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Biomedical subjects

S C Tiwari

Publications and source records attributed to S C Tiwari.

At least 19 recordsLinked to original sources

Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms.

BACKGROUND: Renal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects. METHODS: Twelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of > or =2 years duration and moderate CRI diagnosed by serum creatinine > or =3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes. RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01-3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88-4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97-3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16-2.14 and O.R. 1.81, 95%CI: 1.21-2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34-3.17) were also observed. CONCLUSION: SNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising.

Asian People↗

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Adolescent↗

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Adolescent↗

Fibrillary glomerulonephritis presenting as rapidly progressive renal failure in a young female: a case report.

Fibrillary Glomerulonephritis (FGN) is a rare clinical entity presenting in majority of patients with nephrotic range proteinuria, microscopic hematuria, impaired renal function and hypertension. The mean age of presentation is reported to be beyond 50 years with 50 patients developing end stage renal disease within a few years. A 28-year-old female presented to us with non-nephrotic range proteinuria, rapidly progressive renal failure (RPRF), microscopic hematuria and mild hypertension. The patient had undergone a renal biopsy at a peripheral center, which was reported as membranoproliferative glomerulonephritis (MPGN) and was being treated with steroids without any benefit. The patient on re-biopsy at our center was diagnosed as FGN on electron microscopy (EM). The patient responded to intravenous pulse methylprednislone and oral cyclophosphamide and is off dialysis for 10 months now. This case highlights the varied clinical and histological presentations of FGN which makes the disease difficult to diagnose more so, in a country like ours where EM is available in only a few centers. An accurate diagnosis aided by high index of clinical suspicion and EM can help in the initiation of appropriate therapy, thereby improving the outcome in this disease which otherwise has a poor prognosis.

Adult↗

The effect of renal transplantation on pulmonary function and respiratory muscle strength in patients with end-stage renal disease.

Pulmonary function and respiratory muscle strength was assessed in 29 hemodialysis patients who underwent successful renal transplantation. These tests were performed 7 days prior to transplantation, 30 days following transplantation, and 90 days posttransplantation. Patients with end-stage renal disease showed dyspnea, a restrictive defect in pulmonary function, respiratory muscle weakness, and hypoxia. Following transplantation the dyspnea improved and mechanical indices of respiratory muscle function and lung volume improved. In conclusion transplantation resulted in a significant improvement in lung and respiratory muscle function.

Blood Gas Analysis↗

A prospective randomized study to compare ultrasound-guided with nonultrasound-guided double lumen internal jugular catheter insertion as a temporary hemodialysis access.

UNLABELLED: Internal jugular venous catheters (IJVC) for hemodialysis are a commonly employed temporary vascular access for hemodialysis. Most hospitals still follow the use of blind technique, which uses anatomical landmarks. Even in the most experienced hands this procedure has a variable success rate. Ultrasound guidance can decrease the incidence of periprocedural complications and improve the success rate. In this randomized study we compared the procedure success rate and periprocedural complications in patients undergoing ultrasound guided vs. nonultrasound guided IJVC insertion for a temporary hemodialysis access. METHODS: All patients subjected to insertion of an IJVC between March 2004 and June 2004 were enrolled into the study, randomized to either the blind (group A) or ultrasound guided (group B) procedure, which uses a portable ordinary ultrasound machine without a needle guide. The aseptic Saldinger technique was used for catheterization in both the groups. Baseline characteristics of patient and periprocedural events were recorded. RESULTS: A total of 60 patients were randomized, 30 patients each in two groups. First attempt venous cannulation success rate was 56.7% in group A compared to 86.7% in group B. Chance of occurrence of adverse outcome was significantly more in the blind procedure (P=0.020). A post-procedure chest radiograph done in all patient showed no complications. CONCLUSION: Ultrasound guided procedure for internal jugular vein catheter insertion using an ordinary ultrasound machine was significantly safer and more successful as compared to the blind technique.

Adult↗

Development & standardization of a scale to measure socio-economic status in urban & rural communities in India.

