Background: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. Aims: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. Settings and Design: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. Materials and Methods: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). Statistical Analysis: Fisher's exact test and χ² statistics using SPSS software (Version-15.0). Results: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325) and GSTP1 (I/V) (P=0.001, OR= 0.397, 95%CI=0.225-0.701) with T2DM and no significant association with GSTT1 (P=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496). Conclusions: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk.

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Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is an important public health problem in India. Both parasites produce essentially similar clinical presentations in man, related mainly to the pathology of the lymphatic system. Filariasis is endemic in 17 States and six Union Territories, with about 553 million people at risk of infection. The Government of India has accorded a high priority for elimination of this infection through mass chemotherapy programme (annual, single dose of Diethylcarbamazine citrate, i.e. DEC - 6 mg/kg of bodyweight, plus Albendazole repeated four to six times). This campaign has become a part of the National Vector-Borne Disease Control Programme in 2003 under the National Health Policy 2002 and aims to eliminate filariasis by 2015. We discuss here the epidemiology and current control strategy for filariasis; highlighting key issues, challenges and options in the implementation of the programme, and suggesting measures for mid-course corrections in the elimination strategy.

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Background: Geriatrics is an emerging clinical specialty in India. Information about the appropriateness of prescription medication use among the elderly in India is limited. Aims: To determine the prevalence and predictors of potentially inappropriate medication (PIM) use, and assess the relationship between PIM use and adverse drug reactions (ADRs) in the hospitalized elderly. Settings: Medicine wards at two teaching hospitals. Design: Prospective observational study. Materials and Methods: Patients aged > 60 years admitted to medicine wards between January 2008 and June 2009 were included and reviewed for PIM use according to the Beers Criteria 2003 (BC). Severity of PIM use was classified as per BC as 'high' or 'low'. ADRs observed in the study patients were also recorded. Statistical Analysis: Association between ADRs and PIM use was assessed using Chi Square test. Bivariate analysis and subsequently multivariate logistic regression was used to identify predictors of PIM use. Results: PIM use was observed in 191 of 814 enrolled patients. At least one PIM at admission and during hospital stay was received by 2.4% (20) and 22.1% (180) patients respectively. High-severity PIM use showed a higher prevalence compared to low severity [26.8% (218) vs. 5.5% (45)]. Amongst the patients who received polypharmacy (> 5 concurrent medications), 1.4% (5/362) and 22.1% (163/736) patients received PIMs at admission and during hospital stay respectively. Use of aspirin/clopidogrel/diclofenac in the presence of blood clotting disorder or anticoagulant therapy (8.3%) was the most commonly encountered PIM use. Medications not listed in BC were associated with increased occurrence of ADRs compared to medications listed in BC (349 vs. 11) (χ² =98.4, P<0.001). Increased number of concurrent medications' use (≥9) during the stay in medicine wards was identified as an influential predictor of PIM use [Odds ratio: 1.9, 95% Confidence Interval: 1.34-2.69, P<0.001) in the hospitalized elderly. Conclusion: PIM use was common (23.5%) among the elderly patients during their stay in medicine wards in two tertiary care hospitals. Measures targeted only at BC medications may do little to change the risk of ADRs in elderly.

