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Biomedical subjects

D Mital

Publications and source records attributed to D Mital.

At least 19 recordsLinked to original sources
PubMed2003

Use of collagen injections for vesicoureteral reflux in transplanted kidneys.

Reports in the literature suggest the incidence of vesicoureteral reflux (VUR) in transplanted kidneys to range from 2-79%. Collagen injections have been used with reported success rates of up to 65% to prevent VUR into native orifices in children, but have not been studied in transplant neo-orifices. We evaluated the use of collagen injections in seven patients with transplant kidney neo-orifices who displayed grades II-IV VUR and seemed to be related to symptomatic urinary tract infections (UTIs). Postoperative VCUGs obtained at 2 months showed improvement in the grade of reflux in four of seven (57.1%) patients; one (14.3%), no change; and two (28.6%), worse reflux. All patients also redeveloped symptomatic UTIs after collagen injection. We conclude that the use of collagen injections in kidney transplant neo-orifices did not prevent VUR. Although prevention of VUR may have been achieved short term, VCUG examinations 2 months after initial injection revealed persistent reflux. Etiologies for failure to prevent VUR may be the readily absorbable nature of collagen, technical aspects of the procedure, the degree of reflux, and anatomic differences between native orifices (which lie on a well-supported trigone) and transplant neo-orifices (which lie on the posterior wall with less support).

Collagen↗
PubMed2001

Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection.

BACKGROUND: T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the CD4 molecule as a coreceptor of TCR. The CD28/B7 pathway is a major costimulatory signal for T-cell activation and differentiation. METHODS: The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated. RESULTS: Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival. CONCLUSIONS: Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.

Abatacept↗
PubMed1998

Histological characterization and pharmacological control of chronic rejection in xenogeneic and allogeneic heart transplantation.

BACKGROUND: Chronic allograft rejection remains a major barrier to successful long-term allograft transplantation in humans. Chronic allograft rejection is characterized by the appearance of arterial lesions with concentric intimal thickening. This study investigates the development and control of chronic rejection in hamster cardiac xenografts transplanted into Lewis rats. METHODS: Chronic rejection in the xenograft model involves transplantation of hamster hearts into Lewis rats treated with leflunomide (Lef) continuously at 15 mg/kg/day. The allograft model involves transplantation of Lewis hearts into Fisher-334 rats treated with cyclosporine (CsA) at 2.5 mg/kg for 5 days. RESULTS: The average scores of arterial intimal thickening on day 45 after transplantation were 1.89+/-0.43 in the xenograft and 2.50+/-0.72 in the allograft. The basic pathology of both xenografts and allografts undergoing chronic rejection was arterial intimal thickening comprising smooth muscle cell proliferation, mononuclear cell infiltration, and fibrosis. The majority of cells infiltrating the arterial intima and myocardium were T cells and macrophages. Compared with the allograft, intimal edema, matrix deposition and fibrinoid necrosis were specifically presented in the xenografts and generally involved the larger arteries. The predominant isotype of antibody deposited was IgM in xenografts and IgG in allografts. When combined Lef and CsA therapy was initiated on day 45 after transplantation, the changes of chronic rejection were reversed in both xenografts and allografts by day 90. The scores of intimal thickening were significantly reduced to 0.97+/-0.45 and 1.48+/-0.56, respectively. CONCLUSIONS: We conclude that chronic rejection can be induced in xenografts under conditions of inadequate immunosuppression. Chronic rejection in xenografts involves arterial lesions that bear some histological similarities to, as well as differences from, those observed in chronically rejected allografts. Finally, combination therapy with CsA and Lef reduced the incidence and severity of the intimal lesions in both chronically rejecting xenografts and allografts.

Animals↗
PubMed1998

Immunosuppression preventing concordant xenogeneic islet graft rejection is not sufficient to prevent recurrence of autoimmune diabetes in nonobese diabetic mice.