BACKGROUND & OBJECTIVES: The commonly used available scales for measurement of socio-economic status (SES) with some cross regional applicability are old and have lost their relevance. There is a need for the development of a valid and reliable instrument for measurement of SES in rural and urban communities in India. The present study was undertaken to develop a cross regionally applicable scale for the purpose of enlisting true measures of socio-economic items applicable in multilingual, multicultural, multireligious, setting of the country. METHODS: For developing the scale, seven indicators (house, materials possession, education, occupation, monthly income, land, social participation and understanding), presumably determining the socioeconomic status were selected. These indicators were named as profiles. Thus, initially the scale had seven profiles and every profile contained five alternatives. This instrument was prepared on a 10-point scale. Weightage system of scoring (varying from 2 to 10) was followed from first to sixth profile while the additive pattern of scoring was followed in seventh profile. The final version of the scale was arrived at through three trial administrations on rural and urban families. The basis of selection of the families for the first two trials was stratified random. The validity and reliability of the scale was established through a defined visual analogue scale (VAS) and test-retest methods. RESULTS: Both the initial version as well as the final version of the scale for the measurement of SES of incumbents had seven profiles. The difference between the two versions was in terms of contents and range of items in different categories of SES. The final version was arrived at through field trials and suggestions of the experts. The reliability of the scale was high with a correlation coefficient of 0.998. INTERPRETATION & CONCLUSION: The new scale appears to be a valid and reliable instrument for the assessment of socio-economic status of the families/individuals from urban as well as rural areas in India.

Humans↗

Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: a case report.

Fibrosing cholestatic hepatitis (FCH) is an uncommon complication of renal transplantation. It is usually associated with hepatitis B and C viral infection. It is further rare in renal transplantation in absence of HBV and HCV infection. To the best of our knowledge, only three cases of FCH in renal transplantation, which were both HBV and HCV negative, have been reported to date. Out of these, two cases were diagnosed to have CMV infection and the third was attributed to azathioprin. We are presenting another case of FCH in a renal transplant recipient with CMV infection.

Adult↗

Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient.

Renal transplantation (RT) recipients are at a high risk of developing tuberculosis (TB) following transplantation. Effectiveness of isoniazid (INH) in preventing TB is well documented in immunocompetent as well as immunocompromised persons. There is paucity of data on role of INH prophylaxis in RT recipients. Thus, a prospective randomised trial of INH in RT recipients was carried out to determine the efficacy of daily INH monotherapy in the prevention of TB in these patients. Patients of end stage renal disease (ESRD) taken for RT formed the subjects of study. Patients with active TB and active hepatitis at the time of RT were excluded from the study. Patients were randomised to receive INH 300 mg with pyridoxine 20 mg daily from the day of RT. The duration of the treatment was planned for 1 year or till the development of TB, which ever was earlier. Between October 1998 and September 2000, 114 RT were done at our hospital. Of these, 24 (21%) patients had active TB at the time of RT and thus were excluded. Patients included were randomised with 1:2 ratio of treatment and control group. Of the 90 patients thus enrolled, 30 were randomised in treatment group and 60 in control group. Of the included patients five patients had very early graft loss (three in treatment and two in control group) within days and thus excluded from the analysis. Three of the 27 (11.1%) patients in treatment group and 15 (25.8%) in control group developed TB (P = 0.10). The risk ratio of (RR) of INH versus control group of TB was 0.36 (95% CI, 0.10-1.32) but the difference was not statistically significant (P = 0.12). Only one patient developed INH induced hepatitis. In conclusion, with INH prophylaxis, there was a trend towards protection from TB, though it was not statistically significant. Further, all patients tolerated INH and hepatotoxicity was not a major problem in this group of patients.

Antitubercular Agents↗

Association of complement receptor 1 (CR1, CD35, C3b/C4b receptor) density polymorphism with glomerulonephritis in Indian subjects.

