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ABSTRACT: OBJECTIVE: To study the genetic association between methylenetetrahydrofolate reductase (MTHFR) A1298 polymorphism and recurrent pregnancy loss (RPL). DESIGN: Prospective case-control study, systematic review, and meta-analysis using an electronic database up to July 27, 2012. SETTING: Meta-analysis of four studies on RPL and three studies on spontaneously aborted embryos, including the present study. PATIENT(S): A total of 129 RPL patients and 202 healthy control women with successful pregnancy were analyzed including 40 spontaneously aborted embryos and 40 aborted embryos as control samples. For meta-analysis, 1,080 case and 709 control subjects were included of RPL and 375 case and 384 control samples of spontaneously aborted embryos. INTERVENTION(S): Blood was collected by peripheral venous punctures, and spontaneously aborted embryos were collected by curettage or manual vacuum aspiration. Meta-analysis was done on the basis of heterogeneity of the studies. MAIN OUTCOME MEASURE(S): Genotyping was done by polymerase chain reaction (PCR)-restriction-fragment-length polymorphism (RFLP). DNA sequencing was used to ascertain PCR-RFLP results. Age-adjusted odds ratios were calculated by logistic regression analysis. Meta-analysis on this polymorphism was conducted to support our findings. RESULT(S): We found that presence of rare allele "C" and heterozygous and rare homozygous genotypes significantly increased the risk of RPL. No significant change in the fetal MTHFR A1298C genotype frequency was observed, regardless of chromosomal integrity. Meta-analysis of A1298C polymorphism on both RPL and in spontaneously aborted embryos showed significantly increased risk in the carriers of AC and CC genotypes. CONCLUSION(S): The data of the present study clearly suggests that MTHFR A1298C polymorphism is a genetic risk factor for pregnancy loss.
Fertility and sterility 01/2013; · 3.97 Impact Factor
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ABSTRACT: Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) enzymes of the glutathione detoxification pathway protect the embryo from oxidative stress. This study investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility to pregnancy loss. In a case-control study, 174 early pregnancy loss (EPL) patients, of which 130 were recurrent pregnancy loss (RPL) patients, and 180 healthy controls were investigated. Null genotypes of GSTT1 and GSTM1 were identified in duplex PCR reaction systems. Age-adjusted odds ratios (aOR) were calculated by logistic regression analysis. A meta-analysis was also conducted. The GSTT1 null genotype was significantly associated with EPL (aOR 4.47, P=0.004) and RPL (aOR 4.39, P=0.006). No significant association of the GSTM1 null genotype was found with RPL. In a meta-analysis study, the presence of the GSTM1 null genotype was shown to be a risk for RPL. The GSTT1 null genotype was not found to be a risk factor for pregnancy loss in the pooled population but its association with RPL was found in the Indian population. This study suggests that women carriers of GSTT1 and GSTM1 null genotypes are more often at genetic risk of pregnancy loss. Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1), enzymes of detoxification pathway, protect the embryo from oxidative stress. In the present study we have investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility for early pregnancy loss (EPL) and recurrent pregnancy loss (RPL). Meta-analysis on the polymorphisms was conducted to support our findings that the presence of mutant genotypes at this site increases the risk of pregnancy loss. The GSTT1 null genotype was significantly associated with both EPL and RPL. In the meta-analysis, the overall result showed that the association between GSTM1 null genotype and risk for RPL was statistically significant. On comparing the GSTT1 studies, great heterogeneity was found between studies. A subgroup analysis was performed based on ethnicity. Our results showed a significantly increased risk with the GSTT1 null genotype in the Indian population, but no risk was found in the pooled population. In conclusion, the data of the present study clearly suggest that GSTT1 and GSTM1 polymorphisms are genetic risk factors for pregnancy loss in the study population.
