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Biomedical subjects

R Pollak

Publications and source records attributed to R Pollak.

At least 73 records · Page 4Linked to original sources
PubMed1992

A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction.

Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Introduction of bias in residency-candidate interviews.

We have developed, as part of our resident applicant ranking process, a computerized weighted scoring system incorporating, among other variables, the interview score (IS). This study was undertaken to test the IS as a dependent variable when the applicant file is available during the interview. Over a 3-year period, each of two faculty members interviewed 133 candidates in a "blinded" fashion (file unavailable) or 290 candidates with an "open" file. The mean discrepancy between paired interviewers (1 to 10 scale) was 1.34 +/- 0.10 for the blinded group versus 0.93 +/- 0.06 for the open group (p less than 0.001). Individual and multiple regression analysis were used to test the IS as a dependent variable in the open group, with the blinded group as a control. In each instance (except clerkship grades), the IS correlated more closely with other parameters (p less than 0.05) in the open group. Correlation coefficients were 0.27 (blinded) and 0.64 (open) for weighted scores combining all parameters (p less than 0.001) and 0.39 (blinded) and 0.65 (open) for multiple linear regression analysis (p less than 0.001). We conclude that the IS is significantly influenced if other objective variables are at hand, thus deflating the actual weight of the interview. To accurately quantify the value of the interview, a correction factor must be applied, or, more appropriately, the interview must be conducted blindly.

Academic Medical Centers↗
PubMed1990

Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone.

Prostaglandins of the E series have been shown to have immunosuppressive properties. To study the effects of the prostaglandin E1 analogue misoprostol on renal function and graft rejection after transplantation, we conducted a randomized, double-blind, placebo-controlled trial in 77 renal-allograft recipients. The subjects received misoprostol (200 micrograms four times daily by mouth; n = 38) or placebo (n = 39) for the first 12 weeks after transplantation, in addition to standard immunosuppression with cyclosporine and prednisone. They were then observed for an additional four weeks after the drug or placebo was discontinued. Treatment with misoprostol was associated with a significant improvement in renal function as judged by the mean (+/- SEM) serum creatinine concentration (128 +/- 7 vs. 158 +/- 11 mumol per liter after 12 weeks; P = 0.03) and creatinine clearance (84 +/- 6 vs. 69 +/- 5 ml per minute per 1.73 m2 of body-surface area; P = 0.05). There was a significant reduction in the incidence of acute rejection in the group treated with misoprostol as compared with the placebo group (10 of 38 vs. 20 of 39; P = 0.02), and there was less need for rehospitalization after transplantation (4 +/- 1 days with misoprostol vs. 10 +/- 2 days for placebo; P = 0.03). Although blood levels of cyclosporine did not differ significantly between the groups, they tended to be higher in the misoprostol group, as did the incidence of acute nephrotoxicity due to cyclosporine (13 of 38 vs. 8 of 39). Infectious complications tended to be fewer in the misoprostol-treated group (14 of 38 vs. 21 of 39). We conclude that misoprostol improves renal function and safely reduces the incidence of acute rejection in renal-transplant recipients treated concurrently with cyclosporine and prednisone.

Adult↗
PubMed1990

Evidence that HLA class II disparity is required for the induction of renal allograft enhancement by donor-specific blood transfusions in man.

We studied 46 living-related primary renal allograft recipients between June 1980 and Jan 1988 to determine if enhancement of allograft survival by donor specific transfusions requires a major histocompatibility complex mismatch between the blood/kidney donor and the recipient. Recipients were matched for a single HLA haplotype, but differed at various HLA loci on the unshared haplotype. DST (200 ml) was administered either 3 times at two-week intervals pretransplant (n = 17), or once 3-4 weeks pretransplant, together with oral azathioprine (1 mg/kg/day/28 days) (n = 29). Patients were followed for at least 1 year and all clinical rejection episodes were confirmed histologically. Enhanced graft survival by DST was defined as a rejection-free posttransplant course. Incompatibility for class II determinants on the unshared haplotype of donor had a beneficial effect. A significantly greater proportion of recipients had stable, rejection-free, allograft function if incompatible for the DR locus (80% vs. 44%, P = 0.012), for class II public determinants (100% vs. 58%, P = 0.013), or for at least one of the class II gene products (DR, DQ, class II public) (81% vs. 40%, P = 0.006). Graft loss occurred in 7 of 46 (15%); 6 of the 7 recipients were HLA class II-compatible with their blood/kidney donor. Mismatches for HLA class I private or public determinants and other factors known to affect graft outcome did not influence the results. We conclude that enhanced kidney allograft survival by DST may be predicated by factors within the MHC--specifically class II disparity. These observations also suggest that better HLA matching at the class II locus may account for the apparent "disappearance" of the transfusion effect in cadaver renal transplants in the cyclosporine era.

Blood Transfusion↗
PubMed1990

The survival and nature of the immune response to soft-tissue and composite-tissue allografts in rats treated with low-dose cyclosporine.

We studied a variety of soft-tissue and composite-tissue allografts (CTA) in a histoincompatible rat model to determine the outcome and the nature of the immunologic responses to these tissues using continuous low-dose cyclosporine (CsA) therapy. Brown-Norway (RT1n) rats served as donors of soft tissue and CTA to Lewis (RT1l) rat recipients given low-dose CsA immunosuppressive therapy by gavage. Nine groups were studied. Three control groups were not treated with CsA: group 1, skin grafts alone; group 2, skin flaps alone; and group 3, skin grafts and delayed vessel allotransplants. Six groups were treated with CsA: group 4, skin grafts alone; group 5, skin flaps alone; group 6, skin grafts and delayed vessel allotransplants; group 7, aortas alone; group 8, muscle flaps alone; and group 9, bone grafts alone. Isografts were performed in all groups as technical controls. The appearance posttransplant of donor-directed cytotoxic antibodies was determined in recipient serum using a complement-mediated cytotoxicity assay and was compared to control and pretransplant sera. In the absence of CsA therapy, recipients in groups 1, 2, and 3 rejected their allografts early (8.5-9.4 days) and developed profound antidonor cytotoxic antibody activity posttransplant by day 7. Groups 4, 5, 6, 7, and 9 had prolonged graft survival in the presence of low-dose CsA, despite the presence of antidonor antibody activity. By contrast, group 8 (muscle flaps) were all uniformly rejected in the presence of profound recipient cytotoxic antidonor antibody activity. These results suggest that long-term soft-tissue and CTA survival can be achieved in histoincompatible rat recipients using continuous low-dose CsA immunosuppressive therapy despite the presence of cytotoxic antidonor antibodies.

Animals↗