Başkent Üniversitesi Yayınları
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Item Twenty-Four Hour Steroid Avoidance Immunosuppressive Regimen in Liver Transplant Recipients(Başkent Üniversitesi, 2012-06) Ju, Wei-qiang; Zhu, Xiao-feng; Tai, Qiang; Han, Ming; Hu, An-bin; Wu, Lin-wei; He, Xiao-shun; Ling, Xiaoting; Guo, Zhi-yongObjectives: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. Materials and Methods: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24-hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. Results: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). Conclusions: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.Item Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety(Başkent Üniversitesi, 2012-04) Ju, Wei-qiang; Hu, An-bin; He, Xiaoshun; Zhu, Xiao-feng; Han, Ming; Tai, Qiang; Wu, Lin-wei; Liang, Wen-hua; Guo, Zhi-yongObjectives: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. Materials and Methods: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. Results: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. Conclusions: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.Item Tolerogenic Semimature Dendritic Cells Induce Effector T-cell Hyporesponsiveness by the Activation of Antigen-Specific CD4+ CD25+ T-Regulatory Cells(Başkent Üniversitesi, 2009-09) Fu, Bi-mang; Huang, Jie-fu; Tam, Nga-lei; Wu, Lin-wei; Ma, Yi; Hu, An-bin; Yu, Si; He, Xiao-shunObjectives: Researchers recently discovered a group of semimature dendritic cells that induce autoimmune tolerance by activating host antigen-specific CD4+CD25+ T-regulatory cells. We hypothesized that donor semimature dendritic cells injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4+CD25+ T-regulatory cells. Materials and Methods: Donor myeloid semimature dendritic cells were cultivated for 6 days and were then stimulated with tumor necrosis factor α for 24 hours. BALB/c mice were pretreated with semimature dendritic cells to generate antigen-specific CD4+CD25+ T-regulatory cells in vivo. The role of CD4+CD25+ T-regulatory cells in transplant immunity was studied via mixed lymphocyte culture in vitro. Results: Surface markers and cytokines secreted by semimature dendritic cells differed from those secreted by immature myeloid dendritic cells or mature dendritic cells. Semimature dendritic cells and immature myeloid dendritic cells did not activate allogenic lymphocyte responses in coculture studies. CD4+CD25+ T-regulatory cells of recipients challenged by donor semimature dendritic cells, which expressed a high level of interleukin-10, induced hyporesponsiveness in host effector T cells that were stimulated by donor splenocytes. In contrast, CD4+CD25+ T-regulatory cells did not induce hyporesponsiveness in effector T cells when the host T cells were stimulated by third-party antigen from DBA2 mice splenocytes. Conclusions: Our findings confirm that semimature dendritic cells are an independent subgroup of dendritic cells in both immune function and morphologic profile. It may be the cytokine secretion profile of semimature dendritic cells (rather than that of surface markers) that has a key role in inducing CD4+CD25+ T-regulatory cells to express a high level of interleukin-10. Immunization with donor semimature dendritic cells may be an effective method of inducing transplant tolerance, but further evidence-based studies of that topic are necessary