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Biomedical subjects

Samir K Gupta

Publications and source records attributed to Samir K Gupta.

11 recordsLinked to original sources
PubMed2005

The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) regimens, especially those containing protease inhibitors (PIs), are at increased risk for cardiovascular events. Albuminuria is a known independent predictor for the development of cardiovascular disease and may potentially increase in patients receiving PIs. Alternatively, albuminuria may improve with HAART as a result of treating renal parenchymal HIV infection. Longitudinal studies have not been performed previously addressing the effects of HAART on albuminuria. METHODS: We evaluated the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64 weeks of therapy in 68 previously untreated HIV-infected subjects, without pre-existing diagnosed diabetes or hypertension, enrolled in a randomized trial comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also estimated the prevalence of albuminuria, defined as an ACR > or =3.4 mg/mmol, in these subjects prior to initiation of HAART. RESULTS: The changes in ACR over the initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (-0.4, 0.3)] and in those not receiving PIs [0.0 mg/mmol (-0.5, 0.3)] were not significantly different. There was also no significant difference in the change in the ACR in the group as a whole. However, albuminuria at baseline was found in seven (10%) subjects. Five of these seven subjects had substantial improvements in ACR, ranging from 45 to 95%, with HAART use; three subjects had resolution of albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = -0.25; P = 0.04). CONCLUSION: Albuminuria in HIV-infected, treatment-naïve patients was found more frequently than expected and may be influenced by baseline immune status. Although we did not observe an effect of HAART on ACR during the first 64 weeks of therapy, we cannot exclude the possibility that HAART may be beneficial in those patients with significant albuminuria prior to treatment. Research in larger cohorts is required to investigate more definitively the associations between immune status, antiretroviral therapies and renal function in HIV-infected patients.

Adult↗
PubMed2004

The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection.

BACKGROUND: While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spectrum of other kidney diseases seen among HIV-infected patients. METHODS: This retrospective cohort study included all HIV-infected patients who underwent renal biopsy during the course of their clinical care at six major medical centers. Demographic and clinical information were abstracted from each patient's clinical record. Time to initiation of renal replacement therapy was compared for patients with lesions other than HIVAN to patients with HIVAN using Cox proportional hazards regression. RESULTS: Eighty-nine patients (47 with lesions other than HIVAN and 42 with HIVAN) were available for inclusion. Patients with lesions other than HIVAN were less likely to be black (37/47 vs. 42/42, P= 0.02), more likely to have a positive hepatitis B surface antigen (10/37 vs. 4/42, P= 0.04), less likely to have the diagnosis of hypertension (24/46 vs. 31/42, P= 0.03), more likely to have a greater creatinine clearance at time of biopsy (60.6 vs. 39.0 cc/min, P= 0.008), and have a greater CD4 lymphocyte count at time of biopsy (287 vs. 187 cells/mL, P= 0.04) compared to patients with HIVAN. Lesions other than HIVAN were associated with a longer time to initiation of renal replacement therapy compared with HIVAN (HR 0.33, 95% CI 0.15-0.71, P= 0.005). Other factors associated with a longer time to renal replacement therapy included higher creatinine clearance at time of biopsy, greater CD4(+) lymphocyte count, the absence of hepatitis C antibody, and the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The type of renal disease (HIVAN vs. other) interacted significantly with HIV-1 RNA level and the use of antiretroviral therapy (P= 0.0001 and 0.006, respectively). Among patients with lesions other than HIVAN, the presence of nondetectable HIV-1 RNA was not associated with a greater risk of progression of renal disease (HR 0.27, P= 0.24). Among patients with HIVAN, because all patients had detectable virus at the time of institution of renal replacement therapy, this highly significant association could not be quantified. Among patients with lesions other than HIVAN, the use of antiretroviral therapy was not associated with the progression to renal replacement therapy (HR 3.29, P= 0.06). Among patients with HIVAN, the use of antiretroviral therapy was associated with a slower progression to renal replacement therapy (HR 0.24, P= 0.03). CONCLUSION: Among HIV-infected patients with renal disease other than HIVAN, viral suppression and the use of antiretroviral therapy are not associated with a beneficial effect on renal function; thus, additional therapeutic strategies may need to be utilized. Because renal histology is associated with prognostic differences, these data provide outcomes information that will improve the clinical utility of renal biopsy among HIV-infected patients with renal disease.

