known. However, even among children who were growth retarded and had a total energy deficit compared with requirements, up to 25% of food offered was not consumed. This indicates that dietary quality rather than quantity is the key aspect of complementary food diets that needs to be improved. Targeted fortification or the production of complementary foods fortified with micronutrients and of an adequate macro- and micronutrient composition is one approach to help meet nutritional requirements during the vulnerable period of 6-24 mo."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I811,I811)","v":12885273},{"$f":"(LEN($J811) - LEN(SUBSTITUTE(LOWER($J811),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J811) - LEN(SUBSTITUTE(LOWER($J811),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J811) - LEN(SUBSTITUTE(LOWER($J811),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B811:D811)","v":0},2003,"Molecular targets as therapeutic strategies in the management of breast cancer.","Russo",12885273,"Molecular targets as therapeutic strategies in the management of breast cancer.    Abstract:   Although the molecular and genetic determinants of most sporadic breast cancers remain unknown, increasing understanding of molecular and genetic events affecting breast carcinogenesis has provided information about the potential roles of specific biomarkers in tumour development and spread. It is now recognised that mutations of some tumour suppressor genes appear to play important early roles in the formation of some breast cancers. In addition, alterations in proto-oncogenes may contribute to the development of some breast cancers. The study of breast tumour biology at the molecular level has led to the development of targeted drug design, which provides a variety of agents targeted at specific molecules for the prevention, diagnosis and treatment of breast cancer. This review will describe the recognised molecular targets in breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I812,I812)","v":12864868},{"$f":"(LEN($J812) - LEN(SUBSTITUTE(LOWER($J812),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J812) - LEN(SUBSTITUTE(LOWER($J812),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J812) - LEN(SUBSTITUTE(LOWER($J812),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B812:D812)","v":0},2003,"Intrauterine determinants of diabetic kidney disease in disadvantaged populations.","Nelson",12864868,"Intrauterine determinants of diabetic kidney disease in disadvantaged populations.    Abstract:   Disadvantaged populations worldwide are experiencing an increasing incidence of kidney disease, much of which is attributable to diabetes. This report reviews the evidence that intrauterine exposure to growth retardation, diabetes, and vitamin A deficiency contribute disproportionately to the rising incidence of kidney disease in disadvantaged people, because they encounter these exposures more frequently than people from developed countries. These abnormal intrauterine exposures reduce nephron mass by impairing nephrogenesis, thereby increasing the susceptibility to kidney damage from diseases such as hypertension and diabetes that commonly affect disadvantaged people."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I813,I813)","v":12842416},{"$f":"(LEN($J813) - LEN(SUBSTITUTE(LOWER($J813),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J813) - LEN(SUBSTITUTE(LOWER($J813),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J813) - LEN(SUBSTITUTE(LOWER($J813),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B813:D813)","v":0},2003,"Programming the cardiovascular system, kidney and the brain--a review.","Wintour",12842416,"Programming the cardiovascular system, kidney and the brain--a review.    Abstract:   The concept that life before birth or the first environment is important in determining subsequent risk for the development of cardiovascular/metabolic disease is now gaining acceptance. There are substantial data from animal experiments that complement and enhance the epidemiological data from human studies. We argue that any factor which disrupts nephrogenesis, and lowers nephron number, during the period of active nephrogenesis, will induce malapadaptive changes in the future functioning of that kidney and predispose to the onset of adult hypertension. Such factors include exposure of the mother, to a particular low-protein diet, excess synthetic or natural glucocorticoid at certain critical periods, mild vitamin A deficiency, elevated blood glucose, unilateral nephrectomy during the period of nephrogenesis, as well as the deletion of one allele of a gene (GDNF) involved in normal metanephric development. All of these stresses are associated with a reduction (20-40 per cent) in total nephron number in the adult, and the development of hypertension. In some hypertensive models, (rats) there is evidence of alterations in the components of the hippocampal/hypothalamic/pituitary/adrenal axis, whereas in others (sheep) there are alterations in the expression of angiotensinogen (hypothalamus) and angiotensin II receptor type I (AT(1)) in the medulla oblongata. The surprising finding is that the period when the kidney and brain are most vulnerable is very early in development, when both organs are in an extremely primitive state of development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I814,I814)","v":12833004},{"$f":"(LEN($J814) - LEN(SUBSTITUTE(LOWER($J814),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J814) - LEN(SUBSTITUTE(LOWER($J814),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J814) - LEN(SUBSTITUTE(LOWER($J814),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B814:D814)","v":0},2003,"Management of acne: a report from a Global Alliance to Improve Outcomes in Acne.","Gollnick",12833004,"Management of acne: a report from a Global Alliance to Improve Outcomes in Acne.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I815,I815)","v":12821062},{"$f":"(LEN($J815) - LEN(SUBSTITUTE(LOWER($J815),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J815) - LEN(SUBSTITUTE(LOWER($J815),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J815) - LEN(SUBSTITUTE(LOWER($J815),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B815:D815)","v":0},2003,"[Can breast cancer be chemoprevented in 2003?].","Vinatier",12821062,"[Can breast cancer be chemoprevented in 2003?].    Abstract:   Breast cancer is certainly not preventable at the same degree as lung cancer is by avoiding cigarette smoking or bladder cancer by avoiding exposure to some specific professional carcinogens. Despite the increased availability of screening mammography and the use of adjuvant chemotherapy, breast cancer remains a major cause of morbidity and mortality in women. Chemoprevention could be one of the possible weapons to decrease the morbidity and the mortality due to breast cancer. Experimental, epidemiological and clinical data suggest that one can prevent occurrence of breast cancer. The results of five trials including more than 25,000 patients comparing the effectiveness of tamoxifen with a placebo were published. The results of these trials, at first sight, do not agree. Only in the USA, the results of the five trials have led to licence tamoxifen for chemoprevention of breast cancer. But the Food and Drug Administration stresses the fact that the noxious side effects are too numerous for this molecule to be prescribed with all the patients. It must be reserved for the women presenting an increased risk. The means of identifying the women at increased risk are not yet perfect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I816,I816)","v":12813911},{"$f":"(LEN($J816) - LEN(SUBSTITUTE(LOWER($J816),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J816) - LEN(SUBSTITUTE(LOWER($J816),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J816) - LEN(SUBSTITUTE(LOWER($J816),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B816:D816)","v":0},2003,"Battle of the sexes: new insights into genetic pathways of gonadal development.","Jameson",12813911,"Battle of the sexes: new insights into genetic pathways of gonadal development.    Abstract:   Sex determination is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of gonadal development. Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal development provides an excellent opportunity to identify genes involved in differential organogenesis. The identification of the testis-determining gene, SRY (Sex-reversed on the Y), was a pivotal first step towards unraveling this genetic pathway. It is now clear that numerous other genes, in addition to SRY, are necessary for normal testis development. For example, human mutations in a variety of genes (SOX9, WT1, SF1) impair testis development. Murine models provide evidence for additional genes (Lhx9, Emx2, M33, Dmrt, Fgf9). This lecture will highlight insights gleaned from human mutations in the nuclear receptors, SF1 (Steroidogenic Factor1) (NR5A1) and DAX1 (Dosage-sensitive sex reversal, Adrenal hypoplasia congenita, X chromosome) (NR0B1). These studies reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I817,I817)","v":12807955},{"$f":"(LEN($J817) - LEN(SUBSTITUTE(LOWER($J817),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J817) - LEN(SUBSTITUTE(LOWER($J817),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J817) - LEN(SUBSTITUTE(LOWER($J817),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B817:D817)","v":0},2003,"Chapter 17: Genital human papillomavirus infections--current and prospective therapies.","Stanley",12807955,"Chapter 17: Genital human papillomavirus infections--current and prospective therapies.    Abstract:   Many therapies are available for the treatment of human papillomavirus (HPV)-associated disease, particularly external genital warts. However, at present, these therapies aim to remove the lesion rather than specifically target HPV infection. When disease and infection are local, as in cervical intraepithelial neoplasia (CIN), excisional therapies removing lesion and transformation-susceptible cells are highly effective. However, when infection is regional, as is usually the case for the anogenital warts, vulval intraepithelial neoplasia (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia, and vaginal intraepithelial neoplasia, then current treatments are generally inadequate, with high recurrence rates. Future therapies will be directly or indirectly antiviral, targeting HPV protein functions or enhancing the ability of the immune system to resolve infection or inducing apoptosis indirectly in HPV-infected cells. In the short to the medium term, immunotherapies for low-grade disease are the most likely to be in the clinic. Vaccines targeting the E1 and E2 early proteins combined with immunomodulators or conventional adjuvants that induce a strong cell-mediated HPV antigen-specific response and good immune memory would be the predicted combination. Vaccines designed to target high-grade intraepithelial disease, even when used in combination with immunomodulators, are unlikely to effect lesion clearance in more than a fraction of the cases. However, they may have a role as adjunct therapy after cervical conization to prevent the recurrence of CIN or HPV reinfection. They certainly appear to have a role in multifocal disease, such as VIN and AIN, where partial clearance may be effected and lesion size reduced enough for effective ablative or excisional therapy. It seems unlikely that anti-HPV chemotherapies specifically targeting HPV protein functions will be in the clinic in the medium term. However, agents such as indole-3-carbinol have shown efficacy in small clinical trials, and if these effects are confirmed in larger, randomized, placebo-controlled trials, they could be clinically useful."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I818,I818)","v":12777161},{"$f":"(LEN($J818) - LEN(SUBSTITUTE(LOWER($J818),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J818) - LEN(SUBSTITUTE(LOWER($J818),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J818) - LEN(SUBSTITUTE(LOWER($J818),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B818:D818)","v":0},2003,"Cervical dysplasia: early intervention.","Marshall",12777161,"Cervical dysplasia: early intervention.    Abstract:   Cervical cancer is the second-most common cancer in young women and is one of the most common causes of cancer deaths among women, particularly in minorities and in impoverished countries. Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). Not all women with the virus develop cervical dysplasia or cervical cancer. It has been postulated there are multiple host factors that contribute to progression of disease. Many of these factors, such as nutrient deficiencies, can be reversed, which will result in regression of dysplastic lesions. Studies have shown dietary intervention and nutrient supplementation to be effective in preventing cervical cancer. Additionally, local escharotic treatment combined with systemic treatment shows significant potential in reducing dysplasia. Recent advances in vaccination technology demonstrate the effectiveness of an HPV vaccine. The vaccine, however, may have many social and cost-prohibiting limitations, as well as health side effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I819,I819)","v":12698206},{"$f":"(LEN($J819) - LEN(SUBSTITUTE(LOWER($J819),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J819) - LEN(SUBSTITUTE(LOWER($J819),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J819) - LEN(SUBSTITUTE(LOWER($J819),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B819:D819)","v":0},2003,"Pharmacological modulation of IGF serum concentrations as a therapeutic approach to control the growth of malignant breast tumors.","Singer",12698206,"Pharmacological modulation of IGF serum concentrations as a therapeutic approach to control the growth of malignant breast tumors.    Abstract:   The insulin-like growth factors (IGFs)-1 and -2 have been associated with an increased risk for breast cancer, and have been shown to increase tumor growth and malignant behavior in vitro and in vivo. Both exert their actions through the IGF type 1 receptor (IGF1R), which is able to cooperate with the estrogen receptor in the regulation of growth-associated gene expression. The inhibition of IGF1R signaling, either through receptor blocking or through a reduction of bioactive ligands thus appears to be a highly desirable goal in the suppression of tumor growth. This paper presents a number of compounds that have been shown to reduce IGF serum levels and that might therefore have a potential in controlling tumor growth and possibly metastatic behavior. Some of these are believed to work through a reduction of systemic estrogens, such as anti-estrogens, selective estrogen receptor mediators and aromatase inhibitors, others represent synthetic compounds that belong to the vitamin A and D family."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I820,I820)","v":12669776},{"$f":"(LEN($J820) - LEN(SUBSTITUTE(LOWER($J820),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J820) - LEN(SUBSTITUTE(LOWER($J820),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J820) - LEN(SUBSTITUTE(LOWER($J820),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B820:D820)","v":0},2002,"Current strategies for anticancer chemoprevention and chemoprotection.","Krzystyniak",12669776,"Current strategies for anticancer chemoprevention and chemoprotection.    Abstract:   Relatively new targets in drug design projects in cancer pharmacology include cytostatic agents, immune system modulators, and angiogenesis inhibitors. Preventive oncology applies pharmacological agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy. Prevention of cancer, however, can be accomplished through many strategies, including changes in diet and lifestyle. For example, the vast majority of lung cancers (80-90%) can be attributed to cigarette smoking and therefore, the most effective primary preventive strategy for lung cancer is to quit smoking. Chemoprevention through interruption of multistage careinogenesis include different molecular targets. Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR-gamma) suppress breast carcinogenesis in experimental models and induce differentiation of human liposarcoma cells. Selective PPAR modulators (SPARMs), by analogy to the SERM concept, are designed to have desired effects on specific genes relevant to carcinogenesis. Enzymatic approach in endocrine-related tumors involve inhibition of aromatase to prevent breast cancer and inhibition of 5-alpha-reductase to prevent prostate cancer. Down-regulation of inflammatory prostaglandin synthesis by inhibition of cyclooxygenase-2 (COX-2). inhibition of the inducible nitric oxide synthase (iNOS), and stimulation of phase II detoxication system, are currently examined in experimental models and clinical trials. Overall, potential targets in preventive strategies to reduce the risk of cancer involve agonists of endocrine receptors, factors down-regulating inflammation, factors inducing programmed cell death (PCD)/apoptosis, enzymatic inhibitors and gene therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I821,I821)","v":12653010},{"$f":"(LEN($J821) - LEN(SUBSTITUTE(LOWER($J821),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J821) - LEN(SUBSTITUTE(LOWER($J821),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J821) - LEN(SUBSTITUTE(LOWER($J821),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B821:D821)","v":0},2002,"Nutrition.","Krzystyniak",12653010,"Nutrition.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I822,I822)","v":12603979},{"$f":"(LEN($J822) - LEN(SUBSTITUTE(LOWER($J822),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J822) - LEN(SUBSTITUTE(LOWER($J822),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J822) - LEN(SUBSTITUTE(LOWER($J822),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B822:D822)","v":0},2002,"Premalignant vulval disorders.","Murphy",12603979,"Premalignant vulval disorders.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I823,I823)","v":12586088},{"$f":"(LEN($J823) - LEN(SUBSTITUTE(LOWER($J823),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J823) - LEN(SUBSTITUTE(LOWER($J823),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J823) - LEN(SUBSTITUTE(LOWER($J823),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B823:D823)","v":0},2003,"Specific keynote: chemoprevention of ovarian cancer: the journey begins.","Ozols",12586088,"Specific keynote: chemoprevention of ovarian cancer: the journey begins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I824,I824)","v":12566727},{"$f":"(LEN($J824) - LEN(SUBSTITUTE(LOWER($J824),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J824) - LEN(SUBSTITUTE(LOWER($J824),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J824) - LEN(SUBSTITUTE(LOWER($J824),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B824:D824)","v":0},2003,"SF1 in the development of the adrenal gland and gonads.","Ozisik",12566727,"SF1 in the development of the adrenal gland and gonads.    Abstract:   SF1 (steroidogenic factor-1; NR5A1) is an orphan nuclear receptor that is expressed in the adrenal gland, gonads, spleen, ventromedial hypothalamus and pituitary gonadotroph cells. Combined approaches of targeted mutagenesis in mice and examination of the effects of naturally occurring mutations in humans have clarified the role of SF1 in steroidogenesis and development. Targeted disruption of SF1 (FTZF1) in mice prevents gonadal and adrenal development and causes male-to-female sex reversal. A heterozygous loss-of-function human SF1 mutation (G35E) was described in a patient with adrenal failure and complete 46,XY sex reversal, indicating that haploinsufficiency of this transcription factor is sufficient to cause a severe clinical phenotype. In an infant with a similar clinical phenotype, a homozygous SF1 mutation (R92Q) was identified. In functional assays, this mutant SF1 protein exhibited partial loss of DNA binding and transcriptional activity when compared with the more severe G35E P-box mutant. These patients reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I825,I825)","v":12538447},{"$f":"(LEN($J825) - LEN(SUBSTITUTE(LOWER($J825),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J825) - LEN(SUBSTITUTE(LOWER($J825),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J825) - LEN(SUBSTITUTE(LOWER($J825),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B825:D825)","v":0},2003,"Prevention of ovarian cancer: intraepithelial neoplasia.","Brewer",12538447,"Prevention of ovarian cancer: intraepithelial neoplasia.    Abstract:   To reduce the incidence and mortality associated with invasive cancers, the Intraepithelial Neoplasia (IEN) Task Force recommends that carcinogenesis be viewed as a disease that requires treatment. This publication outlines the current knowledge of IEN of the ovary and reviews chemoprevention possibilities for ovarian cancer. Ovarian cancer has the highest mortality of all of the gynecological cancers and is the fourth leading cause of death from cancer in women. The IEN Task Force has defined precancer as a noninvasive lesion that has genetic abnormalities, loss of cellular control functions, and some phenotypic characteristics of invasive cancer with a substantial likelihood of developing invasive cancer. The IEN Task Force recommends targeting moderate to severe dysplasia for new IEN treatment agents in clinical trials. Ovarian cancer does not have a clear preinvasive lesion yet merits considerable study for new prevention strategies because of the high mortality associated with ovarian cancer. There is a great unmet clinical need for treatments that can prevent ovarian cancer by providing nonsurgical options that treat the entire epithelial layer. New prevention strategies hold significant promise to reduce the mortality from ovarian cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I826,I826)","v":12462073},{"$f":"(LEN($J826) - LEN(SUBSTITUTE(LOWER($J826),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J826) - LEN(SUBSTITUTE(LOWER($J826),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J826) - LEN(SUBSTITUTE(LOWER($J826),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B826:D826)","v":0},2002,"[The genetics of sex determination].","Vialard",12462073,"[The genetics of sex determination].    Abstract:   The male sex determination controls the testis determination and differentiation. So far more than a dozen of gene have been characterised, including the primary Y male sex determinant: SRY gene. All the genes encode transcription factor except FDF9 which encodes a growth factor allowing mesonephritic cell to divide and migrate to the mesenchyme. All these gene products are sensitive in man (but not in the mouse model) to gene dosage: haplo-insufficiency and or duplication of these genes all lead to sex reversal. Today, we still do not know how their products are epistatic in the sex determining cascade. So far no ovary sex determining gene has been characterised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I827,I827)","v":12390328},{"$f":"(LEN($J827) - LEN(SUBSTITUTE(LOWER($J827),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J827) - LEN(SUBSTITUTE(LOWER($J827),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J827) - LEN(SUBSTITUTE(LOWER($J827),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B827:D827)","v":0},2002,"The sodium iodide symporter: its pathophysiological and therapeutic implications.","Spitzweg",12390328,"The sodium iodide symporter: its pathophysiological and therapeutic implications.    Abstract:   The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular lactating mammary gland. Because of its crucial role in the ability of thyroid follicular cells to trap iodide, cloning of NIS opened an exciting and extensive new field of thyroid-related research. Cloning and molecular characterization of NIS allowed investigation of its expression and regulation in thyroidal and nonthyroidal tissues, and its potential pathophysiological and therapeutic implications in benign and malignant thyroid disease. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows diagnostic thyroid scintigraphy as well as effective therapeutic application of radioiodine in benign and malignant thyroid disease. Characterization and application of NIS as a novel therapeutic gene and the presence of high native NIS expression in the majority of breast cancers further suggest a promising role of NIS in diagnosis and therapy of cancer outside the thyroid gland."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I828,I828)","v":12230784},{"$f":"(LEN($J828) - LEN(SUBSTITUTE(LOWER($J828),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J828) - LEN(SUBSTITUTE(LOWER($J828),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J828) - LEN(SUBSTITUTE(LOWER($J828),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B828:D828)","v":0},2002,"Premalignant vulval disorders.","Murphy",12230784,"Premalignant vulval disorders.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I829,I829)","v":12222355},{"$f":"(LEN($J829) - LEN(SUBSTITUTE(LOWER($J829),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J829) - LEN(SUBSTITUTE(LOWER($J829),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J829) - LEN(SUBSTITUTE(LOWER($J829),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B829:D829)","v":0},1998,"Mother-to-child transmission of HIV: issues and implications for Southern Africa.","Jenkins-woelk",12222355,"Mother-to-child transmission of HIV: issues and implications for Southern Africa.    Abstract:   Interventions to reduce mother-to-child HIV transmission or vertical transmission have been successful in Europe and North America, but the transfer of interventions to developing countries is complicated by many factors, including cost. Governments and countries need to reduce vertical transmission through rational strategies sensitive to regional needs and resources. This paper presents an overview of the facts and issues concerning vertical transmission in southern Africa with a perspective on regional needs and resources. The discussion includes antenatal seroprevalence and correlates of transmission; the proportions and timing of vertical transmission in terms of in-utero and intrapartum infection, as well as breast-feeding; the interventions to reduce vertical transmission, which include drug therapy, birth canal cleansing, vitamin A and micronutrient supplementation, cesarean section, limiting breast-feeding, and immune therapy; and the issues and implications specific to southern African regions. This paper also offers recommendations for prevention programs with emphasis on research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I830,I830)","v":12202330},{"$f":"(LEN($J830) - LEN(SUBSTITUTE(LOWER($J830),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J830) - LEN(SUBSTITUTE(LOWER($J830),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J830) - LEN(SUBSTITUTE(LOWER($J830),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B830:D830)","v":0},2002,"Acne vulgaris.","Webster",12202330,"Acne vulgaris.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I831,I831)","v":12133204},{"$f":"(LEN($J831) - LEN(SUBSTITUTE(LOWER($J831),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J831) - LEN(SUBSTITUTE(LOWER($J831),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J831) - LEN(SUBSTITUTE(LOWER($J831),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B831:D831)","v":0},2002,"Can supplements help meet the micronutrient needs of the developing world?","Shrimpton",12133204,"Can supplements help meet the micronutrient needs of the developing world?    Abstract:   Supplementation has many potential advantages over fortification and dietary approaches for improving micronutrient intake. Pregnant and lactating women and infants are most likely to benefit from supplementation. Recent experience with vitamin A supplementation in young children has proved to be remarkably successful. Demonstrated efficacy of vitamin A supplements for improved child survival in many settings and a technical consensus on how to implement interventions were major factors in achieving this success. Bilateral and UN agencies worked together so that in 1999 80 % of children under 5 years of age in the least-developed countries received a vitamin A capsule in the last 6 months. At least one million child lives saved were associated with the increase in coverage in the last 2 years of the 1990s. Experience with Fe-folate supplements has not been as successful. Whilst a technical consensus has been reached on how to implement programmes to control Fe deficiency, the lack of convincing evidence of efficacy of Fe-folate supplements in terms of maternal and child survival outcomes has undoubtedly contributed to the limited pursuit of effective action. A new multiple micronutrient supplement for use amongst women of reproductive age in developing countries has been formulated. UNICEF is employing the supplement in programmes aimed at helping to prevent low birth weight. The new supplement is likely to be more efficacious than Fe-folate supplements for both maternal and child survival and development outcomes. Successful completion of rigorous efficacy trials will be critical for creating the political support needed to achieve universal coverage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I832,I832)","v":12050127},{"$f":"(LEN($J832) - LEN(SUBSTITUTE(LOWER($J832),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J832) - LEN(SUBSTITUTE(LOWER($J832),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J832) - LEN(SUBSTITUTE(LOWER($J832),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B832:D832)","v":0},2002,"Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era.","Seminara",12050127,"Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era.    Abstract:   Despite the rapid advances in medical genetics, many clinicians and investigators remain unaware of the general approaches that can be used to map genes. Although there are specific challenges to using genetic approaches in reproductive medicine, the following report summarizes mapping efforts for three diseases: adrenal hypoplasia congenita, hypergonadotropic ovarian failure, and polycystic ovary syndrome. The themes of rare and novel phenotypes, genetically homogenous populations, and genotype/phenotype correlations are emphasized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I833,I833)","v":12039672},{"$f":"(LEN($J833) - LEN(SUBSTITUTE(LOWER($J833),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J833) - LEN(SUBSTITUTE(LOWER($J833),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J833) - LEN(SUBSTITUTE(LOWER($J833),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B833:D833)","v":0},2002,"Micronutrient malnutrition and the pathogenesis of malarial anemia.","Nussenblatt",12039672,"Micronutrient malnutrition and the pathogenesis of malarial anemia.    Abstract:   Malaria is a leading cause of morbidity and mortality worldwide, and anemia is a common and sometimes serious complication of Plasmodium falciparum infection. Although micronutrient malnutrition is usually highly prevalent in malaria endemic areas, the contribution of micronutrient deficiencies to malarial anemia is often overlooked. Recent investigation suggests that micronutrients such as vitamin A, vitamin E, and zinc, may improve the morbidity of malaria through immune modulation and alteration of oxidative stress. Micronutrients are also involved in the pathogenesis of anemia and likely play a role in malarial anemia, but many clinical trials have not specifically addressed the impact of micronutrient supplementation on malarial anemia. Further work is needed to assess the effect of both clinic and community-based micronutrient interventions on malarial anemia in infants, children, and pregnant women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I834,I834)","v":11990799},{"$f":"(LEN($J834) - LEN(SUBSTITUTE(LOWER($J834),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J834) - LEN(SUBSTITUTE(LOWER($J834),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J834) - LEN(SUBSTITUTE(LOWER($J834),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B834:D834)","v":0},2002,"Concerted regulation of gonad differentiation by transcription factors and growth factors.","Suzuki",11990799,"Concerted regulation of gonad differentiation by transcription factors and growth factors.    Abstract:   It is well known that signals from growth factors regulate gene transcription thus initiating certain steps of cellular and tissue differentiation during development. In gonad differentiation several transcription factors have been identified as the genes underlying human diseases displaying gonadal defects and as the genes necessary for gonad differentiation as demonstrated by gene disruption studies. In addition, one of the growth factors, WNT4, is known to be involved in gonadal differentiation. However, it remains unclear which gene is directly downstream of the WNT4 signal. We have recently demonstrated that Dax1 (NR0B1) gene transcription is significantly up-regulated by the presence of SF1 (NR5A1). Functional analysis showed that DAX1 acts as a repressor against SF1 through direct interaction between the repeated sequences at the N-terminus of DAX1 and a ligand-binding domain of SF1. Considering that the expressions of these factors during gonad differentiation show a sexually dimorphic pattern, it is likely that the Dax1 gene transcription is up-regulated by WNT4 signal and thereafter DAX1 suppresses the genes downstream of SF1 such as Amh and steroidogenic genes in female gonads."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I835,I835)","v":11965516},{"$f":"(LEN($J835) - LEN(SUBSTITUTE(LOWER($J835),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J835) - LEN(SUBSTITUTE(LOWER($J835),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J835) - LEN(SUBSTITUTE(LOWER($J835),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B835:D835)","v":0},2002,"Meat and cancer: meat as a component of a healthy diet.","Biesalski",11965516,"Meat and cancer: meat as a component of a healthy diet.    Abstract:   Based on epidemiological studies it is assumed that meat, especially red meat, enhances risk for cancer, particularly of the colon, breast and prostate. Meat and meat products are important sources of protein, some micronutrients and fat. High fat intake has been blamed for correlation with different diseases, including cancer. Meat protein is reported to contribute to cancer formation. However, meat, including liver, is not only composed of fat and protein, it contains essential nutrients which appear exclusively in meat (vitamin A, vitamin B12) and micronutrients for which meat is the major source because of either high concentrations or better bioavailability (folate, selenium, zinc). In particular, vitamin A, folate and selenium are reported to be cancer-preventive, with respect to colon, breast and prostate cancer. Taken together, meat consists of a few, not clearly defined cancer-promoting and a lot of cancer-protecting factors. The latter can be optimized by a diet containing fruit and vegetables, which contain hundreds of more or less proven bioactive constituents, many of them showing antioxidative and anticarcinogenic effects in vitro."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I836,I836)","v":11965502},{"$f":"(LEN($J836) - LEN(SUBSTITUTE(LOWER($J836),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J836) - LEN(SUBSTITUTE(LOWER($J836),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J836) - LEN(SUBSTITUTE(LOWER($J836),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B836:D836)","v":0},2002,"The anemia of vitamin A deficiency: epidemiology and pathogenesis.","Semba",11965502,"The anemia of vitamin A deficiency: epidemiology and pathogenesis.    Abstract:    OBJECTIVE : To gain insight into vitamin A deficiency as a cause of anemia.  METHODS : Comprehensive review of the scientific literature.  RESULTS : Although vitamin A deficiency is recognized to cause anemia, vitamin A deficiency anemia lacks complete characterization as a distinct clinical entity. Vitamin A appears to be involved in the pathogenesis of anemia through diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection and reduction of the anemia of infection, and mobilization of iron stores from tissues. Epidemiological surveys show that the prevalence of anemia is high in populations affected by vitamin A deficiency in developing countries. Improvement of vitamin A status has generally been shown to reduce anemia, but the actual public health impact on anemia is unclear.  CONCLUSIONS : Further work is needed to elucidate the biological mechanisms by which vitamin A causes anemia. The inclusion of anemia as an outcome measure in future micronutrient intervention studies should help provide further insight into the anemia of vitamin A deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I837,I837)","v":11836189},{"$f":"(LEN($J837) - LEN(SUBSTITUTE(LOWER($J837),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J837) - LEN(SUBSTITUTE(LOWER($J837),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J837) - LEN(SUBSTITUTE(LOWER($J837),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B837:D837)","v":0},2002,"AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.","Breccia",11836189,"AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I838,I838)","v":11773589},{"$f":"(LEN($J838) - LEN(SUBSTITUTE(LOWER($J838),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J838) - LEN(SUBSTITUTE(LOWER($J838),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J838) - LEN(SUBSTITUTE(LOWER($J838),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B838:D838)","v":0},2002,"Effects of certain prenatal drugs on the fetus and newborn.","Boyle",11773589,"Effects of certain prenatal drugs on the fetus and newborn.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I839,I839)","v":11720341},{"$f":"(LEN($J839) - LEN(SUBSTITUTE(LOWER($J839),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J839) - LEN(SUBSTITUTE(LOWER($J839),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J839) - LEN(SUBSTITUTE(LOWER($J839),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B839:D839)","v":0},2001,"Micronutrients and child health: studies in international nutrition and HIV infection.","Duggan",11720341,"Micronutrients and child health: studies in international nutrition and HIV infection.    