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Biomedical subjects

K S Reddy

Publications and source records attributed to K S Reddy.

At least 19 recordsLinked to original sources

Methods for establishing a surveillance system for cardiovascular diseases in Indian industrial populations.

OBJECTIVE: To establish a surveillance network for cardiovascular diseases (CVD) risk factors in industrial settings and estimate the risk factor burden using standardized tools. METHODS: We conducted a baseline cross-sectional survey (as part of a CVD surveillance programme) of industrial populations from 10 companies across India, situated in close proximity to medical colleges that served as study centres. The study subjects were employees (selected by age and sex stratified random sampling) and their family members. Information on behavioural, clinical and biochemical determinants was obtained through standardized methods (questionnaires, clinical measurements and biochemical analysis). Data collation and analyses were done at the national coordinating centre. FINDINGS: We report the prevalence of CVD risk factors among individuals aged 20-69 years (n = 19 973 for the questionnaire survey, n = 10 442 for biochemical investigations); mean age was 40 years. The overall prevalence of most risk factors was high, with 50.9% of men and 51.9% of women being overweight, central obesity was observed among 30.9% of men and 32.8% of women, and 40.2% of men and 14.9% of women reported current tobacco use. Self-reported prevalence of diabetes (5.3%) and hypertension (10.9%) was lower than when measured clinically and biochemically (10.1% and 27.7%, respectively). There was marked heterogeneity in the prevalence of risk factors among the study centres. CONCLUSION: There is a high burden of CVD risk factors among industrial populations across India. The surveillance system can be used as a model for replication in India as well as other developing countries.

Adult↗

Acute rejection risk in kidney transplant recipients on steroid-avoidance immunosuppression receiving induction with either antithymocyte globulin or basiliximab.

Immunosuppression with rapid discontinuation of corticosteroids, usually with induction therapy, is safe in kidney transplant recipients. In 89 patients, we induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17 and 72 patients, respectively). Selection criteria for basiliximab were age (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes mellitus (eligible for pancreas transplant). Steroids were administered through posttransplantation day 4 (five doses); maintenance immunosuppression was with tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%). Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The overall risk of biopsy-proven acute rejection was 12%. At 6 months posttransplantation, acute rejection-free survival was 93% for antithymocyte globulin, 65% for basiliximab (P<.001). Median time to biopsy-proven acute rejection was 27 and 71 days, respectively. The low incidence of biopsy-proven acute rejection with steroid-avoidance immunosuppression may be further reduced with antithymocyte globulin.

Acute Disease↗

Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel.

A panel of fluorescence in situ hybridisation (FISH) probes was used on 894 cases to target chromosome 11q, 13q, 17p deletions (del), trisomy 12 (+12) in all and 6q deletion in 59. Chronic lymphocytic leukaemia (CLL) immunophenotype (CD5 and CD19 with CD23) was found in 509 cases (average age 67.7 years, 319 males and 190 females). Among the 509 CLL cases 349 (68.6%) had FISH (4-probe panel) abnormalities: 160 del 13q [45.8% (122-del 13q, 18-biallelic del 13q, 20-monoallelic/biallelic del 13q)], 71 tri 12 (20.3%), 17 del ATM (5%), 12 del p53 (3.4%) and 89 > or = 2 FISH abnormalities (25.5%). Of 151/509 cases karyotyped, 108 were normal and 43 (43/151 = 28.5%) abnormal. Del 6q was found in 1/59 (1.6%) FISH cases and in 6/151 (4%) karyotypes. In 14 CD23 negative cases IGH/BCL1 FISH detected t(11;14) and was confirmed to be mantle cell lymphoma. Multiple probes/panels that included IGH probe were ordered for 57 CLL cases, 11 had an IGH rearrangement with an unidentified partner. This study favours the inclusion of del 6q and IGH probes in the CLL panel. The FISH panel could also serve to monitor 13q deletion for secondary changes with adverse prognosis. Understanding prognosis in specific types of 13q deletion would enhance outcome prediction.

ADP-ribosyl Cyclase 1↗

Why are urban Indian 6th graders using more tobacco than 8th graders? Findings from Project MYTRI.