AIDS-Associated Nephropathy↗
PubMed2003

Roux-en-Y gastric bypass leak complications.

HYPOTHESIS: Enteric leakage is a significant complication of the Roux-en-Y gastric bypass (RYGB) procedure that can be treated successfully. DESIGN: Retrospective study of 400 consecutive RYGB patients from 1999-2002. SETTING: Community hospital with a university surgical residency. PATIENTS: Hospital records of 400 morbidly obese patients who underwent gastric bypass surgery were reviewed. MAIN OUTCOME MEASURES: Time of discovery of leak, location of leak, treatment, hospital stay, and mortality. RESULTS: Twenty-one patients (5.25%) developed leaks. The mean body mass index (calculated as weight in kilograms divided by the square of height in meters) was 54.2. Thirteen patients were noted to develop a leak at the gastrojejunal anastomosis, with an average time to diagnosis of 7.0 days. Five of these patients underwent reexploration, and 8 were successfully treated with percutaneous drainage alone. Four patients developed leaks at the jejunojejunal anastomosis (mean time to diagnosis, 2.0 days). All of these patients required exploration, and 2 patients died. Four patients were noted to have leaks in other areas (average time to diagnosis, 3.5 days). Two patients were treated with drainage, and 2 underwent exploration. The average hospital stay of all patients was 33 days. CONCLUSIONS: Enteric leakage is a significant complication of the RYGB. Patients who are suspected of having an enteric leak because of signs of sepsis or hemodynamic instability require emergent exploration. Leaks that are more insidious may be treated successfully with percutaneous drainage. Aggressive exploration of patients who appear to be septic, and percutaneous drainage of insidiously developing leaks may decrease patients' morbidity and mortality.

Adult↗
PubMed2003

Single-dose pharmacokinetics and tolerability of pegylated interferon-alpha2b in young and elderly healthy subjects.

AIMS: To assess the single-dose pharmacokinetics and tolerability of pegylated interferon-alpha2b (PEG-Intron) in young and elderly healthy subjects. METHODS: In this parallel-design study, a single 1 microg x kg(-1) PEG-Intron dose was given subcutaneously to 24 subjects in the age groups 20-45, 65-69, 70-74 and 75-80 years (n = 6/group). Blood sampling and tolerability assessments were performed up to 168 h postdose. RESULTS: The pharmacokinetic parameters were similar in all age groups. The elderly to young subject ratios for Cmax were 91.1, 79.5, and 107% for the 65-69 years, 70-74 years and 75-80 years groups, respectively. The corresponding values for AUC(0- infinity ) and CL/F were 111, 102 and 108%, and 82.5, 95.8 and 86.4%, respectively. Mean differences from the 20 to 45 years group and the 65-69 years, 70-74 years and 75-80 years groups for PEG-Intron Vd/F were 108, 128 and 104%, respectively. None of these differences was statistically significant based on ANOVA. Results from a Dunnett's test (as post hoc assessment) confirmed that the pharmacokinetic parameters of Group II, Group III or Group IV were not different from those of Group I. Almost all (23/24; 96%) subjects reported typical interferon-alpha side-effects (flu-like symptoms, headache). One elderly patient had a myocardial infarction 12 h postdose, but recovered fully. CONCLUSIONS: There are no pharmacokinetic reasons for initial dose adjustment of PEG-Intron based on age.

Adult↗
PubMed2002

Pegylated interferon alfa-2b treatment for patients with solid tumors: a phase I/II study.