Abstract:   Increasing data link micronutrient deficiencies to excess childhood morbidity and mortality, and similar relationships have been noted in the study of nutrition and HIV infection. We review epidemiologic studies that have examined the relationship between micronutrient deficiencies and health outcomes in childhood and HIV infection, as well as clinical trials of micronutrient supplementation. Vitamin A supplementation among communities at risk of deficiency effectively reduces mortality and morbidity in children younger than age 5, and vitamin A may be especially effective in HIV-infected children. Vertical transmission of HIV has not to date been affected by maternal micronutrient supplementation. In children with poor dietary zinc intake and/or bioavailability, zinc supplementation reduces the incidence and severity of diarrheal diseases, as well as the occurrence of pneumonia. Vitamin A therapy has not been associated with improved growth, whereas some trials have shown that zinc supplementation is associated with greater increments in height. Further trials of micronutrient supplementation are warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I840,I840)","v":11705005},{"$f":"(LEN($J840) - LEN(SUBSTITUTE(LOWER($J840),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J840) - LEN(SUBSTITUTE(LOWER($J840),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J840) - LEN(SUBSTITUTE(LOWER($J840),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B840:D840)","v":0},2000,"Regulation of sodium/iodide symporter.","Jhiang",11705005,"Regulation of sodium/iodide symporter.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I841,I841)","v":11562285},{"$f":"(LEN($J841) - LEN(SUBSTITUTE(LOWER($J841),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J841) - LEN(SUBSTITUTE(LOWER($J841),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J841) - LEN(SUBSTITUTE(LOWER($J841),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B841:D841)","v":0},2001,"Vitamin D analogs: mechanism of action and therapeutic applications.","Nagpal",11562285,"Vitamin D analogs: mechanism of action and therapeutic applications.    Abstract:   The physiological VDR ligand, 1 alpha,25-dihydroxyvitamin D3, acts upon a wide variety of tissues and cells, both related to and unrelated to calcium and phosphate homeostasis. The noncalcemic actions of natural and synthetic VDR ligands are exemplified by their potent anti-proliferative, prodifferentiative and immunomodulatory activities. As a result, a VDR ligand is an approved drug for the topical treatment of psoriasis. A plethora of actions of 1 alpha,25-dihydroxyvitamin D3 in various systems have suggested wide clinical applications of VDR ligands in such diverse disease states as inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, photoaging and skin rejuvenation), osteoporosis, cancers (breast, prostate, colon, leukemia and myelodysplastic syndrome) and autoimmune diseases (multiple sclerosis, type I diabetes and systemic lupus erythematosus). VDR ligands have shown therapeutic potential in limited human clinical trials as well as in animal models of these diseases. Some of the VDR ligands have shown not only potent preventive but also therapeutic anabolic activities in animal models of osteoporosis. However, the use of VDR in above mentioned indications as well as in oral therapy for psoriasis and even topical therapy for severe psoriasis is hampered by its associated toxicity, namely hypercalcemia. New VDR ligands have been synthesized which exhibit greater specificity by retaining desirable properties, but with reduced calcemic potential. The discovery of novel vitamin D3 analogs along with an increased understanding of the biological functions and mechanisms of action of VDR are likely to result in improved treatments for responsive indications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I842,I842)","v":11523899},{"$f":"(LEN($J842) - LEN(SUBSTITUTE(LOWER($J842),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J842) - LEN(SUBSTITUTE(LOWER($J842),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J842) - LEN(SUBSTITUTE(LOWER($J842),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B842:D842)","v":0},2001,"Regulatory mechanisms of female germ cell apoptosis during embryonic development.","Morita",11523899,"Regulatory mechanisms of female germ cell apoptosis during embryonic development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I843,I843)","v":11509101},{"$f":"(LEN($J843) - LEN(SUBSTITUTE(LOWER($J843),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J843) - LEN(SUBSTITUTE(LOWER($J843),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J843) - LEN(SUBSTITUTE(LOWER($J843),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B843:D843)","v":0},2001,"Effect of micronutrient supplementation on linear growth of children.","Bhandari",11509101,"Effect of micronutrient supplementation on linear growth of children.    Abstract:   This review summarizes the results of published, randomized clinical trials that have examined the impact of administration of micronutrients, singly or in combination to infants, preschool and school children on linear growth. Supplementation of single micronutrients resulted in small or no benefits on linear growth. A meta-analysis of zinc supplementation trials confirmed that zinc has a significant but small impact (0.22 sd units) on length gain in children 0-13 years of age. However, a recent study reported a substantially greater benefit (gt;1 sd) in stunted and non-stunted breast-fed infants 6-12 months of age. With iron supplementation, a beneficial effect was found only in anemic children. Vitamin A supplementation trials have reported little or no benefit on linear growth. Data currently available suggest some impact in children with clinical or biochemical vitamin A deficiency, but this issue needs confirmation. Few studies could be identified where a combination of micronutrients was given as a supplement or as fortified food; in the latter set of studies energy availability was assured. The impact on length without multiple micronutrient supplementation was no greater than that observed with single micronutrients. In conclusion, zinc and iron seem to have a modest effect on linear growth in deficient populations. Vitamin A is unlikely to have an important effect on linear growth. Limited available evidence does not allow us to conclude whether a combination of micronutrients, with or without additional food, would have a greater impact than that seen with zinc alone."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I844,I844)","v":11509093},{"$f":"(LEN($J844) - LEN(SUBSTITUTE(LOWER($J844),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J844) - LEN(SUBSTITUTE(LOWER($J844),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J844) - LEN(SUBSTITUTE(LOWER($J844),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B844:D844)","v":0},2001,"Immunobiology of mild micronutrient deficiencies.","Bhaskaram",11509093,"Immunobiology of mild micronutrient deficiencies.    Abstract:   Nutrition is a critical determinant of the outcome of host microbe interactions through a modulation of the immune response. Besides macronutrient malnutrition, deficiencies of several macronutrients also influence immune homeostasis and thus affect infection-related morbidity and mortality. Deficiencies of micronutrients like vitamin A, iron and zinc are widely prevalent among populations living in developing countries. Besides their severe deficiencies, subclinical deficiencies are known to impair biological functions in the host, immune function being one of them. The effects of these micronutrients on various immune mechanisms are briefly reviewed in this article."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I845,I845)","v":11505163},{"$f":"(LEN($J845) - LEN(SUBSTITUTE(LOWER($J845),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J845) - LEN(SUBSTITUTE(LOWER($J845),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J845) - LEN(SUBSTITUTE(LOWER($J845),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B845:D845)","v":0},2001,"Additional insights into the etiology of cardiac anomalies.","Werler",11505163,"Additional insights into the etiology of cardiac anomalies.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I846,I846)","v":11411262},{"$f":"(LEN($J846) - LEN(SUBSTITUTE(LOWER($J846),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J846) - LEN(SUBSTITUTE(LOWER($J846),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J846) - LEN(SUBSTITUTE(LOWER($J846),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B846:D846)","v":0},2000,"Micronutrient deficiency conditions in the Middle East region: an overview.","Galal",11411262,"Micronutrient deficiency conditions in the Middle East region: an overview.    Abstract:   The Middle East is perhaps the worlds best laboratory for learning more about iron and zinc deficiencies, and their widespread prevalence contributes much to constraining the quality of life for a large share of the population. Always, in the context of endemic IDD, countries in the region need to make sure that the programs are in place to consign this still-serious problem to the history books. Research is not required so much in relation to IDD, but clearly applications need to be monitored. Vitamin A deficiency is probably widespread at mild to moderate levels, and should be addressed by a combination of appropriate case management for infectious disease, breastfeeding promotion, and dietary diversification/nutrition education. Iron deficiency is the most prevalent, and so far the most intractable, micronutrient problem. It probably will not yield to less than a multipronged strategy including fortification of the food supply with iron. Several other micronutrient deficiencies require our eventual attention as well, and looking forward to their solution should be part of the research agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I847,I847)","v":11389365},{"$f":"(LEN($J847) - LEN(SUBSTITUTE(LOWER($J847),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J847) - LEN(SUBSTITUTE(LOWER($J847),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J847) - LEN(SUBSTITUTE(LOWER($J847),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B847:D847)","v":0},2001,"Updates in pediatric nutrition.","Oken",11389365,"Updates in pediatric nutrition.    Abstract:   Ongoing research in several areas of pediatric nutrition has new practical applications for community-based pediatricians. For example, a fresh understanding of risk factors for rickets persuades pediatricians to recognize and treat this disease, which was thought to be nearly extinct in the modern industrialized world. Similarly, an expanded awareness of the antibacterial components of breast milk encourages a more complete dialogue between pediatricians and new mothers about the potential benefits of breast-feeding. For those infants with feeding intolerance, new data help to refine the indications for hypoallergenic formulas, which are increasingly recommended for children with a variety of symptoms. The past year also has seen breakthroughs in our understanding of supplemental nutrition for children. Vitamin A may provide direct benefits for the most vulnerable of children, namely premature infants at high risk for lung disease. At the other end of the pediatric spectrum, adolescent athletes seeking to enhance their performance are consuming poorly studied sports supplements that may not be beneficial and may even be toxic. Finally, a greater appreciation for the epidemic of obesity that is sweeping the United States and other countries suggests that children at high risk may represent a far more diverse population than had been recognized previously."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I848,I848)","v":11386691},{"$f":"(LEN($J848) - LEN(SUBSTITUTE(LOWER($J848),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J848) - LEN(SUBSTITUTE(LOWER($J848),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J848) - LEN(SUBSTITUTE(LOWER($J848),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B848:D848)","v":0},2000,"Global malnutrition.","Stephenson",11386691,"Global malnutrition.    Abstract:   The four most important forms of malnutrition worldwide (protein-energy malnutrition, iron deficiency and anaemias (IDA), vitamin A deficiency (VAD), and iodine deficiency disorders (IDD)) are examined below in terms of their global and regional prevalences, the age and gender groups most affected, their clinical and public health consequences, and, especially, the recent progress in country and regional quantitation and control. Zinc deficiency, with its accompanying diminished host resistance and increased susceptibility to infections, is also reviewed. WHO estimates that malnutrition (underweight) was associated with over half of all child deaths in developing countries in 1995. The prevalence of stunting in developing countries is expected to decline from 36% in 1995 to 32.5% in 2000; the numbers of children affected (excluding China) are expected to decrease from 196.59 millions to 181.92 millions. Stunting affects 48% of children in South Central Asia, 48% in Eastern Africa, 38% in South Eastern Asia, and 13-24% in Latin America. IDA affects about 43% of women and 34% of men in developing countries and usually is most serious in pregnant women and children, though non-pregnant women, the elderly, and men in hookworm-endemic areas also comprise groups at risk. Clinical VAD affects at least 2.80 million preschool children in over 60 countries, and subclinical VAD is considered a problem for at least 251 millions; school-age children and pregnant women are also affected. Globally about 740 million people are affected by goitre, and over two billions are considered at risk of IDD. However, mandatory salt iodisation in the last decade in many regions has decreased dramatically the percentage of the population at risk. Two recent major advances in understanding the global importance of malnutrition are (1) the data of 53 countries that links protein-energy malnutrition (assessed by underweight) directly to increased child mortality rates, and (2) the outcome in 6 of 8 large vitamin A supplementation trials showing decreases of 20-50% in child mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I849,I849)","v":11385132},{"$f":"(LEN($J849) - LEN(SUBSTITUTE(LOWER($J849),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J849) - LEN(SUBSTITUTE(LOWER($J849),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J849) - LEN(SUBSTITUTE(LOWER($J849),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B849:D849)","v":0},2001,"Maternal vitamin A administration and the fetal ductus arteriosus.","Shaul",11385132,"Maternal vitamin A administration and the fetal ductus arteriosus.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I850,I850)","v":11352180},{"$f":"(LEN($J850) - LEN(SUBSTITUTE(LOWER($J850),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J850) - LEN(SUBSTITUTE(LOWER($J850),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J850) - LEN(SUBSTITUTE(LOWER($J850),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B850:D850)","v":0},2001,"Pathogenesis of anemia during human immunodeficiency virus infection.","Semba",11352180,"Pathogenesis of anemia during human immunodeficiency virus infection.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I851,I851)","v":11291787},{"$f":"(LEN($J851) - LEN(SUBSTITUTE(LOWER($J851),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J851) - LEN(SUBSTITUTE(LOWER($J851),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J851) - LEN(SUBSTITUTE(LOWER($J851),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B851:D851)","v":0},2000,"Micronutrient malnutrition--present status and future remedies.","Chakravarty",11291787,"Micronutrient malnutrition--present status and future remedies.    Abstract:   Micronutrient deficiency is a serious public health concern in most of the developing countries which leads to malnutrition syndromes. The micronutient deficiencies which are of greatest public health significance include iron deficiency, vitamin A deficiency and iodine deficiency disorder. National Pilot Programme on Control of Micronutrient Malnutrition was launched in 1995 and the department of biochemistry and nutrition of the All India Institute of Hygiene and Public Health, Calcutta was entrusted to co-ordinate the activities. It presently covers five eastern and north-eastern states. Baseline situation analysis was conducted mainly on iron deficiency anaemia, iodine deficiency disorder and vitamin A deficiency. Comparing with WHO cut off figures, point prevalence of anaemia in various age groups was found to be high. Bitots spot was mainly noted in the age group of 6-71 months. Nightblindness was found in the children of the age group of 24-71 months. High prevalence of nightblindness in pregnant women is a point of concern. Action needed to control micronutrient deficiency includes: Intervention strategies, extensive nutrition and health education, to support the problem specific programmes, to stregthen various state government programmes and strengthen role of NGOs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I852,I852)","v":11291786},{"$f":"(LEN($J852) - LEN(SUBSTITUTE(LOWER($J852),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J852) - LEN(SUBSTITUTE(LOWER($J852),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J852) - LEN(SUBSTITUTE(LOWER($J852),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B852:D852)","v":0},2000,"Nutrition scenario in India--implications for clinical practice.","Balaji",11291786,"Nutrition scenario in India--implications for clinical practice.    Abstract:   India has the highest prevalence (and largest share) of malnourished children, low birth weight babies and anaemia levels amongst children and women in the world. Other micronutrient deficiencies (vitamin A and iodine) also constitute serious public health problems. Various government schemes set up to combat these problems have not had the expected impact in reducing malnutrtion or micronutrient deficiencies. This is not only due to low utilisation or inadequacy of the schemes but also due to the population not adopting appropriate behaviours to improve their health and nutrition. Providing correct and timely technical advice on nutrition to their patients and their families is often given inadequate emphasis by medical practitioners. But when we know that malnutrition contributes to 55% of child mortality which has been stagnating in most states, medical practitioners, whose advice on health matters is very much heeded by the population, can play an important role in reversing this trend."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I853,I853)","v":11291781},{"$f":"(LEN($J853) - LEN(SUBSTITUTE(LOWER($J853),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J853) - LEN(SUBSTITUTE(LOWER($J853),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J853) - LEN(SUBSTITUTE(LOWER($J853),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B853:D853)","v":0},2000,"Prevention of malnutrition.","Roy",11291781,"Prevention of malnutrition.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I854,I854)","v":11255823},{"$f":"(LEN($J854) - LEN(SUBSTITUTE(LOWER($J854),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J854) - LEN(SUBSTITUTE(LOWER($J854),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J854) - LEN(SUBSTITUTE(LOWER($J854),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B854:D854)","v":0},2001,"Caring for women with childbearing potential taking teratogenic dermatologic drugs. Guidelines for practice.","Perlman",11255823,"Caring for women with childbearing potential taking teratogenic dermatologic drugs. Guidelines for practice.    Abstract:    OBJECTIVES : Upon completion of this article, the reader should be able to: 1. Identify the dermatologic drugs with the highest risk of teratogenicity. 2. List the essential information to be obtained from a woman with childbearing potential being considered for treatment with a teratogenic dermatologic agent. 3. Discuss management principles for administration of teratogenic agents to women with childbearing potential. Dermatologic agents can be highly teratogenic, and the gynecologist must be aware of the issues involved in prescribing them. Prescribers should be aware of the risks and ensure that patients taking teratogens do not become pregnant during the course of therapy (or until the drug has been cleared from the body). This can involve taking menstrual and sexual histories and counseling the patient about sexual behavior and contraception."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I855,I855)","v":11243083},{"$f":"(LEN($J855) - LEN(SUBSTITUTE(LOWER($J855),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J855) - LEN(SUBSTITUTE(LOWER($J855),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J855) - LEN(SUBSTITUTE(LOWER($J855),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B855:D855)","v":0},1999,"Integrated Child Development Services scheme (ICDS) and its impact on nutritional status of children in India and recent initiatives.","Kapil",11243083,"Integrated Child Development Services scheme (ICDS) and its impact on nutritional status of children in India and recent initiatives.    Abstract:   Integrated Child Development Services (ICDS) scheme is the largest national programme for the promotion of the mother and child health and their development in the world. The beneficiaries include children below 6 years, pregnant and lactating mothers, and other women in the age group of 15 to 44 years. The package of services provided by the ICDS scheme includes supplementary nutrition, immunization, health check-up, referral services, nutrition and health education, and pre-school education. The distribution of iron and folic acid tablets and megadose of vitamin A is also undertaken, to prevent iron deficiency anaemia and xerophthalmia respectively. The scheme services are rendered essentially through the Anganwadi worker (AWW) at a village centre called quot;Anganwadiquot;. The ICDS had led to (i) reduction in prevalence of severe grades of malnutrition and (ii) better utilization of services of national nutritional anaemia prophylaxis programme and the national programme for prevention of nutritional blindness due to vitamin A deficiency by ICDS beneficiaries. The ICDS scheme is being modified continuously to strengthen the programme. This article presents the impact of Integrated Child Development Services (ICDS) on the nutritional status of mothers and of children under 6 years old in India. ICDS is the first and probably the only program in the country that aims at the holistic development of an individual. The reduction in prevalence of severe malnutrition is comparatively more significant in ICDS scheme population than in other population groups. There has been an extensive improvement in the nutritional status of children living in rural, urban and tribal areas and in those belonging to depressed sections of the community. The new initiative schemes for supplementary nutrition include: (a) improved monitoring mechanisms, (b) increased and improved norms of nutrition, (c) improved acceptability of supplementary recipes, (d) care of the severely malnourished, (e) the formation of a state level committee of experts, (f) inspection of quality, and (g) the introduction of community growth charts for malnourished children. The distribution of iron and folic tablets together with megadoses of vitamin A has also been undertaken for iron deficiency anemia and xerophthalmia prevention. Professionals, administrators, and politicians should feel obliged to continue making their contributions to the effective implementation of ICDS."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I856,I856)","v":11208451},{"$f":"(LEN($J856) - LEN(SUBSTITUTE(LOWER($J856),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J856) - LEN(SUBSTITUTE(LOWER($J856),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J856) - LEN(SUBSTITUTE(LOWER($J856),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B856:D856)","v":0},2000,"Alcohol and the developing fetus--a review.","Chaudhuri",11208451,"Alcohol and the developing fetus--a review.    Abstract:   Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I857,I857)","v":11127968},{"$f":"(LEN($J857) - LEN(SUBSTITUTE(LOWER($J857),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J857) - LEN(SUBSTITUTE(LOWER($J857),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J857) - LEN(SUBSTITUTE(LOWER($J857),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B857:D857)","v":0},2000,"Vitamin A and HIV infection: disease progression, mortality, and transmission.","Kennedy",11127968,"Vitamin A and HIV infection: disease progression, mortality, and transmission.    Abstract:   Among HIV-infected individuals, many nutritional factors that influence disease progress, mortality, and transmission are not well understood. Of particular interest is the role of vitamin A. The benefits of vitamin A have been recognized since ancient times by Egyptian physicians who successfully treated night blindness with vitamin A. Contemporary scientists have since recognized the importance of vitamin A and have provided evidence that it may help in repairing damaged mucosal surfaces; what remains unclear, however, is its role during HIV infection. In this review, we examine the evidence provided in both observational studies and randomized controlled trials that assessed the effect of vitamin A during HIV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I858,I858)","v":11091919},{"$f":"(LEN($J858) - LEN(SUBSTITUTE(LOWER($J858),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J858) - LEN(SUBSTITUTE(LOWER($J858),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J858) - LEN(SUBSTITUTE(LOWER($J858),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B858:D858)","v":0},2000,"Prevention of lung cancer. The new millennium.","Kim",11091919,"Prevention of lung cancer. The new millennium.    Abstract:   Lung cancer is the leading cause of cancer-related death worldwide and in the United States surpassing breast, prostate, and colon cancer. Treatment of this disease over the past 2 decades has advanced incrementally as survival rates have improved only slightly. Alternate approaches to this deadly disease include an emphasis on prevention such as smoking cessation. Chemoprevention has introduced a new arena of treatment options for early intervention in lung carcinogenesis. The use of molecularly targeted therapeutic and biologic agents constitutes novel strategies for lung cancer prevention in the new millennium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I859,I859)","v":11026055},{"$f":"(LEN($J859) - LEN(SUBSTITUTE(LOWER($J859),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J859) - LEN(SUBSTITUTE(LOWER($J859),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J859) - LEN(SUBSTITUTE(LOWER($J859),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B859:D859)","v":0},2000,"[Breast cancer chemoprevention (tamoxifen, raloxifene, and others)].","Funahashi",11026055,"[Breast cancer chemoprevention (tamoxifen, raloxifene, and others)].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I860,I860)","v":10977847},{"$f":"(LEN($J860) - LEN(SUBSTITUTE(LOWER($J860),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J860) - LEN(SUBSTITUTE(LOWER($J860),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J860) - LEN(SUBSTITUTE(LOWER($J860),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B860:D860)","v":0},2000,"ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics.","McPherson",10977847,"ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I861,I861)","v":10904660},{"$f":"(LEN($J861) - LEN(SUBSTITUTE(LOWER($J861),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J861) - LEN(SUBSTITUTE(LOWER($J861),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J861) - LEN(SUBSTITUTE(LOWER($J861),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B861:D861)","v":0},2000,"[Malnutrition and infections in children--a destructive interplay with global dimensions].","Bøhler",10904660,"[Malnutrition and infections in children--a destructive interplay with global dimensions].    Abstract:    BACKGROUND : Seven out of ten deaths among the worlds children are caused by infectious diseases. Malnutrition is a contributing cause in more than half of the childrens deaths. At present, interventions against such diseases in children are the most cost-effective way of reducing the worlds morbidity and mortality.  MATERIAL AND METHODS : This paper discusses how nutritional status affects the immune defence, and vice versa. General protein and energy malnutrition and some specific nutrients are discussed. The paper is based on review of recent literature found in Medline, and key references in the papers identified.  RESULTS : Malnutrition is the most common cause of acquired immune deficiency in children. Malnourished children are especially prone to develop persistent diarrhoea, which in turn aggravates the nutritional status. Iron deficiency may be caused or worsened by hookworm and a number of other gastrointestinal infections. There are indications that iron deficiency in itself reduces the immune defence. Vitamin A supplements have reduced the mortality of measles and other infectious diseases. Some studies have shown reduced vertical transmission of HIV when pregnant women get vitamin A supplements. Chronic diarrhoea may cause zinc deficiency which may aggravate the diarrhoea. In areas where the general populations zinc status is marginal, zinc supplementation has reduced the incidence and duration of persistent diarrhoea.  INTERPRETATION : The interaction between malnutrition and common infections in children causes a considerable fraction of the global burden of disease, yet so far this is not reflected in research, which mainly targets the diseases of the rich."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I862,I862)","v":10895188},{"$f":"(LEN($J862) - LEN(SUBSTITUTE(LOWER($J862),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J862) - LEN(SUBSTITUTE(LOWER($J862),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J862) - LEN(SUBSTITUTE(LOWER($J862),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B862:D862)","v":0},2000,"Dietary macro/micro-nutrients as a breast cancer risk: findings from nutritional case-control study in Jakarta, Indonesia.","Ohno",10895188,"Dietary macro/micro-nutrients as a breast cancer risk: findings from nutritional case-control study in Jakarta, Indonesia.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I863,I863)","v":10878580},{"$f":"(LEN($J863) - LEN(SUBSTITUTE(LOWER($J863),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J863) - LEN(SUBSTITUTE(LOWER($J863),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J863) - LEN(SUBSTITUTE(LOWER($J863),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B863:D863)","v":0},2000,"Role of erbB2 in breast cancer chemosensitivity.","Yu",10878580,"Role of erbB2 in breast cancer chemosensitivity.    Abstract:   The erbB2 gene, which encodes a transmembrane growth factor receptor, is overexpressed in approximately 30% of breast cancers. Overexpressing this gene makes breast cancers resistant to certain chemotherapeutic agents. In this article, we review what is known about ErbB2-mediated chemoresistance and the controversies surrounding it. We also examine the antiapoptotic function of erbB2 as one of the molecular mechanisms of ErbB2-mediated Taxol resistance and describe several emerging strategies for overcoming intrinsic ErbB2-mediated chemoresistance. Finally, we discuss future avenues for studies of chemosensitivity in ErbB2-overexpressing breast cancers that may lead to the development of effective biology-based treatment strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I864,I864)","v":10813462},{"$f":"(LEN($J864) - LEN(SUBSTITUTE(LOWER($J864),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J864) - LEN(SUBSTITUTE(LOWER($J864),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J864) - LEN(SUBSTITUTE(LOWER($J864),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B864:D864)","v":0},2000,"Global outlook on nutrition and the environment: meeting the challenges of the next millennium.","Iyengar",10813462,"Global outlook on nutrition and the environment: meeting the challenges of the next millennium.    Abstract:   As we enter the new millennium, nearly 800 million of the Worlds population will remain chronically malnourished. Nearly 200 million children are moderately to severely underweight, while 70 million are severely malnourished. And those who are yet to be born will be faced with the same set of circumstances that predispose them to malnutrition and its consequences. Eradication of nutritional deficiencies among women and children on a global scale are needed to ensure improved quality of life for the next generation of citizens. Primary deficiencies in vitamin A, iron, iodine, calcium, folic acid and trace elements such as zinc are compounded by pollutants caused by human activity. Environmental lead, arsenic, mercury, and other heavy metals that enter the food chain can seriously deplete body stores of iron, vitamin C and other essential nutrients leading to decreased immune defenses, intrauterine growth retardation, impaired psycho-social faculties and other disabilities associated with malnutrition. Increased susceptibilities to communicable diseases, and those provoked by water or insect borne vectors are additional risks encountered by malnourished individuals. Migration of populations from rural to urban centers and the expansion of major metropolitan areas have had a significant and adverse impact on the quality of life of these citizens. In the next 20 years most of the growth in urban populations will be in Asia and Latin America. Urbanization and the resultant burden on limited national resources is a major contributory factor to malnutrition. There are many other lifestyle-associated disabilities such as use of tobacco (cancer) and alcoholism that require active intervention. Within the family unit, socioeconomic factors and the status of women (literacy, economic independence) are major determinants of the quality of life. In the coming century, the World will have to meet these challenges by careful planning and international cooperation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I865,I865)","v":10789494},{"$f":"(LEN($J865) - LEN(SUBSTITUTE(LOWER($J865),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J865) - LEN(SUBSTITUTE(LOWER($J865),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J865) - LEN(SUBSTITUTE(LOWER($J865),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B865:D865)","v":0},2000,"Prevention of breast cancer.","Carolin",10789494,"Prevention of breast cancer.    Abstract:   With the advent of screening and the increased incidence of breast cancer, concern for the prevention of breast cancer has become forefront in todays society. Determining individual risk is the key to prescribing prevention. Prevention of breast cancer is still under clinical investigation with only one drug, tamoxifen, showing benefit in high risk patients. This paper reviews the possible sites for prevention of neoplastic transformation via biomarkers in a breast cell as well as the investigational drugs and their potential use in the chemoprevention of breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I866,I866)","v":10785332},{"$f":"(LEN($J866) - LEN(SUBSTITUTE(LOWER($J866),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J866) - LEN(SUBSTITUTE(LOWER($J866),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J866) - LEN(SUBSTITUTE(LOWER($J866),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B866:D866)","v":0},2000,"Epidemiology of HIV infection in the newborn.","Thorne",10785332,"Epidemiology of HIV infection in the newborn.    Abstract:   Vertical transmission of HIV infection can take place in utero, during delivery and postnatally through breastfeeding, with about three-quarters of infections occurring around the time of delivery in non-breastfeeding populations. In Europe, in the absence of specific interventions, the vertical transmission rate was 15-20%. High maternal load is the major risk factor for both intra-uterine and intra-partum mother-to-child transmission. Prematurity is the most common adverse neonatal outcome associated with maternal HIV infection. Earlier diagnosis of paediatric HIV infection than previously available is now possible with virological tests, particularly HIV DNA polymerase chain reaction. An estimated one fifth of infected children will have been diagnosed with AIDS or have died by 12 months of age, rising to a third by 6 years of age. Surgical and therapeutic interventions are effective in reducing vertical transmission risk, in addition to the avoidance of breastfeeding. Caesarean section delivery before labour and before rupture of membranes approximately halves the risk of transmission, while prophylactic zidovudine therapy according to the ACTG076 regimen reduces transmission by up to two-thirds, transmission is reduced even further with both interventions. Trials of short-course zidovudine regimens show their effectiveness in reducing vertical transmission, in breastfeeding and non-breastfeeding populations. Nevirapine has been shown to be significantly more effective than short course zidovudine regimens in breastfeeding populations, but is still under evaluation in non-breastfeeding populations additionally receiving routine anti-retroviral prophylaxis. Reports of a small number of serious adverse events in uninfected children exposed in utero or neonatally to antiretroviral therapy need further investigation. Trials of vitamin A supplementation to reduce vertical transmission have had negative results, while the effectiveness of vaginal lavage and passive immune therapy in reducing vertical transmission remains uncertain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I867,I867)","v":10748616},{"$f":"(LEN($J867) - LEN(SUBSTITUTE(LOWER($J867),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J867) - LEN(SUBSTITUTE(LOWER($J867),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J867) - LEN(SUBSTITUTE(LOWER($J867),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B867:D867)","v":0},2000,"Mother-to-child transmission of HIV infection: nutrition/HIV interactions.","Peckham",10748616,"Mother-to-child transmission of HIV infection: nutrition/HIV interactions.