OBJECTIVE: To investigate why urban Indian 6th graders may be using more tobacco than urban Indian 8th graders. DESIGN: Cross-sectional survey of students conducted in the summer of 2004, as the baseline evaluation tool for a group-randomised tobacco prevention intervention trial (Project MYTRI). Mixed-effects regression models were used to (1) examine the relationship between 15 psychosocial risk factors and current use of any tobacco, by grade; and (2) examine differences in psychosocial risk factors, by grade. SETTING: Thirty-two private (high socioeconomic status (SES)) and government (low-mid SES) schools in two large cities in India (Delhi and Chennai). SUBJECTS: Students in the 6th and 8th grade in these schools (n = 11642). Among these, 50.6% resided in Delhi (v Chennai), 61.4% attended a government school (v a private school), 52.9% were enrolled in 6th grade (v 8th), and 54.9% were male (v female). MAIN OUTCOME MEASURE: Current (past 30 day) use of any tobacco, including chewing tobacco (for example, gutkha), bidis, or cigarettes. RESULT: Almost all psychosocial factors were significantly related to tobacco use, for students in both grades. Some of the strongest correlates included social susceptibility to and social norms about use. Exposure to tobacco advertising was a strong correlate of tobacco use for 6th graders, but not for 8th graders. Sixth graders scored lower than 8th graders on almost all factors, indicating higher risk. CONCLUSIONS: The "risk profile" of 6th graders suggests they would be vulnerable to use and to begin using tobacco, as well as to outside influences that may encourage use.

Adolescent↗

Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India.

The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25-79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured. British Gujaratis had higher, mean body mass indices by 6 (4.5-7.4) kg/m(2) mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B(12) were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors. In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.

Adult↗

Steroid avoidance immunosuppression in low-risk kidney transplant recipients.

Recent clinical trials have documented the short-term safety of steroid avoidance (SA) in kidney transplant recipients. Since July 2003, we have used a SA immunosuppression protocol for low-risk kidney transplant recipients. Eligibility criteria are age > or = 18, primary transplant (living or deceased donor), and tacrolimus started by postoperative day 3. Recipients were excluded if peak/current PRA was >50%/20%, or if they had a positive flow crossmatch, or if they had the recent use of corticosteroids (<6 months). All recipients received induction with rabbit anti-thymocyte globulin, total dose 6 mg/kg, or basiliximab. Recipients received 5 daily doses of corticosteroid and mycophenolate mofetil 1 gm twice daily starting on the day of transplantation. Tacrolimus was started when the serum creatinine level decreased by 20%, or by postoperative day 3. The goal for trough tacrolimus levels was 10-15 ng/mL for the first month, 8-12 ng/mL for months 2-3, and 5-10 ng/mL after month 3. Protocol biopsies (bx) were performed at reperfusion, 1 month, 4 months, and 12 months. Ninety-four kidney transplantations were performed during the study period. Sixty-seven recipients (71%) were eligible and enrolled in SA. Characteristics of the 67 SA recipients: mean age, 53 years (range, 26-70); 41% female; 67% Caucasian; 24% Hispanic; 15% African American; and 5% Native American. Also, 77% received a living donor kidney. The mean follow-up was 180 days (range, 10-360). At last follow-up, 91% remained steroid-free. Biopsy-proven acute rejection (BPAR) occurred in 5 recipients (7.5%). Three recipients (4.5%) had clinical BPAR and 2 had subclinical. One recipient died with pneumonia 4 months following transplantation. Posttransplantation diabetes mellitus (PTDM) occurred in 2 (5%) of 38 recipients. In the initial 41 recipients, 27 had protocol bx at 1 month and 13 at 4 months available for analysis. Chronic allograft nephropathy (CAN) was present on protocol bx in 48% at 1 month and 69% at 4 month. Actuarial (Kaplan-Meier method) patient and graft survival rates at 351 days were 97.8% and 96.8%, respectively. SA with anti-thymocyte globulin induction in low-immunologic risk kidney transplant recipients is safe and is associated with a low risk of BPAR. The incidence of PTDM appears to be lower.