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Background: Macrolide (MLS _B ) resistance is the most widespread and clinically important mechanism of resistance encountered with Gram-positive organisms. Resistance may be constitutive (cMLS _B phenotype) or inducible (iMLS _B phenotype). The iMLS _B phenotypes are not differentiated by using standard susceptibility test methods, but can be distinguished by erythromycin-clindamycin disk approximation test (D-test) and demonstration of resistance genes by molecular methods. Aims: To demonstrate in vitro inducible clindamycin resistance (iMLS _B ) in erythromycin-resistant (ER) and clindamycin-susceptible (CLI-S) clinical isolates of Staphylococci spp., and interpretation of susceptibility tests to guide therapy. Materials and Methods: Eight hundred and fifty-one isolates of Staphylococci spp. were recovered from various clinical specimens. All the Staphylococcal spp. were identified by conventional microbiological methods including colony morphology, Gram stain, catalase, slide coagulase and tube coagulase. Antibiotic susceptibility testing was performed by Kirby Bauer disc diffusion method. Erythromycin-resistant isolates were examined for inducible clindamycin resistance (iMLS _B ) by using double disk approximation test (D-test) at 15 mm disk separation. Results: The Staphylococci spp. isolated were 379 S. aureus [31.60% methicillin-resistant S. aureus (MRSA), 12.92% methicillin-sensitive S. aureus (MSSA)] and 472 coagulase-negative Staphylococci (CNS) [37.60% methicillin-resistant coagulase-negative Staphylococci (MRCNS), 17.86% methicillin-sensitive coagulase-negative Staphylococci (MSCNS)]. Four hundred and thirty (50.52%) Staphylococcal spp. isolates showed erythromycin resistance. Constitutive resistance was demonstrated in 202 (46.97%), inducible clindamycin resistance (iMLS _B ) in 101 (23.48%), and non-inducible (MS) in 127 (29.53%). Two distinct induction phenotypes, D (18.13%) and D ⁺ (5.34%) were observed. All iMLS _B isolates were susceptible to linezolid and vancomycin while 78.78% to ciprofloxacin. Conclusions: Fifty percent of Staphylococcal spp. were ER among which 23.48% were iMLS _B phenotypes. Eighty-seven per cent of iMLS _B phenotypes were observed to be methicillin-resistant. The high frequency of methicillin resistance isolates (87.12%) with in vitro inducible clindamycin resistance at our institute raises concern of clindamycin treatment failures with methicillin-resistant infections. So we recommend that microbiology laboratories should include the D-test for inducible resistance to clindamycin in the routine antibiotic susceptibility testing.

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Systemic lupus erythematosus (SLE) is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene, has been found to be associated with several autoimmune diseases like SLE, Grave's disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp) has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility

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Infections, renal failure and cardiovascular disease account for the majority of mortality in systemic lupus erythematosus (SLE). Although most infections are caused by Gram-positive or Gram-negative bacteria, there is an increase in the incidence of Mycobacterium tuberculosis and other opportunistic infections that also account for increased mortality. The higher prevalence of tuberculous infections in SLE is attributed to multiple immune abnormalities seen in these patients. SLE and tuberculosis (TB) interact in complicated ways - they may have similar presentation and may mimic each other. In an individual patient, it becomes important to differentiate one from the other. In this review, we have highlighted the complex interactions of these diseases, the impact of one on the other and the various modalities available for the evaluation and management and their shortcomings. Considering the high prevalence of TB in India, it becomes all the more important for us to be aware of this interaction in our population.

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Background: Understanding the effect of maternal parameters on obstetric outcome has public health importance because these indicators are associated with infant health and survival and influence development and health in later life. Aim: To determine the effects of various maternal indicators on pregnancy outcome in north-Indian women. Settings and Design: A prospective study of all consecutive women with singleton pregnancy, who were registered in the first two months of pregnancy and delivered in the hospital. Materials and Methods: Maternal indicators such as age, height, prepregnancy weight, body mass index (BMI), hemoglobin and parity were correlated with pregnancy outcome. The women with a medical disorder or complication that developed during the course of pregnancy were excluded. Results: A total of 2027 women were analyzed. Maternal height, weight, BMI and parity had a positive significant correlation with birth weight of the newborn (r=0.081, P value < 0.001, r=0.148, P value <0.001, r = 0.121, P value < 0.001 and r = 0.099, P value < 0.001, respectively). Maternal height, weight and period of gestation were significant indicators for low birth weight on multivariate logistic regression. The rate of preterm delivery was significantly higher in women with hemoglobin < 7 g% and women with parity >3. The chances of caesarian section increased significantly with increase in maternal height, weight and BMI. Conclusions: A prepregnancy weight of more than 40 kg, BMI of more than 19.8 and hemoglobin of at least 7g% or more favor good obstetric outcome.