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I868,I868)","v":10729743},{"$f":"(LEN($J868) - LEN(SUBSTITUTE(LOWER($J868),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J868) - LEN(SUBSTITUTE(LOWER($J868),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J868) - LEN(SUBSTITUTE(LOWER($J868),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B868:D868)","v":0},2000,"The number of nephrons in the mammalian kidney: environmental influences play a determining role.","Lelièvre-Pégorier",10729743,"The number of nephrons in the mammalian kidney: environmental influences play a determining role.    Abstract:   Several lines of evidence, mostly derived from animal studies, indicate that changes in the fetal environment may affect the renal development. Fetal growth retardation is associated with a nephron deficit in both humans and animals. Changes in the supply of vitamin A to the fetus may be responsible for the variations in the number of nephrons in the human kidney. In utero exposure to hyperglycemia or drugs may also cause a nephron deficit."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I869,I869)","v":10535323},{"$f":"(LEN($J869) - LEN(SUBSTITUTE(LOWER($J869),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J869) - LEN(SUBSTITUTE(LOWER($J869),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J869) - LEN(SUBSTITUTE(LOWER($J869),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B869:D869)","v":0},1999,"Influence of fetal environment on kidney development.","Merlet-Bénichou",10535323,"Influence of fetal environment on kidney development.    Abstract:   Several lines of evidence, mostly derived from animal studies, indicate that changes in fetal environment may affect renal development. Besides maternal hyperglycemia or drug exposure, that were recently found to alter nephrogenesis, changes in vitamin A supply to the fetus may prove to be responsible for most of the variations in nephron number found in the population. A low vitamin A status in the fetus may be a major cause of inborn nephron deficit, either as a feature of intrauterine growth retardation or independently of growth retardation. The possibility that vitamin A status may also influence renal vascular development is raised. We suggest that low vitamin A supply to the fetus plays a role in the intrauterine programming of chronic renal disease and hypertension."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I870,I870)","v":10527467},{"$f":"(LEN($J870) - LEN(SUBSTITUTE(LOWER($J870),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J870) - LEN(SUBSTITUTE(LOWER($J870),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J870) - LEN(SUBSTITUTE(LOWER($J870),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B870:D870)","v":0},1999,"Maternal vitamin A nutriture and the vitamin A content of human milk.","Haskell",10527467,"Maternal vitamin A nutriture and the vitamin A content of human milk.    Abstract:   Because of the many functions of vitamin A in human physiology, deficiency or excess of the vitamin in lactating women or their infants can adversely affect their health. Infants are born with low body stores of vitamin A, and rely on vitamin A in milk to meet their needs. The vitamin A content of milk is related to maternal vitamin A status and maternal dietary vitamin A intake during lactation. Low-income lactating women in non-industrialized countries have lower milk vitamin A concentrations than lactating women in industrialized countries. Supplementation of lactating women in non-industrialized countries with vitamin A or beta-carotene has resulted in increased milk vitamin A concentrations. However, the optimal timing and dose for sustaining adequate levels of vitamin A in milk throughout the lactation period has not been determined. Further research is needed to understand factors affecting the transfer of vitamin A to milk, and to evaluate various strategies for improving the vitamin A status of mothers and infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I871,I871)","v":10465172},{"$f":"(LEN($J871) - LEN(SUBSTITUTE(LOWER($J871),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J871) - LEN(SUBSTITUTE(LOWER($J871),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J871) - LEN(SUBSTITUTE(LOWER($J871),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B871:D871)","v":0},1999,"Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group.","Coutsoudis",10465172,"Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group.    Abstract:    BACKGROUND : The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixed-fed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1.  METHODS : We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test.  FINDINGS : At 3 months, 18.8% (95% CI 12.6-24.9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21.3% (17.2-25.5) of 393 breastfed children (p=0.5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14.6% [7.7-21.4] vs 24.1% [19.0-29.2], p=0.03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0.52 [0.28-0.98]) and a similar risk to no breastfeeding (0.85 [0.51-1.42]).  INTERPRETATIONS : Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I872,I872)","v":10379880},{"$f":"(LEN($J872) - LEN(SUBSTITUTE(LOWER($J872),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J872) - LEN(SUBSTITUTE(LOWER($J872),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J872) - LEN(SUBSTITUTE(LOWER($J872),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B872:D872)","v":0},1999,"Fertility and infertility: genetic contributions from the hypothalamic-pituitary-gonadal axis.","Achermann",10379880,"Fertility and infertility: genetic contributions from the hypothalamic-pituitary-gonadal axis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I873,I873)","v":10347664},{"$f":"(LEN($J873) - LEN(SUBSTITUTE(LOWER($J873),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J873) - LEN(SUBSTITUTE(LOWER($J873),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J873) - LEN(SUBSTITUTE(LOWER($J873),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B873:D873)","v":0},1999,"[Clinical significance of extra vitamin supplements and enriched food products].","Hermus",10347664,"[Clinical significance of extra vitamin supplements and enriched food products].    Abstract:   Consumers increasingly use vitamin supplements. Also, since June 1996, foodstuffs enriched with vitamins are available on the Dutch market. These sources of extra vitamins may be useful for groups at risk for marginal vitamin deficiencies. These risk groups include the chronically ill (e.g. diabetics), people using medicaments, older people and pregnant women. Extra vitamins from low-dose supplements or enriched foodstuffs may also constitute a valuable and safe supplement to the diet of children, smokers, people eating unbalanced, people on slimming diets, vegetarians and people engaged in intensive sports. According to the advisory group Nutrition of the Health Council, addition of vitamins to foodstuffs causes no risks of any importance for public health, apart from vitamins A and D and of the trace elements selenium, copper and zinc. Consequently, these should only be added to reconstituted foodstuffs or in a substitution product, not in enriched foodstuffs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I874,I874)","v":10099107},{"$f":"(LEN($J874) - LEN(SUBSTITUTE(LOWER($J874),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J874) - LEN(SUBSTITUTE(LOWER($J874),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J874) - LEN(SUBSTITUTE(LOWER($J874),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B874:D874)","v":0},1999,"Transmission of human immunodeficiency virus type 1 through breast-feeding: how can it be prevented?","Van de Perre",10099107,"Transmission of human immunodeficiency virus type 1 through breast-feeding: how can it be prevented?    Abstract:   One-third to two-thirds of maternal transmission of human immunodeficiency virus type 1 (HIV-1) infection to breast-fed infants can be attributed to ingestion of breast milk. The presence of HIV-1 as cell-free and as cell-associated virus in milk has been documented. Several substances in breast milk may be protective against transmission, including maternal anti-HIV antibodies, vitamin A, lactoferrin, and secretory leukocyte protease inhibitor. The portal of virus entry in the infants gastrointestinal tract is unknown but may involve breaches in mucosal surfaces, transport across M cells, or direct infection of other epithelial cells, such as enterocytes. Timing of transmission of HIV-1 during lactation should be further clarified. An early rebound of plasma viremia after withdrawal of antiretrovirals was recently detected. This rebound may reduce the benefit of antiretroviral prophylaxis when women breast-feed their infants. Interventions should be viewed from the public health perspective of risks of infant morbidity and mortality associated with breast-feeding versus risks from formula-feeding."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I875,I875)","v":10066069},{"$f":"(LEN($J875) - LEN(SUBSTITUTE(LOWER($J875),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J875) - LEN(SUBSTITUTE(LOWER($J875),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J875) - LEN(SUBSTITUTE(LOWER($J875),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B875:D875)","v":0},1998,"Cyclins and breast cancer.","Steeg",10066069,"Cyclins and breast cancer.    Abstract:   Cyclins are regulatory subunits for cyclin dependent kinases in the coordination of the cell cycle. Cyclins can also serve non-cell cycle functions, such as the transactivation of estrogen receptor by cyclin D. Evidence for the participation of the G1 cyclins D and E in breast cancer is summarized, including transgenic and knockout mice, transfections, and expression patterns in cohort studies. Overexpression of cyclin D has been reported in ductal carcinoma in situ (DCIS), and similar overexpression of cyclin E is suggested. Strategies to reduce cyclin expression are discussed as potential prevention efforts."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I876,I876)","v":9932513},{"$f":"(LEN($J876) - LEN(SUBSTITUTE(LOWER($J876),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J876) - LEN(SUBSTITUTE(LOWER($J876),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J876) - LEN(SUBSTITUTE(LOWER($J876),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B876:D876)","v":0},1998,"Plasma vitamins A and E in HIV-positive patients.","Constans",9932513,"Plasma vitamins A and E in HIV-positive patients.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I877,I877)","v":9890059},{"$f":"(LEN($J877) - LEN(SUBSTITUTE(LOWER($J877),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J877) - LEN(SUBSTITUTE(LOWER($J877),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J877) - LEN(SUBSTITUTE(LOWER($J877),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B877:D877)","v":0},1998,"Genetic control of gonadal differentiation.","Lim",9890059,"Genetic control of gonadal differentiation.    Abstract:   The study of naturally occurring mutations in humans and induced mutations in mice that cause sex reversal has been instrumental in the cloning and functional analysis of genes involved in gonadal differentiation. Several genes required for this complex developmental process have now been identified. The genes LIM1, WT1 and FTZ-F1 have been demonstrated to be involved in the formation of the gonads prior to their differentiation as testes or ovaries. Subsequent sex-specific gonadal differentiation appears to be mediated by the SRY and SOX9 genes in the testis, and the DAX-1 gene in the ovary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I878,I878)","v":9819558},{"$f":"(LEN($J878) - LEN(SUBSTITUTE(LOWER($J878),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J878) - LEN(SUBSTITUTE(LOWER($J878),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J878) - LEN(SUBSTITUTE(LOWER($J878),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B878:D878)","v":0},1998,"Mammalian sex determination: joining pieces of the genetic puzzle.","Jiménez",9819558,"Mammalian sex determination: joining pieces of the genetic puzzle.    Abstract:   Mammalian sex determination is controlled by the Y-linked gene SRY. Studies of sex-reversed patients and experimental data obtained with mice have identified other genes, such as DAX1, SOX9, SF1, and WT1, which take part in the process, and have suggested how these genes interact to determine the sex of a mammalian embryo. A recent paper in Nature by Swain et al. provides experimental data that basically confirm the previously proposed hypothesis that SRY acts by inhibiting the action of DSS/DAX1, which is a repressor of genes of the male pathway."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I879,I879)","v":9793755},{"$f":"(LEN($J879) - LEN(SUBSTITUTE(LOWER($J879),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J879) - LEN(SUBSTITUTE(LOWER($J879),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J879) - LEN(SUBSTITUTE(LOWER($J879),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B879:D879)","v":0},1998,"Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmanns syndrome): pathophysiological and genetic considerations.","Seminara",9793755,"Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmanns syndrome): pathophysiological and genetic considerations.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I880,I880)","v":9755806},{"$f":"(LEN($J880) - LEN(SUBSTITUTE(LOWER($J880),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J880) - LEN(SUBSTITUTE(LOWER($J880),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J880) - LEN(SUBSTITUTE(LOWER($J880),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B880:D880)","v":0},1998,"A review of breast cancer chemoprevention.","Chang",9755806,"A review of breast cancer chemoprevention.    Abstract:   Breast cancer remains a major cause of mortality and morbidity, and may be amenable to chemoprevention as estrogen stimulation is believed to be responsible for the promotion of this disease. Tamoxifen is the most widely studied compound for chemoprevention and clinical trials involving over 20,000 women world-wide are currently underway. This drug is well-tolerated with low acute toxicity and high compliance, and has a favorable profile in both decreasing serum cholesterol and increasing bone mineral density in postmenopausal women. However, there are fears of its potential carcinogenicity, especially an increased risk of endometrial cancers, which may jeopardize further recruitment and compliance of women in these chemoprevention studies. Meta-analyses of these studies are expected to be conducted in the year 2000 to address the efficacy of tamoxifen in women with an increased familial predisposition and in those with known germline BRCA mutations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I881,I881)","v":9751943},{"$f":"(LEN($J881) - LEN(SUBSTITUTE(LOWER($J881),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J881) - LEN(SUBSTITUTE(LOWER($J881),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J881) - LEN(SUBSTITUTE(LOWER($J881),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B881:D881)","v":0},1998,"Alcohol and cancer.","Seitz",9751943,"Alcohol and cancer.    Abstract:   A great number of epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx, and the esophagus, and for the liver. In contrast to those organs, the risk by which alcohol consumption increases cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumors, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers are controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen, but under certain experimental conditions is a cocarcinogen and/or (especially in the liver) a tumor promoter. The metabolism of ethanol leads to the generation of acetaldehyde and free radicals. These highly reactive compounds bind rapidly to cell constituents and possibly to DNA. Acetaldehyde decreases DNA repair mechanisms and the methylation of cytosine in DNA. It also traps glutathione, an important peptide in detoxification. Furthermore, it leads to chromosomal aberrations and seems to be associated with tissue damage and secondary compensatory hyperregeneration. More recently, the finding of considerable production of acetaldehyde by gastrointestinal bacteria was reported. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P4502E1, associated with an enhanced activation of various procarcinogens present in alcoholic beverages, in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens, alterations in cell cycle behavior such as cell cycle duration leading to hyperregeneration, nutritional deficiencies such as methyl, vitamin A, folate, pyrridoxalphosphate, zinc and selenium deficiency, and alterations of the immune system, eventually resulting in an increased susceptibility to certain viral infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms in the upper gastrointestinal tract and in the rectum may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Thus, all these mechanisms, functioning in concert, actively modulate carcinogenesis, leading to its stimulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I882,I882)","v":9684269},{"$f":"(LEN($J882) - LEN(SUBSTITUTE(LOWER($J882),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J882) - LEN(SUBSTITUTE(LOWER($J882),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J882) - LEN(SUBSTITUTE(LOWER($J882),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B882:D882)","v":0},1998,"Immunonutrition: the pediatric experience.","Levy",9684269,"Immunonutrition: the pediatric experience.    Abstract:   The health benefits of specific nutrients in the diet are reviewed as they pertain to the pediatric population and its unique needs. Secretory immunoglobulins, lysozyme, interferon, and growth factors, among others, are known to confer immunological advantages to breast milk. Inhibition of bacterial pathogens, as well as permissive growth of a protective colonic ecoflora occur as a result of various cellular and biochemical mechanisms at play. The immunomodulatory properties of minerals such as iron, zinc, and selenium, are presented and the newly recognized protective role of vitamin A and its importance in developing countries and in conditions of compromised nutrition are discussed. The review also covers the role of arginine, glutamine, and nucleotides in adaptive responses of the developing gut and in pathologic states such as necrotizing enterocolitis, short bowel syndrome, and inflammatory bowel disease. Probiotics (specific microbial feeds with potential benefits to the host), and prebiotics (dietary components such as complex carbohydrates able to change the colonic microenvironment fostering colonization with non-enteropathogens) are areas of current interest because they offer alternatives for the management of the growing problem of multiple antibiotic resistance and overwhelming infections in the hospitalized patient."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I883,I883)","v":9647913},{"$f":"(LEN($J883) - LEN(SUBSTITUTE(LOWER($J883),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J883) - LEN(SUBSTITUTE(LOWER($J883),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J883) - LEN(SUBSTITUTE(LOWER($J883),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B883:D883)","v":0},1998,"Vitamins in HIV disease progression and vertical transmission.","Fawzi",9647913,"Vitamins in HIV disease progression and vertical transmission.    Abstract:   Human immunodeficiency virus (HIV) infection is a major public health problem worldwide, but particularly in subsaharan Africa and Asia. Numerous observational studies report inverse associations between vitamin status, measured biochemically or as levels of dietary intake, and the risk of disease progression or vertical transmission. Evidence to support these findings has been obtained from a few randomized placebo-controlled trials. In this paper, we review studies that examined the role of vitamins A, B, C, D, and E in HIV disease progression and transmission, and we discuss the potential mechanisms of action of these vitamins. Adequate vitamin intake leads to enhancement of epithelial integrity and systemic immunity and could contribute to improved clinical condition among HIV-infected subjects and reduce vertical transmission by reducing the risk and severity of opportunistic infection and reducing viral load in blood. Adequate vitamin status may also reduce vertical transmission through the intrapartum and breastfeeding routes by reducing HIV viral load in lower genital secretions and breast milk, respectively. Vitamin supplements may be one of a few potential treatments that are inexpensive enough to be made available to HIV-infected persons in developing countries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I884,I884)","v":9629113},{"$f":"(LEN($J884) - LEN(SUBSTITUTE(LOWER($J884),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J884) - LEN(SUBSTITUTE(LOWER($J884),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J884) - LEN(SUBSTITUTE(LOWER($J884),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B884:D884)","v":0},1998,"Unconventional therapies for cancer: 5. Vitamins A, C and E. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative.","Kaegi",9629113,"Unconventional therapies for cancer: 5. Vitamins A, C and E. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I885,I885)","v":9587686},{"$f":"(LEN($J885) - LEN(SUBSTITUTE(LOWER($J885),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J885) - LEN(SUBSTITUTE(LOWER($J885),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J885) - LEN(SUBSTITUTE(LOWER($J885),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B885:D885)","v":0},1998,"Hormonal strategies for the prevention of breast cancer.","Olsen",9587686,"Hormonal strategies for the prevention of breast cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I886,I886)","v":9584502},{"$f":"(LEN($J886) - LEN(SUBSTITUTE(LOWER($J886),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J886) - LEN(SUBSTITUTE(LOWER($J886),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J886) - LEN(SUBSTITUTE(LOWER($J886),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B886:D886)","v":0},1998,"Indonesian recommended dietary allowance.","Muhilal",9584502,"Indonesian recommended dietary allowance.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I887,I887)","v":9571719},{"$f":"(LEN($J887) - LEN(SUBSTITUTE(LOWER($J887),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J887) - LEN(SUBSTITUTE(LOWER($J887),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J887) - LEN(SUBSTITUTE(LOWER($J887),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B887:D887)","v":0},1998,"Combating micronutrient deficiencies: problems and perspectives.","Alnwick",9571719,"Combating micronutrient deficiencies: problems and perspectives.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I888,I888)","v":9496455},{"$f":"(LEN($J888) - LEN(SUBSTITUTE(LOWER($J888),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J888) - LEN(SUBSTITUTE(LOWER($J888),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J888) - LEN(SUBSTITUTE(LOWER($J888),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B888:D888)","v":0},1997,"Micronutrients and breast cancer.","Franceschi",9496455,"Micronutrients and breast cancer.    Abstract:   A large part of the epidemiological debate on diet and breast cancer has been dominated by the issue of whether fat, particularly animal fat, increases risk. Lately, the possible protective effect of various dietary constituents has received more attention. Vitamins C and E, and beta-carotene have antioxidant activity and may thus provide a cellular defence against reactive oxygen species that damage DNA. Dietary fibre may influence oestrogen metabolism. A large case-control study (2,569 breast cancer and 2,588 hospital controls) conducted in six Italian areas between 1991 and 1994 suggested that a diet rich in several micronutrients was associated with significantly lowered risk. After allowance for non-dietary risk correlates, energy intake and the mutual confounding effect of the various micronutrients, beta-carotene, vitamin E and calcium were associated with odds ratios in the highest intake quintile compared to the lowest one of 0.84, 0.75 and 0.81, respectively. Among different types of fibre, only cellulose intake showed a moderate inverse association. Evidence from other studies suggests that a favourable role of some micronutrients is possible, albeit probably less important than for cancers of the stomach and colon-rectum. Indeed, the relationship between fruit and vegetable intake is also less marked/consistent for breast cancer than for other sites. Among agents that have only recently been investigated, isoflavones, which are weak oestrogens, are of particular interest."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I889,I889)","v":9481113},{"$f":"(LEN($J889) - LEN(SUBSTITUTE(LOWER($J889),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J889) - LEN(SUBSTITUTE(LOWER($J889),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J889) - LEN(SUBSTITUTE(LOWER($J889),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B889:D889)","v":0},1998,"Can cervical dysplasia and cancer be prevented with nutrients?","Giuliano",9481113,"Can cervical dysplasia and cancer be prevented with nutrients?    Abstract:   Invasive cervical cancer accounts for 11.6% of all cancers worldwide and is the second most common cancer among women. It is the most common cancer among women living in less developed countries. Although infection with oncogenic-type human papillomaviruses (HPV) is associated with most cases of cervical cancer, HPV infection alone is an insufficient cause of cervical cancer. Research from the last two decades suggests a role for nutrients in the prevention of cervical cancer. However, results from phase III folic acid and beta-carotene chemoprevention trials have been negative. Potential reasons for the lack of treatment effect are discussed within the context of cervical carcinogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I890,I890)","v":9427881},{"$f":"(LEN($J890) - LEN(SUBSTITUTE(LOWER($J890),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J890) - LEN(SUBSTITUTE(LOWER($J890),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J890) - LEN(SUBSTITUTE(LOWER($J890),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B890:D890)","v":0},1997,"quot;Feeding the gutquot;: the scientific basis for continued enteral nutrition during acute diarrhea.","Duggan",9427881,"quot;Feeding the gutquot;: the scientific basis for continued enteral nutrition during acute diarrhea.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I891,I891)","v":9240870},{"$f":"(LEN($J891) - LEN(SUBSTITUTE(LOWER($J891),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J891) - LEN(SUBSTITUTE(LOWER($J891),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J891) - LEN(SUBSTITUTE(LOWER($J891),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B891:D891)","v":0},1997,"Breastfeeding and vertical transmission of HIV-1.","Kreiss",9240870,"Breastfeeding and vertical transmission of HIV-1.    Abstract:   An estimated one-third to one-half of vertical transmission of human immunodeficiency virus type 1 (HIV-1) worldwide is due to breastfeeding. The exact frequency of breast milk HIV-1 transmission is unknown, but it has been estimated to be 14% in the setting of established maternal HIV-1 infection and 29% in the setting of acute maternal infection. The timing of breast milk transmission during the course of lactation also remains unknown, but two studies have found an association between duration of breastfeeding and risk of infant infection. In one such study, prolonged breastfeeding for 15 months or longer was associated with a twofold increased transmission risk. Human immunodeficiency virus type 1 DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and vitamin A deficiency. The presence of breast milk HIV-1 provirus is associated with increased transmission risk. Many current intervention strategies to prevent vertical transmission of HIV-1 are aimed at in utero or perinatal transmission. In developing countries in which breastfeeding by HIV-1 infected women is recommended practice, additional intervention strategies to reduce breast milk transmission warrant evaluation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I892,I892)","v":9094918},{"$f":"(LEN($J892) - LEN(SUBSTITUTE(LOWER($J892),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J892) - LEN(SUBSTITUTE(LOWER($J892),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J892) - LEN(SUBSTITUTE(LOWER($J892),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B892:D892)","v":0},1997,"Regression calibration method for correcting measurement-error bias in nutritional epidemiology.","Spiegelman",9094918,"Regression calibration method for correcting measurement-error bias in nutritional epidemiology.    Abstract:   Regression calibration is a statistical method for adjusting point and interval estimates of effect obtained from regression models commonly used in epidemiology for bias due to measurement error in assessing nutrients or other variables. Previous work developed regression calibration for use in estimating odds ratios from logistic regression. We extend this here to estimating incidence rate ratios from Cox proportional hazards models and regression slopes from linear-regression models. Regression calibration is appropriate when a gold standard is available in a validation study and a linear measurement error with constant variance applies or when replicate measurements are available in a reliability study and linear random within-person error can be assumed. In this paper, the method is illustrated by correction of rate ratios describing the relations between the incidence of breast cancer and dietary intakes of vitamin A, alcohol, and total energy in the Nurses Health Study. An example using linear regression is based on estimation of the relation between ultradistal radius bone density and dietary intakes of caffeine, calcium, and total energy in the Massachusetts Womens Health Study. Software implementing these methods uses SAS macros."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I893,I893)","v":9167141},{"$f":"(LEN($J893) - LEN(SUBSTITUTE(LOWER($J893),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J893) - LEN(SUBSTITUTE(LOWER($J893),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J893) - LEN(SUBSTITUTE(LOWER($J893),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B893:D893)","v":0},1997,"Trace elements and vitamins in immunomodulation in infancy and childhood.","Zuin",9167141,"Trace elements and vitamins in immunomodulation in infancy and childhood.    Abstract:   It has been established that there is a strict and cyclical relationship between infection, immune function and nutritional status with changes in one influencing the other two. Impairment of immune function can occur even in healthy subjects in apparently good nutritional status as a consequence of some nutrient deficiencies. The impact of trace elements and vitamins on immune function are briefly reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I894,I894)","v":9148869},{"$f":"(LEN($J894) - LEN(SUBSTITUTE(LOWER($J894),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J894) - LEN(SUBSTITUTE(LOWER($J894),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J894) - LEN(SUBSTITUTE(LOWER($J894),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B894:D894)","v":0},1997,"Steroid hormone receptors and antineoplastic chemotherapy in human breast cancer.","Görlich",9148869,"Steroid hormone receptors and antineoplastic chemotherapy in human breast cancer.    Abstract:   Several clinical and experimental investigations suggest that the action of antineoplastic chemotherapy in premenopausal women influences the menopause. Such hormonal reactions are mediated via specific steroid hormone receptors. Therefore, connections between hormone receptors and antineoplastic chemotherapy can be assumed making possible to predict success of chemotherapy on the basis of receptor status. Nevertheless, clinical experiences and animal and cell culture experiments yielded controversial results. This was related to the predictive value of receptor status as well as to the benefits of combined hormone and chemotherapy treatments in concurrent or sequential form. It is undeniable that a displacing of steroidal ligand from its receptors by the usual antineoplastic drugs does not occur. Furthermore, the receptor levels remain unchanged after a treatment with antineoplastic drugs. Thus, the mechanism of action of chemotherapeutic drugs is not related directly to the presence or absence of steroid hormone receptors. Despite this fact the receptor status in chemotherapeutic regimes seems to be helpful to define low or high risk patients. Influences on the ER de-novo-synthesis, actions related to parameters representing reduced tumor growth rates, down-regulation of the receptor gene expression or via receptor mediated hormonal actions to other genes, like the apoptosis-related gene bcl-2, are thought to be possible mechanisms of action of antineoplastic drugs on steroid hormone receptors. Future investigations should monitor the ratios between exon lacking receptor variants and the wild-type receptor during chemotherapy or the control of a ligand uptake during chemotherapy by means of the positron emission tomography."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I895,I895)","v":9071865},{"$f":"(LEN($J895) - LEN(SUBSTITUTE(LOWER($J895),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J895) - LEN(SUBSTITUTE(LOWER($J895),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J895) - LEN(SUBSTITUTE(LOWER($J895),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B895:D895)","v":0},1997,"The role of zinc in health and disease: relevance to child health in developing countries.","Bhutta",9071865,"The role of zinc in health and disease: relevance to child health in developing countries.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I896,I896)","v":9471473},{"$f":"(LEN($J896) - LEN(SUBSTITUTE(LOWER($J896),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J896) - LEN(SUBSTITUTE(LOWER($J896),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J896) - LEN(SUBSTITUTE(LOWER($J896),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B896:D896)","v":0},1997,"[Vitamin A. Consequence of a deficiency, of excessive vitamin A, and value of systematic supplementation].","Elefant",9471473,"[Vitamin A. Consequence of a deficiency, of excessive vitamin A, and value of systematic supplementation].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I897,I897)","v":9321953},{"$f":"(LEN($J897) - LEN(SUBSTITUTE(LOWER($J897),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J897) - LEN(SUBSTITUTE(LOWER($J897),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J897) - LEN(SUBSTITUTE(LOWER($J897),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B897:D897)","v":0},1997,"Structure and regulation of platelet activating factor receptor gene.","Shimizu",9321953,"Structure and regulation of platelet activating factor receptor gene.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I898,I898)","v":9185369},{"$f":"(LEN($J898) - LEN(SUBSTITUTE(LOWER($J898),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J898) - LEN(SUBSTITUTE(LOWER($J898),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J898) - LEN(SUBSTITUTE(LOWER($J898),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B898:D898)","v":0},1997,"Prevention of diarrhoea in young children in developing countries.","Huttly",9185369,"Prevention of diarrhoea in young children in developing countries.    Abstract:   An updated review of nonvaccine interventions for the prevention of childhood diarrhoea in developing countries is presented. The importance of various key preventive strategies (breast-feeding, water supply and sanitation improvements) is confirmed and certain aspects of others (promotion of personal and domestic hygiene, weaning education/food hygiene) are refined. Evidence is also presented to suggest that, subject to cost-effectiveness examination, two other strategies-vitamin A supplementation and the prevention of low birth weight-should be promoted to the first category of interventions, as classified by Feachem, i.e. those which are considered to have high effectiveness and strong feasibility. A review of recent evaluations of non-vaccine interventions for the prevention of childhood diarrhea in developing countries both confirmed the importance of standard strategies (e.g., breast feeding, water supply and sanitation improvements) and suggested refinements in approaches to personal and domestic hygiene, weaning education, and food hygiene. Despite the risk of vertical transmission of human immunodeficiency virus in infected areas, the health risks of not breast feeding far outweigh the potential number of lives saved by abandoning this practice. Weaning education programs can produce a 2-12% reduction in diarrhea mortality. Also important is the promotion of food handling, preparation, and storage practices that reduce the risk of fecal contamination. Improvements in water quantity may have a greater impact on diarrhea than improvements in quality alone through their effect on personal and domestic hygiene. Two relatively new strategies, vitamin A supplementation and prevention of low birth weight, should be promoted. Vitamin A intake is significantly associated with both all-cause and diarrhea-specific child mortality; the feasibility of large-scale supplementation programs awaits investigation of their cost-effectiveness, however. The choice of specific diarrheal control strategies depends on local factors such as diarrhea etiologies, the existing infrastructure, and government priorities. In all countries, effective implementation of preventive strategies requires the involvement of a range of sectors (e.g., health, agriculture, water supply, and sanitation)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I899,I899)","v":9141753},{"$f":"(LEN($J899) - LEN(SUBSTITUTE(LOWER($J899),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J899) - LEN(SUBSTITUTE(LOWER($J899),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J899) - LEN(SUBSTITUTE(LOWER($J899),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B899:D899)","v":0},1997,"Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.","Dietz",9141753,"Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.    