Başkent Üniversitesi Yayınları
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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 Fatal Acute Purulent Pericarditis in a Patient with Renal Transplant: A Case Report(Başkent Üniversitesi, 2009-03) Mohsin, Nabil; Abbas, Pakkayara; Ehab, Mohammad; Amitabh, Jha; Budruddin, MohammadObjectives: Acute purulent pericarditis is a life-threatening disease, although it is becoming uncommon in the era of antibiotics. Materials and Methods: We present a case of fatal acute massive purulent pericarditis in a kidney transplant recipient. Results: A 46-year-old woman had an unrelated commercial renal transplant in 2003. She had a history of diabetes mellitus and hepatitis C infection. Kaposi sarcoma developed in the posttransplant period. Her last admission was prompted by the development of acute rejection confirmed by transplant biopsy, and she was treated with intravenous methylprednisolone. Three days before her death, thrombophlebitis of the right forearm was noted. We postulate that this could have been the source of the fulminant purulent pericarditis, as the organism in the pericardial fluid was Staphylococcus aureus, a common pathogen in thrombophlebitis. She was initially resuscitated after cardiac arrest but died shortly after. Conclusions: Severe purulent pericarditis in the immunocompromised patient can occur abruptly. The source of infection may show minimal signs and symptoms. Thrombophlebitis and other apparently minor infections should not be overlooked in such patients.Item A Comparative Study on Suture Versus Cuff Anastomosis in Mouse Cervical Cardiac Transplant(Başkent Üniversitesi, 2010-09) Zhou, Yiming; Chen, Zongyou; Qian, Shiguang; Xiang, Jianbin; Gu, XiaodongObjectives: To compare the cuff technique to traditional suture technique in establishing cervical heart transplant model in mice. Materials and Methods: Eighty transplants were performed by 1 surgeon, 40 using the cuff technique, and 40 using the suture technique, under the same circumstances. Results: The cuff approach was significantly superior to conventional suture anastomosis in higher surgical successful rate, less surgery, and less ischemic time (P < .05). Suture anastomosis required an intensive microsurgical training and at least a 16× surgical microscope, while the cuff anastomosis required less learning time and a 10× surgical microscope. Conclusions: The cuff technique is the preferred method in cervical heart transplant model in mice.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 An Ex-Vivo Model for Hypothermic Pulsatile Perfusion of Porcine Pancreata: Hemodynamic and Morphologic Characteristics(Başkent Üniversitesi, 2010-03) Karcz, Marcin; Papalois, Vassilios; Dorling, Anthony; Gray, Cathy; Sibbons, Paul; Cook, H. TerenceObjectives: Hypothermic machine perfusion is a well-established preservation method for kidneys that allows for better preservation over longer periods and pretransplant assessment of graft viability. This technique has only sporadically been used for pancreatic grafts. The aim of this study was to establish a hypothermic machine perfusion model for porcine pancreas perfusion. Materials and Methods: Fifteen porcine pancreata were subjected to 25 minutes of warm ischemia and 149 minutes of cold ischemia before undergoing meticulous bench work preparation and perfusion, via an aortic segment, on the RM3 perfusion machine with University of Wisconsin (Barr Laboratories Inc., Pomona, NY, USA) solution. Perfusion variables (°C, temperature; mm Hg, systolic perfusion pressure; mL/min, flow volume; mm Hg/mL/min, resistance) were recorded every 30 minutes. Tissue samples were assessed for each pancreas preperfusion and postperfusion using a semiquantitative scoring scale to grade histopathologic changes: acinar cell damage (0-4), islet cell damage (0-3), inflammation (0-3), and edema (0-3). Results: Hypothermic machine perfusion time was set at 315 minutes, and all grafts were maintained between 4-10°C. The results were as follows (range, mean ± SD): systolic perfusion pressures were 5-13 mm Hg (9.61 ± 3.25 mm Hg) during the first 60 minutes (priming), and 15-23 mm Hg (21.07 ± 4.26 mm Hg) during the maintenance period. Target flow volumes reached 141-152 mL/min (147.6 ± 8.969 mL/min) at 60 pulses per minute. Intrapancreatic resistance decreased throughout priming to 0.03-0.09 mm Hg/mL/min (0.083 ± 0.042 mm Hg/mL/min), and remained unchanged until completion of perfusion. Pancreatic weight increase varied from 3.2% to 18.3% (13.36% ± 4.961%). There was significant postperfusion reduction in islet and acinar cell damage (P = .001 and P = .01 respectively). Conclusions: We have developed a model of machine perfusion for porcine pancreata which is simple, reliable, and protects graft histopathologic integrity. The model can be used in further studies to improve the quality of pancreas preservation, and assess and improve the viability of the condition of borderline pancreatic grafts.Item Bentall Procedure for the Treatment of Aortic Dissection After Cardiac