Adrenal Cortex Hormones↗

Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India.

Death from myocardial infarction (MI) in India is exacerbated by smoking of bidis or cigarettes. Smoking among 309 men with incident MI was compared to 618 age matched controls; 56% of the individuals with MI and 26% of controls were current smokers. Current smokers had a relative risk of 4.7 (95% confidence interval (CI) 3.2 to 6.9) compared to never smokers. Relative risks for smoking more than 10 cigarettes or 10 bidis daily were 9.1 (95% CI 4.7 to 17.7) and 8.1 (95% CI 4.3 to 15.3), respectively. It is estimated that smoking may cause 53% (95% CI 47% to 64%) of MIs among urban males in India.

Adult↗

The impact of delayed graft function of the kidney on the pancreas allograft in simultaneous kidney-pancreas transplantation.

UNLABELLED: It is unclear whether delayed graft function (DGF) of the kidney has any influence on pancreas graft function following simultaneous kidney-pancreas transplantation (SKPT). A subgroup analysis was conducted using data from a multicenter study to determine the impact of DGF of the kidney on pancreas graft function following SKPT. METHODS: Of the 297 SKPT patients, 24 (8%) had DGF of the kidney, defined as the need for dialysis during the first week posttransplant. Clinical parameters including patient and graft survival, incidence of acute rejection, and pancreas and renal function were compared between patients with and without DGF at 1 week, and at 1, 3, 6, and 12 months posttransplant. RESULTS: Demographic and transplant characteristics were similar between the two groups except for longer kidney and pancreas cold ischemia times, more males, and more primary cytomegalovirus (CMV) exposure in the DGF group (P <.05). No differences were seen in patient and graft survival rates, but the incidence of acute renal rejection was higher in patients with DGF (42%) than in those without DGF (15%, P =.001). More patients with DGF (25%) received oral hypoglycemic agents at 1-year posttransplant than in those without DGF (5%, P <.01). At 1 year, the mean serum creatinine was 1.8 mg/dL and 1.4 mg/dL in patients with and without DGF, respectively (P <.01). CONCLUSIONS: Patients with DGF of the kidney had a higher incidence of acute renal rejection and received oral hypoglycemic agents more often during the first year posttransplant compared to those who did not have DGF following SKPT.

Cytomegalovirus Infections↗

Evaluation of zinc against salinomycin toxicity in broilers.

Salinomycin was studied for its toxicity and zinc (80 mg/kg) was assessed for prophylactic and therapeutic management in broiler chicks. Male broiler chicks were randomly divided into 7 groups consisting of 6 chicks in each. Group 1, 2 and 3 were maintained as control, therapeutic dose control (60 mg/kg feed) and toxic dose control (120 mg/kg feed), respectively. Group 4 was fed on feed containing salinomycin therapeutic dose and zinc. Group 5 received feed containing toxic dose of salinomycin. Group 6 and 7 were fed on feed containing toxic dose of salinomycin for the first 4 weeks for induction of ionophore toxicity and for the subsequent 2 weeks, group 6 received zinc and group 7 was fed on feed containing toxic dose of salinomycin along with zinc. Weekly body weights revealed a significant (P<0.01) decrease in toxic controls as compared to group 1, 2, 4 and 5. The activity of glutathione peroxidase, glutathione reductase and catalase, and the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, total cholesterol, triglycerides, low density lipoproteins (LDL), urea, creatinine and blood urea nitrogen (BUN) were significantly (P<0.01) elevated in toxic controls, whereas glutathione (GSH) and high density lipoproteins (HDL) were significantly (P<0.01) lowered as compared to group 1, 2, 4 and 5. Following toxicity, zinc supplementation in group 6 and 7, all serobiochemical parameters were revived to normal. Thus, it is enunciated that salinomycin toxicity is due to oxidative damage and use of zinc in feed tends to cure and avoid any accidental toxicity.

Animals↗

Vitamin E inhibits cyclosporin A and H2O2 promoted Epstein-Barr virus (EBV) transformation of human B cells as assayed by EBV oncogene LMP1 expression.