Abstract:   An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation. An estimated 400,000 children die annually due to neonatal tetanus (NT). In 1989, the World Health Organization (WHO) adopted the goal of eliminating NT as a public health problem worldwide. To that end, and in order to control non-neonatal tetanus (non-NT), the WHO recommends that newborn infants be passively protected at birth by the antepartum administration of at least 2 doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least 3 doses of diphtheria-tetanus-pertussis (DTP) vaccine. However, the TT employed must be immunogenic in order for the strategy to work. Although the data are conflicting, concurrent malarial infection may decrease the immune response to TT, while malarial chemoprophylaxis may enhance immune response. Malnutrition does not appear to affect immunogenicity, although a study suggests that vitamin A deficiency is associated with an impaired immune response. A survey of the published literature suggests that there is no basis for accepting the hypothesis that placental transfer of tetanus antibody is impaired in African women. Finally, freezing TT has been shown to decrease its potency, but its effect upon immunogenicity remains to be determined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I900,I900)","v":9108597},{"$f":"(LEN($J900) - LEN(SUBSTITUTE(LOWER($J900),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J900) - LEN(SUBSTITUTE(LOWER($J900),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J900) - LEN(SUBSTITUTE(LOWER($J900),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B900:D900)","v":0},1997,"Perspectives and progress in development of breast cancer chemopreventive drugs.","Kelloff",9108597,"Perspectives and progress in development of breast cancer chemopreventive drugs.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I901,I901)","v":9087069},{"$f":"(LEN($J901) - LEN(SUBSTITUTE(LOWER($J901),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J901) - LEN(SUBSTITUTE(LOWER($J901),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J901) - LEN(SUBSTITUTE(LOWER($J901),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B901:D901)","v":0},1996,"Subclinical vitamin A deficiency: a potentially unrecognized problem in the United States.","Stephens",9087069,"Subclinical vitamin A deficiency: a potentially unrecognized problem in the United States.    Abstract:   Vitamin A deficiency in its subclinical form is a world health problem in young children. The problem is probably under recognized in the United States and other developed countries who do not normally consider their citizens to be malnourished. Lack of a simple screening test to measure subclinical deficiency adds to this problem. Consequently, focused dietary assessment of vitamin A intake by a Food Frequency Questionnaire (FFQ) is a necessary component of health care maintenance, especially for toddlers and preschool age children. Dietary counseling and vitamin supplementation for high risk children is a necessary health promotion intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I902,I902)","v":8783512},{"$f":"(LEN($J902) - LEN(SUBSTITUTE(LOWER($J902),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J902) - LEN(SUBSTITUTE(LOWER($J902),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J902) - LEN(SUBSTITUTE(LOWER($J902),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B902:D902)","v":0},1996,"Epidemiology amp; management of persistent diarrhoea in children of developing countries.","Bhan",8783512,"Epidemiology amp; management of persistent diarrhoea in children of developing countries.    Abstract:   Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised estimates in developing countries including India showed that acute diarrhoea accounts for 35 per cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for 45 per cent of total diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that increase the risk of acute diarrhoea becoming persistent have been identified in India and other developing countries. These include antecedent malnutrition, micronutrient deficiency particularly for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk. Several issues regarding the management of persistent diarrhoea in hospitalized children in India have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated. In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose hasten recovery. The role of antimicrobial agents and individual micronutrients in PD is currently being investigated. A management algorithm appropriate for India and other developing countries has been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I903,I903)","v":8710233},{"$f":"(LEN($J903) - LEN(SUBSTITUTE(LOWER($J903),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J903) - LEN(SUBSTITUTE(LOWER($J903),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J903) - LEN(SUBSTITUTE(LOWER($J903),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B903:D903)","v":0},1996,"Early dietary influence on later immunocompetence.","Hanson",8710233,"Early dietary influence on later immunocompetence.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I904,I904)","v":9142962},{"$f":"(LEN($J904) - LEN(SUBSTITUTE(LOWER($J904),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J904) - LEN(SUBSTITUTE(LOWER($J904),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J904) - LEN(SUBSTITUTE(LOWER($J904),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B904:D904)","v":0},1996,"Novel endocrine therapies in breast cancer.","Klijn",9142962,"Novel endocrine therapies in breast cancer.    Abstract:   Endocrine therapy of breast cancer consists of a variety of both medical and surgical ablative treatment modalities, but ablative therapy is increasingly replaced by medical treatment. Most endocrine therapies have more than one endocrine effect, frequently together with direct growth inhibitory actions via receptors. Endocrine therapy can be effective in all phases of the disease, but curative only in early disease while in advanced cancer it can only prolong survival. In the past decade the number of available endocrine agents has been drastically increased. Novel approaches in the endocrine therapy of breast cancer are application of new antiestrogens, antiprogestins, new potent aromatase inhibitors, analogues of luteinizing hormone-releasing hormone (LHRH-A) and somatostatin, inhibitors of prolactin secretion, vitamin A and D analogues, bisphosphonates, growth factor antagonists, tyrosine protein kinase inhibitors, protease inhibitors, inhibitors of angiogenesis, radiolabeled hormones and monoclonal antibodies. New cell biological factors such as oncogenes and suppressorgenes, secretory proteins and membrane receptors can be used not only as prognostic factors but also for prediction of type of response to endocrine and chemotherapy. Thus, these cell biological parameters can be used to select high and low risk patients, type of systemic treatment, and can also be used as targets for new treatment modalities. Future studies on treatment of all stages of disease will increasingly focus on promising combined treatment modalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I905,I905)","v":9021309},{"$f":"(LEN($J905) - LEN(SUBSTITUTE(LOWER($J905),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J905) - LEN(SUBSTITUTE(LOWER($J905),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J905) - LEN(SUBSTITUTE(LOWER($J905),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B905:D905)","v":0},1996,"Mother-to-child transmission of human immunodeficiency virus type 1.","John",9021309,"Mother-to-child transmission of human immunodeficiency virus type 1.    Abstract:   A great deal of progress has been made in our understanding of mother-to-child transmission of HIV-1. Standardization of case definitions and transmission rate calculation methodologies, and a broader array of diagnostic options for detection of infant HIV-1 infection, will enhance our ability to evaluate and compare cohorts worldwide. In the next decade, several intervention studies should be completed. Carefully designed intervention studies have the potential both to determine which interventions are effective as well as to add to our understanding of vertical transmission of HIV-1. Regional differences in vertical transmission rates reflect a variety of viral, host, and obstetric factors. Intervention strategies will probably need to be regionally designed, taking into consideration these factors. Further research on timing and correlates of vertical transmission is necessary to determine the extent to which specific clinical trials can be extrapolated to public health policy. Research related to maternal-child transmission of human immunodeficiency virus (HIV) has been advanced by standardization of case definitions and transmission rate calculation methodologies as well as enhanced diagnostic options for detecting infant HIV-1 infection. Standardization guidelines have yielded vertical transmission rate estimates of 25-30% in developing countries and 14-25% in developed countries. Mathematical modeling suggests that 95% of infant infections occur later than the last 2 months before delivery. Serial polymerase chain reaction evaluation has identified a 7.7% risk of in utero transmission, a 17.6% risk of combined in utero and intrapartum transmission, and a 4.9% incidence of late postnatal transmission. The risk of transmission through breast feeding has been estimated at 14%, with increases with longer durations. Advanced maternal clinical HIV status, primary infection, decreased maternal cell-mediated immunity, placentitis, ascending genital infection during the peripartum period, and syncytium-inducing HIV-1 strains have been associated with higher rates of maternal-child transmission. Prematurity, lack of cellular immunity, and vitamin A deficiency may be infant risk factors. The finding in an AIDS Clinical Trial Group that zidovudine (AZT) treatment was associated with a 67.5% reduction in risk has prompted widespread use of this regimen in developed countries; however, AZT is expensive and logistically difficult to administer in most developing country contexts. Randomized clinical trials currently underway are assessing the benefits of cesarean section delivery, postpartum HIV-specific immunoglobulin administration to infants, avoidance of breast feeding or early weaning, and antenatal maternal vitamin A administration. Selected intervention strategies should be regionally designed to take into account variations in viral, host, and obstetric factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I906,I906)","v":8959068},{"$f":"(LEN($J906) - LEN(SUBSTITUTE(LOWER($J906),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J906) - LEN(SUBSTITUTE(LOWER($J906),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J906) - LEN(SUBSTITUTE(LOWER($J906),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B906:D906)","v":0},1996,"[Genital erosive lichen planus].","Vilmer",8959068,"[Genital erosive lichen planus].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I907,I907)","v":8814984},{"$f":"(LEN($J907) - LEN(SUBSTITUTE(LOWER($J907),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J907) - LEN(SUBSTITUTE(LOWER($J907),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J907) - LEN(SUBSTITUTE(LOWER($J907),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B907:D907)","v":0},1996,"The E-cadherin/catenin complex in invasion and metastasis.","Bracke",8814984,"The E-cadherin/catenin complex in invasion and metastasis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I908,I908)","v":8678822},{"$f":"(LEN($J908) - LEN(SUBSTITUTE(LOWER($J908),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J908) - LEN(SUBSTITUTE(LOWER($J908),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J908) - LEN(SUBSTITUTE(LOWER($J908),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B908:D908)","v":0},1996,"Teratogenic effects of alcohol: current status of animal research and in vitro models.","Guerri",8678822,"Teratogenic effects of alcohol: current status of animal research and in vitro models.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I909,I909)","v":8846548},{"$f":"(LEN($J909) - LEN(SUBSTITUTE(LOWER($J909),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J909) - LEN(SUBSTITUTE(LOWER($J909),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J909) - LEN(SUBSTITUTE(LOWER($J909),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B909:D909)","v":0},1995,"Maternal nutrition and obstetric outcome.","Steegers-Theunissen",8846548,"Maternal nutrition and obstetric outcome.    Abstract:   In general, maternal nutritional status in civilized countries is not at risk. However, even a marginal malnutritional state for some (micro)nutrients for the pregnant women can adversely affect obstetrical outcome. From the data available so far, only folic acid supplementation is advised. However, the importance of an adequate iron and zinc status has to be stressed. In addition, women should be warned preconceptionally about excessive intake of vitamins, especially of those products containing large amounts of vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I910,I910)","v":8524896},{"$f":"(LEN($J910) - LEN(SUBSTITUTE(LOWER($J910),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J910) - LEN(SUBSTITUTE(LOWER($J910),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J910) - LEN(SUBSTITUTE(LOWER($J910),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B910:D910)","v":0},1995,"Interdependence of vitamin A and iron: an important association for programmes of anaemia control.","Bloem",8524896,"Interdependence of vitamin A and iron: an important association for programmes of anaemia control.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I911,I911)","v":7731628},{"$f":"(LEN($J911) - LEN(SUBSTITUTE(LOWER($J911),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J911) - LEN(SUBSTITUTE(LOWER($J911),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J911) - LEN(SUBSTITUTE(LOWER($J911),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B911:D911)","v":0},1995,"Treatment of vulvar lichen sclerosus in the elderly: an update.","Elchalal",7731628,"Treatment of vulvar lichen sclerosus in the elderly: an update.    Abstract:   Lichen sclerosus et atrophicus is a disorder of the skin that can occur anywhere on the body and in all age groups but mainly affects middle-aged and elderly women in the vulvoperineal area. It consists of ivory or pink papules or macules that eventually coalesce into thin, gray, parchment-like areas. Clinically, the main symptoms are severe and intractable itching and vaginal soreness with dyspareunia. Although it has been described to be associated with an increased risk for epithelial malignancy this, in fact, very rarely occurs. The exact nature of LSA is still unknown. The accumulation of evidence does little to clarify its pathogenesis and etiology. The different reports indicate at least three general possibilities; autoimmune, metabolic, and more recently infectious etiology. The coexistence of such diverse findings in one disease entity may indicate one of the two; either we are facing a group of very similar conditions, which will be separated in the future into several closely related clinical entities, each with its own etiology, or that all findings represent a complex multi-step single pathogenetic mechanism. The latter possibility seems more probable because it has previously been suggested that B. burgdorferi, a recent prime suspect in the pathogenesis of LSA, may induce both metabolic and autoimmune abnormalities in the course of infection. New therapeutic options and attitudes emerge that dramatically improved the conservative treatment of this disease (Table 5).(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I912,I912)","v":8907773},{"$f":"(LEN($J912) - LEN(SUBSTITUTE(LOWER($J912),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J912) - LEN(SUBSTITUTE(LOWER($J912),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J912) - LEN(SUBSTITUTE(LOWER($J912),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B912:D912)","v":0},1995,"Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review.","Kirkwood",8907773,"Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review.    Abstract:   This article describes the background and framework for a systematic review of potential interventions for preventing pneumonia among under-5-year-olds in developing countries. Twenty-eight intervention areas are identified in six groups -- immunization, case management/chemoprophylaxis of high-risk children, improving nutrition, reducing environmental pollution, reducing transmission of pathogens, and improving child care practices. Calculation of the potential impacts is illustrated and the expected outcomes are also described. In March 1992, March 1993, and June 1994, an international expert advisory committee oversaw a systematic and comprehensive review of potential interventions for preventing pneumonia among children aged less than 5 living in developing countries. The World Health Organizations Programme for the Control of Acute Respiratory Infections (ARIs) and the London School of Hygiene and Tropical Medicine conducted the review. There were 28 individual intervention areas identified among six broad intervention groups. Immunization comprises one of the six broad intervention categories. Specific immunization interventions include increased coverage of measles and pertussis and new vaccines for Pneumococcus, H. influenza B, respiratory syncytial virus, and other viral vaccines. Improving nutrition interventions revolve around breast feeding, low birth weight, malnutrition, vitamin A, severe anemia, and other micronutrients (e.g., zinc). The broad intervention category of reducing environmental pollution encompasses indoor air pollution, environmental tobacco smoke, and outdoor air pollution. Severely malnourished children, high risk neonates, ARI (upper tract), helminths, and wheezing fall under the case management and chemoprophylaxis intervention category. Crowding, direct transmission, and HIV are addressed in the category of reducing transmission of pathogens. The category of improving child care practices includes care-seeking, avoiding chilling, other child care practices, maternal education, and child spacing. The specialists conducted modeling to determine the potential impact of various interventions. It showed that the potential impact of an intervention increases independently with the pre-intervention prevalence of the risk category, with the size of the associated relative risk, and with the reduction in risk-category prevalence achieved by the intervention. Modeling will be used to compare the potential impacts of ARI preventive approaches with the impact achievable with the case management strategy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I913,I913)","v":8846497},{"$f":"(LEN($J913) - LEN(SUBSTITUTE(LOWER($J913),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J913) - LEN(SUBSTITUTE(LOWER($J913),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J913) - LEN(SUBSTITUTE(LOWER($J913),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B913:D913)","v":0},1995,"Breast-milk vitamin A as an indicator of the vitamin A status of women and infants.","Stoltzfus",8846497,"Breast-milk vitamin A as an indicator of the vitamin A status of women and infants.    Abstract:   This article reviews the evidence for using breast-milk vitamin A as an indicator of vitamin A status and provides technical information for researchers who want to use this indicator to assess the vitamin A status of women and breast-fed children. Breast-milk vitamin A is a unique indicator for assessing the vitamin A status of lactating women and their breast-fed infants, and has recently been recommended by WHO for use in monitoring global elimination of vitamin A deficiency. Assessing breast-milk vitamin A is less invasive than alternative approaches for assessing a mothers vitamin A status and not at all invasive for her infant. Collection of milk samples in the field is generally feasible and acceptable. Breast-milk vitamin A appears to be an especially good indicator for measuring the impact of vitamin A interventions on women and infants, and for this purpose, it is more responsive than other indicators."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I914,I914)","v":8619644},{"$f":"(LEN($J914) - LEN(SUBSTITUTE(LOWER($J914),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J914) - LEN(SUBSTITUTE(LOWER($J914),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J914) - LEN(SUBSTITUTE(LOWER($J914),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B914:D914)","v":0},1995,"-Results of ongoing breast cancer prevention studies-.","Jungi",8619644,"-Results of ongoing breast cancer prevention studies-.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I915,I915)","v":7486827},{"$f":"(LEN($J915) - LEN(SUBSTITUTE(LOWER($J915),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J915) - LEN(SUBSTITUTE(LOWER($J915),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J915) - LEN(SUBSTITUTE(LOWER($J915),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B915:D915)","v":0},1995,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.","Demczuk",7486827,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.    Abstract:   DiGeorge syndrome (DGS) is a developmental defect which associates hypo- or aplasia of the thymus and parathyroids, facial dysmorphism and conotruncal cardiac malformations. The etiological factor in a great majority of DGS patients is monosomy for the 22q11.2 chromosomal region either through a large interstitial deletion of that region (inherited or de novo) or through an unbalanced translocation involving chromosome 22. In one instance, a balanced translocation of chromosome 22 was associated with a DGS phenotype. Extensive analyses of this region of chromosome 22 has led to the obtention of precise physical maps of the corresponding genomic region, to the cloning of the balanced translocation breakpoint and to the isolation of different genes from the minimal critical deleted region."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I916,I916)","v":7955084},{"$f":"(LEN($J916) - LEN(SUBSTITUTE(LOWER($J916),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J916) - LEN(SUBSTITUTE(LOWER($J916),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J916) - LEN(SUBSTITUTE(LOWER($J916),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B916:D916)","v":0},1994,"Evaluation of chemopreventive agents against breast cancer and proposed strategies for future clinical intervention trials.","el-Bayoumy",7955084,"Evaluation of chemopreventive agents against breast cancer and proposed strategies for future clinical intervention trials.    Abstract:   This review is based on literature data pertaining to the use of single agents or complex mixtures that have been shown to offer protection against mammary cancer in rodents. The species and strains of animals, dose, route, frequency and duration of carcinogen administration, as well as types, levels, route of administration and duration of chemopreventive treatments are described in detail. A brief description regarding the mechanism(s) responsible for the chemopreventive action of each class of agent is provided. The reader is encouraged to use additional sources for detailed information. The epidemiological observations that implicate certain agents or complex mixtures as playing a role in reducing human breast cancer are also reported and a comparison is made with results from assays in laboratory animals. Possible intermediate biomarkers that indicate risk for breast cancer are discussed. The purpose of this review is to provide the reader with a fairly concise knowledge of the subject. The information in this review is gathered together to stimulate studies toward appropriate strategies for future clinical chemoprevention trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I917,I917)","v":7802623},{"$f":"(LEN($J917) - LEN(SUBSTITUTE(LOWER($J917),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J917) - LEN(SUBSTITUTE(LOWER($J917),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J917) - LEN(SUBSTITUTE(LOWER($J917),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B917:D917)","v":0},1994,"[The problem of a high content of vitamin A in the liver of calves, cattle, sheep and swine for the consumer. Amount of accumulation and mechanism of teratogenic effect (review article)].","Kolb",7802623,"[The problem of a high content of vitamin A in the liver of calves, cattle, sheep and swine for the consumer. Amount of accumulation and mechanism of teratogenic effect (review article)].    Abstract:   Cases of hypervitaminosis A in men--especially in pregnant women, with development of malformations--are reported. The existence of withdrawal times to slaughter after the application of vitamin-A-containing preparations with a content of 10,000 to 10(6) international units and more is described. The content of vitamin A in the liver of monogastric animals is closely related to that in the feed. In ruminants about 40 to 70% of the vitamin A of the feed is decomposed by the microorganisms in the forestomachs. The amount of vitamin A stored in the liver after a therapeutic application is dependent of the initial content. The velocity of the depletion of the stores at a carotene- and vitamin-A-poor feeding is described. In ruminants and pigs in the account of the properties of the placenta no embryotoxicity of a therapeutic dose of vitamin A is to be expected. The mechanism of the teratogenesis by vitamin A in mice is described."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I918,I918)","v":7955642},{"$f":"(LEN($J918) - LEN(SUBSTITUTE(LOWER($J918),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J918) - LEN(SUBSTITUTE(LOWER($J918),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J918) - LEN(SUBSTITUTE(LOWER($J918),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B918:D918)","v":0},1994,"Nutritional influences on fetal growth.","Luke",7955642,"Nutritional influences on fetal growth.    Abstract:   Fetal growth is a complex, multifactorial phenomena, influenced predominately by the mother and the uterine environment. Although nutrient requirements during the first trimester are quantitatively small, nutritional deprivations during this period can adversely affect placental structure and, indirectly, ultimate birthweight. Maternal pregravid weight and gestational weight gain strongly influence fetal growth, with the effect of weight gain lessening as pregravid weight increases. As shown in the famine studies of World War II, below a threshold lower limit of maternal weight, poor maternal nutrition adversely affects both the placental and fetal weight. Specific nutrients may be associated with growth retardation, such as vitamin A, folate, and iron, whereas supplementation with calcium and magnesium may increase birthweight and length of gestation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I919,I919)","v":7970293},{"$f":"(LEN($J919) - LEN(SUBSTITUTE(LOWER($J919),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J919) - LEN(SUBSTITUTE(LOWER($J919),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J919) - LEN(SUBSTITUTE(LOWER($J919),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B919:D919)","v":0},1994,"Maternal vitamin A deficiency is associated with increased mother-to-child transmission of the human immunodeficiency virus (HIV).","Underwood",7970293,"Maternal vitamin A deficiency is associated with increased mother-to-child transmission of the human immunodeficiency virus (HIV).    Abstract:   Children generally acquire human immunodeficiency virus (HIV) infection through mother-to-child transmission. Currently, an estimated 1 million children are infected with HIV. A recent study in Malawi has shown that vitamin A status is an important risk factor for mother-to-child transmission of HIV. Among HIV-infected mothers a monotonic association between serum vitamin A and subsequent mother-to-child transmission rates was observed. The relative risk of HIV transmission was fourfold greater in mothers with serum vitamin A less than 0.70 mumol/L compared to those with serum vitamin A greater than 1.40 mumol/L."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I920,I920)","v":7950891},{"$f":"(LEN($J920) - LEN(SUBSTITUTE(LOWER($J920),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J920) - LEN(SUBSTITUTE(LOWER($J920),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J920) - LEN(SUBSTITUTE(LOWER($J920),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B920:D920)","v":0},1994,"Chemoprevention of breast cancer.","Costa",7950891,"Chemoprevention of breast cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I921,I921)","v":8172117},{"$f":"(LEN($J921) - LEN(SUBSTITUTE(LOWER($J921),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J921) - LEN(SUBSTITUTE(LOWER($J921),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J921) - LEN(SUBSTITUTE(LOWER($J921),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B921:D921)","v":0},1994,"Micronutrients and cancer risk.","Willett",8172117,"Micronutrients and cancer risk.    Abstract:   An abundance of epidemiologic evidence, based on numerous and remarkably consistent observations that persons who consume high intakes of fruits and vegetables have reduced risks of most human cancers, supports the concept that micronutrients may play important roles in the prevention of human cancers. Many studies suggest that carotenoid compounds in fruits and vegetables may be important in reducing risk of lung cancer. At least some forms of fiber may contribute to reduced risk of colon cancer, but recent analyses of colonic polyps suggest that folic acid may also play a protective role. Evidence for breast cancer is more limited but protective associations with vitamin A from both carotenoid and preformed sources have been seen in several studies. Although we cannot be certain which compounds are responsible, the evidence is overwhelming that an abundant intake of fruits and vegetables can play an important role in reducing cancer incidence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I922,I922)","v":8003403},{"$f":"(LEN($J922) - LEN(SUBSTITUTE(LOWER($J922),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J922) - LEN(SUBSTITUTE(LOWER($J922),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J922) - LEN(SUBSTITUTE(LOWER($J922),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B922:D922)","v":0},1994,"Expanded programme on immunization. Programme review.","Costa",8003403,"Expanded programme on immunization. Programme review.    Abstract:   In Bangladesh an evaluation of the Expanded Programme on Immunization (EPI) was conducted in February 1993. Data, including immunization coverage based on random surveys, were collected from all 4 divisions, 8 rural districts, 25 sub-districts (thanas) and from the cities of Dhaka and Chittagong. The Review Team assessed and made several recommendations concerning immunization coverage, surveillance for the EPI target diseases, immunization in urban areas, the cold chain and logistics, training, communication and social mobilization, other primary health care (PHC) interventions, vaccine supply, and the sustainability of EPI achievements. The population of Bangladesh is 110 million, with an estimated 3.6 million newborns during 1993. More than 90% of the 108,000 routine monthly immunization services are being conducted as scheduled. Nationally, among children 0-11 months of age, BCG coverage is 89%, as measured by evaluation surveys, coverage with 3 doses of diphtheria/pertussis/tetanus (DPT3) and oral polio vaccine (OPV3) is 63%, and measles coverage is 59%. Coverage with a second dose of tetanus toxoid (TT2) for pregnant women is 80%. In urban areas, BCG coverage for infants is 92%, DPT3/OPV3 76%, measles 68%, and TT2 for pregnant women 82%. In 2/3 of the sites visited, immunization was combined with vitamin A supplementation, oral rehydration treatment, or family planning. The coverage for both BCG and DPT3/OPV3 increased from only 2% in 1985 to almost 90% of infants having BCG immunization services in 1992. Yet only 50% of children are reached before their first birthday, and at least 20% of newborns are not protected against neonatal tetanus at birth. DPT1 and DPT3 drop-out is 29% nationally and 17% in urban areas. In 1992, an estimated 117,000 cases of neonatal tetanus and 6700 cases of poliomyelitis were prevented by immunization. Surveys of neonatal tetanus in selected districts have confirmed a reduction in incidence from 40/1000 live births in 1986 to 10/1000 in 1991."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I923,I923)","v":8974361},{"$f":"(LEN($J923) - LEN(SUBSTITUTE(LOWER($J923),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J923) - LEN(SUBSTITUTE(LOWER($J923),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J923) - LEN(SUBSTITUTE(LOWER($J923),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B923:D923)","v":0},1994,"Recent findings on the mechanisms by which alcohol damages the developing nervous system.","West",8974361,"Recent findings on the mechanisms by which alcohol damages the developing nervous system.    Abstract:   General etiologic categories related to possible mechanisms of fetal alcohol-induced brain damage are explored. Possible general mechanisms include alterations in protein synthesis, prostaglandins, gangliosides, hypoxia and free radical damage. A multiple systems cascade is presented to illustrate how multiple mechanisms could act together to produce a variety of effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I924,I924)","v":8206496},{"$f":"(LEN($J924) - LEN(SUBSTITUTE(LOWER($J924),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J924) - LEN(SUBSTITUTE(LOWER($J924),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J924) - LEN(SUBSTITUTE(LOWER($J924),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B924:D924)","v":0},1994,"Vitamins and cancer: a practical means of prevention?","Michels",8206496,"Vitamins and cancer: a practical means of prevention?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I925,I925)","v":7832055},{"$f":"(LEN($J925) - LEN(SUBSTITUTE(LOWER($J925),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J925) - LEN(SUBSTITUTE(LOWER($J925),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J925) - LEN(SUBSTITUTE(LOWER($J925),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B925:D925)","v":0},1994,"Interactions between zinc, vitamins A and D and hormones in the regulation of growth.","Bunce",7832055,"Interactions between zinc, vitamins A and D and hormones in the regulation of growth.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I926,I926)","v":7832048},{"$f":"(LEN($J926) - LEN(SUBSTITUTE(LOWER($J926),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J926) - LEN(SUBSTITUTE(LOWER($J926),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J926) - LEN(SUBSTITUTE(LOWER($J926),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B926:D926)","v":0},1994,"The role of vitamin A in child growth, development and survival.","Underwood",7832048,"The role of vitamin A in child growth, development and survival.    Abstract:   Vitamin A is essential for growth, development and survival. For children in deprived settings an adequate vitamin A status may be more critical to survival protection than to growth and development. During infancy breast milk from malnourished mothers is protective against the development of xerophthalmia; it needs to be complemented after six months by other dietary sources of vitamin A to provide full health protection. Correcting the low vitamin A content of breast milk from malnourished mothers within the first four weeks of delivery by a high dose oral vitamin A supplement can be an effective short-term preventive strategy while efforts are made to improve the dietary intake for the long-term solution."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I927,I927)","v":7533562},{"$f":"(LEN($J927) - LEN(SUBSTITUTE(LOWER($J927),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J927) - LEN(SUBSTITUTE(LOWER($J927),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J927) - LEN(SUBSTITUTE(LOWER($J927),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B927:D927)","v":0},1994,"The potential role of the heparin-binding growth factor pleiotrophin in breast cancer.","Riegel",7533562,"The potential role of the heparin-binding growth factor pleiotrophin in breast cancer.    Abstract:   We propose that the secreted protein pleiotrophin (PTN) is a major factor in the malignant progression of breast cancer. This hypothesis is based on the growth-stimulatory effects of PTN on cells in vitro and in vivo and on its high levels of expression in 60% of tumor samples from breast cancer patients. The stimulation of proliferation and tube formation of endothelial cells by PTN suggests that it can serve as an angiogenesis factor during tumor growth. We hypothesize that PTN has the potential to support growth of breast cancer at its primary site and to enhance the ability of tumor cells to metastasize. Furthermore, we suggest that specific endocrine signals interact to regulate the expression of PTN in vitro and in vivo. Finally, we propose that understanding the functions of PTN and its hormonal regulation can lead to the development of novel therapeutic strategies for breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I928,I928)","v":8108848},{"$f":"(LEN($J928) - LEN(SUBSTITUTE(LOWER($J928),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J928) - LEN(SUBSTITUTE(LOWER($J928),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J928) - LEN(SUBSTITUTE(LOWER($J928),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B928:D928)","v":0},1993,"Diarrhoeal disease: current concepts and future challenges. The impact of oral rehydration and other therapies on the management of acute diarrhoea.","Behrens",8108848,"Diarrhoeal disease: current concepts and future challenges. The impact of oral rehydration and other therapies on the management of acute diarrhoea.    Abstract:   The development of oral rehydration therapy (ORT) has resulted in clear and practical methods for replacing fluid and electrolyte losses during diarrhoea. Rehydration salts can be provided in 3 ways; a pre-packed, easy to use, package which requires controlled formulation and distribution, a cereal-based formula from widely available ingredients which require preparation and cooking, or a home-made recipe of sugar with salt, which is relatively easily prepared. Poor retention of knowledge on the correct way to prepare solutions, inadequate availability of ingredients and practical problems of home production are major problems in ORT programmes. Although ORT may be life saving in severe dehydrating diarrhoea, it may not have an impact on milder illness, dysentery or persistent diarrhoea. Breast feeding is a natural and effective method for preventing and reducing diarrhoeal morbidity and its role needs repeated promotion. Early feeding in diarrhoea reduces duration, severity and adverse nutritional sequelae. The benefit of vitamin A and folic acid supplements are as yet unproved; zinc may have a role in aiding recovery of malnourished children. Drug treatment should be limited to parasitic gut infections, cholera or dysenteric disease. Widespread prescribing of drugs for diarrhoea by health workers may be hindering the success of ORT."