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We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 ± 1.9 days in the Neoral group vs 7.8 ± 4.9 days in the Sandimmune group (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13 %) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60 %) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early posttransplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year posttransplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24 % in these 59 patients compared to our historical experience of 70 % using Sandimmune.

Cytomegalovirus (CMV) remains the most important infection in the renal transplant recipient. Few data are available that provide guidance for approaches that seek to reduce the reactivation of latent disease after transplantation. To test the efficacy of polyimmune gammaglobulin in kidney and kidney/pancreas transplantation, consenting recipients with serologic evidence of previous CMV disease were randomized to receive i.v. polyimmune gammaglobulin (500 mg/kg) within 3 days of transplant with 250 mg/kg at weeks 1, 2, 4, and 6 or no prophylaxis. Both groups received identical induction and rejection immunosuppressive therapy. Polyimmune gammaglobulin prophylaxis reduced CMV reactivation infections. The incidence of reactivation infections was half in patients receiving Nashville/rabbit antithymocyte serum (N/R-ATS) compared with those receiving monoclonal anti-CD-3 therapy. Patients receiving polyimmune gammaglobulin along with N/R-ATS had an incidence of infection of only 10%. Reactivation infections were twice as common in patients who had primary nonfunction and nearly three times as common in patients with acute rejection. Both risk factors were associated with longer anti-T-cell therapy. Polyimmune gammaglobulin prophylaxis should be considered in transplant patients with previous CMV exposure who will be receiving prolonged anti-T-cell therapy because of acute rejection or primary nonfunction.

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.

The effect of race upon renal allograft survival is controversial. Between 1981 and 1987, at Vanderbilt University Medical Center, 448 patients (75 black, 373 white) received azathioprine, 3 mg/kg daily; prednisone, 30 mg daily; and intravenous antithymocyte sera, 0.2 mL/kg/day for 14 days, after transplantation. Prednisone doses were decreased gradually to 10 mg daily within 6 months of transplantation. Azathioprine was maintained at doses of 2 to 3 mg/kg/daily; lower doses were administered if significant myelosuppression occurred. One-year graft survival was 72% and 85% among black and white recipients, respectively (P less than .01). Two hundred thirty-six patients have been treated with azathioprine (3 mg/kg initially tapered during the first week to 1.5 to 2 mg/kg); prednisone, 30 mg daily; and cyclosporine, 10 mg/kg per day. Cyclosporine therapy was begun after recipient serum creatinine levels had decreased below 3 mg/dL. Before therapy was initiated and until levels of cyclosporine were maintained between 150 and 200 ng/mL (whole blood), antithymocyte serum was administered. This immunosuppressive protocol resulted in 1-year graft survival of 90% and 87% in black and white recipients, respectively. Not only was graft loss markedly reduced, but the interracial difference noted before the use of cyclosporine was no longer evident. The type of immunosuppressive therapy used clearly affected 1-year allograft survival among black recipients. The combination of azathioprine, cyclosporine, and prednisone resulted in improved graft survival overall, but had the most significant effect among blacks.

Immunosuppressive efficacy of Neoral and Prograf following primary hepatic transplantation was comparable. Incidence of rejection episodes, infectious complications, hypertension, and postoperative diabetes mellitus was comparable. Although clinical use of both immunosuppressants was associated with early compromise in renal function, no progressive renal dysfunction was observed.

The advent of potent immunosuppressive drugs to prevent rejection has led to a phenomenal improvement in renal transplant results increasing spectacularly the number of transplant recipients to arrive in the transplant clinic who remain for many years. This has engendered a series of questions about the most appropriate cyclosporine dosing for these patients that prevents rejection while avoiding toxicity. Three separate issues were analyzed: the most appropriate combination strategy with cyclosporine as a base "double" or "triple" therapy; the possibility of conversion from regimens containing cyclosporine to those devoid of it; and the optimal cyclosporine dose for a maintenance regimen. A meta-analysis of seven individual prospective and randomized trials of double versus triple therapy encompassing 1,080 patients revealed no statistical difference between the two regimens in terms of graft survival at 1 or 5 yr, patient survival, the rejection rate per patient, or the infection rate. In an analysis of 17 separate studies in which conversion away from cyclosporine was attempted, in 629 individuals with 702 individuals left on cyclosporine as controls, a significant risk of acute rejection (P0.001) was found in the withdrawn group without evidence of improved graft survival. Certain factors such as previous rejection, race, and degree of reactivity predicted even more rejection in the withdrawn group. Analyzing six separate studies of renal transplant recipients maintained on cyclosporine for up to 5 yr with renal functional stability, one can conclude that a dose of approximately 4.0 mg/kg per day is optimal. Because of variant pharmacokinetics or concomitant medicines, blood levels can confirm a therapeutic concentration with this target dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD.

Die hohe Morbiditat und Mortalitat resezierender Eingriffe am Pankreas werden bedingt durch Insuffizienz der pankreatodigestiven Anastomose (1), durch Pankreatitiden mit Nekrosenbildung (1, 2) sowie durch Entgleisung des Glucosestoffwechsels in folge des Verlustes der Inselzellen (2, 3). Eine Operationsmethode ist somit erforderlich, die eine Insuffizienz der Anastomose unmoglich macht, eventuell entstehende Pankreasnekrosen drainiert, gleichzeitig das verbleibende Organ denerviert und dessen endokrine Funktion nicht beeintrachtigt.