BACKGROUND: We and others have reported previously that the immunosuppressant, leflunomide (Lef), can prevent allogeneic and xenogeneic islet graft rejection in streptozocin (STZ)-induced diabetic animals. However, whether Lef required to prevent islet graft rejection is sufficient to prevent the recurrence of autoimmune diabetes has not been addressed. METHODS: The effect of Lef on concordant xenogeneic islet graft in STZ-induced diabetic mice and autoimmune nonobese diabetic (NOD) mice were studied. Then, whether Lef prevents the onset of spontaneous diabetes in young NOD mice and the recurrence of diabetes after major histocompatibility complex (MHC)-matched islet transplantation in diabetic NOD mice were investigated. RESULTS: In STZ-induced diabetic BALB/c mice, Lef treatment significantly prolonged rat islet graft survival. However, Lef could not significantly prolong rat islet graft survival in autoimmune diabetic NOD mice. For prevention studies, treatment with Lef at 30 mg/ kg/day from 4 weeks to 20 weeks of age significantly reduced the incidence of spontaneous diabetes in NOD mice. However, when the NOD mice were treated from 8 to 24 weeks of age, the incidence of spontaneous diabetes was not significantly reduced as compared to the incidence of diabetes in the untreated female NOD mice at 28 weeks of age. Finally, in the MHC-matched islet transplant model, Lef could not significantly prolong MHC-matched nonobese diabetes-resistant mice islet graft survival in NOD mice. CONCLUSIONS: Lef preventing concordant xenogeneic islet graft rejection is not sufficient to prevent the recurrence of autoimmune diabetes in NOD mice. We believe that controlling autoimmunity after islet transplantation will lead the way to promote successful clinical islet transplantation in the future.

Animals↗
PubMed1997

Prolongation of rat islet allograft survival by the immunosuppressive agent leflunomide.

The purpose of this study was to investigate the effect of Leflunomide (Lef), alone or in combination with a suboptimal dose of cyclosporine (CsA), on rat allogeneic islet transplantation. Two thousands islets were transplanted under the left kidney capsule of a streptozocin-induced diabetic Lewis recipient. In the ACI to Lewis combination, the mean survival time (MST) of the untreated group was 5.2 +/- 0.8 days. Lef at 2.5, 5, and 10 mg/kg/day for 14 days significantly prolonged MSTs to 19.0 +/- 1.6, 29.8 +/- 3.7, and 29.0 +/- 5.3 days (P<0.01), respectively. CsA at 5 mg/kg/day also prolonged graft survival to 21 +/- 3.5 days. When CsA (5 mg/ kg/day) was combined with Lef (5 or 10 mg/kg/day) and administered for 14 days, the survival rate of the islet allografts was further increased to 34.8 -/+ 4.7 and 36.0 -/+ 6.6 days, respectively. When Lef or CsA monotherapy was extended to 28 days at a dose of 5 mg/kg/ day, MSTs were further increased to 45.8 -/+ 8.8 or 37.4 -/+ 4.7 days, respectively. Graft MST was 56.4 -/+ 9.9 days when Lef and CsA combination therapy was administered for 28 days. In the Brown-Norway to Lewis combination, MST of the allogeneic islets in untreated rats was 6.2 -/+ 0.8 days. When Lef or CsA alone, at 5 mg/kg/day, was administered for 28 days, two of seven Lef-treated rats remained normoglycemia for more than 100 days. Graft survival longer than 100 days occurred in one of five CsA-treated rats, and in five of eight rats treated with the combination of Lef and CsA. The graft-bearing left kidney was removed after 100 days in rats with functional islet allografts, and a second Brown-Norway islet graft was transplanted into the right kidney. In all recipients, the second graft was rejected by 9.8 -/+ 1.5 days. In summary, our findings demonstrate that Lef prolonged allogeneic islet graft survival, and its immunosuppressive effect was improved when combined with CsA.

Animals↗
PubMed1997

In vivo effects of leflunomide on normal pancreatic islet and syngeneic islet graft function.

