The addition of either 2 mg/day sirolimus or 5 mg/day sirolimus to CsA/corticosteroid therapy significantly reduces the incidence of acute rejection episodes in primary mismatched renal allograft recipients, without an increase in immunosuppressant-related side effects, including infections and malignancy, at 6 months and at 1 year after transplantation.

No abstract

A series of 32 recipients of liver, kidney, or pancreas transplants who were treated with sirolimus and low-dose tacrolimus experienced a low rate of rejection and excellent graft function without drug-related toxic effects.

Attitudes toward older people were better in fourth-year than first-year medical students. A more-positive attitude toward older people increased the likelihood of considering a career in GM. An intensive 8-day course in GM had no significant effect on attitudes but increased the likelihood of fourth-year students considering a career in GM.

Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP-12) with greater avidity than tacrolimus (TAC), animal studies have shown that SRL and TAC act synergistically to prevent rejection. Dose-related toxicity is more often the cause of TAC discontinuation than rejection. We hypothesized that SRL would allow for a substantial reduction in the concomitant dose of TAC after liver transplantation to levels less than the threshold for toxicity. A series of 56 liver transplant recipients were administered a combination of SRL and TAC (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient and graft survival were 52 patients (93%) and 51 grafts ( P hase III randomized controlled trials of sirolimus (SRL) performed for registration in North America of Rapamune (Wyeth-Ayerst, Princeton, NJ) were conducted using SRL in combination with full-dose cyclosporine (CsA) in renal transplantation. This combination was chosen because it was known that SRL synergistically increased the inhibitory effect of CsA on lymphocyte proliferation. 1 Both registration studies showed that the addition of SRL in a fixed-dose regimen of 2 or 5 mg/d halved the rate of acute rejection of renal allografts in the first year. 2,3 Patients administered the greater dose of SRL had greater serum creatinine levels at 1 year than the control group. This might have been caused by increased exposure to CsA in SRLtreated individuals. 4 Principle toxicities associated with SRL were bone-marrow suppression and hyperlipidemia. Phase II studies conducted in Europe in which concentration-controlled SRL was substituted for CsA confirmed the difference between SRL and CsA with respect to unwanted effects. 5