Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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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 Mini-Incision Donor Nephrectomy Techniques: A Systematic Review(Başkent Üniversitesi, 2010-06) Aboutaleb, Esam; Hakim, Nadey; Crane, Jeremy; Herbert, PaulObjectives: The aim of this article is to compare different mini-incision donor nephrectomy techniques in the literature. Materials and Methods: We did a literature search using PUBMED using the search term “donor nephrectomy.” We compared different surgical techniques using different parameters like length of incision, length of operation, pain medications required after the operation, site of the operation, and intraoperative and postoperative complications. Results: We found 7 different surgical techniques of mini-invasive donor nephrectomy. Hakim and associates described the smallest initial incision size of 4 cm. There also are limited data on the analgesia requirements in 4 of the series, and 3 series that describe the requirements vary. Conclusions: These techniques offer advantages and disadvantages to the donor and the kidney. We hope to encourage further work. Ideally, there must be a working discussion, long-term outcomes of donor kidney and recipient, as well as accurate pain records, both quantitative and qualitative, and a discussion of time to mobilization.Item Comparison of Peripheral Blood Stem Cell Transplant With Bone Marrow Transplant in Class 3 Thalassemic Patients(Başkent Üniversitesi, 2010-03) Iravani, Masoud; Ghavamzadeh, Ardeshir; Khatami, Farnaz; Ashouri, Asiyeh; Babaie, Molouk Hadji; Tavakoli, EmytisObjectives: This study aimed to compare outcome of bone marrow transplant with peripheral blood stem cell transplant in class 3 thalassemic patients. Materials and Methods: Respectively, 32 and 20 class 3 thalassemic patients received bone marrow transplant and peripheral blood stem cell transplant from human leukocyte antigen identical sibling donors. Conditioning regimen consisted of busulfan (16 mg/kg) and cyclophosphamide (160 mg/kg) followed by cyclosporine and methotrexate as graft-versus-host disease prophylaxes. Results: Median time to absolute neutrophil count was significantly shorter in the peripheral blood stem cell transplant group (12 vs 23 days); however, there was no significant difference regarding platelet recovery between the 2 groups (20 vs 28 days). Acute graft-versus-host disease occurred in 47% of patients. Chronic graft-versus-host disease developed in 28% of patients which was significantly higher in the peripheral blood stem cell transplant group (P = .06). During 50 months’ follow-up, thalassemia recurrence, overall survival, and thalassemia-free survival were 17%, 80%, and 65%, respectively, and there were no significant differences between the 2 groups. Conclusions: These results showed that stem cell transplant is an effective treatment in class 3 thalassemic patients with the outcome relatively similar to bone marrow transplant. Although engraftment time is shorter in peripheral blood stem cell transplant method, it is associated with higher rate of chronic graft-versus-host disease.Item Characteristics of Patients With Banff Borderline Changes in Renal Allograft Biopsies(Başkent Üniversitesi, 2009-12) Wafa, Ehab W.; Ghoneim, Mohamed A.; El-Agroudy, Amgad E.; El-Baz, Mahmoud; Gheith, Osama A.; El-Husseini, Amr; Abbas, Tarek M.Objectives: The aim of this retrospective study was to characterize the patients who experienced borderline rejection. Materials and Methods: Patients with a minimum follow-up of 2 years were enrolled in this study. Forty-seven patients out of 106 patients with borderline rejection (after exclusion of those with associated chronic interstitial fibrosis) were compared with patients with acute cellular rejection grade 1 (n=650), and patients free of rejection episodes (n=444) regarding the different characteristics. Results: Patients aged 20 years or younger were frequently in borderline rejection group than other groups (which was statistically significant) (P = .001). Significant differences were found in recipient and donor ages, consanguinity, pretransplant blood transfusion, and immunosuppression plan. Most patients in borderline rejection group received triple immunosuppression therapy than other groups (P = .001). Univariate and multivariate regression analysis of different variables on graft survival in borderline rejection patients revealed that none of them was statistically significant. Conclusions: Borderline rejection is a frequent finding in biopsy-proven acute rejection after kidney transplant. Time of occurrence, frequency, treatment or not, and response to therapy were not predictors to graft survival.Item Leflunomide Derivative FK778 Inhibits Production of Antibodies in an Experimental Model of Alloreactive T-B Cell Interaction(Başkent Üniversitesi, 2009-12) Ramos-Barrón, M. Angeles; Arias, Manuel; Merino, Ramón; Merino, Jesus; Gimenez, Teresa; Benito, Adalberto; Cosme, Lorena