Thyroid Autoimmunity and Subclinical Hypothyroidism in Prolactinoma: A Case Control Study.

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls.

Effect Modification of LHCGR Gene Variant (rs2293275) on Clinico-Biochemical Profile, and Levels of Luteinizing Hormone in Polycystic Ovary Syndrome Patients.

 Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Calcitonin gene-related peptide (CGRP) concentrations outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine / Concentrações de peptídeo relacionado ao gene da calcitonina (CGRP) fora dos ataques de enxaqueca no sangue periférico como um potencial biomarcador para enxaqueca crônica

Introduction: Chronic migraine is a debilitating condition that affects a significant portion of the population. Accurate diagnosis and treatment of chronic migraine remain a challenge due to the lack of objective biomarkers. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in the pathophysiology of migraine and has been proposed as a potential biomarker for migraine. Methods: We measured CGRP levels in peripheral blood samples collected from 142 participants with chronic or episodic migraine and 24 healthy controls during ictal periods, i.e., outside migraine attacks. We compared CGRP levels between the three groups and assessed the correlation between CGRP levels and clinical features of chronic migraine. Conclusion: Our study provides evidence that CGRP levels in peripheral blood during ictal periods may serve as a potential biomarker for chronic migraine. Further studies are needed to validate these findings and to explore the clinical utility of CGRP as a biomarker for chronic migraine.

Introdução: A enxaqueca crônica é uma condição debilitante que afeta uma parcela significativa da população. O diagnóstico preciso e o tratamento da enxaqueca crónica continuam a ser um desafio devido à falta de biomarcadores objetivos. O peptídeo relacionado ao gene da calcitonina (CGRP) é um neuropeptídeo envolvido na fisiopatologia da enxaqueca e foi proposto como um potencial biomarcador para enxaqueca. Métodos: Medimos os níveis de CGRP em amostras de sangue periférico coletadas de 142 participantes com enxaqueca crônica ou episódica e 24 controles saudáveis ​​durante períodos ictais, ou seja, fora das crises de enxaqueca. Comparamos os níveis de CGRP entre os três grupos e avaliamos a correlação entre os níveis de CGRP e as características clínicas da enxaqueca crônica. Conclusão: Nosso estudo fornece evidências de que os níveis de CGRP no sangue periférico durante os períodos ictais podem servir como um potencial biomarcador para enxaqueca crônica. Mais estudos são necessários para validar estes resultados e explorar a utilidade clínica do CGRP como biomarcador para enxaqueca crónica.

TGF-ß signaling: A recap of SMAD-independent and SMAD-dependent pathways.

Transforming growth factor-ß (TGF-ß) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF-ß-mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF-ß serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF-ß signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF-ß-mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF-ß-mediated SMAD-dependent andSMAD-independent pathways. This manuscript emphasizes the functions of TGF-ß as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively.

A case-control study of tumor necrosis factor-alpha promoter polymorphism and its serum levels in patients with chronic obstructive pulmonary disease in Kashmir, North India.

AIM: Data about polymorphism in tumor necrosis factor-alpha (TNF-α) and its serum levels in chronic obstructive pulmonary disease (COPD) are conflicting. We aimed to evaluate the association of TNF-α-308 G > A polymorphism in patients with COPD in Kashmir (North India), a high burden area and also determined the serum TNF-α levels in these patients. MATERIALS AND METHODS: One hundred spirometrically confirmed COPD patients and 163 controls resident from Kashmir valley (North India) were recruited. Genotyping of the promoter region of TNF-α was carried out using polymerase chain reaction-restriction fragment length polymorphism. The serum TNF-α was quantified using the Cytometric Bead Array flex system by flow cytometry. Results were subjected to appropriate statistical treatment andP < 0.05 was considered statistically significant. RESULTS: Ninety-one COPD patients (91%) had G/G (wild homozygous) genotype and nine patients (9%) had G/A (heterozygous) genotype. Among the control population, 150 (92%) had G/G genotype and 13 (8%) had G/A genotype. The variant allele "A" was not detected in either of the two groups. Serum levels of TNF-α were significantly higher in patients compared to control group (8.0 ± 10.1 pg/ml vs. 3.3 ± 0.42 pg/ml, respectively,P = 0.0001). CONCLUSION: While serum levels of TNF-α are higher in COPD patients compared to the controls, there was no difference in the prevalence of TNF-α-308 polymorphism in the ethnic Kashmiri population with COPD.

Differential Impact of Insulin Sensitizers vs. Anti-Androgen on Serum Leptin Levels in Vitamin D Replete PCOS Women: A Six Month Open Labeled Randomized Study.

