Başkent Üniversitesi Yayınları
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Item Cyclosporine Therapeutic Monitoring With Cmax in Kidney Transplant Recipients: Does it Fit for All Populations?(Başkent Üniversitesi, 2008-12) El-Agroudy, Amgad E.; Ghoneim, Mohamed A.; Nassar, Mohamed; Ismail, Amani M.Background: We sought to assess whether the single cyclosporine concentration taken 2 hours after administration (C2) is a good parameter to predict a drug’s maximal concentration (Cmax) value in Egyptian kidney transplant recipients Materials and Methods: Fifty stable Egyptian kidney transplant recipients with a previously diagnosed schistosomal infection were compared with 50 Egyptian kidney transplant recipients without a schistosomal infection regarding cyclosporine concentrations at time 0 (trough), and then at 1.5, 2, 2.5, 3, and 3.5 hours after a dose of cyclosporine. We used a linear regression analysis to assess any statistically significant differences between the different cyclosporine time concentrations and drug dosages Results: Patients in the schistosomal group had significantly lower C2 levels (511 ± 118 nmol/L) compared with those in the nonschistosomal (control) group (669 ± 213 nmol/L) (P < .05), whereas the C2.5 level was significantly higher (730 ± 215 and 527 ± 129 nmol/L, respectively; P < .05). A significant linear regression relation was determined for only C2.5 in the schistosomal group with both morning cyclosporine dose and cyclosporine dose expressed as mg/kg/d (P = .0123, r = .573018). Conclusions: Egyptian patients have special characteristics with regard to drug absorption and metabolism, mostly owing to schistosomal infection, and they may need the use of C2.5 to monitor cyclosporine. If confirmed by subsequent, larger studies, our findings may have a significant effect on our understanding and management of cyclosporine immunosuppression in clinical renal transplants with persons of different ethnicities.Item Transplantation of Insulin-Producing Clusters Derived From Adult Bone Marrow Stem Cells to Treat Diabetes in Rats(Başkent Üniversitesi, 2008-09) Gabr, Mahmoud M.; Ghoneim, Mohamed A.; Refaie, Ayman F.; Zakaria, Mahmoud M.; Sobh, Mohamed M.Objectives: Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested. Materials and Methods: Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days. Results: At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy. Conclusions: Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.Item Immunosuppression Modifications and Graft Outcome in Patients With Chronic Allograft Nephropathy(Başkent Üniversitesi, 2008-09) El-Agroudy, Amgad E.; Ghoneim, Mohamed A.; Shokeir, Ahmed A.; El-Baz, Mahmoud; Ismail, Amani M.; Mahmoud, Khaled; El-Dahshan, KhaledObjectives: This retrospective study was done to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy Materials and Methods: One hundred seventy-four cyclosporine-treated renal transplant recipients were studied. Patients were included if they had biopsy-proven chronic allograft nephropathy (mild to moderate) with a serum creatinine level of 300 µmol/L or less. The treatments groups were (1) mycofenolate mofetil and reduced-dosage cyclosporine (group MMF/CsA; n=132) and (2) azathioprine and reduced-dosage tacrolimus (group Aza/Tac; n=42). Patient records were checked for graft function, survival, and comorbidities after conversion. Results: Mean follow-up before conversion was 52.2 ± 31.1 and 47.9 ± 27.4 month in groups MMF/CsA and Aza/Tac, respectively. There was a significant deterioration of graft function in group Aza/Tac after 5 years (P < .05). Ten-year actuarial graft survival in group MMF/CsA was 38%; in group Aza/Tac it was 19% (P = .04). Nine patients started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = .05) but a significantly higher incidence of diabetes mellitus (P = .04). There were no significant changes or differences in blood pressure between the groups. Conclusions: Our results suggest that in patients with chronic allograft nephropathy and deteriorating allograft function, cyclosporine minimization and addition of mycofenolate mofetil achieve favorable effects in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.Item Nomogram That Predicts Graft Survival Probability Following Living-Donor Kidney Transplant(Başkent Üniversitesi, 2008-03) Akl, Ahmed; Ghoneim, Mohamed A.; Mostafa, AmaniObjectives: The goal of this project was to develop a nomogram that predicts the probability of graft survival at 5 years. Materials and Methods: From our dataset, 1581 patients were used to construct a nomogram (modeling group), the remaining 319 patients (testing group) were used for its validation. Initially, the modeling group variables were correlated with graft survival by univariate analysis. Significant factors were subjected to a multivariate analysis using a Cox regression model. The results formed the basis of our nomogram construction. Internal validation was done first by discrimination using the concordance index. Second, the calibration was assessed graphically. And finally, for external validation, the nomogram was used to predict graft survival using the testing group. The predicted probability(s) was compared with the actual survival estimates. Results: Validation of the nomogram yielded a concordance index of 0.77, and the observed correspondence between predicted and actual outcomes suggested a high level of calibration. Nomogram predictions of the testing group revealed no differences in the means of predicted and observed graft survival at 5 years, with a high correlation coefficient and accepted predictive accuracy (concordance index, 0.72). Conclusions: We developed a well-validated and reasonably precise nomogram for predicting 5-year graft survival.