PubMed Health⌕ Search

Biomedical subjects

Prabir Roy-Chaudhury

Publications and source records attributed to Prabir Roy-Chaudhury.

At least 19 recordsLinked to original sources
PubMed2006

Alternative medicine use in dialysis patients: potential for good and bad!

Although alternative medicines are widely used within the general population, the extent of their use within the dialysis population is unknown. It is possible that dialysis patients may be more likely to turn towards alternative therapies in view of the chronicity of their disease. In addition, this particular patient population could be at an increased risk of toxicity from these therapies due to an absence of renal excretion. A detailed assessment of complementary and alternative medicine use in our dialysis patients revealed that 18% of our patients had used or were using some form of alternative medicine therapy. An additional 63% of our patients, however, were willing to use a complementary or alternative medication. Our results suggest that hemodialysis patients are extremely receptive to the use of such therapies and are therefore exposed to all their potential benefit and harm.

Adult↗
PubMed2006

Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model.

BACKGROUND: Haemodialysis vascular access dysfunction is currently a huge clinical problem. In an attempt to reduce the morbidity associated with haemodialysis vascular access dysfunction, we have previously developed and validated a local perivascular paclitaxel release system that has been shown to release paclitaxel for at least 3 weeks. The aim of the current study was to evaluate the in vivo use of these perivascular wraps (for both safety and efficacy) at different time points in our pig model of arteriovenous graft stenosis. METHODS: Paclitaxel-loaded ethylene vinyl acetate wraps were placed around the graft-vein anastomosis on one side, with control polymers being placed on the contralateral side in our pig model of arteriovenous graft stenosis. Animals were sacrificed at early (10-11 days), middle (23-24 days) and late (32-38 days) time points. The entire graft-vein anastomosis was removed at the time of sacrifice and assessed for the extent of luminal stenosis using histomorphometric techniques. RESULT: Graft-vein anastomoses treated with the paclitaxel-loaded polymers had an almost complete absence of luminal stenosis at the middle (23-24 days) and late (32-38 days) time points (when one would expect the development of neointimal hyperplasia) as compared with the contralateral control graft-vein anastomoses (37.90% luminal stenosis in the controls vs 0.10% in the paclitaxel group). There were minimal local side effects from this procedure. CONCLUSIONS: Our results demonstrate the safety and efficacy of paclitaxel-loaded perivascular wraps in the setting of a pig model of arteriovenous graft stenosis. We believe that such a local approach which could be easily applied at the time of surgery is ideally suited for use in the clinical setting of haemodialysis vascular access dysfunction. It is likely that this novel approach could result in a significant reduction in the huge economic and health morbidity costs currently associated with this recalcitrant clinical problem.

Animals↗
PubMed2006

Development of a local perivascular paclitaxel delivery system for hemodialysis vascular access dysfunction: polymer preparation and in vitro activity.

Hemodialysis vascular access dysfunction (HVAD) is currently a huge clinical problem. The major cause of HVAD is venous stenosis (as a result of venous neointimal hyperplasia) which leads to thrombosis in polytetrafluoroethylene dialysis access grafts and fistulae. Despite the magnitude of the clinical problem there are currently no effective therapeutic interventions for this condition. In an attempt to reduce the morbidity associated with HVAD, we have developed and validated a local perivascular paclitaxel release system for use in a pig model of arteriovenous graft stenosis. Ethylene vinyl acetate polymers with 5% paclitaxel were formulated. The release profile of paclitaxel was then manipulated to maximize its biological impact in the in vivo situation. In vitro experiments were performed to confirm that the paclitaxel released from the polymer was biologically active against cell types that were similar to those present in the in vivo lesion of neointimal hyperplasia. Our results demonstrate that the paclitaxel polymer wraps which we have developed are mechanically stable with a burst release phase followed by a slower continuous release phase. The paclitaxel released from these polymeric wraps retains its physicochemical and biological properties and is able to inhibit the proliferation of smooth muscle cells, endothelial cells and fibroblasts in vitro. We believe that these paclitaxel-loaded polymeric wraps could be ideally suited for perivascular drug delivery in the context of dialysis access grafts and fistulae.

Arteriovenous Shunt, Surgical↗
PubMed2006

Simultaneous corticosteroid avoidance and calcineurin inhibitor minimization in renal transplantation.