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I929,I929)","v":8287079},{"$f":"(LEN($J929) - LEN(SUBSTITUTE(LOWER($J929),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J929) - LEN(SUBSTITUTE(LOWER($J929),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J929) - LEN(SUBSTITUTE(LOWER($J929),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B929:D929)","v":0},1993,"Fat-soluble vitamin deficiency in infants and children.","Argao",8287079,"Fat-soluble vitamin deficiency in infants and children.    Abstract:   Fat-soluble vitamin deficiency is known to result in various complications that may be prevented if the problem is recognized and managed appropriately. In infants and children with chronic cholestasis, replacement therapy of the fat-soluble vitamins, vitamins A, D, E, and K, may prove extremely difficult because low concentrations of intraluminal bile acids lead to malabsorption of these compounds and other fat-soluble substances. Recent progress in the use of a water-soluble form of vitamin E, d-alpha-tocopheryl polyethylene glycol-1000 succinate, has enabled correction of vitamin E-deficiency states in these patients. It has also allowed for the admixture and coadministration of other fat-soluble vitamins and compounds in d-alpha-tocopheryl polyethylene glycol-1000 succinate to enhance their absorption. For managing vitamin K deficiency, similar success has been achieved using a vitamin K compound solubilized in glycocholate and lecithin. Vitamin A deficiency has been implicated in the higher incidence of childhood mortality and morbidity in Third World countries. Increased risk of childhood cancer has recently been associated with intramuscular injection of vitamin K to newborns. Finally, it is worth noting that among the pediatric population, exclusively breastfed infants, in general, are at risk for hypovitaminosis D, and at even greater risk in the absence of adequate exposure to sunlight or when the maternal diet is not sufficient to provide for vitamin D requirements."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I930,I930)","v":8210781},{"$f":"(LEN($J930) - LEN(SUBSTITUTE(LOWER($J930),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J930) - LEN(SUBSTITUTE(LOWER($J930),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J930) - LEN(SUBSTITUTE(LOWER($J930),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B930:D930)","v":0},1993,"Breast cancer prevention and detection update.","Smith",8210781,"Breast cancer prevention and detection update.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I931,I931)","v":8400625},{"$f":"(LEN($J931) - LEN(SUBSTITUTE(LOWER($J931),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J931) - LEN(SUBSTITUTE(LOWER($J931),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J931) - LEN(SUBSTITUTE(LOWER($J931),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B931:D931)","v":0},1993,"Assessment of the effectiveness of animal developmental toxicity testing for human safety.","Newman",8400625,"Assessment of the effectiveness of animal developmental toxicity testing for human safety.    Abstract:   Evaluations of studies for four well-known human developmental toxicants clearly suggest that a margin of exposure of 1/100th the NOAEL for the most sensitive animal species tested provides adequate safety for the human conceptus. The lowest reported human teratogenic exposures occurred at doses at least one log above the estimated quot;safequot; or acceptable daily exposure based on the most sensitive animal species, that is, 1/100th animal NOAEL. (The MOE ranged from lt; 1 to 10.). The data and analyses are consistent with the conclusion that, regardless of the type of in utero effect produced in animals, the margin of safety of 100 is likely to protect the human conceptus in utero from developmental perturbation, and it is a scientifically reasonable and conservative default number."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I932,I932)","v":8103565},{"$f":"(LEN($J932) - LEN(SUBSTITUTE(LOWER($J932),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J932) - LEN(SUBSTITUTE(LOWER($J932),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J932) - LEN(SUBSTITUTE(LOWER($J932),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B932:D932)","v":0},1993,"[Recent development of new anticancer drugs in Japan].","Tsukagoshi",8103565,"[Recent development of new anticancer drugs in Japan].    Abstract:   Recent development of new anticancer drugs in Japan was reviewed. Since there are a high incidence of cancer of the digestive organs, lung cancer and breast cancer in Japan, we have been looking for novel anticancer drugs effective against these solid cancers. Currently, some of fluoropyrimidine compounds, methotrexate analogues, tubulin inhibitors from plant origins have shown their clinical activities against human non-small cell lung cancer and/or breast cancer. As the end-point on these drug development, we have put an emphasis to find drugs to contribute for the survival prolongation and improvement of quality of life of the treated patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I933,I933)","v":8351799},{"$f":"(LEN($J933) - LEN(SUBSTITUTE(LOWER($J933),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J933) - LEN(SUBSTITUTE(LOWER($J933),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J933) - LEN(SUBSTITUTE(LOWER($J933),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B933:D933)","v":0},1993,"The effects of nitrate, nitrite, and N-nitroso compounds on animal health.","Bruning-Fann",8351799,"The effects of nitrate, nitrite, and N-nitroso compounds on animal health.    Abstract:   The clinical signs of acute nitrate toxicity vary according to species. In general, ruminant animals develop methemoglobinemia while monogastric animals exhibit severe gastritis. Nitrate ingestion has also been linked to impairment of thyroid function, decreased feed consumption, and interference with vitamin A and E metabolism. Hematologic changes seen with chronic high nitrate exposure include both compensatory increases in red blood cells and anemia, along with increased neutrophils and eosinophils. Unlike nitrate, nitrite is capable of inducing methemoglobinemia in a wide range of species, ie cattle, sheep, swine, dogs, guinea pigs, rats, chickens and turkeys. In rats, chronic nitrite exposure causes pathologic changes in a variety of tissues, alterations in motor activity and brain electrical activity, and alters gastric mucosal absorption. Nitrite affects the metabolism of sulfonamide drugs in animals such as the pig, guinea pig, and rat. The N-nitroso compound dimethylnitrosamine causes toxic hepatosis in cattle, sheep, mink, and fox. Nitrosamines have been reported in cows milk and been found to pass into the milk of goats under experimental conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I934,I934)","v":8374640},{"$f":"(LEN($J934) - LEN(SUBSTITUTE(LOWER($J934),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J934) - LEN(SUBSTITUTE(LOWER($J934),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J934) - LEN(SUBSTITUTE(LOWER($J934),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B934:D934)","v":0},1993,"Clinical teratology.","Brent",8374640,"Clinical teratology.    Abstract:   Genetic causes account for 20% to 25% of human birth defects, but the largest proportion of birth defects have no definitive etiology and some of these malformations may be due to intrinsic, quot;nonpreventablequot; spontaneous errors of development. Environmental causes, which include maternal disease states, maternal infection, mechanical factors, problems of constraint, chemicals, drugs, and physical agents, are responsible for only about 10% of human birth defects. The scientific basis for understanding the risk of congenital malformations from exposure to environmental agents is based on several tenets of toxicology and embryology dogma. The first tenet is that essentially all teratogens that have been studied have a typical toxicologic dose response relationship and a no-effect dose. Secondly, the stage of gestation is critical to the effects that are expected, and all stages of embryogenesis and fetogenesis can have vulnerability to environmental toxicants. Thirdly, the response of the embryo and fetus is characteristic for each teratogenic agent, although there is some similarity in the effect of certain teratogens. Appropriately designed developmental toxicology studies and basic embryologic and biologic concepts are all used to estimate the potential reproductive hazard for embryonic death, growth retardation, congenital malformation, and functional deficit."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I935,I935)","v":8016056},{"$f":"(LEN($J935) - LEN(SUBSTITUTE(LOWER($J935),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J935) - LEN(SUBSTITUTE(LOWER($J935),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J935) - LEN(SUBSTITUTE(LOWER($J935),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B935:D935)","v":0},1993,"[Vitamins and their role in the functioning of the reproductive system].","Babichev",8016056,"[Vitamins and their role in the functioning of the reproductive system].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I936,I936)","v":8429398},{"$f":"(LEN($J936) - LEN(SUBSTITUTE(LOWER($J936),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J936) - LEN(SUBSTITUTE(LOWER($J936),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J936) - LEN(SUBSTITUTE(LOWER($J936),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B936:D936)","v":0},1993,"Nutritional epidemiology of cervical neoplasia.","Potischman",8429398,"Nutritional epidemiology of cervical neoplasia.    Abstract:   There appears to be a natural progression of some preinvasive cervical lesions to more advanced lesions. Although research has evaluated the associations between nutrients and particular preinvasive lesions or invasive disease, little work has been done to compare results across the spectrum of lesions in the progression to invasive disease. This review compiles studies that have evaluated the relation between nutrients and cervical neoplasia and evaluates the general consistency of the literature across stage of disease. Preformed vitamin A does not appear to be related to risk of any preinvasive or invasive lesions, whereas vitamin C has been associated with a reduced risk for dysplasia, in situ cancer, and invasive disease, particularly among smokers. There was evidence of reduced risks associated with various carotenoids and vitamin E at all stages of the disease process, although these studies were inconsistent and further work is needed. Folate was the only nutrient that appeared to be protective for dysplastic lesions and not related to risk of in situ or invasive disease. Red blood cell folate was a better predictor of dysplasia than were serum or dietary folate, and further investigation using this marker of folate status is warranted. Research is needed across a spectrum of lesions within one study, with particular attention to interactions between nutrients and other risk factors for disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I937,I937)","v":8375903},{"$f":"(LEN($J937) - LEN(SUBSTITUTE(LOWER($J937),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J937) - LEN(SUBSTITUTE(LOWER($J937),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J937) - LEN(SUBSTITUTE(LOWER($J937),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B937:D937)","v":0},1993,"Child nutrition in India: priorities for the coming decade.","Reddy",8375903,"Child nutrition in India: priorities for the coming decade.    Abstract:   The author briefly reviews the current status of child nutrition in India and identifies priority actions to be taken over the coming decade so that the nutrition goals set for the year 2000 may be met. Maternal nutrition and low birth weight, lactation performance and infant growth, child mortality, major nutritional problems, protein energy malnutrition, vitamin A deficiency, nutritional anemia, and iodine deficiency disorders are all problem areas of concern which must be addressed and ameliorated. Each topic is discussed in turn. Relatively inexpensive, time tested, and well-proven technologies are available to confront existing nutritional problems, but they need to be implemented. Revising current strategies and shifting the focus from severe to milder forms of malnutrition, with more emphasis on long term sustainable actions, may even allow the nutrition goals set for the year 2000 to be realized. Improving the educational and social status of women, obtaining better health care facilities, environmental sanitation, and general community development are also important elements of improving the nutritional status of children"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I938,I938)","v":8414269},{"$f":"(LEN($J938) - LEN(SUBSTITUTE(LOWER($J938),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J938) - LEN(SUBSTITUTE(LOWER($J938),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J938) - LEN(SUBSTITUTE(LOWER($J938),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B938:D938)","v":0},1993,"Undernutrition in Nigeria: dimension, causes and remedies for alleviation in a changing socio-economic environment.","Igbedioh",8414269,"Undernutrition in Nigeria: dimension, causes and remedies for alleviation in a changing socio-economic environment.    Abstract:   Undernutrition in Nigeria is a long standing problem which has persisted since the 1960s and whose magnitude is on the increase. This is because food consumption, both in quality and quantity, has decreased appreciably, especially with the commencement of the structural adjustment programme (SAP) in 1986. Available studies from limited data have indicated that the introduction of economic reforms more than anything else has contributed to reduced food intake and the near collapse of nutrition oriented health delivery services. Since the economic reforms may continue into the next decade and beyond, sustainable remedies for alleviation of the problem are urgently needed. Suggested remedial programmes include increased support for the rural farmers, strengthening of the rural credit schemes that are specifically targeted at the poor, distribution of vitamin A and iron supplements in rural health centres, encouraging production of low cost weaning diets and integrating nutrition education in primary health care schemes and in educational curricula. In Nigeria, the beginning of the structural adjustment program (SAP) in 1986 marked the beginning of a considerable decrease in real income and an unparalleled increase in food prices. This economic crisis stimulated reduced food consumption, particularly that of nutritious foods, and an increase in malnutrition. For example, in Borno/Yobe States in 1987, SAP contributed to an average decrease in energy and protein intake of 27% and 33%, respectively. SAP also contributed greatly to the almost complete destruction of nutrition oriented health delivery services. Different surveys of nutritional assessment in Nigeria reveal low intakes of protein, energy, iron, calcium, zinc, thiamin, and riboflavin in almost all age groups and in both sexes. Malnutrition and related diseases (diarrhea, measles, anemia, and gastroenteritis) are the cause of most deaths in infants and young children. The underlying causes of malnutrition in Nigeria are poverty, inadequate food production, inadequate food intake, ignorance and uneven distribution of food, poor food preservation techniques, improper preparation of foods, food restrictions and taboos, and poor sanitation. Economic reforms will likely continue into the first decade of the 21st century, so Nigeria really needs sustainable remedies to alleviate malnutrition. Recommended remedial programs are more support for rural farmers through input subsidies and high producer prices, improving rural credit schemes (e.g., the Peoples Bank) that target the poor, distribution of vitamin A and iron supplements in rural health centers, promoting production of low cost weaning diets, and integrating nutrition education in primary health care programs and in educational curricula."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I939,I939)","v":12319275},{"$f":"(LEN($J939) - LEN(SUBSTITUTE(LOWER($J939),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J939) - LEN(SUBSTITUTE(LOWER($J939),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J939) - LEN(SUBSTITUTE(LOWER($J939),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B939:D939)","v":0},1992,"Nutrition and child feeding patterns in the Sudan.","Harrison",12319275,"Nutrition and child feeding patterns in the Sudan.    Abstract:   Only 14% of the 208 million potentially cultivable acres in the Sudan are being cultivated. Insufficient infrastructure keeps the Sudan from reaching its socioeconomic potential. Recurring localized drought, agricultural pests, and environmental degradation plague the country. Studies estimate that moderate to severe undernutrition ranges from 15% to 75% in the Sudan. Geographical location of residence and age of child were the most significant predictors of malnutrition. Geographic differences were due to local food availability and differential availability of food aid in different regions at different times. Chronic and acute malnutrition and micronutrient deficiencies in children are endemic in the Sudan. Some relatively common micronutrient deficiencies include vitamin A deficiency, iodine deficiency, and scurvy. Child eating patterns depend largely on the cereal staple in the region. Wheat is an important cereal staple in Northern Province, while millet is important in North and South Darfour and in Kordofan. Men and older boys eat meals before women and young children. In wealthy traditional households, the two groups eat in separate areas of the house. Almost every mother breast feeds her infant. In fact, traditional breast feeding is the single most important factor protecting the health of Sudanese children. Children are breast fed for 15-21 months. A 1987 study shows that 62% of mothers in rural Khartoum supplemented breast milk with bottle feeding as early as the first few days of life. Mothers tend to directly introduce children to a household diet without transitional weaning foods at around 9 months. Mothers tend to withhold breast milk during illness. The Sudan has some taboos against some foods. For example, pregnant women should avoid fattening foods to keep the fetus small and to make for an easier delivery. These findings should be used to strengthen the nutrition communications project in the Sudan."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I940,I940)","v":1448358},{"$f":"(LEN($J940) - LEN(SUBSTITUTE(LOWER($J940),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J940) - LEN(SUBSTITUTE(LOWER($J940),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J940) - LEN(SUBSTITUTE(LOWER($J940),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B940:D940)","v":0},1992,"Breast cancer.","Ellerhorst-Ryan",1448358,"Breast cancer.    Abstract:   Breast cancer will continue to be a major health problem for women as long as there is a lack of prevention strategies and underuse of early detection programs. The role of the nurse in health promotion must focus on educating women about the ambiguity surrounding risk factors and the importance of participating in early detection practices."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I941,I941)","v":1407207},{"$f":"(LEN($J941) - LEN(SUBSTITUTE(LOWER($J941),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J941) - LEN(SUBSTITUTE(LOWER($J941),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J941) - LEN(SUBSTITUTE(LOWER($J941),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B941:D941)","v":0},1992,"[Teratogenic risks of high-dosage vitamin A].","Knijn",1407207,"[Teratogenic risks of high-dosage vitamin A].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I942,I942)","v":1470569},{"$f":"(LEN($J942) - LEN(SUBSTITUTE(LOWER($J942),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J942) - LEN(SUBSTITUTE(LOWER($J942),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J942) - LEN(SUBSTITUTE(LOWER($J942),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B942:D942)","v":0},1992,"Fetal environmental toxins.","Holmes",1470569,"Fetal environmental toxins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I943,I943)","v":1444034},{"$f":"(LEN($J943) - LEN(SUBSTITUTE(LOWER($J943),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J943) - LEN(SUBSTITUTE(LOWER($J943),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J943) - LEN(SUBSTITUTE(LOWER($J943),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B943:D943)","v":0},1992,"Safety issues regarding the use of vitamin supplements.","Bendich",1444034,"Safety issues regarding the use of vitamin supplements.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I944,I944)","v":1329128},{"$f":"(LEN($J944) - LEN(SUBSTITUTE(LOWER($J944),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J944) - LEN(SUBSTITUTE(LOWER($J944),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J944) - LEN(SUBSTITUTE(LOWER($J944),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B944:D944)","v":0},1992,"Nutrition and cancer prevention.","Schapira",1329128,"Nutrition and cancer prevention.    Abstract:   Of all cancers in the United States, 35% are estimated to be caused by dietary factors and may be preventable. Diets high in fat or calories, for example, are said to be associated with five of the six most common cancers: breast, colorectal, pancreatic, prostatic, and uterine. Conversely, some dietary components such as vitamin A, in fruits and vegetables, and fiber may help protect against certain cancers. Obesity may confer a small risk of breast cancer on a woman, but women with upper body fat localization are at significantly higher risk of developing breast cancer and endometrial cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I945,I945)","v":1609298},{"$f":"(LEN($J945) - LEN(SUBSTITUTE(LOWER($J945),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J945) - LEN(SUBSTITUTE(LOWER($J945),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J945) - LEN(SUBSTITUTE(LOWER($J945),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B945:D945)","v":0},1992,"The potential role for biological therapy in the treatment of breast cancer.","Sparano",1609298,"The potential role for biological therapy in the treatment of breast cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I946,I946)","v":1526926},{"$f":"(LEN($J946) - LEN(SUBSTITUTE(LOWER($J946),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J946) - LEN(SUBSTITUTE(LOWER($J946),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J946) - LEN(SUBSTITUTE(LOWER($J946),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B946:D946)","v":0},1992,"Effects of nutrient deficiencies and excesses on reproductive efficiency of livestock.","Dunn",1526926,"Effects of nutrient deficiencies and excesses on reproductive efficiency of livestock.    Abstract:   Successful reproduction is dependent on a host of macro- and micronutrients and ceases well before an animal expires from deficiency of a particular nutrient. This review focuses on the functional roles phosphorus, vitamin A and beta-carotene, protein, and energy play in reproductive processes. Although it is not known whether deficiencies of these nutrients limit reproduction through common or discrete mechanisms, appropriate quantities of these nutrients are required for optimal reproduction. Mechanisms through which nutritional status is perceived by the hypothalamic-pituitary-gonadal axis remain unclear but seem to impinge on hypothalamic regions that selectively regulate production and release of pituitary trophic hormones. Body condition, or degree of fatness, seems to be the most reliable indicator of well-being of an animal, and, when coupled with changes in BW, provides a useful method to assess reproductive potential."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I947,I947)","v":1442286},{"$f":"(LEN($J947) - LEN(SUBSTITUTE(LOWER($J947),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J947) - LEN(SUBSTITUTE(LOWER($J947),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J947) - LEN(SUBSTITUTE(LOWER($J947),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B947:D947)","v":0},1992,"Growth factors and other targets for rational application as intervention agents.","Mulshine",1442286,"Growth factors and other targets for rational application as intervention agents.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I948,I948)","v":1355997},{"$f":"(LEN($J948) - LEN(SUBSTITUTE(LOWER($J948),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J948) - LEN(SUBSTITUTE(LOWER($J948),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J948) - LEN(SUBSTITUTE(LOWER($J948),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B948:D948)","v":0},1992,"Breast cancer chemoprevention.","Veronesi",1355997,"Breast cancer chemoprevention.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I949,I949)","v":1289113},{"$f":"(LEN($J949) - LEN(SUBSTITUTE(LOWER($J949),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J949) - LEN(SUBSTITUTE(LOWER($J949),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J949) - LEN(SUBSTITUTE(LOWER($J949),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B949:D949)","v":0},1992,"Persistent diarrhea in children: epidemiology, risk factors, pathophysiology, nutritional impact, and management.","Lima",1289113,"Persistent diarrhea in children: epidemiology, risk factors, pathophysiology, nutritional impact, and management.    Abstract:   A review of data on the morbidity and mortality caused by persistent diarrhea (more than 14 days duration) was undertaken from studies in several geographic areas, including Bangladesh, Brazil, Ethiopia, India, Indonesia, and Peru, over the last 3 decades. An estimated 3-5 billion diarrheal illnesses and 5-10 million diarrhea-related deaths occur annually among 3 billion people in Africa, Asia, and Latin America. Mostly the 338 million to 1 billion episodes and 4.6 million deaths annually. A study from India showed that the incidence of persistent diarrhea was greater in the age group 0-11 months (31 episodes/100 child-years) than at age 12-23 months (9 episodes/100 child years) or 24-35 months (6 episodes/100 child-year). Similar results were obtained in periurban Peru, periurban northeastern Brazil, and rural guatemala. Diarrhea is believed to precipitate and exacerbate malnutrition while malnutrition predisposes to diarrhea. 2 studies in both Bangladesh and Peru indicate that the risk of developing diarrhea inversely parallels delayed-type hypersensitivity reactions to standard skin-test antigens. In a cohort of 175 children under 5 years of age over a 28-month period in an urban slum in northeastern Brazil the children had an average of 11 episodes/year and spent 82 days/year with diarrhea. The leading potential pathogens seen with persistent diarrhea in some areas are enteroaggregative E. coli and Cryptosporidium. Other pathogens include Shigella, Salmonella, enteropathogenic (LA (local)) E. coli, and variably Giardia lamblia. Recent nutritional management promotes breast feeding, dietary supplementation with vitamin A, zinc, iron, folate, and vitamin B 12, and improved oral rehydration solutions with glucose polymers (such as rice starch) and possibly neutral amino acids (such as alanine or glycine) and glutamine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I950,I950)","v":1890067},{"$f":"(LEN($J950) - LEN(SUBSTITUTE(LOWER($J950),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J950) - LEN(SUBSTITUTE(LOWER($J950),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J950) - LEN(SUBSTITUTE(LOWER($J950),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B950:D950)","v":0},1991,"Chemoprevention in head and neck cancer.","Heyne",1890067,"Chemoprevention in head and neck cancer.    Abstract:   It is not a coincidence that the aerodigestive tract has proven such a fertile ground for the evaluation of chemoprevention. The incidence of second primaries and the concept of field cancerization made the need for prevention acute and showed the limitations of even the most curative of treatments. New and presumably less toxic agents are being evaluated; chemoprevention is being applied to asymptomatic populations at higher risk for lung, colon, breast, and other neoplasias. Biomarkers may be instrumental in rapid development of these new clinical applications, but much is still to be done. Yet unanswered is whether suppression of premalignant lesions will ultimately decrease cancer incidence. Survival in the second primary prevention trial has not thus far shown a significant improvement and toxicities were significant. Many questions remain in the study of chemoprevention; head and neck cancer provides a conducive model in which these answers might be found."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I951,I951)","v":1651963},{"$f":"(LEN($J951) - LEN(SUBSTITUTE(LOWER($J951),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J951) - LEN(SUBSTITUTE(LOWER($J951),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J951) - LEN(SUBSTITUTE(LOWER($J951),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B951:D951)","v":0},1991,"Diet, obesity, fat distribution and cancer in women.","Schapira",1651963,"Diet, obesity, fat distribution and cancer in women.    Abstract:   Thirty-five percent of all cancers in the United States are estimated to be caused by dietary factors and may be preventable. Diets high in fat or calories, for example, are said to be associated with five of the six most common cancers: breast, colorectal, pancreatic, prostatic, and uterine. Conversely, some dietary components such as vitamin A in fruits and vegetables and fiber may help protect against certain cancers. Although some of these findings are controversial, the dietary guidelines they engender are not, as the recommendations are healthy for other reasons as well. Obesity may confer a small risk of breast cancer on a woman, but women with upper body fat localization are at significantly higher risk of developing breast cancer. This risk appears to be reduced with weight loss."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I952,I952)","v":1862276},{"$f":"(LEN($J952) - LEN(SUBSTITUTE(LOWER($J952),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J952) - LEN(SUBSTITUTE(LOWER($J952),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J952) - LEN(SUBSTITUTE(LOWER($J952),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B952:D952)","v":0},1991,"Epidemiology of acute respiratory infections in children of developing countries.","Berman",1862276,"Epidemiology of acute respiratory infections in children of developing countries.    Abstract:   Acute respiratory infections cause four and a half million deaths among children every year, the overwhelming majority occurring in developing countries. Pneumonia unassociated with measles causes 70% of these deaths; post-measles pneumonia, 15%; pertussis, 10%; and bronchiolitis and croup syndromes, 5%. Both bacterial and viral pathogens are responsible for these deaths. The most important bacterial agents are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. The data on bacterial etiology of pneumonia during the first 3 months of life are limited, and almost no information on the role of chlamydia and pertussis in this age period is available. The distribution of viral pathogens in developing countries can be summarized as follows: respiratory syncytial virus, 15%-20%; parainfluenza viruses, 7%-10%; and influenza A and B viruses and adenovirus, 2%-4%. Mixed viral and bacterial infections occur frequently. Risk factors that increase the incidence and severity of lower respiratory infection in developing countries include large family size, lateness in the birth order, crowding, low birth weight, malnutrition, vitamin A deficiency, lack of breast feeding, pollution, and young age. Effective interventions for prevention and medical case management are urgently needed to save the lives of many children predisposed to severe disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I953,I953)","v":1924994},{"$f":"(LEN($J953) - LEN(SUBSTITUTE(LOWER($J953),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J953) - LEN(SUBSTITUTE(LOWER($J953),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J953) - LEN(SUBSTITUTE(LOWER($J953),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B953:D953)","v":0},1991,"The fortification of yellow fats with vitamins A and D. Report of the Working Group on the Fortification of Yellow Fats.","Wolf",1924994,"The fortification of yellow fats with vitamins A and D. Report of the Working Group on the Fortification of Yellow Fats.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I954,I954)","v":1906205},{"$f":"(LEN($J954) - LEN(SUBSTITUTE(LOWER($J954),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J954) - LEN(SUBSTITUTE(LOWER($J954),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J954) - LEN(SUBSTITUTE(LOWER($J954),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B954:D954)","v":0},1991,"Recent developments in the nutritional management of diarrhoea. 1. Nutritional strategies to prevent diarrhoea among children in developing countries.","Tomkins",1906205,"Recent developments in the nutritional management of diarrhoea. 1. Nutritional strategies to prevent diarrhoea among children in developing countries.    Abstract:   This paper discusses various ways in which diarrhoea may be prevented from occurring in children living in developing countries, where it is still a major cause of morbidity and mortality. Possible strategies include promotion of breastfeeding, dietary supplementation with vitamin A, zinc and iron, the prevention of protein-energy malnutrition as far as possible, and improvement in the standard of preparation and hygiene of available weaning foods, involving in particular the wider use of fermented foods."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I955,I955)","v":12346027},{"$f":"(LEN($J955) - LEN(SUBSTITUTE(LOWER($J955),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J955) - LEN(SUBSTITUTE(LOWER($J955),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J955) - LEN(SUBSTITUTE(LOWER($J955),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B955:D955)","v":0},1990,"Nutrition health profile and intervention strategies for underprivileged adolescent girls in India: a selected review.","Kanani",12346027,"Nutrition health profile and intervention strategies for underprivileged adolescent girls in India: a selected review.    Abstract:   Four studies conducted between 1979 and 1986 showed that girls 10-15 years old had growth deficiencies. About 50-66% of girls in the study samples were either wasted, stunted, or both wasted and stunted, based on Waterlows classification. Girls also showed weight-for-height deficits. Greater deficits were apparent for weight-for-age measures than for height-for-age measures. Over 66% of girls had weights below 75% of the standards. Over 33% had heights below 90% of the standards. An Indian Council of Medical Research study published in 1972 indicated that girls from lower socioeconomic groups and 10-18 years old gained an average of 17.7 kg of weight compared to the NCHS standard of 25.4kg. Weight was lower than the standard for girls even in the high-income group. Height deficits were not as great. A National Nutrition Monitoring Bureau reported in 1981 that low-income group adolescents had height, weight, and growth rates about 70-80% those of high-income adolescents. Studies in 1985 by Tripathi and in 1976 by Chadha reported similar findings. These studies also reported that girls from low-income groups had delayed menarche and maturation of breast and genitalia. A Government of India report in 1988 indicated that a girls growth spurt was arrested and full physical maturation was prevented due to repeated adolescent pregnancies. Rohde in 1986 reported that about 50% of first borns to adolescent girls were low birth weight infants. Some evidence has been presented by Gopalan and Srikantia that adolescent girls catch up on their growth, particularly rural girls. Hyderabad found that girls with severely stunted growth showed larger height increases at 18 years than girls with moderate or normal growth retardation. Studies have shown that short girls menstruate later than tall girls and low income girls have later ages of menarche. Studies have indicated that about 25-50% of adolescent girls had ocular signs of vitamin A deficiency: conjunctival xerosis and Bitot spots. About 60% of adolescent girls were anemic. Caloric intake deficiencies were most prominent at ages 1-3 and 15-20 years. One suggestion was to compensate for deficiencies in pre-adolescence with 60 mg of iron for 60 days two times a year and with vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I956,I956)","v":2205360},{"$f":"(LEN($J956) - LEN(SUBSTITUTE(LOWER($J956),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J956) - LEN(SUBSTITUTE(LOWER($J956),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J956) - LEN(SUBSTITUTE(LOWER($J956),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B956:D956)","v":0},1990,"Nutrition and breast cancer.","Kritchevsky",2205360,"Nutrition and breast cancer.    Abstract:   International comparisons have provided striking correlations between fat consumption and risk of breast cancer, but these comparisons do not often consider variations in life style. Case-control studies carried out in several countries showed no real association between fat intake and breast cancer. There is some evidence that vitamin A or carotenoid intake may exert a protective effect. Alcohol intake, on the other hand, seems to be positively associated with breast cancer risk. Elevated body weight, body mass, stature, and frame size have been found to be associated as risk factors for breast cancer in women. Animal studies found that caloric restriction inhibits growth of spontaneous and induced mammary tumors, an observation that held up even when the calorie-restricted animals ingest more fat than the ad-libitum-fed controls. College women who exercise have a lower incidence of breast cancer than their more sedentary classmates. Exercise is another means of reducing caloric availability."