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Biomedical subjects

R Pollak

Publications and source records attributed to R Pollak.

At least 37 records · Page 2Linked to original sources
PubMed1998

A prospective study of the predictive value of polymerase chain reaction assay for cytomegalovirus in asymptomatic kidney transplant recipients.

Cytomegalovirus (CMV) infection carries the potential for high morbidity in transplant recipients. The institution of pre-emptive therapy prior to the onset of clinical disease on the basis of CMV-polymerase chain reaction (PCR) is very attractive. We prospectively studied 52 asymptomatic kidney transplant recipients to test the hypothesis that serial CMV-PCR assays during the first 3 months post-transplant would identify patients at risk for CMV disease. Twenty-three patients (44.2%) had positive CMV-PCR tests at least once; 2 (8.6%) developed CMV. None of the 29 patients continuously negative for CMV-PCR developed CMV disease. CMV-PCR status did not influence patient and graft survival or the incidence of acute rejection. We conclude that while a substantial number of kidney transplant recipients become positive for CMV-PCR in the early post-transplant period, only a minority will develop CMV disease. Negative CMV-PCR assay is an accurate negative predictor for CMV disease but the value of CMV-PCR as a guide for pre-emptive anti-CMV therapy in kidney transplant recipients appears limited.

Adult↗
PubMed1997

Intrasplenic hepatocyte allotransplantation in dalmation dogs with and without cyclosporine immunosuppression.

Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude that the dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

Animals↗
PubMed1997

Safety and tolerability of cyclosporine microemulsion versus cyclosporine: two-year data in primary renal allograft recipients: a report of the Neoral Study Group.

BACKGROUND: The new microemulsion formulation of cyclosporine (CsA-ME) is more bioavailable than cyclosporine (CsA) in de novo renal transplant patients. Therefore, it was of interest to compare the safety profile of each formulation in such patients. METHODS: In a multicenter, double-blind, parallel-group study, 101 renal transplant recipients were randomized after transplantation to receive either CsA (n=50) or CsA-ME (n=51) capsules twice daily for 2 years. Of these patients, 54 (CsA, n=26; CsA-ME, n=28) completed 1 year of the study and entered the second-year, double-blind extension. Initial dose at the time of transplantation was 5 mg/kg b.i.d.; doses were titrated to target trough levels. METHODS: The mean (+/- SD) doses at the end of 2 years were 4.6 +/- 1.8 and 3.8 +/- 1.1 mg/kg per day for CsA- and CsA-ME-treated patients, respectively. The mean (+/- SD) CsA trough levels at end point were 187 +/- 63 and 210 +/- 95 ng/ml for CsA- and CsA-ME-treated patients, respectively. At least one adverse event was reported by 25/26 (96%) of CsA- and 27/28 (96%) of CsA-ME-treated patients. No patient discontinued the study because of adverse events. No deaths occurred during the study. Renal function, as measured by serum creatinine levels, and blood pressure were comparable over time in both treatment groups. CONCLUSIONS: There was no significant difference in safety and tolerability between CsA- and CsA-ME-treated kidney recipients for 2 years after transplantation.

Adolescent↗
PubMed1997

Safety of oral terbinafine for toenail onychomycosis.

This open-label multicenter study evaluated the safety and efficacy of 12, 18, and 24 weeks of daily treatment with a 250-mg tablet of terbinafine for onychomycosis of the toenails. The safety data for 1,508 patients with a mean age of 50 years are reported here. Percentages below are based on this denominator. All patients received at least 12 weeks of therapy, with a possible addition of 6 or 12 weeks depending on disease extent. Patients were evaluated at baseline and at weeks 6, 12, 24, 30, 36, 48, and 72. Adverse events were reported in 674 (44.7%) patients; the events were considered unrelated to terbinafine in 557 (36.9%) patients and causally related or of uncertain relationship to terbinafine in 117 (7.8%) patients. Most events involved the skin, the gastrointestinal system, or the respiratory system. Statistically similar results were found for the elderly (over 60 years) and diabetic subpopulations. The study results confirm the safety of terbinafine in the population at large and show no differences for either the elderly or diabetic patients, who are at increased risk for onychomycosis and who frequently take concomitant medications with potential for drug interactions.

Antifungal Agents↗
PubMed1997

OKT3 therapy increases cyclosporine blood levels.