Complement receptor 1 (CR1, CD35, C3b/C4b receptor), a polymorphic membrane bound glycoprotein is important both as a complement regulatory protein, and as a vehicle for immune complex clearance. It is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have either suggested or refuted the functional and physiological significance of genomic (HH, high erythrocyte CR1 expression; HL, intermediate and LL, low expression) polymorphism of CR1 in health and disease. Prevalence of autoimmune disorders like RA, GN and SLE is higher in Asian-Indians compared to the western world. Although several studies from India emphasize the modulation of E-CR1 levels as a key factor in the pathophysiology of glomerulonephritis (GN), none of them, however, provide much information on the role of CR1 gene variance in this context. We, therefore, carried out the study of CR1 polymorphism in 117 normal Indian subjects and 65 patients suffering from glomerulonephritis in order to study its possible association with the disease and E-CR1 levels. This is the first study of its kind in the Indian population, in which, the direct effect of a particular genotype on the E-CR1 levels and its possible association with the disease has been studied simultaneously.

Adult↗

Immunological monitoring of posttransplant allograft sensitization following living related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for development of new therapeutic strategies and also for individualization of immunosuppression. The objective of this study was to analyze the clinical relevance of immune parameters, such as recipient sensitization status, donor-specific antibodies, and anti-HLA antibodies, which are major predictors of graft outcome following renal transplantation. Sera from 264 renal recipients at different posttransplant period were included for detection of anti-donor antibodies (by flowcytometry); anti-HLA, antibody (by ELISA), and panel-reactive antibodies (PRA) by complement-dependent cytotoxicity (CDC) methods. Graft survival was analyzed in relation to posttransplant PRA at 2 years follow-up time: overall survival was significantly compromised in the highly sensitized group (group III) compared to the other two groups (overall chi2 = 24.20, P = 5.5 x 10(-06)). Flow cytometric cross-matches revealed the presence of anti-donor class I antibodies (T+) in 39 patients who had a poor graft survival of 51% compared with 85% survival in 225 antibody-negative patients. (chi2 = 22.260, P = 2.381 x 10(-.06)). Further analysis was performed based on the presence or absence of FCXM and ELISA-detected antibodies. Recipients belonging to group I (ELISA+/FCXM+) showed significantly lower graft survival (43%) compared with that observed in group II, which were essentially nonsensitized individuals (90%; P = 3.1 x 10(-08)). The graft survival in the ELISA-/FCXM+ group was 63%, which was significantly lower than that in group II (P = 5.14 x 10(-03)). Group IV (ELISA+/FCXM-) including 38 (14%) serum samples with nondonor but HLA-specific antibodies was associated with significantly poorer graft survival (63%) compared with group II (P = 6.6 x 10(-05)). Our data also show that while FCXM is the most sensitive test to detect donor-specific antibodies, the ELISA method offers the additional advantage of detecting anti-HLA class-I antibodies, which are detrimental for renal graft survival. Thus the use of multiple parameters to assess recipient immune profile can predict graft outcome more accurately thus helping the individualization and optimization of immunosuppression.

Follow-Up Studies↗

Modulation of urinary CR1 in systemic lupus erythematosus.

The decline in the levels of erythrocyte complement receptor 1 (ECR1) in systemic lupus erythematosus (SLE) has been widely reported. The most probable cause for this decline is excessive proteolytic shedding of CR1 from the cell surface. Similarly a decline in glomerular CR1 (GCR1) has also been reported in SLE. Because CR1 is excreted in urine it is imperative to study the relationship of urinary CR1 (uCR1) with ECR1 and GCR1, and their overall correlation with disease activity. We have determined the levels of uCR1, ECR1 and GCR1 in SLE patients and compared them with normal controls and minimal change disease (MCD) patients. We found a significant decline in both uCR1 and GCR1 in SLE but not in MCD; levels of uCR1 in MCD were either comparable to those of controls or higher. Immunofluorescence for GCR1 was very high in MCD. We did not find any correlation between ECR1, uCR1 and kidney function tests on divariate scatter analyses. The correlation coefficient for uCR1 and GCR1 was highly significant and positive. Our findings thus suggest that uCR1 reflects the levels of GCR1 expression, which decline drastically in SLE. Therefore we envisage uCR1 as a potential marker for glomerular involvement in SLE.

Case-Control Studies↗