Steroids and calcineurin inhibitors (CNI) have been mainstays of immunosuppression but both have numerous side effects that are associated with substantial morbidity and mortality. This study was carried out to determine if steroids can be eliminated with early discontinuation of cyclosporine A (CsA) and later discontinuation of mycophenolate mofetil (MMF). Ninety-six patients with kidney transplants were entered into four subgroups of two pilot studies. All patients received Thymoglobulin induction, rapamycin (RAPA), and the immunonutrients arginine and an oil containing omega-3 fatty acids. Mycophenolate mofetil was started in standard doses and discontinued by 2 years. CsA was given in reduced doses for either 4, 6, or 12 months. Follow-up was 12-36 months. Thirteen first rejection episodes occurred during the first year (14%). Combining all patients, 86% were rejection-free at 1 year, 80% at 2 years and 79% at 3 years. No kidney has been lost to acute rejection. Ninety percent of the 84 patients at risk at the end of the study were steroid-free and 87% were off CNI. Fifty-seven percent of 54 patients with a functioning kidney at 3 years were receiving monotherapy with RAPA. We conclude that this therapeutic strategy is worthy of a prospective multi-center clinical trial.

Adrenal Cortex Hormones↗
PubMed2006

Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy.

Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1(p44), and VP1(p108). Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1(p44)) and 5 of 10 (VP1(p108)) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1(p44) were more abundant than against VP1(p108) in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1(p36) and VP1(p100). A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses.

Adult↗
PubMed2006

Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population. The major cause of hemodialysis vascular access dysfunction is venous stenosis as a result of neointimal hyperplasia. Despite the magnitude of the clinical problem, however, there has been a paucity of novel therapeutic interventions in this field. This is in marked contrast to a recent plethora of targeted interventions for the treatment of arterial neointimal hyperplasia after coronary angioplasty. The reasons for this are two-fold. First there has been a relative lack of cellular and molecular research that focuses on venous neointimal hyperplasia in the specific setting of hemodialysis vascular access. Second, there have been inadequate efforts by the nephrology community to translate the recent advances in molecular and interventional cardiology into therapies for hemodialysis vascular access. This review therefore (1) briefly examines the different forms of hemodialysis vascular access that are available, (2) describes the pathology and pathogenesis of hemodialysis vascular access dysfunction in both polytetrafluoroethylene grafts and native arteriovenous fistulae, (3) reviews recent concepts about the pathogenesis of vascular stenosis that could potentially be applied in the setting of hemodialysis vascular access dysfunction, (4) summarizes novel experimental and clinical therapies that could potentially be used in the setting of hemodialysis vascular access dysfunction, and, finally, (5) offers some broad guidelines for future innovative translational and clinical research in this area that hopefully will reduce the huge clinical morbidity and economic costs that are associated with this condition.

Angioplasty↗
PubMed2005

Body weight alterations under early corticosteroid withdrawal and chronic corticosteroid therapy with modern immunosuppression.

BACKGROUND: Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. METHODS: Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. RESULTS: One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). CONCLUSIONS: Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.

Adrenal Cortex Hormones↗
PubMed2005

Paclitaxel impairs endothelial cell adhesion but not cytokine-induced cellular adhesion molecule expression.

Local delivery of antiproliferative agents using drug-eluting stents has become a productive area of research for preventing in-stent restenosis. Recently, the microtubule stabilizing drug paclitaxel has been used to coat stents. While the actions of paclitaxel on smooth muscle are well documented, effects on endothelial cells (ECs) are largely unknown. Nevertheless, restoration of EC function is a critical step in repairing the vascular lesion. We assessed the effects of paclitaxel by examining three events that are critical in controlling the severity of vascular injury: (1) adhesion of ECs to matrix proteins, (2) EC migration, and (3) cytokine-stimulated cellular adhesion molecule (CAM) expression on the surface of ECs. Paclitaxel inhibited both EC adhesion and migration of ECs; however, it had no effect on tumor necrosis-stimulated CAM expression on ECs. The mechanisms of paclitaxel action on matrix adhesion and migration are not clear, but protein kinase C and myosin light chain kinase do not appear to play a role as they are unaffected by treatment of the cells with paclitaxel. On the other hand, the MAP kinase ERK1/2 is modestly inhibited by paclitaxel. While paclitaxel-coated endovascular stents may prevent smooth muscle proliferation, their attenuation of EC migration and adhesion to the lesion coupled with an inability to reduce cytokine-induced CAM expression on ECs may limit their effectiveness.