BACKGROUND: We have previously shown that oxidative stress induced by H2O2 or cyclosporin A (CsA) can promote Epstein-Barr virus (EBV) transformation of human B cells as analyzed by colony formation, cell number, and by 3H-thymidine incorporation. In this report, we used EBV oncogene LMP1 as a marker to analyze H2O2 or CsA promotion of EBV transformation of human B cells and to test whether antioxidant vitamin E could inhibit H2O2 or CsA promoted LMP1 expression in the EBV-infected cells. MATERIALS AND METHODS: Human splenocytes were prepared by centrifugation and plating technique to provide a greater than 80% pure preparation of B cells and were used for EBV infection. The EBV infected cells were treated with H2O2 (0.1 mM, 10 min), or with CsA (500 ng/ml) with or with out vitamin E (40 microM). The cells were cultured for up to 4 weeks. Samples were taken every week and were stained with phycoerythrin-conjugated mouse anti-LMP1 monoclonal antibody to assay LMP1 positive population by flow cytometry. RESULTS: In EBV-infected cells, the LMP1-positive cell population reached 14% after 4 weeks of culture. CsA or H2O2 treatment promoted LMP1 positive population to 43% and 41% after 4 weeks of culture. Vitamin E (40 microM) completely inhibited LMP1 expression in EBV-infected cells and in CsA- or H2O2-treated cells. CONCLUSION: In agreement with our previous observation, CsA or H2O2 can promote EBV transformation of human B cells. This oxidative stress induced promotion of EBV transformation can be blocked by antioxidant Vitamin E. This finding may have future therapeutic implications for post-transplant lymphoproliferative disorder.

Antioxidants↗

Evaluation of vitamin E against deltamethrin toxicity in broiler chicks.

Deltamethrin toxicity was studied in broilers and vitamin E was evaluated for therapeutic management. Day old male broiler chicks were randomly divided into 3 groups consisting of 6 chicks in each. Group 1 was maintained as control for 6 wks, group 2 was fed on deltamethrin (100 mg/kg feed) for 6 wks and group 3 was fed on deltamethrin for the first 4 wks and during the subsequent 2 wks with vitamin E (300 mg/kg feed) with out deltamethrin. Weekly body weights, feed conversion ratio, glutathione (GSH) concentration and high density lipoproteins (HDL) were significantly (P < 0.05) reduced, while the activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), catalase, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and the lipid profile and renal biomarkers were increased significantly (P < 0.05) in group 2 and 3 at the end of 4th wk as compared to group 1. Following treatment with vitamin E during the last 2 wks in group 3, all the parameters in study revealed improvement. From this study, it is concluded that deltamethrin induces toxicity by oxidative damage in biological system and supplementing vitamin E in feed is useful in treating accidental toxicity.

Animals↗

Differences in body mass index and waist: hip ratios in North Indian rural and urban populations.

Overweight could be a major factor in determining the increasing rates of coronary heart disease in the Indian population, by its influence on blood pressure, diabetes and insulin resistance. We studied the prevalence of overweight in north Indian urban and rural population samples. The urban sample population (n = 3050) was selected using a multistage sampling with stratification for geographical zone and the type of residential colony and cluster sampling of urban blocks in each stratum. The rural sample (n = 2487) was selected by random sampling of villages stratified for population size followed by coverage of all eligible persons in the village. All participating individuals were 35-64 years of age. Women constituted 52.2% (n = 1594) and 57% (n= 1417) of urban and rural samples, respectively. The study reveals that overweight is widely prevalent in the adult urban Delhi population, whereas underweight is a significant problem in the rural population. This was noted across all the age groups in both men and women. We estimated 'comprehensive coronary risk estimates' based on the New Zealand Heart foundation guidelines and noted that the proportion of high and very high risk subjects increased in a continuous manner even within the 'normal' ranges of BMI. This difference in prevalence in the urban population could represent the demographic transition in the Indian population.

Adult↗

Anesthetic stabilization of protein intermediates: myoglobin and halothane.