Leflunomide (Lef) is a novel immunosuppressant that can prevent islet allograft and xenograft rejection. In this study, we investigated the in vivo effects of Lef on the function of normal pancreatic islets and syngeneic islet grafts in rats and compared its effect to cyclosporine (CsA) and FK506. Different groups of rats were treated with Lef (10 and 20 mg/kg/day), CsA (20 mg/kg/day), or FK506 (2 mg/kg/day). After 4 and 6 weeks, nonfasting blood glucose (BG) levels of all the treatment groups were not different from that of the control group. Intravenous glucose tolerance test revealed that the rate of glucose disappearance was normal in Lef-treated groups. However, the rate of glucose disappearance in the CsA- and FK506-treated rats was impaired. In contrast, long-term (7 months) treatment of rats with CsA (10 mg/kg/day) resulted in five of seven rats developing hyperglycemia. However, normal BG was observed in all rats treated for 7 months with Lef (10 mg/kg/day). In the second experimental model, streptozocin-induced diabetic ACI rats were grafted with an average of 1200 syngeneic islets into the liver or kidney capsule. Diabetes in these ACI recipients was stably reversed for 6 months, then these rats were treated with Lef (20 mg/kg/day), CsA (20 mg/kg/day), and FK506 (2 mg/kg/day). After 14 days of treatment, nonfasting BG levels were significantly increased in rats treated with CsA (before: 105 +/- 2.9 mg/ dl, after: 275.8 +/- 60 mg/dl) as well as in rats treated with FK506 (before: 108 +/- 2.4 mg/dl, after: 209 +/- 10.1 mg/dl). In contrast, the BG levels of the Lef-treated rats were indistinguishable from those of the untreated control groups. Site of transplantation, i.e., liver and kidney, did not affect the results. Our results indicating that Lef has no diabetogenic property in vivo lends support to the promise that leflunomide may be effective for clinical islet transplantation.

Animals↗
PubMed1997

Prediction of abstinence from ethanol in alcoholic recipients following liver transplantation.

The prediction of abstinence from ethanol may be crucial to the optimal selection of liver transplantation candidates with alcoholism. Of 84 consecutive end-stage alcoholic patients who underwent transplantation (1986-1994) at our institution, we analyzed 63 long-surviving recipients for pretransplantation variables to predict posttransplantation abstinence (follow-up: 49.3 +/- 21 mo). Thirty-three pretransplantation variables were reviewed from our transplantation data base and supplemented and confirmed with interviews with recipients. The psycho-social inclusion criteria included the following: patient recognition of alcoholism, a domicile, an occupation, and at least one close personal relationship. The incidence of abstinence from ethanol was (50/63) 79%. A logistic regression of the 33 variables in conjunction with our above inclusion criteria accurately predicted abstinence (90% accuracy, chi2 model, P < .00001) based on the absence of previous history of any illicit drug use (Drug Use: yes = 1/no = 0), the presence of an active, personal life insurance policy (Life Ins: yes = 1/no = 0), number of alcoholic sisters (ETOH-SIS), and the length of pretransplantation abstinence (PRE-TRANS-ABS, mos): Prob. of abstinence = 1/1 + e(-F), F = -0.33 +/- 0.89 (DRUG USE) -1.02 (LIFE INS) -1.68 (ETOH-SIS) +0.24 (PRE-TRANS-ABS). In contrast, receiver-operating characteristic curve analysis found that 7 and 9 months of pretransplantation abstinence were the best cut-off points in predicting subsequent abstinence, but poor utility was noted at these points with this specific value alone (sensitivity 61-84%, specificity 64-68%). A separate analysis of high-risk patients with poly-drug use (n = 15, alcohol recidivism 8/15, 53%) and the remaining low-risk group of purely alcohol dependent patients (n = 48, alcohol recidivism 5/48, 10%) found no combination of variables was predictive of abstinence in either group. The length of pretransplantation abstinence is a relatively poor predictor of posttransplantation abstinence. Variables of comorbid substance use, social function, and possibly family history are more predictive in conjunction with our standard criteria and might be useful as tools in evaluating liver transplantation candidates whose primary diagnosis is alcohol-induced cirrhosis.

Adult↗
PubMed1996

Renal transplantation without sutures using the vascular clipping system for renal artery and vein anastomosis--a new technique.

A cadaveric renal transplant was performed on a 63-year-old woman. The donor renal artery and vein were anastomosed to the recipient external iliac vessels using the vascular clipping system. These vascular anastomoses were performed with four stay sutures and several clips for each anastomosis, without a continuous vascular suture. The time taken was 8 min for each anastomosis. There were no postoperative complications and the patient went home after 6 days in the hospital. At 1 month follow-up her serum creatinine was 1.3 mg/dl. We conclude that cadaveric renal transplantation can be performed using clips for the vascular anastomoses. This technique permits an expeditious, interrupted anastomosis. Since the arcuate legged clips are nonpenetrating, there is minimum trauma to the vascular intima. In pediatric transplantation this interrupted technique may be of special importance, since it should allow the anastomoses to grow with time. The ability to quickly perform this type of anastomosis may reduce warm ischemia time as well. The safety and technical ease of this technique should allow its application in the anastomosis of other tubular structures as well. This might further improve the currently excellent outcomes of solid organ transplantation.

Arteriovenous Shunt, Surgical↗