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Background: Apolipoprotein E (APOE) is known as a major regulator of blood lipid levels in humans. A number of APOE gene allelic variants have been reported including E2, E3 and E4. Recent studies suggested a role for APOE in obesity and increased Body Mass Index (BMI) and plasma lipid levels in obese children. Aim: The aim of this study was to examine the association between APOE genetic variants and the BMI and lipid profile in an Iranian cohort. Setting and Design: Samples were obtained from subjects who participated in a study based on the WHO-designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study for coronary artery disease risk assessment in Zone 17 of Tehran. The study was approved by the local ethical committee. Informed consent was obtained from all subjects included in this study. Materials and Methods: Subjects (n=320) were recruited. The level of triglyceride (TG) and total serum cholesterol was tested for all subjects in this study. Genotyping for APOE was carried using polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP)technique. Statistical Analysis: Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8) software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. Results: The frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2). Conclusion: The association found in this study between allele E2 and lower total cholesterol level had been reported in previous studies. We have also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with abnormal cholesterol (P=0.003 OR 2.4 95% CI; 1.3-4.6). Our data needs to be repeated in a larger population with more information for serum LDL and HDL levels and their subgroups.

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Takotsubo cardiomyopathy (TC) is a condition which was first acknowledged in Japan and is characterized by a reversible systolic dysfunction of the apical or mid segments of the left ventricle. Typically affecting women in the post-menopausal population, it is triggered by intense emotional, physical or medical stress. Also known as apical ballooning syndrome or stress cardiomyopathy, TC derives its name from the left ventricular angiographic appearance of a 'Takotsubo', literally translated as an 'octopus fishing trap' in Japanese. Patients often describe chest pain, have ischemic electrocardiogram (ECG) changes and positive cardiac enzymes mimicking an acute coronary syndrome. Obstructive coronary artery disease is excluded with prompt cardiac catheterization. We present the case of a 78-year-old lady, post gynecological surgery, presenting with palpitations and ECG confirming fast atrial fibrillation. Despite spontaneous cardioversion, she went on to develop ECG changes and cardiac enzyme elevations suggestive of an acute myocardial infarction. Cardiac catheterization was performed and confirmed the diagnosis of TC. It highlights an atypical presentation of TC, which can present initially as an arrhythmia in the postoperative phase as a consequence of the supraphysiological effects of elevated circulating plasma catecholamines. It reiterates the importance of prompt diagnosis and treatment to prevent cardiac decompensation in a condition poorly understood.

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There are no published case reports of esomeprazole-induced photoallergic dermatitis. We report here a 58-year-old lady with prior history of propylthiouracil and carbimazole-induced photoallergy, who presented with heartburn and dysphagia. She was diagnosed to have erosive esophagitis and was treated with esomeprazole, following which she developed photoallergic dermatitis. It improved on cessation of the drug and did not recur on subsequent treatment with ranitidine. Naranjo score for this adverse drug event was 8, thereby making it a probable adverse drug reaction. This reaction may be due to sulphur moiety, which is common to all these drugs. Physicians must be aware of this possible side-effect, especially in patients with prior history of photoallergy to other drugs.

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Vestibular schwannomas are not uncommon, and gamma knife radiosurgery is one of the treatment options for symptomatic tumors. Hydrocephalus is a complication of gamma knife treatment of vestibular schwannoma, though the mechanism of the development of hydrocephalus remains controversial. We present an unusual case of normal pressure hydrocephalus (NPH) after gamma knife radiosurgery of a vestibular schwannoma in which the timeline of events strongly suggests that gamma knife played a contributory role in the development of the hydrocephalus. This is probably the first case of NPH post radiosurgery with normal cerebrospinal fluid protein. Communicating hydrocephalus should be treated with placement of shunt while non-communicating hydrocephalus can be treated with third ventriculostomy. Frequent monitoring and early intervention post radiosurgery is highly recommended to prevent irreversible cerebral damage.