Halothane, an inhaled anesthetic, destabilizes the folded structure of myoglobin. To determine whether this is due to preferential interactions with less stable folded conformers of myoglobin versus the completely unfolded state, we used photoaffinity labeling, hydrogen exchange, fluorescence spectroscopy, and circular dichroism spectroscopy. Apomyoglobin was used as a model of a less stable conformer of myoglobin. Halothane destabilizes myoglobin and binds with low affinity and stoichiometry but stabilizes and binds with higher affinity to apomyoglobin. The same halothane concentration has no effect on cytochrome c stability. The apomyoglobin/halothane complex is favored at pH 6.5 as compared to pH 4.5 or pH 2.5. Halothane photoincorporates into several sites in apomyoglobin, some allosteric to the heme pocket. Guanidinium unfolding of myoglobin, monitored by CD spectroscopy, shows destabilization at less than 1.3 M Gdm but stabilization at greater than 1.3 M Gdm, consistent with the hypothesis that less stable conformers of myoglobin bind halothane preferentially. We suggest the structural feature underlying preferential binding to less stable conformers is an enlarged cavity volume distribution, since myoglobin has several intermediate-sized cavities, while cytochrome c is more well packed and has no cavities detected by GRASP. Specific binding to less stable intermediates may underlie anesthetic potentiation of protein activity.

Amino Acid Sequence↗

Segmental amplification of 11q23 region identified by fluorescence in situ hybridization in four patients with myeloid disorders: a review.

Four cases with a segmental amplification of 11q23 region were detected by FISH. The amplification was either contiguous amplification on chromosome 11, or multiple markers involving the 11q23 region. The markers were derivative chromosomes, or isochromosomes. Amplification of 11q23 region was associated with complex karyotypes at the time of diagnosis or following treatment in secondary leukemias. Three were AML cases belonging to either AML-M5a or AML-1 subtypes and one was a myeloproliferative disorder. These cases were resistant to treatment. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) studies using MLL, 11 painting, or 11 centromere probes ascertained the segmental amplification. Since the patients did not respond to treatment the amplification of gene or genes that map to 11q23 may be responsible for the unfavorable prognosis. Hence, this type of amplifications could have clinical significance.

Acute Disease↗

Cyclosporine directly causes oxidative stress and promotes Epstein-Barr virus transformation of human B cells.

BACKGROUND: We have previously shown that oxidative stress alone can promote transformation of human B cells infected with Epstein-Barr virus (EBV) in vitro, an accepted model mimicking posttransplant lymphoproliferative disorders (PTLDs). Our laboratory has investigated the direct effects of cyclosporine A (CyA) as an oxidant promoting B-cell transformation and we have proposed that CyA directly promotes B-cell transformation and that this effect can be blocked by antioxidants. METHODS: Human splenocytes were prepared by centrifugation and plating technique to provide a greater than 80% pure preparation of B cells that was used for the direct oxidative stress experiments. These cells were cocultured with CyA (500 ng/ml) and hydrogen peroxide (H(2)O(2), 0.15 mM) with or without antioxidant vitamin E (40 microM). Oxidative stress was evaluated by using a commercial lipid hydroperoxide (LPO) assay kit. In another set of three separate experiments, human B lymphocytes infected with EBV were cultured with CyA (500 ng/ml), H(2)O(2) (0.15 mM), and vitamin E (40 microM). B-Cell transformation by EBV was evaluated by counting colony number and [(3)H]-thymidine incorporation. RESULTS: At therapeutic concentrations, CyA (500 ng/mL) had an oxidative effect on human splenocytes in vitro, similar to the effect of H(2)O(2) (90 and 97% increases, respectively in LPO production over control P < 0.005), which was abrogated by the addition of vitamin E. Similarly, both CyA and H(2)O(2) promoted transformation of B cells infected with EBV(75 and 108% increases respectively in colony counts over control, P < 0.005). This effect was also blocked by vitamin E. CONCLUSIONS: Both CyA and H(2)O(2) have a direct oxidative effect on human B cells and cause promotion of EBV-induced transformation of B cells. These effects are blocked by the antioxidant vitamin E. These findings may have future therapeutic implications for PTLDs.

Antioxidants↗