San; Agüeros, Consuelo; Santiuste, Ines; Gómez-Alamillo, CarlosObjectives: The contribution of humoral immune response in allograft and xenograft rejection has been clearly demonstrated in recent years. For this reason, inhibition of alloantibody production has become essential in managing transplanted patients. Here, we assessed the effects of the leflunomide derivative FK778 (FK778) in the control of antibody production resulting from semiallogeneic cognate T-B–cell interactions. Materials and Methods: BALB/c mice were tolerized at birth with semiallogeneic spleen cells from (BALB/c × C57BL/6) F1 mice, with or without overexpression of human bcl-2 transgene in B cells. These tolerized mice were treated with different dosages of FK778, either from birth, or from the third week of age, when autoantibody production was detected. The production of autoantibodies, used as markers of semiallogeneic cognate T-B–cell interactions, was evaluated at different time points during drug administration or after the interruption of treatment. Results: FK778 treatment started at birth inhibited the production of semiallogeneic-driven antibodies in a dose-dependent manner. In addition, FK778 also reduced the levels of preformed circulating autoantibodies in adult mice, although the dosage required was 4 times higher than that used in neonates. However, the levels of IgG antibodies in these tolerized mice increased after FK778 withdrawal, indicating that FK778 failed to induce tolerance to semiallogeneic host CD4+ Th2 and/or donor B cells. Conclusions: Our results demonstrate the efficacy of FK778 in the control of antibody production resulting from semiallogeneic cognate T-B–cell interactions.Item Postlung Transplant Rehospitalization: A Study of Causes, Health Care Burden, and Outcomes(Başkent Üniversitesi, 2009-09) Faeghi, Jamileh; Masjedi, Mohammad Reza; Dezfouli, Azizollah Abbasi; Najafizadeh, Katayoun; Parsa, Tahereh; Shadmehr, Mohammad Behgam; Dabir, Shideh; Mohammadi, Foruzan; Tabarsi, Payam; Lankarani, Maryam Moghani; Assari, Shervin; Marjani, Majid; Fahimi, Fanak; Shafaghi, ShadiObjectives: Rehospitalization is a significant burden for transplant systems, which use data on hospitalization to monitor practice outcomes. In this study, all rehospitalizations after successful lung transplant performed in our medical center during an 8-year period were assessed for cause, health care resource use, cost, and outcome. Materials and Methods: We performed a retrospective chart review of all rehospitalizations of lung transplant recipients in Masih Daneshvari Hospital in Darabad, Tehran, between 2000 and 2008. Baseline data (each patient’s age at transplant and rehospitalization, sex, primary lung disease, medications used), cause of rehospitalization (infection, graft rejection, surgical complications, type of infection), health care resources use (length of hospital stay, intensive care unit stay, physician visits, imaging), rehospitalization costs (accommodations, personnel, drugs, paraclinical [ie, laboratory] tests, supplies, procedures) and outcome (death, survival) were noted. Results: In 69% of patients who were rehospitalized after having received a lung transplant, the cause was infection. Other causes were acute rejection in 31% and surgical complications in 6.9%. In 10.3% of those patients, the primary cause for rehospitalization could not be specified. The mean (SD) duration of rehospitalization was 12.8 ± 10.4 days. Treatment in the intensive care unit was necessary for 93.1% of the study subjects. The mean (SD) number of physician visits was 27.8 ± 27.7, and the fatality rate in the patients studied was 13.8%. Conclusions: These data may guide the monitoring of the causes, burden, and outcomes of lung transplants performed in our medical center in Iran and in other medical centers.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 Inflammatory Mediators of Liver Ischemia-Reperfusion Injury(Başkent Üniversitesi, 2009-06) Walsh, Kyle B.; Toledo-Pereyra, Luis H.; Lopez-Neblina, Fernando; Rivera-Chavez, Fernando A.; Toledo, Alexander H.Liver ischemia and reperfusion — which cause liver damage that is significant in a variety of diseases, injuries, and procedures (including but not limited to trauma and transplant) — have been the focus of many investigations in recent years. Although the mechanisms of ischemia-reperfusion injury are numerous and complex, many advances in treatment have been made. The following review considers recent advances in the understanding of hepatic ischemia-reperfusion injury and focuses on inflammatory mediators of significance. To provide a unique analysis and evaluation, we emphasized the most recent pertinent investigations of the last decade. Specific topics addressed include reactive oxygen species, nitric oxide, toll-like receptors, ischemic preconditioning, T cells, heme oxygenase-1, heat shock proteins, erythropoietin, selectins, protein kinases, matrix metalloproteinases, and cytokines.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 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.