Transplant: A Case Report(Başkent Üniversitesi, 2009-12) Saritas, Bulent; Aslamaci, Sait; Akay, Tankut; Ozkan, Murat; Korun, Oktay; Sezgin, AtillaAortic dissection affecting the donor aorta after cardiac transplant is a rarely seen complication. Data on the literature about the subject is restricted to case reports. Here, we present a case of type A aortic dissection after cardiac transplant that was successfully treated by the Bentall procedure.Item Autologous Bone Marrow Derived Mononuclear Cell Therapy for Spinal Cord Injury: A Phase I/II Clinical Safety and Primary Efficacy Data(Başkent Üniversitesi, 2009-12) Kumar, Arachimani Anand; Baskaran, Mayakesavan; Arul, Kanagarajan; Narayanan, Raghavachary; Kumar, Sankaran RajObjective: We sought to assess the safety and therapeutic efficacy of autologous human bone marrow derived mononuclear cell transplantation on spinal cord injury in a phase I/II, nonrandomized, open-label study, conducted on 297 patients. Materials and Methods: We transplanted unmanipulated bone marrow mononuclear cells through a lumbar puncture, and assessed the outcome using standard neurologic investigations and American Spinal Injury Association (ASIA) protocol, and with respect to safety, therapeutic time window, CD34+ cell count, and influence on sex and age. Results: No serious complications or adverse events were reported, except for minor reversible complaints. Sensory and motor improvements occurred in 32.6% of patients, and the time elapsed between the injury and the treatment considerably influenced the outcome of the therapy. The CD34+ cell count determined the state of improvement, or no improvement, but not the degree of improvement. No correlation was found between level of injury and improvement, and age and sex had no role in the outcome of the cellular therapy. Conclusion: Transplant of autologous human bone marrow derived mononuclear cells through a lumbar puncture is safe, and one-third of spinal cord injury patients show perceptible improvements in the neurologic status. The time elapsed between injury and therapy and the number of CD34+ cells injected influenced the outcome of the therapy.Item An International Survey of the Diagnosis, Management, and Treatment of Hepatitis C in Patients with End-Stage Renal Disease(Başkent Üniversitesi, 2009-12) Araya, Victor; Ortiz, Jorge; Olson, Mira R.; Grewal, Kevin S.; Bingaman, Adam; Zaki, Radi; Stewart, Shelby; Horton, JohnObjectives: Hepatitis C is one of the leading causes of death from liver disease in the United States, and is frequently associated with renal disease. Two major organizations—the American Association for the Study of Liver Disease and the National Kidney Foundation—have published recommendations regarding the treatment of hepatitis C in the presence of chronic kidney disease; however, these guidelines do not always provide the same recommendations. Given the paucity of data on adherence to the current guidelines, a survey was conducted to provide information about the current practices of physicians in comparison to the published guidelines. Materials and Methods: An observational study was conducted via a global survey asking physicians treating patients who had concurrent hepatitis C and chronic kidney disease. Results: The 218 questionnaires collected requested the physician’s subspecialty, the number of transplants performed at the hospital, the usual method of screening for hepatitis C, the preferred route, the indication and frequency of liver biopsy, the use of ribavirin and interferon, the use of hepatitis-C–positive donors in kidney transplant, and consent requirements. Conclusions: Our results showed that many physicians do not follow current recommendations. We argue that a consensus group be formed to set forth guidelines for the management of hepatitis C to optimize outcomes, and improve overall morbidity.Item An Unusual Case of Posttransplant Osteoid Osteoma(Başkent Üniversitesi, 2009-06) Ossareh, Shahrzad; Naseem, Soubia; Shooshtarizadeh, TinaPosttransplant tumors are one of the important long-term complications of renal transplant. However, aside from noninvasive Kaposi sarcomas, increased production of benign tumors has not been observed after renal transplantation, and to our knowledge, no cases of posttransplant osteoid osteoma have been reported so far. Osteoid osteoma is a common, benign, bone neoplasm that occurs typically in the long bones and presents with severe, intractable pain. Here, we present a 49-year-old man, who presented with increasing bone pain in the right upper arm, 7 months after a renal transplant. Despite an initial normal right humerus radiograph, a raised subperiosteal tumor was diagnosed in the medial border of the right humerus a few months later. An excisional biopsy was performed, and the pathologic report was an osteoid osteoma. The patient’s pain, which had been resistant to most analgesics, completely disappeared after surgery, and he is currently devoid of any lesions, 9 months after excision of the tumor.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.