Numerous drugs have been reported to alter cyclosporine (CSA) blood levels, most notably, those drugs that interfere with cytochrome P450 metabolism. Our clinical experience suggested that OKT3 therapy may alter CSA blood levels as well. The purpose of this study was to assess the effect of OKT3 therapy on CSA trough blood levels. We reviewed medical records of all CSA-treated renal transplant recipients during a 3-yr period to identify patients who received antilymphocyte induction therapy. Patients receiving drugs known to interact with CSA were excluded from analysis. The study population (n = 33) was divided into two groups: the OKT3 group consisting of 17 patients who received OKT3 therapy for 7 d post-transplant (OKT3 group) and the control consisting of 16 patients who received ALG induction therapy for 7 d post-transplant (ALG group). Oral CSA (14 mg/kg) was administered preoperatively. Postoperatively, oral CSA (4 mg/kg) was administered twice daily, in addition to corticosteroids and azathioprine. We evaluated CSA through levels on days 1, 3, 5, and 7 of antilymphocyte therapy and 3 d following completion of antilymphocyte therapy. On days 1 and 3, CSA trough levels did not differ between the two groups. However, median CSA trough levels (HPLC) were significantly higher among OKT3-treated patients on day 5 of therapy (265 ng/ml), as compared to ALG-treated patients (136 ng/ml; p < 0.0001; Mann-Whitney U-test). On days 7 and 10, CSA trough levels did not differ between the two groups. CSA does, however, had been adjusted based on levels obtained on day 5. We conclude that OKT3 therapy causes a significant rise in CSA trough levels. Recognition of this potential drug interaction is essential in titrating CSA doses in the early post-transplant period to minimize risks of CSA toxicity or early rejection following induction therapy.

Adult↗
PubMed1997

Thrombocytopenia in an established solitary pancreas graft recipient.

Isolated, life-threatening thrombocytopenia from a previously well tolerated pancreas allograft has not been reported in the literature. Herein we report such a case where a 31-year-old, Caucasian, Type I diabetic male developed severe thrombocytopenia 6 months following isolated pancreas transplantation and 2 wk after enteric conversion of the graft. Despite extensive diagnostic work-up, the cause remained unclear and his thrombocytopenia did not remit with standard treatment, but did resolve upon explantation. Pathologic examination of the pancreatic graft showed evidence of chronic rejection along with CMV pancreatitis. We conclude that unremitting isolated thrombocytopenia in solitary pancreas grafts may reflect a localized DIC phenomenon that requires graft explantation.

Adult↗
PubMed1997

Iliac reconstruction with arterial allograft during pancreas-kidney transplantation.

An intraoperative dissection of the external iliac artery during pancreas transplantation was successfully repaired using the donor iliac artery allograft as a conduit between the internal iliac and distal external iliac artery. An angiogram performed 6 months after surgery showed a patent bypass without stricture or pseudoaneurysm. At 1 yr follow-up after transplant the grafts are functioning well, and the affected extremity is normal. In immunosuppressed recipients of solid organ transplants, fresh arterial allografts may be successfully used for iliac artery reconstruction. Further study will be needed to determine the role of arterial allografts for lower extremity bypass surgery in immunosuppressed patients.

Adult↗
PubMed1996

Effect of pretransplant erythropoietin therapy on renal allograft outcome.

Erythropoietin (EPO) is widely used among patients with end-stage renal disease awaiting transplantation. Data suggest that EPO therapy may be immunomodulatory. The purpose of this study was to assess the effects of pretransplant EPO therapy on renal allograft outcome. We evaluated 120 consecutive renal transplant recipients to assess the effect of EPO on graft outcome following renal transplantation. Among the study population, 58 patients were receiving EPO before transplantation (EPO group) and 62 patients were not treated with EPO (non-EPO group). Twenty-four of 58 EPO-treated patients (41%) experienced delayed graft function after transplantation, compared with 11 of 62 (18%) non-EPO-treated patients (P<0.05). The incidence of acute rejection, time to first rejection, and 1-year graft survival rate did not differ between the two groups. In conclusion, pretransplant EPO therapy does not appear to adversely impact on the incidence of acute rejection or 1 year graft survival rate. However, EPO-treated patients may be predisposed to the development of delayed graft function.

Acute Disease↗
PubMed1996

The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. The Neoral Study Group.

This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

Adolescent↗
PubMed1996

The safety and tolerability of cyclosporine emulsion versus cyclosporine in a randomized, double-blind comparison in primary renal allograft recipients. The Neoral Study Group.