Antineoplastic Agents↗
PubMed2005

Vascular access in hemodialysis: issues, management, and emerging concepts.

This article (1) identifies the types of hemodialysis access, (2) summarizes the clinical standard of care for dialysis access grafts and fistulae, (3) describes the pathology and pathogenesis of venous stenosis in dialysis access grafts and fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access dysfunction and speculates on the rea-sons for the lack of effective therapies, and (5) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. The possibility that dialysis access grafts and fistulae could be the ideal clinical model for testing novel local therapies to block neointimal hyperplasia is discussed.

Arteriovenous Anastomosis↗
PubMed2005

African-American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African-Americans (AAs) have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. As a result, AAs are often excluded from corticosteroid withdrawal (CSWD) protocols. Modern immunosuppression has reduced rejections and improved graft survival in AAs and may allow successful CSWD. Outcomes in 56 AAs were compared to 56 non-AAs. All patients were enrolled in one of four early CSWD protocols. Results are reported as AA versus non-AA. Acute rejection at 1-year was 23% and 18%; (p = NS); creatinine clearance at 1-year was 75 versus 80 mL/min (p = NS); patient and graft survival was 96% versus 98% and 91% versus 91%; (p = NS). AAs benefit from early CSWD with significantly improved blood pressure, LDL < 130 mg/dL and HDL > 45 mg/dL at 1-year, post-transplant diabetes of 8.7%, and mean weight change at 1-year of 4.8 +/- 7.2 kg. In conclusion, early CSWD in AAs is associated with acceptable rejection rates, excellent patient and graft survival, and improved cardiovascular risk, indicating that the risks and benefits of early CSWD are similar between AAs and non-AAs. Additional follow-up is needed to determine long-term renal function, graft survival, and cardiovascular risk in AAs with early CSWD.

Adrenal Cortex Hormones↗
PubMed2005

Multivariate analysis of risk factors for acute rejection in early corticosteroid cessation regimens under modern immunosuppression.

The purpose of this study was to define risk factors for acute rejection with early corticosteroid withdrawal (CSWD; within 7 days posttransplant) in renal transplantation. Data from prospective, IRB-approved early CSWD trials were analyzed. Overall acute rejection rate in 308 patients was 17.1%. Acute rejection rates and observed risks (OR) in patients with individual risk factors were: repeat transplants 38.6%; current PRA >25%; 29.4%; African Americans 23.5%; delayed graft function (DGF) 26.1%; HLA DR mismatches >0 17.9%; female gender 19.7%; Thymoglobulin induction 15.3%; type 1 diabetes 30.8%; type 2 diabetes 11.1%; deceased donor recipients 21%; and living donor recipients 14%. Logistic regression analysis provided the following risks (OR) for acute rejection: repeat transplant 2.51; current PRA > 25% 1.53; African Americans 1.47; DGF 1.58; HLA DR mismatches > 0 1.61; female gender 1.43; Thymoglobulin induction 0.61; type 1 diabetes 2.23, type 2 diabetes 0.5, deceased donor recipients 1.11, and living donor recipients 0.9. Risk factors for acute rejection under early corticosteroid withdrawal are similar to those previously defined under chronic corticosteroid therapy. These observations provide implications for future CSWD trials including: use of T cell depleting antibody induction therapy (thymoglobulin) to reduce acute rejection risk, 2) enrollment stratification for high risk groups, and 3) modified immunosuppression for high risk groups.

Acute Disease↗
PubMed2005

Novel therapies for hemodialysis vascular access dysfunction: fact or fiction!

Hemodialysis vascular access dysfunction is a major cause of morbidity in the hemodialysis population and contributes significantly to the overall cost of end-stage renal disease programs. At a histological level, most hemodialysis vascular access dysfunction (in both native arteriovenous fistulae and PTFE dialysis access grafts) is due to venous stenosis and thrombosis, secondary to venous neointimal hyperplasia. However, despite a wealth of experimental and clinical data on the use of novel therapeutic interventions that target neointimal hyperplasia in the setting of coronary artery disease, there are unfortunately no effective therapeutic interventions for hemodialysis vascular access dysfunction at the present time. This is particularly unfortunate, since neointimal hyperplasia in the setting of hemodialysis vascular access fistulae and grafts could be the ideal clinical model to test novel therapeutic interventions for neointimal hyperplasia.

