Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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Item Impact of Donor and Recipient Age on Allograft Tolerance(Başkent Üniversitesi, 2009-06) Martins, Paulo N.The elderly represent the fastest growing segment of the population with end-stage organ disease and the use of aged grafts increased exponentially. Since aging of the immune system, or "immunosenscence" is generally associated with weaker immune responses, one might expect the elderly to be less reactive against transplanted organs than younger patients and therefore to show better results in terms of transplant outcome. Paradoxically, however, experimental studies and clinical data of organ transplantation show that old age of either the recipient or the donor is associated with poorer outcomes. On the other hand transplant tolerance is easier to be induced in the neonatal period. One potential reason for this discrepancy may lie in the effects of immunosenescence on the induction of tolerance. While the impact of aging on acute and chronic allograft rejection has been extensively studied, its role on establishing transplant tolerance is not well known. Since tolerance is an active process, and not just the absence of an immune response, the immunologic changes associated with the aging process may interfere with graft survival. In experimental and clinical transplantation, most successful tolerance induction protocols have been tested on young individuals, using grafts from young donors. However, some experiments that have utilized aged animals have demonstrated resistance to tolerance induction. Extrapolation of these results to humans suggests that protocols for clinical tolerance induction may not be effective in the elderly and may need to be revised for this population. The resistance to achieving immunological tolerance with aging is complex and multifactorial. Here, we review the age associated changes that may interfere with immunologic tolerance. Understanding this phenomenon may help in developing novel therapeutic approaches to reverse the crucial dysfunctions of the aging immune system and achieve effective tolerance regimens for the elderly.Item Aggressive Use of Ribavirin and Prolonged Course of Peginterferon to Improve the Rate of Viral Response in Liver Transplant Patients with Recurrent Hepatitis C Viral Infection(Başkent Üniversitesi, 2010-09) Singhal, Aaditya; Black, Martin; Burke, Monika; Jain, Ashokkumar B.Objectives: There are different approaches for treating recurrent hepatitis C viral infection after a liver transplant. However, sustained virologic response is achieved in < 40% of infected allografts. We examined sustained virologic response improvement using a prolonged course of peginterferon and aggressive use of ribavirin. Patients and Methods: From October 1998 to May 2008, 24 patients (13 male, 11 female; mean age at transplant, 49.4 ± 7.7 years) received a prolonged course of peginterferon and ribavirin (range, 48-180 weeks). The mean interval from liver transplant to hepatitis C antiviral therapy was 26.6 ± 27.8 months. Patients began weight-based standard dosages of peginterferon and ribavirin. In case of hemolysis, patients were treated with Epogen, with and without blood transfusions. Results: Fourteen patients (58.3%) had an end of treatment response, and 8 patients (33.3%) maintained sustained virologic response after the first course of therapy. Of 10 patients who did not respond to the first course, 6 received an extended course of antiviral therapy after a mean of 15 ± 4.6 weeks from completion of first course. Five of these 6 patients achieved end of treatment response and maintained a sustained virologic response, resulting in an overall end of treatment response in 17 patients and a sustained virologic response in 13 patients. Twenty-two patients experienced hemolysis and were treated with Epogen. Fifteen patients received blood transfusions. Ribavirin dosage was reduced in 12 patients, and peginterferon dosage was reduced in 2 patients. Conclusions: Aggressive use of ribavirin and prolonged course of peginterferon provided sustained virologic response in 54.1% of liver transplant recipients with recurrent hepatitis C virus-infection. More prospective studies are warranted to evaluate the benefit of this approach fully.Item Antioxidant Enzymes and Lipid Peroxidation in Cold Ischemic Lung Preservation(Başkent Üniversitesi, 2009-06) Yeginsu, Ali; Ergin, MakbuleObjectives: Our purpose was to investigate antioxidant enzymes and lipid peroxidation in time course ischemic lung preservation in rats. Materials and Methods: Thirty-six Wistar rats were divided into 6 groups of 6 rats each. After having been anesthetized, the rats