Reproductive biomedicine online 12/2012; · 2.04 Impact Factor
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ABSTRACT: Apoptosis during the early stages of pregnancy enables the remodeling of the uterus for proper placentation. Apoptosis in the maternal activated cytotoxic T lymphocytes allows maternal immune tolerance to pregnancy and in glandular and stromal cells it helps with trophoblastic endometrial invasion. FAS gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered FAS expression may result in altered apoptosis and ultimately affects both immune response and implantation. FAS -1377 G>A and FAS -670 A>G functional polymorphisms in the promoter region of FAS gene modulate its expression at transcriptional level. In a case-control study the contribution of FAS -1377 G>A and FAS -670 A>G polymorphisms to the risk of recurrent early pregnancy loss (REPL) was evaluated. DNA from 134 cases with a history of three or more REPL and 124 healthy controls with successful pregnancy outcomes were genotyped through PCR-RFLP. DNA sequencing was used to ascertain PCR-RFLP results. The genotype and allele frequencies for FAS -1377 G>A and FAS -670 A>G polymorphisms were compared in REPL and controls. FAS -1377 AA and AG genotypes were associated with an increased risk of REPL (OR, 3.25; 95%CI, 1.52-6.98 and OR, 2.62; 95%CI, 1.48-4.64, respectively), whereas FAS -670 genotypes conferred no risk. The -1377 AA/-670 GG genotypes combination of FAS polymorphisms showed highest risk (OR, 8.15; 95%CI, 2.75-25.81). Genotype combinations -1377 GA/-670 AA and -1377 GA/-670 AG were also statistically significant, suggestive of their role in REPL risk.
Journal of Reproductive Immunology 02/2012; 93(2):114-8. · 2.97 Impact Factor
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ABSTRACT: Recurrent early pregnancy loss (REPL) is a multifactorial disorder as both genetic and environmental factors contribute to the development of disease. Folate metabolism is an important mechanism to ensure proper fetal growth. Hyperhomocysteinemia leads to a number of disorders and REPL is one of them. In a case-control study DNA from 106 cases with the history of 3 or more REPL and 140 healthy fertile controls with successful pregnancy outcomes were genotyped for C677T single-nucleotide polymorphism (SNP) of the MTHFR (methylenetetrahydrofolate reductase) gene through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), which was further confirmed by sequencing. Allele frequencies of REPL cases were compared with healthy controls and a statistically significant association was found between REPL and the mutant T allele (χ² = 8.786, odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.323-3.9658, P = .003). The genotype frequencies of SNP C677T also differ significantly between these 2 groups (χ² = 8.237, P = .016). The OR for heterozygous CT in the REPL versus controls is 1.9591 (95% CI = 1.0285-3.7318, P = .04). The OR for TT homozygous is 6.3009 (95% CI = 1.2065, P = .02). Combined odds ratio of CT and TT against the control has been calculated as 2.2194 (95% CI = 1.2029-4.0952, P = .02) which is also significant. Thus the present study clearly indicates that homozygosity and heterozygosity for the MTHFR C677T polymorphism confer a 6.3009- and 1.9591-fold increased risk of idiopathic REPL, respectively.
Reproductive sciences (Thousand Oaks, Calif.) 12/2011; 19(2):210-5. · 2.31 Impact Factor
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Journal of vascular and interventional radiology: JVIR 12/2011; 22(12):1778-80. · 1.81 Impact Factor
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ABSTRACT: Angiogenesis, invasion and decidualization play an important role in uterine preparation and embryo development. Matrix metalloproteinases (MMP) are crucial for the degradation/remodelling of the extracellular matrix and are involved in spiral artery formation and invasion of endometrium during implantation. A functional single-nucleotide polymorphism (SNP) in the MMP9 promoter, 1562C/T, is known to influence expression in an allele-specific manner. The present study evaluated the association between maternal genotype of SNP 1562C/T of MMP9 and recurrent early pregnancy loss (REPL) risk. This case–control study was comprised of REPL patients (n = 106) and women having one healthy child as controls (n = 111). Genotyping for SNP 1562C/T of MMP9 was performed by PCR/restriction fragment length polymorphism followed by DNA sequencing. Allele and genotype distribution did not differ significantly between patients and controls (by allele, chi-squared 0.228, odds ratio 1.12, 95% confidence interval 0.695–1.816; by genotype, chi-squared 0.893). Thus SNP 1562C/T of MMP9 was not associated with REPL risk in this population and further study in other populations will verify whether it is associated with REPL risk or not. REPL is a multifactorial pathology and other genetic or environmental factors may be contributing to the complex aetiology of REPL.
Reproductive biomedicine online 09/2011; 24(1):61-5. · 2.04 Impact Factor
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ABSTRACT: Necrotizing fasciitis of the lower limb is not uncommon, with poor outcome. This study reviewed 118 cases (78 males and 40 females) with mean age of 45 + 16.5 years (range 12-95 years) of lower limb necrotizing fasciitis admitted to the Department of Surgery, BHU in India between 1995 and 2007. Most patients (n = 97) presented with fever. Other presenting symptoms included painful swelling, bullae, erythema, ulcer, and necrosis. Comorbid conditions such as diabetes, tuberculosis, malignancy, and immunosuppressive therapy were associated in 72 (61%) cases. Amputations were done in 24 patients. Thirty one patients developed septic shock. Renal dialysis was done in 16 patients and ventilatory support was needed in 12 patients. The most common organism identified was beta-hemolytic streptococci (n = 42). Eighteen patients died, a mortality of 15%. The authors consider early diagnosis and aggressive surgical intervention to be crucial for the successful treatment of disease.