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I957,I957)","v":2124617},{"$f":"(LEN($J957) - LEN(SUBSTITUTE(LOWER($J957),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J957) - LEN(SUBSTITUTE(LOWER($J957),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J957) - LEN(SUBSTITUTE(LOWER($J957),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B957:D957)","v":0},1990,"Protein-energy malnutrition--its epidemiology and control.","Latham",2124617,"Protein-energy malnutrition--its epidemiology and control.    Abstract:   The four most important deficiency diseases in developing countries today are protein-energy malnutrition (PEM), xerophthalmia, nutritional anemias, and iodine deficiency disorders. Of these, PEM is the most important and the most difficult to control. The immediate cause is usually insufficient intake or proper utilization of energy and protein. However, the interaction of nutrition and infections plays an important role in PEM. Underlying causes include poverty, inequity, poor food production and distribution, and lack of knowledge. We now recognize that protein deficiency is less important than energy and food deficiency. The actual cause of the edema in kwashiorkor is still not proven. Better ways of defining PEM have been accepted. Mild or moderate PEM are best judged by anthropometry; regular weighing, for monitoring growth, may be a useful control strategy. Because infections play such an important role in PEM, three practical approaches-immunization, deworming of children, and oral rehydration therapy for diarrhea--are discussed. Modernization and Westernization have sometimes aggravated the problem of malnutrition in nonindustrialized countries. The decline in breast-feeding and greater use of infant formula provide a good example of this problem. Finally, economic improvement in the Third World is essential if PEM is to be greatly reduced."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I958,I958)","v":2261393},{"$f":"(LEN($J958) - LEN(SUBSTITUTE(LOWER($J958),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J958) - LEN(SUBSTITUTE(LOWER($J958),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J958) - LEN(SUBSTITUTE(LOWER($J958),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B958:D958)","v":0},1990,"Approaches to breast cancer prevention.","Stoll",2261393,"Approaches to breast cancer prevention.    Abstract:   It may be possible to delay the step-by-step progression towards frank invasive cancer by avoiding one or more of the well-known clinical risk factors. In addition current clinical trials in the USA and Europe are assessing whether the use of tamoxifen, vitamin analogues or a low-fat diet can delay the appearance of overt disease in women known to be at high risk, but it will be several years before such trials can be evaluated. For women seeking advice on prevention, non-toxic supplements to the diet such as beta-carotene, vitamin A analogues or selenium compounds, and the avoidance of alcohol and obesity, are examples of practical advice which can do no harm yet may help to protect against breast cancer development. In the case of the very anxious first degree relative of a breast cancer patient, the current choice lies essentially between regular monitoring, mastectomy with reconstruction, early termination of ovarian activity and anti-oestrogen therapy. Currently, considerable research is being directed towards identifying oncogenes and growth factors which are involved in the growth of breast cancer. In the meantime, more research needs to be devoted to the effect of various progestagens in counteracting oestrogen support of breast cancer growth, and to biological observations on different formulations and doses of combined oestrogen/progestagen preparations which may reduce breast cancer risk both in pre- and postmenopausal women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I959,I959)","v":2286216},{"$f":"(LEN($J959) - LEN(SUBSTITUTE(LOWER($J959),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J959) - LEN(SUBSTITUTE(LOWER($J959),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J959) - LEN(SUBSTITUTE(LOWER($J959),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B959:D959)","v":0},1990,"The epidemiology of acute respiratory infections in children and adults: a global perspective.","Graham",2286216,"The epidemiology of acute respiratory infections in children and adults: a global perspective.    Abstract:   While a number of advances have been made in our understanding of the epidemiology of acute respiratory infections in the past two decades, a number of serious questions still require urgent answers. The associations of factors such as chronic disease in adults, direct smoking, passive smoking, crowding, and breast feeding to acute respiratory infections are now well documented. Appropriate changes in public health policy need not be predicated on results from still further studies. However, in virtually all of the other areas cited in this review, further data are required. In developing countries, studies being currently conducted on vitamin A supplementation, malnutrition, and indoor air pollution will help address the most pressing issues. More studies are also needed on the relations between HIV infection and acute respiratory infections, as well as low birth weight and respiratory infection. The National Research Council studies have provided important additional data on etiologic agents in children in developing countries, but data on adult pneumonia remain sparse. In developed countries the issues that may be of greatest interest are the relation between maternal antibody levels and passive immunity in infants, the reasons for the increase in pneumonia mortality in older age groups, and the relation between air pollution and acute respiratory infections (as opposed to morbidity from bronchial reactivity). From a methodological viewpoint, the relation between previous respiratory infection (particularly in the first year of life) and subsequent acute respiratory infection morbidity has been inadequately explored. Adjustment for autocorrelation in multivariate models may be necessary if this relation is strong. Greater standardization of data collection methods in developed and developing countries also needs to be more seriously addressed. Given that some advances have been made in this area, the time may be right for development of acute symptom questionnaires, akin to the American Thoracic Society chronic respiratory questionnaire, for use in both developed and developing countries. Standardization of diaries, although somewhat more difficult, would also be extremely useful in many instances. Virtually only researchers from developed countries have done studies of risk factors for acute respiratory infections (ARIs) since these countries have an infrastructure that can support large multidimensional epidemiologic studies while developing countries do not. Yet results from these countries studies are not always relevant to developing countries since risk factor exposures in developing countries. For example, the predominant problem in developing countries is that ARIs in children is that ARIs in children 5 years old often result in death whereas in developed countries morbidity predominates. Based on studies in developed countries, there is plenty of evidence that strong associations exist between ARIs and chronic disease in adults, direct and passive smoking, and breast feeding. Thus policy need not request additional studies to base proper changes in public health policy. Yet researchers do need to collect more data on the associations between ARIs and HIV infections, low birth weight, and other possible risk factors. In fact, some are now examining relationships between ARIs and malnutrition, vitamin A supplementation, and indoor air pollution in developing countries. Some of the more important issues in developed countries are the links between maternal antibody levels and passive immunity in infants, the links between air pollution and ARIs, and the reasons for a rise in pneumonia in the aged. Another area that scientists need to explore is the association between respiratory infection (especially between 1-12 months old) and subsequent ARI. Further epidemiologists should standard data collection methods in both developed and developing countries. For example, the chronic respiratory questionnaire of the American Thoracic Society can serve as a model for acute symptom questionnaires."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I960,I960)","v":2200466},{"$f":"(LEN($J960) - LEN(SUBSTITUTE(LOWER($J960),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J960) - LEN(SUBSTITUTE(LOWER($J960),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J960) - LEN(SUBSTITUTE(LOWER($J960),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B960:D960)","v":0},1990,"The role of nutrition in neural tube defects.","Scott",2200466,"The role of nutrition in neural tube defects.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I961,I961)","v":2693633},{"$f":"(LEN($J961) - LEN(SUBSTITUTE(LOWER($J961),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J961) - LEN(SUBSTITUTE(LOWER($J961),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J961) - LEN(SUBSTITUTE(LOWER($J961),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B961:D961)","v":0},1989,"An approach to setting maxima in infant formulas.","Wharton",2693633,"An approach to setting maxima in infant formulas.    Abstract:   It is clearly necessary to set upper limits for a nutrient in a formula where the nutrient can have a direct toxic effect (e.g., vitamin A) or can lead to a reduced margin of safety (e.g., high dietary renal solute load during gastroenteritis). In addition, there are plausible arguments for setting upper limits for any nutrient added during manufacture. Various expert groups have used different approaches in setting upper limits, particularly for fat and minerals. Evidence of clinical toxicity and various biochemical measurements have been commonly used to determine appropriate upper levels. Less use has been made of the empirical evidence provided by nutrient concentrations in commonly used foods, e.g., breast milk and cows milk. Four quot;rulesquot; for setting maxima are suggested: a) Use evidence of clinical toxicity or reduced margin of safety if available; b) Avoid nutrient concentrations that lead to biochemical values in body fluids or tissues very different from those seen in breast-fed babies; c) An upper limit should be set for even apparently harmless nutrients that are added during manufacture; and d) When a nutrient is added, its final concentration should not normally exceed that in breast or cows milk, whichever is the greater. Using these quot;rules,quot; suggested maxima for 33 nutrients are listed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I962,I962)","v":2694158},{"$f":"(LEN($J962) - LEN(SUBSTITUTE(LOWER($J962),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J962) - LEN(SUBSTITUTE(LOWER($J962),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J962) - LEN(SUBSTITUTE(LOWER($J962),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B962:D962)","v":0},1989,"Cancer chemoprevention by supplemental carotenoids in animals and humans.","Santamaria",2694158,"Cancer chemoprevention by supplemental carotenoids in animals and humans.    Abstract:   Experiments were carried out in mice demonstrating that dietary carotenoids (beta-carotene or canthaxanthin), starting before cancer initiation and continuing throughout the experiment, have a protective effect against indirect skin carcinogenesis induced by benzo[a]pyrene +/- UVA and breast cancer induced by 8-methoxypsoralen + UVA. Experiments in rats demonstrated that carotenoids also prevent the direct gastric carcinogenesis induced by N-methyl-N-nitro-nitroso-guanidine. Recently, prevention by beta-carotene against colon cancer induced in mice by dimethylhydrazine, another indirect carcinogen, was confirmed by others. The prospects for carotenoid intervention with humans were based on their antitumorigenic effect, which is quite independent of pro-vitamin A activity, their lack of toxicity even after prolonged administration, and their immunostimulating activity. These facts helped to build up a rationale predicting that any epithelial cancer, after radical surgery, can be chemoprevented with supplemental carotenoids. Thus, it is expected that the remaining initiated epithelial tissue will be protected by quenching oxygen radical formation, against the onset of a second primary malignancy. This type of prevention can be envisaged in organs like the lung, urinary bladder, breast, stomach, and colon-rectum. At present, human intervention protocols with a randomized drug/placebo method are underway under the supervision of the Centro Tumori of Pavia to chemoprevent with beta-carotene second primary lung or bladder cancer after radical surgery. Preliminary observations regarding findings in humans without randomization (1980-1988) in Pavia are also reported here. This consisted of chemoprevention with beta-carotene plus canthaxanthin against recurrence of different epithelial malignancies after radical treatment (surgery +/- chemoradiotherapy). None of the 11 cases recruited, on the basis of radical nature of treatment and patient adherence, have shown any recurrence beyond their expected disease-free intervals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I963,I963)","v":2662095},{"$f":"(LEN($J963) - LEN(SUBSTITUTE(LOWER($J963),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J963) - LEN(SUBSTITUTE(LOWER($J963),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J963) - LEN(SUBSTITUTE(LOWER($J963),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B963:D963)","v":0},1989,"Experimental models of anterior segment dysgenesis.","Cook",2662095,"Experimental models of anterior segment dysgenesis.    Abstract:   Normal anterior segment embryogenesis is summarized followed by a review of syndromes of spontaneous and inherited conditions of abnormal development in humans and animals. The study of teratogen-induced malformations in animal models has provided valuable information about critical periods during gestation for the initiation of anterior segment dysgenesis. Although the major developmental events leading to iridocorneal angle formation occur during the third trimester, it appears that embryonic insult much earlier in human gestation (during the first three to five weeks post fertilization) can induce an abnormal sequence of events leading to anterior segment dysgenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I964,I964)","v":2654228},{"$f":"(LEN($J964) - LEN(SUBSTITUTE(LOWER($J964),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J964) - LEN(SUBSTITUTE(LOWER($J964),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J964) - LEN(SUBSTITUTE(LOWER($J964),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B964:D964)","v":0},1989,"Recent developments in the roles of vitamins and minerals in reproduction.","Hurley",2654228,"Recent developments in the roles of vitamins and minerals in reproduction.    Abstract:   Vitamins and minerals affect reproductive function. Vitamin A deficiency has long been known to affect reproductive function in cattle. More recently, a role has been proposed for the vitamin A percursor, beta-carotene, in reproductive efficiency. Dietary supplementation with vitamin E and selenium may reduce the incidence of retained placenta, but these nutrients may also affect reproductive function in other ways. Calcium and phosphorus deficiencies affect reproduction in cattle, and vitamin D may directly affect reproductive function in addition to its role in calcium and phosphorus metabolism. Dietary manipulation of a number of other vitamins and minerals also influences reproductive function. However, the specific roles of nutrients in reproductive tissues are not well-defined in dairy cattle, and nutrient requirements for optimal reproductive efficiency in modern dairy cattle deserve careful reevaluation. This review provides a background of the effect of vitamins and minerals on reproduction and it attempts to provide a basis for further investigation of specific mechanisms by which reproductive function is affected. The interface between nutritional science and reproductive physiology provides considerable potential for optimizing reproductive efficiency in dairy cattle."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I965,I965)","v":2656045},{"$f":"(LEN($J965) - LEN(SUBSTITUTE(LOWER($J965),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J965) - LEN(SUBSTITUTE(LOWER($J965),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J965) - LEN(SUBSTITUTE(LOWER($J965),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B965:D965)","v":0},1989,"Clinical pharmacokinetics of clofazimine. A review.","Holdiness",2656045,"Clinical pharmacokinetics of clofazimine. A review.    Abstract:   Clofazimine is useful in the treatment of Hansens disease (leprosy) and some dermatological disorders, and is currently being used in drug regimens for patients with human immunodeficiency viral infections who are also infected with Mycobacterium avium complex. After an oral dose, absorption is variable, but when given in an oil-wax suspension is approximately 70%. Administration with food appears to increase the peak plasma drug concentration and reduce the time to peak level. Data on the volume of distribution and percentage or type of protein binding are not available; however, the drug undergoes extensive tissue distribution. Clofazimine does not cross the blood-brain barrier, but does cross the placenta, and is found in human breast milk. To date 3 urinary metabolites have been identified in man, but their biological activity is unknown. A substantial portion of the unchanged drug is excreted in faeces. The elimination half-life is variable, with values as long as 70 days being quoted in the literature. Frequently reported side effects of clofazimine are hyperpigmentation of the skin and conjunctiva, and abdominal pain. These resolve upon cessation of therapy. Biochemical and haematological adverse effects have been reported, but are generally not clinically relevant. Pharmacokinetic drug interactions of potential clinical significance have been observed with dapsone, oestrogen, rifampicin and vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I966,I966)","v":2673070},{"$f":"(LEN($J966) - LEN(SUBSTITUTE(LOWER($J966),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J966) - LEN(SUBSTITUTE(LOWER($J966),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J966) - LEN(SUBSTITUTE(LOWER($J966),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B966:D966)","v":0},1989,"The role of vitamins in the etiology of cervical neoplasia: an epidemiological review.","Schneider",2673070,"The role of vitamins in the etiology of cervical neoplasia: an epidemiological review.    Abstract:   Diet may act as a cofactor in the development of cancer of the cervix. A consistent correlation exists between low tissue concentrations, low serum level, and low intake of vitamin A, beta-carotene, vitamin C, or folic acid and an increased prevalence of cervical neoplasia. A moderate effect is seen in clinical trials with vitamin treatment of cervical intraepithelial neoplasias. The studies reviewed here were not consistent especially in the choice of controls and methods for the assessment of dietary and confounding factors. Proper morphologic identification of cervical intraepithelial neoplasia was not always achieved. Longitudinal and prospective cohort studies using more reliable methods for diet monitoring may be valuable for future research in this field."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I967,I967)","v":2507706},{"$f":"(LEN($J967) - LEN(SUBSTITUTE(LOWER($J967),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J967) - LEN(SUBSTITUTE(LOWER($J967),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J967) - LEN(SUBSTITUTE(LOWER($J967),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B967:D967)","v":0},1989,"Teratogenicity of vitamin A.","Underwood",2507706,"Teratogenicity of vitamin A.    Abstract:   There are few documented reports in humans that link teratogenic consequences to high intakes of supplemental R or RE, taken either acutely or chronically. This is in contrast to the well-documented teratogenicity in humans of RA and some of its synthetic derivatives. Both R and RE are documented teratogens in animals. Therefore, until more is known about the mechanisms of placental transfer and control as well as about the dose-related teratogenicity of vitamin A at different stages of gestation, there are few justifications for routine ingestion by fertile women of supplemental vitamin A in excess of 8-10,000 IU. Exceptions are when clinical signs are evident and habitual diets are unusually deficient. Even then, however, high dosages should be restricted to single administrations followed by frequent or daily dosages not exceeding 10,000 IU. Available evidence indicates that high-dosage supplements of beta-carotene can be safely taken; the dosages probably should be of a level to sustain blood concentrations below 300 micrograms/dl."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I968,I968)","v":12178516},{"$f":"(LEN($J968) - LEN(SUBSTITUTE(LOWER($J968),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J968) - LEN(SUBSTITUTE(LOWER($J968),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J968) - LEN(SUBSTITUTE(LOWER($J968),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B968:D968)","v":0},1988,"Diet, malnutrition in sub-Saharan Africa.","Serdula",12178516,"Diet, malnutrition in sub-Saharan Africa.    Abstract:   This study analyzes the association of protein energy malnutrition and mortality in preschool (non-emergency) children in Sub-Saharan Africa. 2 functional consequences of malnutrition are discussed: retarded physical growth (anthropometry) and mortality. The anthropometric measures used to assess malnutrition are weight-for-age, weight for height, and mid-upper arm circumference. The major factors associated with malnutrition and mortality include dietary intake, severity and frequency of infections, social, demographic, economic and cultural factors (area of residence, seasonality, socioeconomic status, mothers age and educational level, family support and cohesiveness, birth order of index child and birth interval between children and number of children under 5 in the family, maternal nutritional status and health and adequacy of breast milk volume and composition for young infants. Understanding these factors will identify children-at-risk for malnutrition and target them for intervention programs. The article focuses on the association of malnutrition with mortality in relation to: 1) breastfeeding and weaning practice; 2) vitamin A and 3) infection. Reviews of African and Asian studies on the subject demonstrated that higher mortality rates were associated with malnutrition, however, the causal associations remain unclear. Since malnourished children are at higher risk for illness, short-term interventions should include growth monitoring, nutrition education, prevention and treatment of infections, food supplementation, hospital rehabilitation, home gardens and improved agricultural practices; while long-term interventions should include improvement in the economic and environmental conditions. (authors modified)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I969,I969)","v":3048634},{"$f":"(LEN($J969) - LEN(SUBSTITUTE(LOWER($J969),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J969) - LEN(SUBSTITUTE(LOWER($J969),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J969) - LEN(SUBSTITUTE(LOWER($J969),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B969:D969)","v":0},1988,"Diet and cancer. Any progress in the interim?","Byers",3048634,"Diet and cancer. Any progress in the interim?    Abstract:   It has been 5 years since the National Research Council (NRC) Committee on Diet, Nutrition and Cancer published quot;Interim Dietary Guidelinesquot; for the nutritional prevention of cancer. The term quot;interimquot; implies that these recommendations should be regarded as temporary, pending more definitive findings from additional scientific research. This article reviews findings relevant to the connections between diet and cancer that have emerged from nutritional epidemiology subsequent to the 1982 the NRC report. Some recent research has supported the earlier work which served as a basis for the interim recommendations, some has not, and additional hypotheses have emerged. There continues to be evidence, although it is inconsistent, that dietary fat may be an important factor in colon cancer, and that something related to fruits and vegetables, perhaps carotene, may lower the risk of lung cancer. However, the hypothesized relationships between dietary fat and breast cancer and between dietary fiber and colon cancer have been less consistently supported by new findings. Meanwhile, a new hypothesis has emerged relating alcohol intake to breast cancer risk, although many important questions remain regarding the age at which alcohol use may affect risk, and the dose above which risk is increased. The last 5 years seem to have been characterized by only slow progress in our understanding of the relationship between diet and cancer. It is clear that in 1988 we are still very much in the interim. Critical methodologic assessments of the reasons for the discrepancies in findings among the various studies, and meta analytic approaches may be helpful in increasing our understanding of the set of epidemiologic research conducted to date. More important, however, are the many types of studies now underway, including more rigorously designed observational studies and chemo-preventive and dietary-preventive trials. These studies will likely provide more definitive future answers to the questions we still face in the interim."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I970,I970)","v":3153130},{"$f":"(LEN($J970) - LEN(SUBSTITUTE(LOWER($J970),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J970) - LEN(SUBSTITUTE(LOWER($J970),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J970) - LEN(SUBSTITUTE(LOWER($J970),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B970:D970)","v":0},1988,"[Requirements of nutrients which participate in erythropoiesis].","Byers",3153130,"[Requirements of nutrients which participate in erythropoiesis].    Abstract:   Proteins, some minerals and vitamins, play important roles in erythropoiesis and the survival of the red blood cell. This article deals specifically with the physiological requirements and recommended intakes of iron, folate and vitamin B12. A comparison of the physiologic iron requirements according to age and sex, and the amount of iron which is actually absorbed from the diets consumed by the lower socioeconomic strata of the Venezuelan population; indicates that these diets do not satisfy the requirements at all ages. Such disparity is most marked in children below three years of age, in adolescents and in women during their reproductive age. Failure to do so leads to varying degrees of iron deficiency. This low bioavailability of the Venezuelan diet is also observed in other Latin American diets consumed by the same low socioeconomic strata, which explains the high prevalence of iron-deficiency anemia in the vulnerable groups. The low intake of fruits and vegetables by the lower socioeconomic strata of the Latin American population prevents these sectors from consuming an adequate intake of folate, failing to fulfill the daily recommended intake (3.3 - 3.6 micrograms/kg body weight). This situation is aggravated in pregnant and lactating women who require an additional intake of 300 micrograms and 100 micrograms, respectively. Prevalence of folate deficiency in the first stage may be in the order of 30% in some regions. In the second stage of deficiency, characterized by megaloblastic changes in the bone marrow and an erythrocyte folate concentration of less than 50 micrograms/lt, it could be as high as 40% in pregnant women. Nutritional vitamin B12 deficiency does not constitute a health problem in Latin America. Various surveys in the lower socioeconomic strata have reported normal or higher than normal serum B12 concentrations, compared to well-nourished populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I971,I971)","v":3153129},{"$f":"(LEN($J971) - LEN(SUBSTITUTE(LOWER($J971),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J971) - LEN(SUBSTITUTE(LOWER($J971),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J971) - LEN(SUBSTITUTE(LOWER($J971),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B971:D971)","v":0},1988,"[Abuse of megadoses of vitamins].","Arroyave",3153129,"[Abuse of megadoses of vitamins].    Abstract:   There is no evidence of any nutritional benefit derived from the consumption of vitamin supplements in excess of the daily intakes recommended by the various international and national expert committees. Furthermore, in the case of certain of the vitamins such as vitamin A and vitamin D, excessive intakes result in toxic effects. To a lesser extent this is also the case for vitamin C and nicotinic acid. In addition, the use of high supplements or megadoses of any vitamin results in a wasteful misuse of economic resources. This reduces the capacity to acquire foods which would have clear nutritional benefits for the whole family. Consequently, the indiscriminate use of these megadoses must be discouraged. Their application is exclusively justified in clinical situations under direct medical supervision."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I972,I972)","v":3153128},{"$f":"(LEN($J972) - LEN(SUBSTITUTE(LOWER($J972),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J972) - LEN(SUBSTITUTE(LOWER($J972),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J972) - LEN(SUBSTITUTE(LOWER($J972),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B972:D972)","v":0},1988,"[3 problem vitamins in Latin America].","Arroyave",3153128,"[3 problem vitamins in Latin America].    Abstract:   The list of vitamins recognized as essential in human nutrition is extensive. Only some of them, however, are attributed an important role in public health. The present paper deals with three of these selected because their deficiencies still prevail in important sectors of population in the Latin American Region: vitamin A, vitamin C and vitamin D. For each vitamin the paper discusses the scientific bases for their requirements, as well as pragmatic considerations to be taken into account for the derivation of recommended dietary intakes. Reference is made to the logic of applying the concepts of nutrient density when developing guidelines for the design of diets for the family and the community. Adequate nutrient density means that when a diet is consumed in sufficient amounts to satisfy energy requirements, the needs for essential nutrients are also being met. For the above reasons, the principle of expressing the recommended levels of intake of vitamin A and C per 1,000 kilocalories has been followed. This is not the case with vitamin D which, in view of its special feature of being synthesized endogenously, is not really a vitamin in the strict sense of the term and, therefore, a rational and consistent relationship with the energy of the diet cannot be established."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I973,I973)","v":3292794},{"$f":"(LEN($J973) - LEN(SUBSTITUTE(LOWER($J973),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J973) - LEN(SUBSTITUTE(LOWER($J973),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J973) - LEN(SUBSTITUTE(LOWER($J973),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B973:D973)","v":0},1988,"Clinical applications of fish oils.","Yetiv",3292794,"Clinical applications of fish oils.    Abstract:   Fish oil supplements are currently being nationally advertised, and many physicians are being queried about their clinical utility. Epidemiologic studies reveal a low incidence of cardiovascular disease in people, such as the Eskimos, who eat large amounts of seafood. Cardiovascular health may be improved because fish and fish oil supplements lower plasma lipid levels (especially triglycerides), inhibit platelet aggregation, and may decrease blood pressure and viscosity and increase high-density lipoprotein (HDL) levels. Preliminary observations also suggest a potential future role for fish oils in the treatment of some autoimmune diseases, such as atopic dermatitis, psoriasis, and rheumatoid arthritis. Patients with serum triglyceride levels greater than 5.64 mmol/L and/or cholesterol levels greater than 7.75 mmol/L refractory to dietary management may benefit from a medically supervised trial of fish oil supplements. Data currently available are insufficient to recommend fish oil supplements for the general public, or for patients with other diseases, and side effects must also be considered. These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I974,I974)","v":3287506},{"$f":"(LEN($J974) - LEN(SUBSTITUTE(LOWER($J974),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J974) - LEN(SUBSTITUTE(LOWER($J974),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J974) - LEN(SUBSTITUTE(LOWER($J974),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B974:D974)","v":0},1988,"Postnatal effects of prenatal insult.","Johnson",3287506,"Postnatal effects of prenatal insult.    Abstract:   Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or abberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad-based susceptibility, subtlety of expression and potential of long-lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low-dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development may be."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I975,I975)","v":2840328},{"$f":"(LEN($J975) - LEN(SUBSTITUTE(LOWER($J975),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J975) - LEN(SUBSTITUTE(LOWER($J975),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J975) - LEN(SUBSTITUTE(LOWER($J975),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B975:D975)","v":0},1986,"[Causative and preventive factors concerning food in cancer].","Evans",2840328,"[Causative and preventive factors concerning food in cancer].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I976,I976)","v":3019955},{"$f":"(LEN($J976) - LEN(SUBSTITUTE(LOWER($J976),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J976) - LEN(SUBSTITUTE(LOWER($J976),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J976) - LEN(SUBSTITUTE(LOWER($J976),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B976:D976)","v":0},1986,"Food in the aetiology of cancer.","Thomas",3019955,"Food in the aetiology of cancer.    Abstract:   During recent years much evidence has accumulated indicating that diet and nutrition may be important in the aetiology of human cancer. This paper discusses some of the components of diet that have been implicated as both causative and protective agents. Total calorie intake and overnutrition have been associated with breast and uterine cancers, high fat intake with cancer of the breast and large bowel and nitrates with gastric cancer. High fibre intakes are suggested to protect against colo-rectal cancer, and vitamin A, selenium and vitamin E have been inversely associated with various cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I977,I977)","v":3456709},{"$f":"(LEN($J977) - LEN(SUBSTITUTE(LOWER($J977),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J977) - LEN(SUBSTITUTE(LOWER($J977),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J977) - LEN(SUBSTITUTE(LOWER($J977),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B977:D977)","v":0},1986,"The value of case reports in human teratology.","Goldberg",3456709,"The value of case reports in human teratology.    Abstract:   Birth defects caused by human teratogens are an important and potentially preventable cause of perinatal morbidity and mortality. Case reports provide an initial suggestion that a specific agent may be a human teratogen and provide the basis for further study. This review discusses the importance of case reports in human teratology and provides guidance in evaluating new case reports."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I978,I978)","v":3006202},{"$f":"(LEN($J978) - LEN(SUBSTITUTE(LOWER($J978),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J978) - LEN(SUBSTITUTE(LOWER($J978),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J978) - LEN(SUBSTITUTE(LOWER($J978),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B978:D978)","v":0},1986,"Diet in the etiology of cancer.","Vaughan",3006202,"Diet in the etiology of cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I979,I979)","v":3538053},{"$f":"(LEN($J979) - LEN(SUBSTITUTE(LOWER($J979),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J979) - LEN(SUBSTITUTE(LOWER($J979),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J979) - LEN(SUBSTITUTE(LOWER($J979),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B979:D979)","v":0},1986,"The Diet and Cancer Branch, NCI: current projects and future research directions.","Butrum",3538053,"The Diet and Cancer Branch, NCI: current projects and future research directions.    Abstract:   Diet, perhaps more than any other environmental factor, has a significant potential for reducing the incidence of cancer. It has been projected that as much as 35 percent of all human cancer can be prevented through effective dietary modification strategies. The comprehensive research program of the DCB significantly directs diet and cancer research toward the ultimate cancer prevention goal of modifying dietary habits of the general population for optimal health. The DCB is currently supporting projects along the entire continuum from laboratory research to human intervention trials: basic research projects in food composition, encompassing dietary fiber, vitamin A and carotenoids and development of INFOODS; physiologic studies establishing safe and effective levels of dietary fiber and carotenoids; modification of eating behavior; human intervention trials of low fat diets in prevention of breast cancer; and clinical nutrition research units."