PURPOSE: The efficacy of interferon alfa has been established in treating advanced melanoma and renal cell carcinoma (RCC) patients. We conducted a phase I/II study to determine the maximum-tolerated dose (MTD), the safety and tolerability, and the preliminary efficacy of once-weekly pegylated interferon alfa-2b (IFNalpha-2b) in patients with advanced solid tumors (primarily RCC). PATIENTS AND METHODS: To determine the MTD, 35 patients with a variety of advanced solid tumors received 0.75 to 7.5 micro g/kg/wk of pegylated IFNalpha-2b by subcutaneous injection for 12 weeks. An additional 35 previously untreated RCC patients received 6.0 and 7.5 micro g/kg/wk for up to 12 weeks. Patients with a response or stable disease after 12 weeks were eligible for the extension protocol and were treated for up to 1 year or until disease progression. RESULTS: The MTD for pegylated IFNalpha-2b at 12 weeks was 6.0 micro g/kg/wk. One year of 6.0 micro g/kg/wk was well tolerated with appropriate dose modification; no grade 3 or 4 fatigue occurred, and safety was comparable with that with nonpegylated IFNalpha-2b. The most common nonhematologic adverse events included mild to moderate nausea, anorexia, and fatigue. Six patients had grade 3 or 4 hematologic toxicity. Twenty-nine patients continued on the extension protocol. Four patients had a complete response, and five patients had a partial response. Among 44 previously untreated RCC patients, the objective response rate was 14%. Median survival for all RCC patients was 13.2 months. CONCLUSION: Pegylated IFNalpha-2b was active and well tolerated in patients with metastatic solid tumors, including RCC, at doses up to 6.0 micro g/kg/wk.

Adenocarcinoma↗
PubMed2002

Exogenous cushing syndrome mimicking human immunodeficiency virus lipodystrophy.

A 45-year-old man infected with human immunodeficiency virus (HIV) developed abnormal fat accumulations that initially were believed to be caused by HIV lipodystrophy. Further clinical evaluation revealed, however, that the patient had developed exogenous Cushing syndrome, which presumably was caused by the inhibition of CYP3A4's metabolism of inhaled fluticasone by the protease inhibitor ritonavir. Clinicians should be aware that clinical clues may indicate conditions other than lipodystrophy that may cause abnormal fat accumulation and that fluticasone should be cautiously administered to patients who are receiving ritonavir.

Androstadienes↗
PubMed2002

Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models.

BACKGROUND: Combination therapy of ribavirin with interferon alfa-2b and pegylated interferon alfa-2b is currently approved for the treatment of chronic hepatitis C. Approved ribavirin dosages vary from a fixed dosage of 800 mg/d to as much as 1200 mg/d on the basis of body weight. OBJECTIVE: Our objective was to evaluate ribavirin dosing strategies by comparison of their relative efficacy and toxicity profiles. METHODS: Three models were developed on the basis of data collected from a large phase III trial. A population pharmacokinetic model was used to describe the ribavirin dose-concentration relationship and the influence of covariates. Logistic regression models were developed for both sustained virologic response and hematologic toxicity. Ribavirin concentration was an important explanatory variable for both response and toxicity. Simulations of these models were developed for different ribavirin doses to obtain efficacy and toxicity profiles across the various dosing strategies. These strategies included a fixed 800-mg/d dose, empiric weight-adjusted doses (ie, 1000 mg/d for patients who weighed < or =75 kg and 1200 mg/d for patients who weighed >75 kg [1000/1200 mg/d on the basis of body weights < or =75/>75 kg] and 800 mg/d for patients who weighed <65 kg, 1000 mg/d for patients who weighed from 65 to 85 kg, and 1200 mg/d for patients who weighed >85 kg [800/1000/1200 mg/d on the basis of body weights <65/65-85/>85 kg]), a dose of 13 mg/kg per day, and other per-body weight doses between 9 and 16 mg/kg per day. RESULTS: Simulation results showed that both efficacy and toxicity increased as the milligrams-per-kilogram dose of ribavirin increased. The body weight-based 800/1000/1200-mg/d dose had overall response and toxicity rates that were 6.3% and 2.5% higher than those of the fixed 800-mg/d dose. In particular, patients with genotype-1 disease had a 7.4% increase in response rate. There were no differences in response and toxicity rates between the 800/1000/1200-mg/d and 13-mg/kg per day dose groups. CONCLUSIONS: This simulation suggests that ribavirin dosage (in combination with pegylated interferon alfa-2b) for patients with chronic hepatitis C should be based on body weight.

Adult↗
PubMed2002

Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.

Aged↗