Women with PCOS are linked to insulin resistance, inflammation, and vitamin D (VD) deficiency. The study endeavors to comprehend the differential impact of insulin sensitizers vs. anti-androgen on serum leptin levels among women with PCOS rendered vitamin D replete with high VD oral supplement. This was open-labeled randomized study that screened 180 eligible women presenting to Endocrine clinic with oligomenorrhea or features of hyperandrogenism. Ninety-nine women who furnished written informed consent and fulfilled the Rotterdam 2003 criteria for diagnosis of PCOS were randomized into 3 drug treatment arms to receive either spironolactone (50 mg/d; n=30), metformin (1000 mg/d; n=30) or pioglitazone (30 mg/d; n=30). These women were also administered oral VD (4000 IU/day) in addition to the allocated drug for a period of 6 months. Detailed history, clinical examination, and laboratory evaluation was carried out at baseline and 6 months after intervention. Number of menstrual cycles/year increased while as Ferriman-Gallwey score, blood glucose, HOMA-IR, and plasma insulin levels significantly decreased in all the three arms with better outcomes in spironolactone and pioglitazone arms (p<0.05). Similarly, serum leptin levels superiorly improved in spironolactone and pioglitazone group. Pioglitazone group showed better efficacy in lowering serum total testosterone (p<0.05). Co-supplementation of high dosage VD with spironolactone or pioglitazone are more effective in reducing plasma leptin levels than metformin, and thus might prove to be better therapeutic strategies for women with PCOS.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study.

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1ß, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome: An observational pilot study.

Background & objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS. Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits. Results: Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance. Interpretation & conclusions: OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.

PHA-Induced Peripheral Blood Cytogenetics and Molecular Analysis: a Valid Diagnostic and Follow-up Modality for Acute Promyelocytic Leukemia Patients Treated with ATRA and/or Arsenic Tri-oxide.

BACKGROUND: Acute promyelocytic leukemia (APML) is characterized by the reciprocal translocation t(15;17) (q22;q12) resulting in the PML-RARα fusion gene. A dual diagnostic and follow up approach was applied including cytogenetic demonstration of the t(15;17) translocation and detection of PML-RARα chimeric transcripts by molecular means. PURPOSE: Conventional cytogenetics involving bone marrow is beset with high probability of poor metaphase index and was substituted with phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis as a diagnostic and follow up modality in APML patients of Kashmir (North India). Both qualitative (RT-PCR) and quantitative (Q-PCR) tests were simultaneously carried out to authenticate the modified cytogenetics. MATERIALS AND METHODS: Patient samples were subjected to the said techniques to establish their baseline as well as follow-up status. RESULTS: Initial cytogenetics revealed 30 patients (81%) positive for t(15;17) whereas 7 (19%) had either cryptic translocation or were negative for t(15;17). Two cases had chromosome 16q deletion and no hallmark translocation t(15;17). Q-PCR status for PML-RARα was found to be positive for all patients. All the APML patients were reassessed at the end of consolidation phase and during maintenance phase of chemotherapy where 6 patients had molecular relapse, wherein 4 also demonstrated cytogenetic relapse. CONCLUSIONS: It was found that PHA-induced peripheral blood cytogenetics along with molecular analysis could prove a reliable modality in the diagnosis and assessment of follow up response of APML patients.

Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia: Response to treatment with cabergoline.

INTRODUCTION: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters. METHODS: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) µg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment. RESULTS: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment. CONCLUSION: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women.

Earlier data on the relationship of 25 hydroxyvitamins (25OHD) levels with various components of polycystic ovary syndrome (PCOS) has been conflicting. We studied 122 normal body mass index (BMI) women with PCOS (cases) and 46 age and BMI-matched healthy women (controls) and assessed the impact of serum 25OHD levels on clinical, biochemical and insulin sensitivity parameters in these lean Indian women with PCOS. The mean age and BMI of the cases and controls were comparable. Mean serum 25OHD levels respectively were 10.1 ± 9.9 and 7.9 ± 6.8 ng/ml with 87.7% and 91.1% vitamin D (VD) deficient. No significant correlation was noted between 25OHD levels and clinical, biochemical and insulin sensitivity parameters except with the total testosterone levels (p = 0.007). Also, no significant difference in these parameters was observed once the PCOS women were stratified into various subgroups based on the serum 25OHD levels. We conclude that VD deficiency being common in normal BMI Indian women with or without PCOS does not seem to alter the metabolic phenotype in these women.

Oral glucose tolerance test significantly impacts the prevalence of abnormal glucose tolerance among Indian women with polycystic ovary syndrome: lessons from a large database of two tertiary care centers on the Indian subcontinent.

OBJECTIVE: To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation. DESIGN: Cross-sectional clinical study. SETTING: Tertiary care center. PATIENT(S): A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed. INTERVENTION(S): In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered. MAIN OUTCOME MEASURE(S): Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence. RESULT(S): The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects. CONCLUSION(S): We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS.

A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied. OBJECTIVE: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. MATERIALS AND METHODS: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/non-parametric tests. RESULTS: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p = 0.177 and 0.43, respectively). CONCLUSION: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India.