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I980,I980)","v":3537858},{"$f":"(LEN($J980) - LEN(SUBSTITUTE(LOWER($J980),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J980) - LEN(SUBSTITUTE(LOWER($J980),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J980) - LEN(SUBSTITUTE(LOWER($J980),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B980:D980)","v":0},1986,"An evaluation of figure-eight maze activity and general behavioral development following prenatal exposure to forty chemicals: effects of cytosine arabinoside, dinocap, nitrofen, and vitamin A.","Gray",3537858,"An evaluation of figure-eight maze activity and general behavioral development following prenatal exposure to forty chemicals: effects of cytosine arabinoside, dinocap, nitrofen, and vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I981,I981)","v":3905268},{"$f":"(LEN($J981) - LEN(SUBSTITUTE(LOWER($J981),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J981) - LEN(SUBSTITUTE(LOWER($J981),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J981) - LEN(SUBSTITUTE(LOWER($J981),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B981:D981)","v":0},1985,"Parathyroid tumors.","Granberg",3905268,"Parathyroid tumors.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I982,I982)","v":3926298},{"$f":"(LEN($J982) - LEN(SUBSTITUTE(LOWER($J982),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J982) - LEN(SUBSTITUTE(LOWER($J982),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J982) - LEN(SUBSTITUTE(LOWER($J982),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B982:D982)","v":0},1985,"Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins.","Welsch",3926298,"Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins.    Abstract:   The carcinogen-induced rat mammary carcinoma model, developed a quarter of a century ago by Dr. Charles Brenton Huggins, is today the standard laboratory animal model in the study of human breast cancer. This model has a number of features that make it particularly attractive to the experimental oncologist, e.g., tumor induction ease and reliability, organ site specificity, tumors of ductal origin, tumors of predominantly carcinomatous histopathological characteristics, tumors of varying growth factor and/or hormone responsiveness, and the potential to examine tumor initiation and promotion processes. Since the development of this model, an extensive literature describing the biological behavior and responsiveness of these tumors has been provided. The purpose of this communication is to condense, summarize, and integrate this vast literature into a single review with the intent on facilitating information acquisition and conceptualism by both the new and the established experimental oncologist. In addition, and equally important, this communication is a tribute to Dr. Huggins, whose pioneering efforts in the development of this model and whose scientific contributions and dedication to the oncological sciences in general have made an important and lasting impact on us all."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I983,I983)","v":3900157},{"$f":"(LEN($J983) - LEN(SUBSTITUTE(LOWER($J983),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J983) - LEN(SUBSTITUTE(LOWER($J983),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J983) - LEN(SUBSTITUTE(LOWER($J983),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B983:D983)","v":0},1985,"Hereditary epidermolysis bullosa.","Haber",3900157,"Hereditary epidermolysis bullosa.    Abstract:   Hereditary epidermolysis bullosa (EB) is a group of disorders of skin characterized by formation of blisters following minor trauma. There are at least sixteen types of hereditary EB. These types are reviewed in this article. There are several classifications of hereditary EB, and they are discussed, as well as current ideas on pathogenesis. Last, the treatment of this often recalcitrant group of diseases is discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I984,I984)","v":3916200},{"$f":"(LEN($J984) - LEN(SUBSTITUTE(LOWER($J984),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J984) - LEN(SUBSTITUTE(LOWER($J984),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J984) - LEN(SUBSTITUTE(LOWER($J984),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B984:D984)","v":0},1985,"Multiethnic studies of diet, nutrition, and cancer in Hawaii.","Kolonel",3916200,"Multiethnic studies of diet, nutrition, and cancer in Hawaii.    Abstract:   Epidemiologic studies of diet and cancer have been facilitated in Hawaii by the multiethnic composition of its population and the consequent heterogeneity in dietary intakes. Studies of migrant populations, particularly the Japanese, have firmly supported the conclusions that environmental factors are of predominant etiologic significance for most major sites of cancer, and that these factors may exert their influences at particular periods of life. Recent observations on Filipino migrants reproduce most of the findings in the Japanese, although they do not show the same abrupt increase in colon cancer rates to the high levels found in Caucasians. Data on dietary intakes in these populations support several of the prevailing hypotheses regarding the etiology of certain gastrointestinal and hormone-dependent cancers. Several case-control studies of diet and cancer have been completed or are ongoing in Hawaii. Some of these have included comparable studies in Japan, but the findings in Hawaii have generally not been reproduced in Japan. Weak associations with dietary fat have been found in Hawaii for breast cancer (particularly in Japanese women) and for prostate cancer (particularly in men greater than or equal to 70 years of age). Vitamin A (especially carotene) has been shown to be inversely associated with lung cancer risk in men, but positively associated with prostate cancer risk in older men. Vitamin C may be inversely related to bladder cancer risk, but has shown no relationship to lung or prostate cancer risk. These and other findings are discussed in terms of future needs for epidemiologic research in this field."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I985,I985)","v":3911268},{"$f":"(LEN($J985) - LEN(SUBSTITUTE(LOWER($J985),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J985) - LEN(SUBSTITUTE(LOWER($J985),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J985) - LEN(SUBSTITUTE(LOWER($J985),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B985:D985)","v":0},1985,"Functional consequences of zinc deficiency.","McClain",3911268,"Functional consequences of zinc deficiency.    Abstract:   Zinc is an essential trace element necessary for over 200 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. During the past two decades there has been a rapid expansion of knowledge concerning zinc metabolism in both normal and disease situations, including mechanisms for zinc absorption, excretion and internal redistribution of zinc after stress or trauma. Acrodermatitis enteropathica has been recognized to be a disease of impaired zinc absorption in man. A host of disease processes now are recognized to be complicated by zinc deficiency including alcoholic liver disease, sickle cell anemia, protein calorie malnutrition, and a variety of intestinal diseases including Crohns disease, sprue, short bowel syndrome and after jejunal ileal bypass. Zinc has proved to be an extremely interesting mineral to nutritionists and physicians because of its importance in normal physiology and biochemistry and because of the diverse presenting features of zinc deficiency. This paper reviews ten functional consequences of zinc deficiency and emphasizes certain consequences in which there have been new discoveries concerning their mechanism (e.g., anorexia) or their clinical importance (e.g., immune dysfunction)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I986,I986)","v":3903756},{"$f":"(LEN($J986) - LEN(SUBSTITUTE(LOWER($J986),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J986) - LEN(SUBSTITUTE(LOWER($J986),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J986) - LEN(SUBSTITUTE(LOWER($J986),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B986:D986)","v":0},1985,"Taurine in human nutrition: overview.","Gaull",3903756,"Taurine in human nutrition: overview.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I987,I987)","v":3896272},{"$f":"(LEN($J987) - LEN(SUBSTITUTE(LOWER($J987),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J987) - LEN(SUBSTITUTE(LOWER($J987),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J987) - LEN(SUBSTITUTE(LOWER($J987),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B987:D987)","v":0},1985,"Zinc and reproduction.","Apgar",3896272,"Zinc and reproduction.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I988,I988)","v":3887778},{"$f":"(LEN($J988) - LEN(SUBSTITUTE(LOWER($J988),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J988) - LEN(SUBSTITUTE(LOWER($J988),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J988) - LEN(SUBSTITUTE(LOWER($J988),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B988:D988)","v":0},1985,"Vitamins and immunocompetence.","Panush",3887778,"Vitamins and immunocompetence.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I989,I989)","v":3025165},{"$f":"(LEN($J989) - LEN(SUBSTITUTE(LOWER($J989),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J989) - LEN(SUBSTITUTE(LOWER($J989),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J989) - LEN(SUBSTITUTE(LOWER($J989),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B989:D989)","v":0},1985,"Diet and nutrition as risk factors for cancer.","Wogan",3025165,"Diet and nutrition as risk factors for cancer.    Abstract:   Involvement of diet and nutrition as risk factors for human cancers has been established by two general types of evidence. Epidemiological studies in human populations have identified associations between patterns of incidence for various forms of cancer and diet composition or food consumption patterns. Such associations are particularly evident in studies on migrant populations and in patterns of geographic localization of specific forms of cancer. Reduction in gastric cancer (and increase in colon cancer) incidence has been observed in immigrants from Japan to the U.S. via Hawaii with concurrent change in dietary habits. High fat consumption has been linked to increased incidence of breast and colon cancer, and evidence is accumulating that suggests increased intake of dietary fiber (or some specific component of it) may be associated with diminished risk of colorectal cancer. Laboratory studies have demonstrated the existence of dietary constituents that might impact cancer risk in people consuming them. Substances in this class fall into two general categories: genotoxic carcinogens/mutagens; and protective factors which inhibit experimentally-induced chemical carcinogenesis in animals. Numerous naturally-occurring carcinogens/mutagens have been identified. Examples include aflatoxins, cycasin, and bracken fern carcinogen(s), among others. Genotoxic substances associated with the use of intentional food additives are the N-nitroso compounds formed as nitrosation products from nitrite. Potential carcinogenic risk from food constituents also comes from mutagens found in foods as natural components, or formed in the course of cooking.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I990,I990)","v":3010379},{"$f":"(LEN($J990) - LEN(SUBSTITUTE(LOWER($J990),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J990) - LEN(SUBSTITUTE(LOWER($J990),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J990) - LEN(SUBSTITUTE(LOWER($J990),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B990:D990)","v":0},1985,"Diet, nutrition, and cancer.","Palmer",3010379,"Diet, nutrition, and cancer.    Abstract:   Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. Frequent consumption of cured, pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer, however, the specific causative agents in these foods are not clearly identified. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. The mechanisms of action of dietary factors on carcinogenesis are poorly understood. The NRC committee, and more recently, the National Cancer Institute and the American Cancer Society have proposed interim dietary guidelines to lower the risk of cancer. These guidelines are consistent with general dietary recommendations proposed by U.S. government agencies for maintenance of good health.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I991,I991)","v":6428773},{"$f":"(LEN($J991) - LEN(SUBSTITUTE(LOWER($J991),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J991) - LEN(SUBSTITUTE(LOWER($J991),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J991) - LEN(SUBSTITUTE(LOWER($J991),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B991:D991)","v":0},1984,"Implications of nutritional status on human biochemistry, physiology, and health.","Sauberlich",6428773,"Implications of nutritional status on human biochemistry, physiology, and health.    Abstract:   Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I992,I992)","v":6230219},{"$f":"(LEN($J992) - LEN(SUBSTITUTE(LOWER($J992),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J992) - LEN(SUBSTITUTE(LOWER($J992),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J992) - LEN(SUBSTITUTE(LOWER($J992),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B992:D992)","v":0},1984,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?","Ovesen",6230219,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?    Abstract:   Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I993,I993)","v":6442234},{"$f":"(LEN($J993) - LEN(SUBSTITUTE(LOWER($J993),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J993) - LEN(SUBSTITUTE(LOWER($J993),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J993) - LEN(SUBSTITUTE(LOWER($J993),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B993:D993)","v":0},1984,"Strategies for the control of malnutrition and the influence of the nutritional sciences.","Latham",6442234,"Strategies for the control of malnutrition and the influence of the nutritional sciences.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I994,I994)","v":6300495},{"$f":"(LEN($J994) - LEN(SUBSTITUTE(LOWER($J994),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J994) - LEN(SUBSTITUTE(LOWER($J994),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J994) - LEN(SUBSTITUTE(LOWER($J994),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B994:D994)","v":0},1983,"Environmental etiology of large-bowel cancer.","Zaridze",6300495,"Environmental etiology of large-bowel cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I995,I995)","v":6341395},{"$f":"(LEN($J995) - LEN(SUBSTITUTE(LOWER($J995),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J995) - LEN(SUBSTITUTE(LOWER($J995),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J995) - LEN(SUBSTITUTE(LOWER($J995),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B995:D995)","v":0},1983,"[Actions of vitamin A in tumor and inflammation].","Kanda",6341395,"[Actions of vitamin A in tumor and inflammation].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I996,I996)","v":6338505},{"$f":"(LEN($J996) - LEN(SUBSTITUTE(LOWER($J996),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J996) - LEN(SUBSTITUTE(LOWER($J996),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J996) - LEN(SUBSTITUTE(LOWER($J996),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B996:D996)","v":0},1983,"The function of vitamin A: current concepts.","Zile",6338505,"The function of vitamin A: current concepts.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I997,I997)","v":6375154},{"$f":"(LEN($J997) - LEN(SUBSTITUTE(LOWER($J997),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J997) - LEN(SUBSTITUTE(LOWER($J997),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J997) - LEN(SUBSTITUTE(LOWER($J997),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B997:D997)","v":0},1983,"Vitamin A: technology and applications.","Bauernfeind",6375154,"Vitamin A: technology and applications.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I998,I998)","v":6341320},{"$f":"(LEN($J998) - LEN(SUBSTITUTE(LOWER($J998),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J998) - LEN(SUBSTITUTE(LOWER($J998),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J998) - LEN(SUBSTITUTE(LOWER($J998),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B998:D998)","v":0},1983,"Dietary supplementation of lactating Gambian women. I. Effect on breast-milk volume and quality.","Prentice",6341320,"Dietary supplementation of lactating Gambian women. I. Effect on breast-milk volume and quality.    Abstract:   In order to test whether lactational capacity can be improved by dietary interventions, a nutritionally balanced supplement was provided under carefully controlled conditions to 130 nursing mothers in Keneba, The Gambia over 12 months. Maternal mean energy intake (+/- s.e.) increased from 1568 +/- 15 kcal/d (6.56 +/- 0.06 MJ/d) to 2291 +/- 14 kcal/d (9.59 +/- 0.06 MJ/d). Protein intake was in excess of the WHO/FAO recommended intake after supplementation and serious deficits of riboflavin, vitamin A, vitamin C and calcium were rectified. The supplement had no effect on breast-milk volume, compared with retrospective controls, at any stage of lactation or in any season of the year. There was no selective effect on women with poor milk outputs. The average milk protein concentration was slightly improved over the entire period of lactation (+ 6.6 per cent, P less than 0.01), but the total energy content was unchanged since an increase in breast-milk fat concentration (+ 7.9 per cent, n.s.) was offset by a decrease in the milk lactose concentration (- 7.6 per cent, P less than 0.01). Breast milk vitamin content was improved for those vitamins for which the supplement provided a significant proportion of the recommended dietary intake."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I999,I999)","v":6340122},{"$f":"(LEN($J999) - LEN(SUBSTITUTE(LOWER($J999),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J999) - LEN(SUBSTITUTE(LOWER($J999),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J999) - LEN(SUBSTITUTE(LOWER($J999),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B999:D999)","v":0},1983,"Biochemical mechanisms of vitamin A action.","Weber",6340122,"Biochemical mechanisms of vitamin A action.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1000,I1000)","v":6300915},{"$f":"(LEN($J1000) - LEN(SUBSTITUTE(LOWER($J1000),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1000) - LEN(SUBSTITUTE(LOWER($J1000),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1000) - LEN(SUBSTITUTE(LOWER($J1000),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1000:D1000)","v":0},1983,"Chemical structure and the changing concept of vitamin A activity.","Pitt",6300915,"Chemical structure and the changing concept of vitamin A activity.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1001,I1001)","v":6188282},{"$f":"(LEN($J1001) - LEN(SUBSTITUTE(LOWER($J1001),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1001) - LEN(SUBSTITUTE(LOWER($J1001),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1001) - LEN(SUBSTITUTE(LOWER($J1001),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1001:D1001)","v":0},1982,"[Recent developments in chemotherapy of malignant diseases].","Moser",6188282,"[Recent developments in chemotherapy of malignant diseases].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1002,I1002)","v":6818512},{"$f":"(LEN($J1002) - LEN(SUBSTITUTE(LOWER($J1002),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1002) - LEN(SUBSTITUTE(LOWER($J1002),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1002) - LEN(SUBSTITUTE(LOWER($J1002),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1002:D1002)","v":0},1982,"Infantile malnutrition in the tropics.","Solomons",6818512,"Infantile malnutrition in the tropics.    Abstract:   One of the major factors in the development of severe protein-energy malnutrition (PEM) is infection, such as diarrhea, upper respiratory infection, and malaria. Social and environmental factors include family size, access to land and occupation of parents, and exposure of rural populations to urban centers. Breast milk has been shown to play a role in the prevention of infections; however, the mother must be well-nourished to provide the optimum product. Traditional foods available to rural children in most developing countries are difficult to digest and low in energy and protein and inadequate nutritional education prevents the inclusion of good protein sources in childrens diets. Severe PEM, called marasmus and kwashiorkor is indicated by wasting of muscles, absence of subcutaneous fat, wrinkled skin, thin and sparse hair, and weakness. The basic treatment for severe PEM is dietary. Treatment of kwashiorkor and marasmus is divided into 3 stages: 1) attending to acute problems, 2) restoring nutritional balance, and 3) ensuring nutritional rehabilitation. Care must be taken to ensure a minimum daily intake of 3-4 gm of protein and 120-150 Kcal of energy/kg of body weight. There must be, in addition, replacement of vitamin A, zinc, potassium, magnesium, and iron. An initial regimen which has been advocated is based on dry skim milk, sugar, and vegetable oil, divided into 6-12 feedings/day, which prevents vomiting. It is not necessary to remove lactose from the diet, and other animal protein sources such as meat and meat extracts are also well accepted. Soy and vegetable protein have been used successfully. In treating mild and moderate PEM it is important to ensure the intake of these food supplements by the child and to avoid a major substitution effect in the household diet. It is crucial for the physicians, nutritionists, public health workers, and educators to convince parents about the safety of using foods that are fed only to adults and older children. In addition nutritional and health education must not be restricted to the rehabilitation of the child but the prevention of nutritonal deterioration of the entire family and sometimes to the entire community."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1003,I1003)","v":7050193},{"$f":"(LEN($J1003) - LEN(SUBSTITUTE(LOWER($J1003),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1003) - LEN(SUBSTITUTE(LOWER($J1003),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1003) - LEN(SUBSTITUTE(LOWER($J1003),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1003:D1003)","v":0},1982,"Possible role of beta-carotene in improving fertility in dairy cattle.","Hemken",7050193,"Possible role of beta-carotene in improving fertility in dairy cattle.    Abstract:   Recent interest in beta-carotene has been stimulated by reports that reproductive performance in cattle was improved with dietary supplementation of beta-carotene even when the diet was supplemented with vitamin A. Vitamin A requirements for cattle are based on studies with beta-carotene as the vitamin A source and with studies with vitamin A in the ester or alcohol form. Most of the studies with cattle that demonstrate the need for vitamin A for optimum reproduction were when beta-carotene was the source of vitamin A. Recent German reports show an improvement in conception rate, intensity of estrus, and changes in luteinizing hormone patterns when cattle received beta-carotene supplementation of low carotene diets. These diets were supplemented with vitamin A. A similar study from Israel did not detect benefits of beta-carotene. The active form of vitamin A for reproduction in rats and other species has not been determined; however, vitamin A does meet the reproductive requirements. The ruminant animal does have differences in carotene metabolism from the rat. Before the role of beta-carotene for reproduction in cattle can be clarified, the specific function of carotene or the specific form of vitamin A for reproduction needs to be determined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1004,I1004)","v":6283750},{"$f":"(LEN($J1004) - LEN(SUBSTITUTE(LOWER($J1004),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1004) - LEN(SUBSTITUTE(LOWER($J1004),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1004) - LEN(SUBSTITUTE(LOWER($J1004),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1004:D1004)","v":0},1982,"[Relationship between nutrition and tumor formation].","Kolb",6283750,"[Relationship between nutrition and tumor formation].    Abstract:   The tumours of man mainly develop under the influence of the long-term intake of carcinogens and cocarcinogens. There is a correlation between the level of the intake of meat and the development of tumours of the colon and the mamma. In vegetarians these forms of tumours very rarely appear. For their prevention it is necessary to decrease the consumption of sorts of meat and sausage rich in fat, so that less than 50 g of animal fat are taken in a day. It is to be recommended an increase of the consumption of food-stuffs rich in raw fibers. The caretenes, the vitamin A and the vitamin-A-acid proved as anticarcinogens. In smokers an intake of carotene and vitamin A which overwhelms the need is useful. With smoked food-stuffs in small quantities benzpyrene and nitrosamines are taken in, a restriction of the consumption of smoked meat and fish is not to be recommended. a carcinogenic effect have also aflatoxines, for which purpose no food-stuffs infested by fungi must be taken in."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1005,I1005)","v":7042664},{"$f":"(LEN($J1005) - LEN(SUBSTITUTE(LOWER($J1005),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1005) - LEN(SUBSTITUTE(LOWER($J1005),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1005) - LEN(SUBSTITUTE(LOWER($J1005),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1005:D1005)","v":0},1981,"Nutritional aspects of cancer prevention: an overview.","Silverman",7042664,"Nutritional aspects of cancer prevention: an overview.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1006,I1006)","v":6272264},{"$f":"(LEN($J1006) - LEN(SUBSTITUTE(LOWER($J1006),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1006) - LEN(SUBSTITUTE(LOWER($J1006),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1006) - LEN(SUBSTITUTE(LOWER($J1006),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1006:D1006)","v":0},1981,"[Nutrition and cancer - an overview (authors transl)].","Müller",6272264,"[Nutrition and cancer - an overview (authors transl)].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1007,I1007)","v":7031395},{"$f":"(LEN($J1007) - LEN(SUBSTITUTE(LOWER($J1007),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1007) - LEN(SUBSTITUTE(LOWER($J1007),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1007) - LEN(SUBSTITUTE(LOWER($J1007),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1007:D1007)","v":0},1981,"The curly-tail mouse: an experimental model for human neural tube defects.","Seller",7031395,"The curly-tail mouse: an experimental model for human neural tube defects.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1008,I1008)","v":7276552},{"$f":"(LEN($J1008) - LEN(SUBSTITUTE(LOWER($J1008),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1008) - LEN(SUBSTITUTE(LOWER($J1008),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1008) - LEN(SUBSTITUTE(LOWER($J1008),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1008:D1008)","v":0},1981,"Effect of oral contraceptive use on ascorbic acid and vitamin A in lactation.","Cumming",7276552,"Effect of oral contraceptive use on ascorbic acid and vitamin A in lactation.    Abstract:   A large prospective study is being undertaken on the effects of OCs (oral contraceptives) on vitamins and trace elements in the plasma and milk of lactating women. Results presented here are of progestagen-only OC effects on ascorbic acid and vitamin A in the plasma and milk of 5 volunteers. 3 of the women took 350 mcg norethisterone and the other 2 took 30 mcg levonorgestrel daily. Their pretherapy age, height, weight, dietary data, and breast feeding history were recorded. Blood samples and fasting milk samples were taken for 19 weeks and the results graphed and analyzed. Findings of the study in general suggest that progestagen-only OCs have little or not effect on milk or plasma levels of vitamin A and ascorbic acid. Actual results show little change in plasma ascorbic acid but a slight, nonsignificant, decrease in milk ascorbic acid levels. Supplementation with ascorbic acid pills promptly increased milk ascorbic acid levels. Milk fluctuations were greater for vitamin A than for ascorbic acid. There was little weekly variation in plasma vitamin A. Changes in vitamin A and ascorbic acid levels were also observed in 9 breast feeding women who were not taking OCs. The lack of effect was expected since most changes in vitamin status have been attributed to estrogen content of OCs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1009,I1009)","v":6261114},{"$f":"(LEN($J1009) - LEN(SUBSTITUTE(LOWER($J1009),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1009) - LEN(SUBSTITUTE(LOWER($J1009),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1009) - LEN(SUBSTITUTE(LOWER($J1009),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1009:D1009)","v":0},1981,"Epidermal growth factor receptors.","Adamson",6261114,"Epidermal growth factor receptors.    Abstract:   EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1010,I1010)","v":6997784},{"$f":"(LEN($J1010) - LEN(SUBSTITUTE(LOWER($J1010),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1010) - LEN(SUBSTITUTE(LOWER($J1010),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1010) - LEN(SUBSTITUTE(LOWER($J1010),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1010:D1010)","v":0},1980,"Anemia and menstrual blood loss.","Cohen",6997784,"Anemia and menstrual blood loss.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1011,I1011)","v":6445537},{"$f":"(LEN($J1011) - LEN(SUBSTITUTE(LOWER($J1011),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1011) - LEN(SUBSTITUTE(LOWER($J1011),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1011) - LEN(SUBSTITUTE(LOWER($J1011),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1011:D1011)","v":0},1980,"Nutritional concerns during adolescence.","Marino",6445537,"Nutritional concerns during adolescence.    Abstract:   Adolescent food habits often run counter to the special nutritional needs of this age group. Suggestions for nutrient supplements are offered, with particular emphasis on fulfilling the unique needs of the obese, athletic, or pregnant teenager. Selected aspects of adolescent nutrition are reviewed. Focus is on adolescent nutrient requirements, food habits, and the special nutritional needs of obese, athletic, or pregnant teenagers. The nutritional implications of alcohol abuse, oral contraceptive (OC) use, and acne during the adolescent period are discussed. Although the critical role of nutrition in pubertal growth and development actually begins before adolescence--during childhood, total nutrient needs are higher during adolescence than at any other time in the life cycle. A failure to consume an adequate diet at this time can potentially retard growth and delay sexual maturity. The weight gain of both adolescent males and females is appreciable, but the rate, amount, and composition of tissue generated differs between the 2 sexes. Based on nutrient needs for growth, recommended dietary allowances have been made for adolescents by the Food and Nutrition Board of the National Research Council. The recommendations for protein and all vitamins and minerals, presented here in table form, include a safety factor so that the needs of quot;practically all healthyquot; adolescents are met. The skipping of meals is a common phenomenon among adolescents. Because of busy schedules during and after school, the teenager may eat sparingly of poor quality foods and then quot;catch upquot; on food intake during the late evening. Snacking is definitely part of adolescent food behavior. 1 health concern is the prevalence of adolescent obesity and its associated problems. Supportive dietary counseling is mandatory in a weight reduction program for the adolescent. A program of physical activity is another component of any successful weight reduction program."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1012,I1012)","v":6986619},{"$f":"(LEN($J1012) - LEN(SUBSTITUTE(LOWER($J1012),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1012) - LEN(SUBSTITUTE(LOWER($J1012),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1012) - LEN(SUBSTITUTE(LOWER($J1012),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1012:D1012)","v":0},1980,"Role of nutrition in immunologic function.","Gross",6986619,"Role of nutrition in immunologic function.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1013,I1013)","v":6182689},{"$f":"(LEN($J1013) - LEN(SUBSTITUTE(LOWER($J1013),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1013) - LEN(SUBSTITUTE(LOWER($J1013),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1013) - LEN(SUBSTITUTE(LOWER($J1013),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1013:D1013)","v":0},1980,"Systemic mode of action of vitamin A.","Ganguly",6182689,"Systemic mode of action of vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1014,I1014)","v":6162280},{"$f":"(LEN($J1014) - LEN(SUBSTITUTE(LOWER($J1014),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1014) - LEN(SUBSTITUTE(LOWER($J1014),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1014) - LEN(SUBSTITUTE(LOWER($J1014),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1014:D1014)","v":0},1980,"[Adjuvanticity of vitamin A in advanced irradiated cervical cancer (authors transl)].","Kucera",6162280,"[Adjuvanticity of vitamin A in advanced irradiated cervical cancer (authors transl)].    Abstract:   For treatment of patients with inoperable cervical cancer (FIGO III) a randomized trial has been initiated. Patients were randomized to receive either conventional irradiation therapy together with vitamin A palmitate (1.5 mill. IU/day; total dose 30 mill. IU), applied orally, or irradiation alone. 42 patients have been included in this study. Patients were monitored by several immunological tests. Delayed cutaneous hypersensitivity reaction to a battery of recall antigens did not reveal any changes, neither within nor between the treatment groups. A challenge reaction to DNCB could be evoked after treatment in 50% of the patients in both treatment groups. No significant changes of immunoglobulin levels have been observed after termination of therapy in each treatment group. When lymphocyte reactivity to PHA (maximum response during therapy) was compared within the groups, it was found, that 66% of the patients who received an irradiation combined with vitamin A palmitate, showed an increase in their blastogenic response, while in irradiated patients without vitamin A palmitate a response was only in 33%. This difference being statistically significant in comparison to pretreatment values. From immunological data it can be concluded that vitamin A has an effect on functional response of T-cells. Concerning the clinical outcome, after an observation period of 12 months relapse rates were lower in the vitamin A group, but not significantly reduced. Therefore further follow up is warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1015,I1015)","v":396681},{"$f":"(LEN($J1015) - LEN(SUBSTITUTE(LOWER($J1015),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1015) - LEN(SUBSTITUTE(LOWER($J1015),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1015) - LEN(SUBSTITUTE(LOWER($J1015),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1015:D1015)","v":0},1979,"Vitamin metabolism and therapy in ophthalmology.","Hoyt",396681,"Vitamin metabolism and therapy in ophthalmology.    Abstract:   Vitamin deficiency states are important in the genesis of many ocular disorders. Deficiencies may be due to poor dietary intake, or to alterations in metabolism produced by some commonly prescribed medications or by certain diseases. Furthermore, some vitamins may exert important pharmacologic effects on the normal eye. The ocular effects of deficiencies and excesses of specific vitamins, and the therapeutic uses of each vitamin, are reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1016,I1016)","v":492633},{"$f":"(LEN($J1016) - LEN(SUBSTITUTE(LOWER($J1016),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1016) - LEN(SUBSTITUTE(LOWER($J1016),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1016) - LEN(SUBSTITUTE(LOWER($J1016),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1016:D1016)","v":0},1979,"Paraneoplastic hypercalcemia in ovarian tumors.","Holtz",492633,"Paraneoplastic hypercalcemia in ovarian tumors.    Abstract:   Two cases of paraneoplastic hypercalcemia secondary to ovarian tumors are presented. Both cases were secondary to ectopic parathormone (PTH) production. Other mediators postulated to cause this syndrome are prostaglandins, vitamin D-like sterols, non-vitamin D sterols, vitamin A, cortisol, and quot;osteoclast-activating factor. The key treatment modalities for acute hypercalcemia are hydration and diuresis with furosemide; phosphates, steroids, antiprostaglandins, and hemodialysis may also be of value. Calcitonin is theoretically the most attractive treatment modality, but the rapid development of resistance limits its use to acute management. Mithramycin is most effective for long-term palliation of hypercalcemia if tumor-directed therapy is unsuccessful. Review of the literature confirms the previously made observation that mesonephromas are disproportionaately represented in association with this syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1017,I1017)","v":333318},{"$f":"(LEN($J1017) - LEN(SUBSTITUTE(LOWER($J1017),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1017) - LEN(SUBSTITUTE(LOWER($J1017),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1017) - LEN(SUBSTITUTE(LOWER($J1017),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1017:D1017)","v":0},1977,"The effect of oral contraceptive agents on plasma vitamin A in the human and the rat.","Jelliffe",333318,"The effect of oral contraceptive agents on plasma vitamin A in the human and the rat.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1018,I1018)","v":192435},{"$f":"(LEN($J1018) - LEN(SUBSTITUTE(LOWER($J1018),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1018) - LEN(SUBSTITUTE(LOWER($J1018),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1018) - LEN(SUBSTITUTE(LOWER($J1018),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1018:D1018)","v":0},1977,"Diet and cancer.","Lowenfels",192435,"Diet and cancer.    