The International Journal of Lower Extremity Wounds 07/2009; 8(2):112-6. · 1.20 Impact Factor
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ABSTRACT: Anemia is a common health problem but control of anemia in pregnant women is less well studied. The purpose was to study prevalence of anemia in young pregnant women, correlate with indices and study significance of identification of hemoglobinopathies. Of the 120 pregnant women, Hb was less than 8 g% in 58 (44.2%). Seventy-eight (65%) had iron deficiency, 22 (18.3%) had dimorphic anemia, and 14 (11.6%) had hemolytic anemia. Megaloblastic anemia was present in 6 (5%). Of hemolytic anemia, 50% were thalassemia trait. MCV< 76 fl was observed in 88 (73.3 %) cases. MCV<76 fl and MCH < 27 pg had 100 % sensitivity and 28.7 % specificity for screening of beta-thalassemia trait. NESTROFT had comparable sensitivity but lower specificity (14.9%). Sixty-three percent (60/78) of IDA had increased RDW whereas 78 % (11/14) of hemolytic anemia had RDW value in normal range (p value< 0.05). MCV/RBC of <14 was more specific parameter (96.8%) for beta-thalassemia trait. Four high-risk couples were identified. Thus, moderate to severe anemia was observed in most pregnant women. Hemoglobinopathies should be screened in antenatal clinics to identify the couples that would need a prenatal test. A lower MCV/RBC with RDWin the normal range may be useful in screening for thalassemia trait in pregnant women.
Indian Journal of Pathology and Microbiology 08/2006; 49(3):373-5. · 0.68 Impact Factor
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ABSTRACT: Hydatid disease usually affects liver and lungs, but may affect any organ, posing a diagnostic and therapeutic dilemma. We analysed 110 patients with hydatid cyst over 21 years in our general surgical unit, which included 24 cases in unusual sites. The spleen was the most common, followed by skin and soft tissues.
Tropical Doctor 11/2005; 35(4):233-5. · 0.66 Impact Factor
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Tropical Doctor 05/2004; 34(2):107-8. · 0.66 Impact Factor
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ABSTRACT: Patients with uveitis such as the patient whose case is reported here are often referred to rheumatologists for investigation of possible underlying systemic diseases. This patient presented with decreased vision, photophobia, weight loss, and fevers and was found to have uveitis, elevated creatinine, and interstitial nephritis. This raised consideration of a variety of systemic diseases before she was determined to have the tubulointerstitial nephritis with uveitis (TINU) syndrome. The TINU syndrome, although known to some ophthalmologists and nephrologists, is still rather obscure. Uncommon but not rare with 133 cases in the literature, TINU syndrome should be one more diagnosis to be considered in patients with uveitis. The median age of onset is 15, but it ranges from 9 to 74. There is a 3:1 female preponderance. Response to corticosteroids, which are used in 80% of reported cases, is rapid. The prognosis for the renal disorder is excellent, although the uveitis often recurs or remains chronic.
JCR Journal of Clinical Rheumatology 03/2004; 10(1):25-7. · 1.36 Impact Factor
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ABSTRACT: To estimate the value of estrogen receptor (ER) in benign breast diseases and to find out if the response of benign breast diseases to danazol depends on the ER status of the tissue.
Prospective study.
University hospital, India.
Samples of tissue from benign breast lesions, 40 fibrocystic disease and 10 fibroadenomas.
Enzyme immunoassay for the presence of cytosolic ER.
ER concentrations, and correlation with effect of treatment with danazol.
Fibrocystic disease and fibroadenomas showed 30% and 40% ER positivity, respectively. The mean (SD) ER concentration was significantly higher in premenopausal than postmenopausal patients 14.75 (3.79) fmol/mgm compared with 6.2 (1.59) fmol/mg (p < 0.05). All ten patients with mastalgia who had ER-positive lesions (n = 26) responded to danazol, compared with 6 of 16 patients who had ER-negative lesions (p < 0.05). Lesions with diffuse fibrosis (n = 14) and five with lymphocytic infiltration on histology were all ER-negative.
The patients with ER positive breast disease responded better to danazol than patients with ER negative breast disease.
The European Journal of Surgery 02/2002; 168(11):631-4.