Insulin resistance, metabolic syndrome and chronic low grade inflammation in Sheehan's syndrome on standard replacement therapy: a case control study.

BACKGROUND: Increased clustering of metabolic risk factors has been demonstrated in patients with hypopituitarism on standard replacement therapy. This usually has been attributed to persistent growth hormone deficiency, though contribution from underlying etiology of hypopituitarism cannot be underestimated. We, therefore, studied conventional metabolic risk factors and pro inflammatory markers in a cohort of hypopituitary patients in whom the etiology was Sheehan's syndrome. MATERIAL & METHODS: We studied 30 GH naive patients with Sheehan's syndrome (SS) on standard replacement therapy and compared with healthy age, BMI and parity matched controls. All subjects were normotensive, non-diabetic, non-smokers and none had history of any acute or chronic illness. We recorded height, weight, BMI, waist circumference and waist hip ratio, besides measuring biochemical parameters like lipid profile, fasting plasma glucose and insulin, sVCAM-1, ICAM-1 and hsCRP. RESULTS: Metabolic syndrome and impaired glucose tolerance were more common with SS patients. Similarly total cholesterol (mean ± SD, 5.21 ± 0.98 vs 4.57 ± 0.88, P = 0.00), LDL-cholesterol (3.15 ± 0.90 vs 2.67 ± 0.75, P = 0.02), triglycerides (2.14 ± 1.00 vs 1.43 ± 0.45, P = 0.00) and pro-inflammatory markers i.e. hsCRP (3.95 ± 2.58 vs 1.45 ± 2.77, P = 0.00) were significantly higher in patients with SS. hsCRP positively correlated with fasting insulin (r = 0.40, P = 0.02), HOMA-IR (r = 0.38, P = 0.03) and negatively with HDL (r = - 0.33, P = 0.05). CONCLUSIONS: GH naïve SS patients on standard replacement therapy have increased clustering of metabolic and pro-inflammatory risk factors.

Prevalence of metabolic syndrome in the family members of women with polycystic ovary syndrome from North India.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most complex and common endocrine disorder of women in reproductive years. In addition to irregular menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin resistance, dysglycemia, increased risk of cardiovascular disease or possibly endometrial cancer. Familial clustering of PCOS in consistence with the genetic susceptibility has been described. MATERIALS AND METHODS: The present study assessed the clinical, biochemical and hormonal parameters including prevalence of metabolic syndrome by two different criteria in the first- degree relatives of patients with PCOS. RESULTS: The average age of 37 index patients was 23 ± 3.6 years, with the mean age of menarche as 13.3 ± 1.2 years. The mean age and age of menarche in mothers (n = 22) was 48.8 ± 5.1 and 13 ± 1.3 years, respectively, whereas as it was 23.5 ± 4.7 and 13.3 ± 1.2 years in sisters (n = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters, 17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was in 8 index patients, 5 sisters, 16 mothers and 11 fathers. CONCLUSION: The presence of MS or related metabolic derangements is high in the family members of women with PCOS.

RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.

RAD51 - a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population.

Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study.

CONTEXT: To improve the treatment outcomes in women with polycystic ovary syndrome (PCOS), various drugs like glitazones, oral contraceptive pills, or antiandrogens have been combined with metformin. OBJECTIVE: The aim of the study was to compare the efficacy of the combination of low-dose spironolactone and metformin with either drug alone in the management of women with PCOS. DESIGN AND SETTING: The present study was an open-label, randomized study conducted at a tertiary care referral center. PATIENTS AND INTERVENTION: Of 204 women who met the 2006 Androgen Excess-PCOS criteria for PCOS, 198 were randomized into 3 equal groups to receive metformin (1000 mg/d), low-dose spironolactone (50 mg/d), or a combination of both drugs for a period of 6 months. A total of 169 subjects (n = 56 metformin, 51 spironolactone, 62 combination) completed the study. MAIN OUTCOME MEASURES: Menstrual cycle pattern, Ferriman-Gallwey score, body mass index (BMI), waist-hip ratio, blood pressure, LH, FSH, total T, glucose and insulin sensitivity indices were measured at baseline (0 mo) and 3 and 6 months after the intervention. Recording of adverse events and drug compliance was assessed at each of the visits. RESULTS: The 3 groups had comparable mean age and BMI at baseline. By 6 months, menstrual cycles/y increased, whereas Ferriman-Gallwey score, serum total T, and area under the curve-glucose and -insulin decreased significantly (P < .05) in the combination group as compared to either drug alone. There was no significant change in body weight, BMI, waist-hip ratio, and blood pressure in any of the 3 groups. The combination group had better compliance than either drug alone, and the adverse event rate was not higher. CONCLUSION: The combination of low-dose spironolactone with metformin seems superior to either drug alone in terms of clinical benefits and compliance in women with PCOS.