Abstract:   Differences in food intake patterns are positively correlated with differences in the incidence of various cancers in world populations. It is postulated here that dietary factors play a vital role in the genesis of several major neoplasms, specifically gastric and colon carcinomas. In addition to the food consumed, such variables as total caloric intake, nutrtional excess or deficit, exposure to carcinogens and consumption of alcohol also increase the risk of cancer. Through recognition of these factors and subsequent long-term manipulation of diet, it should be possible to reduce cancer morbidity and mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1019,I1019)","v":326160},{"$f":"(LEN($J1019) - LEN(SUBSTITUTE(LOWER($J1019),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1019) - LEN(SUBSTITUTE(LOWER($J1019),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1019) - LEN(SUBSTITUTE(LOWER($J1019),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1019:D1019)","v":0},1977,"Vitamin toxicity.","DiPalma",326160,"Vitamin toxicity.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1020,I1020)","v":322746},{"$f":"(LEN($J1020) - LEN(SUBSTITUTE(LOWER($J1020),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1020) - LEN(SUBSTITUTE(LOWER($J1020),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1020) - LEN(SUBSTITUTE(LOWER($J1020),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1020:D1020)","v":0},1977,"Considerations on the problem of critical period during the development of limb skeleton.","Merker",322746,"Considerations on the problem of critical period during the development of limb skeleton.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1021,I1021)","v":793396},{"$f":"(LEN($J1021) - LEN(SUBSTITUTE(LOWER($J1021),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1021) - LEN(SUBSTITUTE(LOWER($J1021),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1021) - LEN(SUBSTITUTE(LOWER($J1021),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1021:D1021)","v":0},1976,"Evaluation of emotional reactions to oral contraceptive use.","Kane",793396,"Evaluation of emotional reactions to oral contraceptive use.    Abstract:   A review of available clinical studies indicates that 10 to 40 per cent of oral contraceptive users may suffer mild to moderate depression syndromes. Clinical and animal data indicate that a variety of mechanisms may be involved, including alterations in folate, pyridoxine, and vitamine B12 metabolism, as well as related effects on biogenic amine metabolism. Interactive effects may result, such as impairment of usual coping mechnisms and psychological defenses by altered central nervous system function. Literature on the association of oral contraceptives (OCs) with psychological disturbances is reviewed. The data from available clinical studies indicate that perhaps 10-40% of OC users may experience mild to moderate depression syndromes characterized by tiredness, lethargy, sadness and, in some cases, loss of libido. These psychological alterations may involve numerous mechanisms including changes in folate, pyridoxine, and Vitamin-B12 metabolism, and related effects on biogenic amine metabolism. The interaction of these impaired mechanisms may disturb usual coping functions and psychological defenses by altered central nervous system activity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1022,I1022)","v":962297},{"$f":"(LEN($J1022) - LEN(SUBSTITUTE(LOWER($J1022),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1022) - LEN(SUBSTITUTE(LOWER($J1022),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1022) - LEN(SUBSTITUTE(LOWER($J1022),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1022:D1022)","v":0},1976,"The effects of drugs on embryonic development.","Netzloff",962297,"The effects of drugs on embryonic development.    Abstract:   A review of the literature demonstrated the difficulties in evaluating the teratogenic effect of drugs in man. Since epidemiologic studies provide suggestive rather than definitive data and results of the current drug testing in laboratory animals may not be applicable to man, the need to develop alternative methods of predicting teratogenicity was apparent. To develop such techniques by studying a possible mechanism of teratogenesis, experiments were performed using a teratogenic folic acid-deficiency and antagonism with 9-methyl pteroylglutamic acid in the pregnant rat. Embryos developing abnormally in response ot this regimen consumed oxygen at a significantly decreased rate. Similar significant reductions in oxygen consumption were found both in rat embryos malforming in response to maternal vitamin A acetate administration, and in mouse embryos in response to teratogenic doses of diphenylhydantoin. It was suggested that such measurements of oxidative metabolism or related techniques may have application in predicting drug teratogenicity and could aid present epidemiologic and empiric approaches to identification of human teratogens."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1023,I1023)","v":781682},{"$f":"(LEN($J1023) - LEN(SUBSTITUTE(LOWER($J1023),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1023) - LEN(SUBSTITUTE(LOWER($J1023),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1023) - LEN(SUBSTITUTE(LOWER($J1023),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1023:D1023)","v":0},1976,"Vitamins in Western diets.","Morton",781682,"Vitamins in Western diets.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1024,I1024)","v":770204},{"$f":"(LEN($J1024) - LEN(SUBSTITUTE(LOWER($J1024),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1024) - LEN(SUBSTITUTE(LOWER($J1024),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1024) - LEN(SUBSTITUTE(LOWER($J1024),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1024:D1024)","v":0},1976,"Nutrition and cancer.","Wynder",770204,"Nutrition and cancer.    Abstract:   There is increasing epidemiological evidence that nutrition plays a dominant role in the pathogenesis of several types of human cancers. There is considerable epidemiological evidence showing that alcoholism in part because of associated nutritional deficiencies, significantly increases the risk of smokers for cancer of the alimentary tract. There is also some suggestion that nutritional deficiencies may relate to cancers of the stomach, cervix, and thyroid. Of particular importance, and based on relatively new concepts, are data indicating that overnutrition significantly affects the development of certain cancers, including cancers of the colon and pancreas, kidney, breast, ovary endometrium, and prostate. Except for cancer of the endometrium, and kidney cancer in women, there is no significant relationship to obesity. Rather, the evidence suggests both epidemiologically and experimentally that the etiological factors relate to a high intake of fats and possibly other variables associated with high fat intake. While we are investigating the mechanistic nature of the epidemiological and experimental observations, the question that needs to be asked is whether it is not prudent for us to associate ourselves with the recommendation of our colleagues in the cardiovascular disease field who call on both individuals and the food industry to practice a quot;Prudent Diet,quot; i.e., one that is lower in total calories, total fat, saturated fats and cholesterol than is the present American diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1025,I1025)","v":768831},{"$f":"(LEN($J1025) - LEN(SUBSTITUTE(LOWER($J1025),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1025) - LEN(SUBSTITUTE(LOWER($J1025),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1025) - LEN(SUBSTITUTE(LOWER($J1025),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1025:D1025)","v":0},1976,"Zinc deficiency in pregnant, fetal and young rats.","Wynder",768831,"Zinc deficiency in pregnant, fetal and young rats.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1026,I1026)","v":1265106},{"$f":"(LEN($J1026) - LEN(SUBSTITUTE(LOWER($J1026),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1026) - LEN(SUBSTITUTE(LOWER($J1026),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1026) - LEN(SUBSTITUTE(LOWER($J1026),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1026:D1026)","v":0},1976,"Behavioral teratogenesis: a critical evaluation.","Coyle",1265106,"Behavioral teratogenesis: a critical evaluation.    Abstract:   A critical review of some relevant literature concerning the effects of prenatal administration of drugs and several other substances on postnatal behavior. Significant variables and problems in the adequate design of experiments to assess these effects are discussed. Although the evidence concerning prenatal drug effects on behavior is equivocal, sufficient data exist to indicate that this will continue to be a viable and important area of research in the future. Present results demonstrate the complexity of drug interactions with other variables."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1027,I1027)","v":824857},{"$f":"(LEN($J1027) - LEN(SUBSTITUTE(LOWER($J1027),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1027) - LEN(SUBSTITUTE(LOWER($J1027),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1027) - LEN(SUBSTITUTE(LOWER($J1027),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1027:D1027)","v":0},1976,"Xerophthalmia.","Oomen",824857,"Xerophthalmia.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1028,I1028)","v":824850},{"$f":"(LEN($J1028) - LEN(SUBSTITUTE(LOWER($J1028),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1028) - LEN(SUBSTITUTE(LOWER($J1028),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1028) - LEN(SUBSTITUTE(LOWER($J1028),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1028:D1028)","v":0},1976,"Physiological and practical considerations of nutrient function and requirements.","Beaton",824850,"Physiological and practical considerations of nutrient function and requirements.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1029,I1029)","v":822591},{"$f":"(LEN($J1029) - LEN(SUBSTITUTE(LOWER($J1029),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1029) - LEN(SUBSTITUTE(LOWER($J1029),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1029) - LEN(SUBSTITUTE(LOWER($J1029),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1029:D1029)","v":0},1976,"Vitamin A deficiency and xerophthalmia. Report of a Joint WHO/USAID Meeting.","Beaton",822591,"Vitamin A deficiency and xerophthalmia. Report of a Joint WHO/USAID Meeting.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1030,I1030)","v":798418},{"$f":"(LEN($J1030) - LEN(SUBSTITUTE(LOWER($J1030),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1030) - LEN(SUBSTITUTE(LOWER($J1030),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1030) - LEN(SUBSTITUTE(LOWER($J1030),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1030:D1030)","v":0},1976,"Recommended nutrient allowances.","Masek",798418,"Recommended nutrient allowances.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1031,I1031)","v":798150},{"$f":"(LEN($J1031) - LEN(SUBSTITUTE(LOWER($J1031),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1031) - LEN(SUBSTITUTE(LOWER($J1031),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1031) - LEN(SUBSTITUTE(LOWER($J1031),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1031:D1031)","v":0},1976,"Significance of vitamins in cancer.","Basu",798150,"Significance of vitamins in cancer.    Abstract:   The relationship of vitamins to cancer is very complex. Three types of interactions are possible: the effect of vitamins on tumor growth, the effect of tumors on vitamin metabolism, and the effect of vitamins on chemical carcinogens and anti-tumor chemotherapeutic agents. The significance of vitamins with particular references to vitamins A,B-complex and C, in cancer has been reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1032,I1032)","v":790782},{"$f":"(LEN($J1032) - LEN(SUBSTITUTE(LOWER($J1032),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1032) - LEN(SUBSTITUTE(LOWER($J1032),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1032) - LEN(SUBSTITUTE(LOWER($J1032),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1032:D1032)","v":0},1976,"Vitamin A deficiency in Indian children.","Pereira",790782,"Vitamin A deficiency in Indian children.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1033,I1033)","v":770369},{"$f":"(LEN($J1033) - LEN(SUBSTITUTE(LOWER($J1033),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1033) - LEN(SUBSTITUTE(LOWER($J1033),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1033) - LEN(SUBSTITUTE(LOWER($J1033),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1033:D1033)","v":0},1976,"Cytological basis for permanent vaginal changes in mice treated neonatally with steroid hormones.","Takasugi",770369,"Cytological basis for permanent vaginal changes in mice treated neonatally with steroid hormones.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1034,I1034)","v":769494},{"$f":"(LEN($J1034) - LEN(SUBSTITUTE(LOWER($J1034),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1034) - LEN(SUBSTITUTE(LOWER($J1034),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1034) - LEN(SUBSTITUTE(LOWER($J1034),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1034:D1034)","v":0},1976,"Effects of oral contraceptives on vitamin metabolism.","Anderson",769494,"Effects of oral contraceptives on vitamin metabolism.    Abstract:   Literature on the effects of oral contraceptives (OCs) on vitamin metabolism is reviewed. OCs have been reported to markedly increase serum levels of Vitamin-A. OCs may induce a thiamine deficiency and lower levels of Vitamin-B2. Concentrations of ascorbic acid in platelets, white cells, plasma, and urine are decreased by OCs. Decreased plasma and red blood cell concentrations of folic acid have been reported in OC users, though it does not appear that absorption of folate polyglutamate is affected. OC users may develop megaloblastic anemia because of folic acid deficiency. OCs have been reported to markedly reduce serum levels of Vitamin-B12. Some OC users who excrete abnormal amounts of tryptophan metabolites have some degree of true Vitamin-B6 deficiency. Evidence of altered tryptophan metabolism and/or absolute Vitamin-B6 deficiency has been found in emotionally depressed women taking OCs. OCs, especially estrogens, produce tryptophan metabolism abnormalities in the great majority of users. An effect of OCs on alpha-tocopherol plasma concentrations has yet to be demonstrated in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1035,I1035)","v":768933},{"$f":"(LEN($J1035) - LEN(SUBSTITUTE(LOWER($J1035),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1035) - LEN(SUBSTITUTE(LOWER($J1035),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1035) - LEN(SUBSTITUTE(LOWER($J1035),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1035:D1035)","v":0},1976,"[Side effects of oral contraceptives].","Kuczyńska-Sicińska",768933,"[Side effects of oral contraceptives].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1036,I1036)","v":1102224},{"$f":"(LEN($J1036) - LEN(SUBSTITUTE(LOWER($J1036),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1036) - LEN(SUBSTITUTE(LOWER($J1036),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1036) - LEN(SUBSTITUTE(LOWER($J1036),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1036:D1036)","v":0},1975,"Vitamin passage across the placenta.","Malone",1102224,"Vitamin passage across the placenta.    Abstract:   A pregnant woman who has adequate nutrition available in the form of a standard diet will provide the vitamins required by the fetus for normal development. Active transport of the water-soluble vitamins plus easy oral absorption after birth insure nutritional sufficiency at any gestational age. The fat-soluble vitamins which have a much slower transfer rate as the result of facilitated diffusion do not achieve the same degree of storage in the developing fetus. Thus, the premature infant who has decreased stores and who may have impaired oral absorption initially may become deficient in a fat-soluble vitamin (A, D, E, K) during the first 4 to 6 weeks of life. Oral or possibly parenteral supplementation following birth, however, would seem more appropriate than subtoxic doses administered to the mother prenatally."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1037,I1037)","v":1095013},{"$f":"(LEN($J1037) - LEN(SUBSTITUTE(LOWER($J1037),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1037) - LEN(SUBSTITUTE(LOWER($J1037),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1037) - LEN(SUBSTITUTE(LOWER($J1037),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1037:D1037)","v":0},1975,"Vitamin absorption (excluding vitamin A).","Morava",1095013,"Vitamin absorption (excluding vitamin A).    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1038,I1038)","v":1091947},{"$f":"(LEN($J1038) - LEN(SUBSTITUTE(LOWER($J1038),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1038) - LEN(SUBSTITUTE(LOWER($J1038),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1038) - LEN(SUBSTITUTE(LOWER($J1038),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1038:D1038)","v":0},1975,"Lipid metabolism and membrane functions of the mammary gland.","Patton",1091947,"Lipid metabolism and membrane functions of the mammary gland.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1039,I1039)","v":805504},{"$f":"(LEN($J1039) - LEN(SUBSTITUTE(LOWER($J1039),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1039) - LEN(SUBSTITUTE(LOWER($J1039),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1039) - LEN(SUBSTITUTE(LOWER($J1039),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1039:D1039)","v":0},1975,"Human vitamin A deficiency.","Srikantia",805504,"Human vitamin A deficiency.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1040,I1040)","v":788039},{"$f":"(LEN($J1040) - LEN(SUBSTITUTE(LOWER($J1040),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1040) - LEN(SUBSTITUTE(LOWER($J1040),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1040) - LEN(SUBSTITUTE(LOWER($J1040),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1040:D1040)","v":0},1975,"Vitamin A.","McLaren",788039,"Vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1041,I1041)","v":4596894},{"$f":"(LEN($J1041) - LEN(SUBSTITUTE(LOWER($J1041),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1041) - LEN(SUBSTITUTE(LOWER($J1041),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1041) - LEN(SUBSTITUTE(LOWER($J1041),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1041:D1041)","v":0},1974,"The fetal and neonatal pig in biomedical research.","Book",4596894,"The fetal and neonatal pig in biomedical research.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1042,I1042)","v":4596797},{"$f":"(LEN($J1042) - LEN(SUBSTITUTE(LOWER($J1042),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1042) - LEN(SUBSTITUTE(LOWER($J1042),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1042) - LEN(SUBSTITUTE(LOWER($J1042),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1042:D1042)","v":0},1974,"[Oral contraceptives and vitamins].","Larsson-Cohn",4596797,"[Oral contraceptives and vitamins].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1043,I1043)","v":4617396},{"$f":"(LEN($J1043) - LEN(SUBSTITUTE(LOWER($J1043),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1043) - LEN(SUBSTITUTE(LOWER($J1043),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1043) - LEN(SUBSTITUTE(LOWER($J1043),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1043:D1043)","v":0},1974,"The fat-soluble vitamins in modern medicine.","Marks",4617396,"The fat-soluble vitamins in modern medicine.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1044,I1044)","v":4616468},{"$f":"(LEN($J1044) - LEN(SUBSTITUTE(LOWER($J1044),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1044) - LEN(SUBSTITUTE(LOWER($J1044),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1044) - LEN(SUBSTITUTE(LOWER($J1044),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1044:D1044)","v":0},1974,"The determination of vitamin A and some aspects of its distribution, mobilization and transport in health and disease.","Underwood",4616468,"The determination of vitamin A and some aspects of its distribution, mobilization and transport in health and disease.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1045,I1045)","v":4597668},{"$f":"(LEN($J1045) - LEN(SUBSTITUTE(LOWER($J1045),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1045) - LEN(SUBSTITUTE(LOWER($J1045),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1045) - LEN(SUBSTITUTE(LOWER($J1045),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1045:D1045)","v":0},1973,"[Supply of vitamins and iron to premature babies].","Lindberg",4597668,"[Supply of vitamins and iron to premature babies].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1046,I1046)","v":4587052},{"$f":"(LEN($J1046) - LEN(SUBSTITUTE(LOWER($J1046),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1046) - LEN(SUBSTITUTE(LOWER($J1046),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1046) - LEN(SUBSTITUTE(LOWER($J1046),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1046:D1046)","v":0},1973,"The influence of nutrition response to infectious disease.","Newberne",4587052,"The influence of nutrition response to infectious disease.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1047,I1047)","v":4569986},{"$f":"(LEN($J1047) - LEN(SUBSTITUTE(LOWER($J1047),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1047) - LEN(SUBSTITUTE(LOWER($J1047),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1047) - LEN(SUBSTITUTE(LOWER($J1047),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1047:D1047)","v":0},1973,"Progress in swine nutrition for the veterinarian.","Bowland",4569986,"Progress in swine nutrition for the veterinarian.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1048,I1048)","v":4566403},{"$f":"(LEN($J1048) - LEN(SUBSTITUTE(LOWER($J1048),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1048) - LEN(SUBSTITUTE(LOWER($J1048),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1048) - LEN(SUBSTITUTE(LOWER($J1048),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1048:D1048)","v":0},1973,"Recommended intakes of vitamins for normal growth and development.","Kodicek",4566403,"Recommended intakes of vitamins for normal growth and development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1049,I1049)","v":4566400},{"$f":"(LEN($J1049) - LEN(SUBSTITUTE(LOWER($J1049),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1049) - LEN(SUBSTITUTE(LOWER($J1049),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1049) - LEN(SUBSTITUTE(LOWER($J1049),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1049:D1049)","v":0},1973,"Enrichment and fortification of foods for infants and children.","Kübler",4566400,"Enrichment and fortification of foods for infants and children.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1050,I1050)","v":4644266},{"$f":"(LEN($J1050) - LEN(SUBSTITUTE(LOWER($J1050),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1050) - LEN(SUBSTITUTE(LOWER($J1050),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1050) - LEN(SUBSTITUTE(LOWER($J1050),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1050:D1050)","v":0},1972,"A review of teenage nutrition in the United States.","Huenemann",4644266,"A review of teenage nutrition in the United States.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1051,I1051)","v":4556123},{"$f":"(LEN($J1051) - LEN(SUBSTITUTE(LOWER($J1051),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1051) - LEN(SUBSTITUTE(LOWER($J1051),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1051) - LEN(SUBSTITUTE(LOWER($J1051),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1051:D1051)","v":0},1972,"A conspectus of research on vitamin A requirements of man.","Rodriguez",4556123,"A conspectus of research on vitamin A requirements of man.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1052,I1052)","v":4616082},{"$f":"(LEN($J1052) - LEN(SUBSTITUTE(LOWER($J1052),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1052) - LEN(SUBSTITUTE(LOWER($J1052),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1052) - LEN(SUBSTITUTE(LOWER($J1052),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1052:D1052)","v":0},1972,"Nutrition and reproduction in sheep.","Cloete",4616082,"Nutrition and reproduction in sheep.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1053,I1053)","v":4551863},{"$f":"(LEN($J1053) - LEN(SUBSTITUTE(LOWER($J1053),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1053) - LEN(SUBSTITUTE(LOWER($J1053),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1053) - LEN(SUBSTITUTE(LOWER($J1053),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1053:D1053)","v":0},1972,"Management and treatment of ichthyosis.","Goldsmith",4551863,"Management and treatment of ichthyosis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1054,I1054)","v":4343258},{"$f":"(LEN($J1054) - LEN(SUBSTITUTE(LOWER($J1054),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1054) - LEN(SUBSTITUTE(LOWER($J1054),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1054) - LEN(SUBSTITUTE(LOWER($J1054),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1054:D1054)","v":0},1972,"Vitamin A and spermatogenesis in the rat.","Goldsmith",4343258,"Vitamin A and spermatogenesis in the rat.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1055,I1055)","v":4555501},{"$f":"(LEN($J1055) - LEN(SUBSTITUTE(LOWER($J1055),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1055) - LEN(SUBSTITUTE(LOWER($J1055),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1055) - LEN(SUBSTITUTE(LOWER($J1055),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1055:D1055)","v":0},1972,"Effect of oral contraceptive agents on vitamin and mineral needs: a review.","Theuer",4555501,"Effect of oral contraceptive agents on vitamin and mineral needs: a review.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1056,I1056)","v":4339020},{"$f":"(LEN($J1056) - LEN(SUBSTITUTE(LOWER($J1056),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1056) - LEN(SUBSTITUTE(LOWER($J1056),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1056) - LEN(SUBSTITUTE(LOWER($J1056),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1056:D1056)","v":0},1972,"Effect of hormones on bone development.","Raisz",4339020,"Effect of hormones on bone development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1057,I1057)","v":4114167},{"$f":"(LEN($J1057) - LEN(SUBSTITUTE(LOWER($J1057),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1057) - LEN(SUBSTITUTE(LOWER($J1057),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1057) - LEN(SUBSTITUTE(LOWER($J1057),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1057:D1057)","v":0},1972,"[Experimental congenital heart diseases].","Onishi",4114167,"[Experimental congenital heart diseases].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1058,I1058)","v":4942864},{"$f":"(LEN($J1058) - LEN(SUBSTITUTE(LOWER($J1058),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1058) - LEN(SUBSTITUTE(LOWER($J1058),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1058) - LEN(SUBSTITUTE(LOWER($J1058),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1058:D1058)","v":0},1971,"Nutritive influences upon reproduction.","Moustgaard",4942864,"Nutritive influences upon reproduction.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1059,I1059)","v":4916225},{"$f":"(LEN($J1059) - LEN(SUBSTITUTE(LOWER($J1059),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1059) - LEN(SUBSTITUTE(LOWER($J1059),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1059) - LEN(SUBSTITUTE(LOWER($J1059),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1059:D1059)","v":0},1970,"Nutritional diseases of exotic animals.","Wallach",4916225,"Nutritional diseases of exotic animals.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1060,I1060)","v":4912684},{"$f":"(LEN($J1060) - LEN(SUBSTITUTE(LOWER($J1060),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1060) - LEN(SUBSTITUTE(LOWER($J1060),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1060) - LEN(SUBSTITUTE(LOWER($J1060),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1060:D1060)","v":0},1970,"A review of developments in nutrition as it is related to fertility in cattle: 1964-9.","McClure",4912684,"A review of developments in nutrition as it is related to fertility in cattle: 1964-9.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1061,I1061)","v":4930376},{"$f":"(LEN($J1061) - LEN(SUBSTITUTE(LOWER($J1061),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1061) - LEN(SUBSTITUTE(LOWER($J1061),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1061) - LEN(SUBSTITUTE(LOWER($J1061),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1061:D1061)","v":0},1970,"[Dehydrogenation and enzymatic isomerization of delta 5-3 beta-hydroxysteroids].","Grangaud",4930376,"[Dehydrogenation and enzymatic isomerization of delta 5-3 beta-hydroxysteroids].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1062,I1062)","v":4922143},{"$f":"(LEN($J1062) - LEN(SUBSTITUTE(LOWER($J1062),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1062) - LEN(SUBSTITUTE(LOWER($J1062),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1062) - LEN(SUBSTITUTE(LOWER($J1062),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1062:D1062)","v":0},1970,"Hypervitaminosis A of the cat.","Seawright",4922143,"Hypervitaminosis A of the cat.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1063,I1063)","v":4915969},{"$f":"(LEN($J1063) - LEN(SUBSTITUTE(LOWER($J1063),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1063) - LEN(SUBSTITUTE(LOWER($J1063),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1063) - LEN(SUBSTITUTE(LOWER($J1063),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1063:D1063)","v":0},1970,"Vitamin A AND VITAMIN A acid in the prophylaxis and therapy of epithelial tumours.","Bollag",4915969,"Vitamin A AND VITAMIN A acid in the prophylaxis and therapy of epithelial tumours.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1064,I1064)","v":4906655},{"$f":"(LEN($J1064) - LEN(SUBSTITUTE(LOWER($J1064),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1064) - LEN(SUBSTITUTE(LOWER($J1064),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1064) - LEN(SUBSTITUTE(LOWER($J1064),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1064:D1064)","v":0},1970,"A report on the first fifty years of the Nutrition Research Laboratories, Hyderabad.","Gopalan",4906655,"A report on the first fifty years of the Nutrition Research Laboratories, Hyderabad.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1065,I1065)","v":4316909},{"$f":"(LEN($J1065) - LEN(SUBSTITUTE(LOWER($J1065),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1065) - LEN(SUBSTITUTE(LOWER($J1065),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1065) - LEN(SUBSTITUTE(LOWER($J1065),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1065:D1065)","v":0},1970,"Degradation processes in bone and cartilage.","Reynolds",4316909,"Degradation processes in bone and cartilage.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1066,I1066)","v":4259238},{"$f":"(LEN($J1066) - LEN(SUBSTITUTE(LOWER($J1066),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1066) - LEN(SUBSTITUTE(LOWER($J1066),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1066) - LEN(SUBSTITUTE(LOWER($J1066),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1066:D1066)","v":0},1970,"[Vitamin A, steroid hormones and nutrition].","Grangaud",4259238,"[Vitamin A, steroid hormones and nutrition].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1067,I1067)","v":4916873},{"$f":"(LEN($J1067) - LEN(SUBSTITUTE(LOWER($J1067),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1067) - LEN(SUBSTITUTE(LOWER($J1067),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1067) - LEN(SUBSTITUTE(LOWER($J1067),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1067:D1067)","v":0},1969,"A review of the causes of reproductive failure in swine.","Rasbech",4916873,"A review of the causes of reproductive failure in swine.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1068,I1068)","v":4888341},{"$f":"(LEN($J1068) - LEN(SUBSTITUTE(LOWER($J1068),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1068) - LEN(SUBSTITUTE(LOWER($J1068),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1068) - LEN(SUBSTITUTE(LOWER($J1068),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1068:D1068)","v":0},1969,"[Nutrition of the pregnant and nursing mother].","Glatzel",4888341,"[Nutrition of the pregnant and nursing mother].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1069,I1069)","v":4318822},{"$f":"(LEN($J1069) - LEN(SUBSTITUTE(LOWER($J1069),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1069) - LEN(SUBSTITUTE(LOWER($J1069),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1069) - LEN(SUBSTITUTE(LOWER($J1069),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1069:D1069)","v":0},1968,"[Kidney and vitamin E].","Arvy",4318822,"[Kidney and vitamin E].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1070,I1070)","v":4256644},{"$f":"(LEN($J1070) - LEN(SUBSTITUTE(LOWER($J1070),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1070) - LEN(SUBSTITUTE(LOWER($J1070),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1070) - LEN(SUBSTITUTE(LOWER($J1070),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1070:D1070)","v":0},1968,"Management of benign intracranial hypertension (pseudotumor cerebri).","Greer",4256644,"Management of benign intracranial hypertension (pseudotumor cerebri).    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1071,I1071)","v":4899546},{"$f":"(LEN($J1071) - LEN(SUBSTITUTE(LOWER($J1071),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1071) - LEN(SUBSTITUTE(LOWER($J1071),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1071) - LEN(SUBSTITUTE(LOWER($J1071),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1071:D1071)","v":0},1967,"[Some current problems of experimental teratology].","Dyban",4899546,"[Some current problems of experimental teratology].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1072,I1072)","v":4229758},{"$f":"(LEN($J1072) - LEN(SUBSTITUTE(LOWER($J1072),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1072) - LEN(SUBSTITUTE(LOWER($J1072),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1072) - LEN(SUBSTITUTE(LOWER($J1072),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1072:D1072)","v":0},1966,"Recent advances in the physiology of vitamin A.","Pitt",4229758,"Recent advances in the physiology of vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1073,I1073)","v":14238547},{"$f":"(LEN($J1073) - LEN(SUBSTITUTE(LOWER($J1073),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1073) - LEN(SUBSTITUTE(LOWER($J1073),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1073) - LEN(SUBSTITUTE(LOWER($J1073),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1073:D1073)","v":0},1964,"[THE VITAMIN CONTROL OF CALCIUM METABOLISM].","RAOUL",14238547,"[THE VITAMIN CONTROL OF CALCIUM METABOLISM].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1074,I1074)","v":14117753},{"$f":"(LEN($J1074) - LEN(SUBSTITUTE(LOWER($J1074),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1074) - LEN(SUBSTITUTE(LOWER($J1074),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1074) - LEN(SUBSTITUTE(LOWER($J1074),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1074:D1074)","v":0},1964,"NUTRITIONAL DISEASE AND THE EYE.","MCLAREN",14117753,"NUTRITIONAL DISEASE AND THE EYE.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I1075,I1075)","v":13410607},{"$f":"(LEN($J1075) - LEN(SUBSTITUTE(LOWER($J1075),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J1075) - LEN(SUBSTITUTE(LOWER($J1075),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J1075) - LEN(SUBSTITUTE(LOWER($J1075),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B1075:D1075)","v":0},1957,"[Review of acute hydrocephalus caused by administration of vitamin A in massive doses in nursing infants; based on 100 cases].","MONTERO RODRIGUEZ",13410607,"[Review of acute hydrocephalus caused by administration of vitamin A in massive doses in nursing infants; based on 100 cases].    Abstract:  "]

{"sheet":"Abstract","index":1,"n_rows":5,"n_cols":4,"rows_kept":5,"cut":false,"hidden":false,"merged":[[0,0,0,1]]}
["Abstract with highlights"]
["Article:",{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & C2,C2)","v":8801178},8801178,"Pub Yr: 1996"]
[]
["Title:","Embryonic development and pattern formation.",null,"Fauthor: Morriss-Kay"]
["Title and Abstract:","Embryonic development and pattern formation.    Abstract:   During embryogenesis, information encoded in the genome is translated into cell proliferation, morphogenesis, and early stages of differentiation. Embryonic pattern arises from the spatial and temporal regulation and coordination of these events. The vitamin A (retinol) derivative retinoic acid (RA) is essential for normal development. Mammalian embryos are protected against vitamin A deficiency by maternal retinoid homeostasis until stored retinoids fall to very low levels. Retinol binding protein, which is synthesized in the yolk sac placenta of rodent embryos and in the syncytiotrophoblast of the human placenta, is essential for access of retinol to the embryo. Synthesis and metabolism of RA may involve cytoplasmic binding proteins, but the observation that mutants lacking these proteins are normal or near-normal suggests that they are not essential. Severe congenital vitamin A deficiency results in a spectrum of malformations including defects of the eye, lungs, cardiovascular system, and urogenital system. Extreme deficiency results as well in forelimb abnormalities and cleft face, but the embryos are not viable. Similar abnormalities are observed in embryos lacking two retinoid receptors, but loss of one receptor results in either normal development or mild abnormalities. Two single-receptor null mutants, RARgamma-/- and RXRalpha-/-, show regional pattern-specific resistance to teratogenic levels of RA. Mutations leading to abnormality of the structure or regulation of RA signaling pathway genes may be an important cause of human congenital abnormality."]

{"sheet":"Notes","index":2,"n_rows":3,"n_cols":8,"rows_kept":3,"cut":false,"hidden":false,"merged":[]}
[null,"My Notes"]
["Chemical","PMID ","DOI","Note ","Title","LinkDOI","LinkID","Link"]
[null,{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & G3,G3)","v":15203181},null,"GABA and cp; picrotoxin and 3-mercaptopropionic acid","Cleft palate by picrotoxin or 3-MP and palatal shelf elevation in GABA-deficient mice.",null,15203181]