A 12-week, randomized, double-blind, multicenter pharmacokinetics study was conducted to compare the clinical safety and tolerability of cyclosporine capsules and oral solution for microemulsion and cyclosporine in 101 primary renal transplant recipients Cyclosporine emulsion has more complete absorption and improved bioavailability compared with cyclosporine, and dosing of both cyclosporine formulations was adjusted to achieve comparable whole-blood trough levels. Mean serum creatinine values were higher in the cyclosporine emulsion group at baseline, 8, and 12 weeks (P<0.05). The incidence of acute rejection was similar in both treatment groups although fewer patients required monoclonal antibody therapy in the cyclosporine group (31% vs. 82%, respectively). Despite the increased bioavailability of cyclosporine emulsion, no significant differences in the incidence of adverse events were observed; the safety, tolerability, and efficacy of cyclosporine emulsion and cyclosporine were comparable.

Administration, Oral↗
PubMed1996

The impact of quadruple immunosuppression with OKT3 on kidney transplantation in black recipients.

BACKGROUND: Black recipients of kidney transplants have been shown to have lower graft survival than other racial groups. There is ongoing controversy about the optimal immunosuppressive protocol for blacks after kidney transplantation. PATIENTS AND METHODS: Five hundred-eighty-two recipients of kidney transplants performed between 1985 and 1994 were divided into three groups: (1) nonblacks who received cyclosporine and prednisone (N = 292); (2) blacks who received "quadruple" cyclosporine based immunosuppression with OKT3 induction (N = 98); and (3) blacks who received cyclosporine and prednisone only (N = 192). Patient and graft survival and incidence of acute rejection episodes were compared among the groups. RESULTS: Blacks had lower graft survival when compared with nonblacks. However, in the subgroup of black recipients who received quadruple immunosuppression, graft survival at 1 year was higher and the incidence of acute rejection episodes was significantly decreased compared with blacks without induction. Graft survival and the incidence of acute rejection in blacks on quadruple therapy was comparable with nonblacks. CONCLUSIONS: Our data support the principle that quadruple immunosuppression should be used routinely for black recipients of kidney transplants.

Adult↗
PubMed1996

Antibody-mediated hemolytic anemia following ABO-mismatched organ transplantation: contributory role of HLA matching and polyclonal antilymphocyte globulin.

We report three instances of antibody-mediated hemolytic anemia following ABO-mismatched, but compatible, renal (n = 2) and simultaneous pancreas-kidney (n = 1) transplantation. The two renal allograft recipients had received a 6-antigen matched transplant; one received polyclonal antilymphocyte globulin to treat an early rejection episode. The simultaneous pancreas-kidney transplant received polyclonal antilymphocyte globulin (ALG) as part of a quadruple therapy induction regimen. All three patients developed severe, but self-limited, antibody-mediated hemolytic anemia within two weeks of their transplants. Serologic testing demonstrated the hemolysis to be antibody mediated; furthermore, testing of the ALG lots demonstrated high titers of anti-red blood cell antibodies. The possible contribution of ALG and HLA matching to the hemolysis seen in these patients after ABO mismatched organ transplantation is discussed.

ABO Blood-Group System↗
PubMed1996

Effect of oral pentoxyfylline on the OKT3-induced cytokine-release syndrome among renal allograft recipients.

Recent data suggest that pentoxyfylline administration results in a significant reduction in serum TNF levels among OKT3-treated patients. However, the effect of pentoxyfylline on the clinical syndrome that ensues following OKT3 administration remains undefined. We evaluated 32 OKT3-treated renal transplant recipients to assess the impact of pentoxyfylline on OKT3 adverse reactions. The study population consisted of two groups: (i) a prospective group comprising 16 patients who received oral pentoxyfylline 600 mg 1-2 h prior to the first dose of OKT3 and then 600 mg every 8 h for 72 h, in addition to corticosteroids, acetaminophen and diphenhydramine, and (ii) an historical control group (n = 16) treated with corticosteroids, acetaminophen and diphenhydramine alone. All patients were evaluated for signs and symptoms consistent with the OKT3-induced cytokine-release syndrome. The incidence and clinical severity of OKT3-related adverse reactions were similar among the two groups. We conclude that oral administration of pentoxyfylline does not appear to affect the incidence or severity of OKT3-related adverse reactions.

Administration, Oral↗