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A desmoplastic small round cell tumor (DSRCT) is an uncommon tumor characterized by polyphenotypic expression and a specific reciprocal translocation t (11; 22) (p13; q12). It has been rarely identified in the head and neck region. Herein, we describe a DSRCT in the maxilla of a young man, who was initially diagnosed with a primitive neuroectodermal tumor (PNET), based on histopathological appearance of a round cell tumor, with MIC2 and -FLI-1 positivity, on immunohistochemistry (IHC). Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT-PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1. The case is presented to highlight the value of molecular diagnosis in round cell sarcomas at uncommon sites, especially when similar IHC markers can be expressed in a PNET and a DSRCT. An exact diagnosis of a round cell sarcoma has a therapeutic relevance.

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This case report describes a lady who underwent investigations as a part of a clinical study. A 32-year-old woman with a history of episodes of severe migraine with aura, deep vein thrombosis and recurrent epistaxis, presented with two episodes of stroke with no particular cause evident on routine investigations. A contrast echocardiogram demonstrated a patent foramen ovale (PFO). She was found to be positive for the Factor V Leiden mutation. The PFO was closed percutaneously. However, a substantial right to left shunt of 14% persisted. Pulmonary angiography revealed multiple arterio-venous malformations (AVMs) and she was diagnosed with hereditary hemorrhagic telangiectasia. The AVMs were embolized and she has had no further cerebral events. Interestingly, her episodes of 'migraine' have also improved dramatically following the closure of the PFO and the embolization of the AVMs. This case demonstrates the complex relationship between right to left shunts, cryptogenic stroke and migraine.

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The clinical utility of measuring the Muscle Brain (MB) isoenzyme of creatine kinase (CK) in the diagnosis of myocardial injury is well established. CK/CK-MB measurement in combination or CK-MB alone is widely used and reporting the results of CK-MB in absolute unit is the common current practice. CK-MB is widely measured by "Immunoinhibition" in India, which gives falsely elevated CK-MB results in the following circumstances: Central nervous system damage, childbirth, macro CK-immunoglobulin complex, in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. But, reporting %CK-MB rather than the absolute CK-MB results assists in detection of macroCK (or CK variants), associated proliferative and autoimmune pathologies and their prognosis.

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Background and Aims: Coronary heart disease (CHD) is the leading cause of death in India resulting in loss of young Indians. Statins have proved to reduce the CHD mortality in various clinical trials. The aim of the study is to find the cost-effectiveness ratio (CER) for each major coronary event averted and a coronary death avoided by use of statins in different clinical settings based on the data from the major clinical trials on statins. Materials and Methods: Using electronic database and as per our inclusion and exclusion criteria we selected the West of Scotland Coronary Prevention Study (WOSCOPS), the Air Force Coronary Atherosclerosis Prevention Study (AFCAPS) and the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA) study for primary prevention; the Cholesterol and Recurrent Events Trial (CARE), the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study and the Scandinavian Simvastatin Survival Study (4S) for secondary prevention and two studies, the Heart Protection Study (HPS) and the Pravastatin in elderly individuals at risk of vascular disease (PROSPER) study for high-risk patients. The results of these studies were used for cost-effectiveness analysis of statins in different patient groups. Statistical Analysis: Absolute risk reduction, Number Needed to Benefit (NNTB), NNTB/year for total sample and in subgroups of males, females and age >65 was derived. CER for branded and generic versions was calculated by using the prices of statins listed in Indian Drug Review Triple i. Results: Cost-effectiveness ratio (CER) in primary prevention studies i.e., the WOSCOPS, the AFCAPS and the ASCOT-LLA was Rs. 25.8 lacs, Rs. 23.8 lacs and Rs. 7.9 lacs per major coronary event averted respectively. CER in secondary prevention studies i.e., the CARE and the LIPID was approximately Rs. 20 lacs per major coronary event averted while it was Rs. 52.4 lacs and Rs. 37 lacs per coronary heart disease (CHD) death avoided. CER from the 4S was Rs. 6.9 lacs per major coronary event and Rs. 16.9 lacs per CHD death averted. CER in the HPS and the PROSPER study was Rs. 17.9 lacs and Rs. 27.1 lacs per major coronary event avoided in high-risk patients. Conclusion: Cost associated with the use of statins is higher in primary prevention as compared to secondary prevention. More studies are needed to confirm the cost-effectiveness of statins to make any decision for health policy.

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