were intubated and connected to a rodent ventilator. Lung-heart blocks were excised. In the control group, the lungs were immediately stored at –80°C after removal. The lungs from the other groups were preserved in 40 mililiters of low potassium dextran solution at 4°C for 6, 12, 24, 48, and 72 hours, respectively. Antioxidant enzyme activity and malondialdehyde levels were then measured. Results: Superoxide dismutase activity significantly increased at the 12th hour and remained higher up to the 72nd hour (P < .001). Glutathione peroxidase activity was higher than that in the control group from the 6th to the 24th hour but was significant only at the 12th hour (P < .001) and decreased below the level in the control group after the 48th hour. Catalase activity was significantly higher than that in the control group in all preservation periods (P < .001). The nitric oxide level slowly increased and reached a significantly higher level than that in the control group at the 24th and 72nd hours (P = .028) and then decreased to the level found in the control group. The malondialdehyde level slightly increased from the 6th to the 24th hour, but that increase, when compared with the level in the control group, had no statistical significance (P = .110). Conclusions: In ischemic lung preservation, oxidative stress begins during the early phase of preservation and continues for up to 72 hours. Although oxidative stress continues for a significant period, an antioxidant mechanism adequately prevents its harmful effects on the lung. Thus no significant lipid peroxidation occurred in long-term ischemic lung preservation in the murine model studied.Item Acute Tubular Necrosis After Renal Allograft Segmental Infarction: The Nephrotoxicity of Necrotic Material(Başkent Üniversitesi, 2008-12) Ardalan, Mohammad Reza; Shoja, Mohammadali Mohajel; Ghabili, Kamyar; Nasri, HamidObjectives: Renal allograft dysfunction can be caused by renal vessel thrombosis, acute tubular necrosis, hyperacute or acute rejection, nephrotoxicity induced by cyclosporine or tacrolimus, thrombotic microangiopathy, or urinary tract obstruction. Materials and Methods: We describe a renal transplant recipient in whom oliguria developed during the first week after transplant, although his early renal allograft function was good. Results: A Doppler ultrasonographic study revealed a lack of perfusion in the lower pole of the allograft. A perfusion defect was noted in the lower pole that was supplied by a polar artery, which had been damaged during engraftment. Light microscopy disclosed tubular cell necrosis without evidence of vascular or humoral rejection. Conclusions: We suggest that toxic molecules such as tumor necrosis factor-alpha released from a segmental infarcted area can induce tubular cell damage and necrosis leading to renal allograft dysfunction.Item Association Between Increased Body Mass Index, Calcineurin Inhibitor Use, and Renal Graft Survival(Başkent Üniversitesi, 2008-09) Ghahramani, Nasrollah; Hollenbeak, Christopher; Reeves, W. BrianObjectives: Using data from the US Renal Data System, we examined the relation between body mass index and graft survival as mediated through calcineurin inhibitor use. Materials and Methods: Adult patients who received a first kidney-only transplant, with at least 6 months’ survival were classified into 5 categories (underweight, normal, overweight, obese, and extremely obese) according to body mass index. Associations between calcineurin inhibitor use, body mass index categories, and outcomes were investigated. Results: Underweight and normal-weight recipients lived longer than the other 3 categories, regardless of calcineurin inhibitor use. Graft survival was significantly inferior among obese and extremely obese patients. Average graft survival was significantly higher for recipients with a normal body mass index than it was for overweight, obese, and extremely obese recipients. Risk ratio for graft failure was constant for the calcineurin inhibitor versus the noncalcineurin inhibitor group across all body mass index categories. Mean body mass index for the group with rejection episodes was similar to the group with no rejections; there was no correlation between body mass index and rejection risk. Conclusions: Increased body mass index is associated with inferior patient and graft survival, independent of calcineurin inhibitor use. Because we found no correlation between body mass index and risk of rejection, we assume that, at least after the initial 6 months, the adverse effect of obesity on graft outcome is partially mediated through nonimmunologic mechanisms. When analyzing graft and patient survival rates, we recommend that body mass index be considered a risk factor.