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- Östraat, Ö., et al.
(författare)
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Thalidomide prolonged graft survival in a rat cardiac transplant model but had no inhibitory effect on lymphocyte function in vitro
- 1996
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Ingår i: Transplant Immunology. - 1878-5492. ; 4:2, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- The effects of thalidomide on in vitro interleukin 2 (IL-2) production and thymidine uptake by human peripheral blood lymphocytes or rat splenocytes were investigated. Phytohaemagglutinin-stimulated human lymphocytes were incubated in the presence of thalidomide added at culture initiation. No immunosuppressive effect of thalidomide was observed in these experiments. Primary human mixed lymphocyte cultures treated with thalidomide for 6 days were also unaffected. A microsomal rabbit liver homogenate was prepared for metabolizing thalidomide. Stimulated lymphocytes secreted significantly more IL-2 in the presence of microsomal-treated thalidomide than did controls. The effect of thalidomide was then studied either as single therapy or in combination with cyclosporin A (CyA) in a rat allograft cardiac transplantation model. In addition, T cell subsets were analysed by flow cytometry in untransplanted rats treated with thalidomide. Treatment was given as induction therapy from the day of transplantation until day 9. Graft survival in rats treated with thalidomide was significantly prolonged compared to the untreated group. No difference in graft survival was detected between rats treated with thalidomide or CyA only. Graft survival was found to be slightly prolonged in rats given thalidomide and CyA in combination compared to rats treated with CyA alone. In untransplanted rats given thalidomide a decrease of CD4 positive T cells was detected on days 3 and 5. The T helper/cytotoxic-suppressor cell ratio was significantly diminished but, after 1 week of treatment, values for T cell subsets had almost returned to baseline levels. No inhibitory effect was obtained when phytohaemagglutinin-stimulated rat splenocytes were cultured with metabolized thalidomide.In summary, the ability of thalidomide to improve allograft survival in a solid organ transplant model was verified. The occurrence of thalidomide-induced changes in T cell subset ratios was demonstrated. In in vitro studies, however, there was no decrease but an increase in IL-2 production, and no change in thymidine uptake. The mechanism responsible for the immunosuppressive effect of thalidomide remains to be elucidated.
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- Ekberg, H, et al.
(författare)
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Similar treatment success rate after renal transplantation in diabetic and nondiabetic patients due to improved short- and long-term diabetic patient survival
- 1996
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 9:6, s. 64-557
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Tidskriftsartikel (refereegranskat)abstract
- In the early era of transplantation, it was common practice to exclude diabetic patients since the outcome in such cases was usually poor. At our center in Malmö, Sweden, diabetic nephropathy was never regarded as a contraindication. During the 22-year period from 1972 to 1993, 223 renal allografts were transplanted in 189 uremic diabetics, representing 24% of all renal transplant recipients (n = 788). The two subgroups - patients with and without diabetes - did not differ significantly in graft survival rates for the 22-year period, which was characterized by a successive improvement in the success rate that was especially striking in the diabetic nephropathy subgroup. Among transplantations performed before 1988, the overall patient survival rate was significantly lower in the diabetic subgroup than in the remainder. After 1988 (when a series of new procedures had been adopted), the patient survival rate in the diabetic subgroup was similar to that in the nondiabetic subgroup, a similarity that persisted for at least 5 years. The 1st year post-transplant mortality rate was reduced in diabetic patients from 24% before 1988 to 0% in those transplanted after 1988. In the 22-year period as a whole, cardiovascular or cerebrovascular events were the most common cause of death in both subgroups; the risk of cardiovascular or cerebrovascular death was reduced after 1988, and the rates were similar in both subgroups. The improved success rate of renal transplantation in patients with diabetic nephropathy supports continuation of the renal transplant program, which is based on careful management of the early stages of the disease.
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