Arteriovenous Shunt, Surgical↗
PubMed2004

West Nile virus encephalitis in organ transplant recipients: another high-risk group for meningoencephalitis and death.

West Nile virus infection has been spreading westward across the continental United States since 1999. Although it often presents as a mild, self-limiting viral illness, it can result in a devastating meningoencephalitis in some patient populations, particularly the elderly. We report in this article on two immunosuppressed transplant patients who developed a severe meningoencephalitis caused by mosquito-borne West Nile virus infection. Suggestions for the prevention, diagnosis, and treatment of West Nile virus infection in this patient population are described.

Adult↗
PubMed2004

Polyomavirus nephropathy in kidney transplantation.

Polyomavirus nephropathy has become an important complication in kidney transplantation, with a prevalence of 1% to 8%. Unfortunately, the risk factors for polyomavirus nephropathy and renal allograft loss are not well defined. The definitive diagnosis is made through assessment of a kidney transplant biopsy. Recently, noninvasive urine and serum markers have been used to assist in polyomavirus nephropathy diagnosis and monitoring. Primary treatment is immunosuppression reduction, but must be balanced with the risks of rejection. No antiviral treatments for polyomavirus nephropathy have been approved by the Food and Drug Administration. Although cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Graft loss due to polyomavirus nephropathy should not be a contraindication to retransplantation; however, experience is limited. This review presents potential risk factors, screening, diagnostic and monitoring methods, therapeutic management, and retransplantation experience for polyomavirus nephropathy.

Antiviral Agents↗
PubMed2004

Basic and clinical research in polyomavirus nephropathy.

Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence of 1%-8% in renal transplant recipients and is most commonly reported within the first 12 months posttransplant. The human polyomavirus, BK virus, is thought to be the primary etiologic agent of PVN. Risk factors for PVN are not well defined and are most likely a result of a complex interaction between multiple donor and recipient factors. Definitive diagnosis of PVN is made through histological assessment of a renal allograft biopsy. Recent studies have also evaluated noninvasive urine and serum markers for screening of BK virus replication and as adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is immunosuppression reduction, but this must be balanced against the risks of rejection. If rejection occurs concurrently with PVN, a brief increase in immunosuppression to treat the rejection episode followed by a subsequent reduction in immunosuppression is recommended. No antiviral treatments for PVN have been approved by the Food and Drug Administration. Although the antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Small series of patients treated with leflunomide and intravenous immune globulin therapy for PVN have also recently been reported. Retransplantation after graft loss due to PVN is feasible, but experience is limited. Current research is focusing on identifying PVN risk factors, refining screening, diagnostic and monitoring methods, and developing therapy for prophylaxis and treatment of PVN with the goals of decreasing the prevalence of PVN and improving allograft outcomes in renal transplant recipients diagnosed with PVN. This review will present recent advances in basic and clinical research related to PVN and renal transplantation.

Humans↗
PubMed2003

MALToma: a Helicobacter pylori-associated malignancy in transplant patients: a report from the Israel Penn International Transplant Tumor Registry with a review of published literature.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma (MALToma) is a Helicobacter pylori-related tumor of B-cell origin, the malignant potential for which remains to be defined in immunosuppressed patients. METHODS: Review of the Israel Penn International Transplant Tumor Registry identified six cases of gastric MALToma. Patient demographics, management, and outcomes were compared and published literature was reviewed. RESULTS: MALToma developed in six transplant recipients (three kidney, two heart, one kidney-pancreas). All were treated with immunosuppression minimization and therapy for H. pylori, resulting in disease regression in five patients. One patient developed progression to high-grade MALToma despite documented H. pylori eradication, required surgery and chemotherapy, and died, with significant disease at autopsy. CONCLUSIONS: Treatment of MALToma with immunosuppression minimization and anti-H. pylori therapy results in a majority of patients becoming disease free. Observation of malignant degeneration into an aggressive, high-grade lymphoma in one patient indicates the malignant potential. Diligent follow-up of these patients with endoscopy and biopsy is therefore indicated.

Adult↗