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 Epididymo-Orchitis and Central Nervous System Nocardiosis in a Bone Marrow Transplant Recipient for Acute Lymphoblastic Leukemia(Başkent Üniversitesi, 2009-12) Dehghani, Mehdi; Davarpanah, Mohammad-AliObjectives: We report a case of epididymo-orchitis and central nervous system nocardiosis in a 22-year-old man with T-cell acute lymphoblastic leukemia; he was an allogeneic marrow recipient with acute and chronic graft-versus-host disease. Materials and Methods: He had microscopic hematuria and cytomegalovirus antigenemia. He deteriorated subsequently while on cyclosporine and steroids, requiring hospital admission owing to fever and swelling of the left testis and generalized tonic-clonic convulsions. Results: Brain magnetic resonance imaging showed abnormal signal area in right parietal and left parieto-occipital lobes. The lesions had mass effect, edema, and ring enhancement. Findings were indicative of a brain abscess. A testicular biopsy from the lower pole of the left testis was done. A white-to-yellowish discharge was seen and subsequently, Nocardia grew in culture. Conclusions: Trimethoprim-sulfamethoxazole was prescribed, and significant improvement was seen after 2 weeks. The patient was discharged. He was subsequently referred after 3 weeks due to graft-versus-host disease and died of pancytopenia.Item Off-Pump Coronary Surgery for Allograft Vasculopathy 8 Years After Heart Transplant(Başkent Üniversitesi, 2009-12) Michel, Sebastian; Vicol, Calin; Reichart, Bruno; Abicht, Jan; Ueberfuhr, Peter; Beiras-Fernandez, Andres; Kaczmarek, IngoCardiac allograft vasculopathy is a severe complication after heart transplant, and is the major cause of death in patients surviving 1 year after transplant. We present a 59-year-old patient undergoing off-pump, coronary artery bypass surgery, 8 years after heart transplant. Owing to toxic liver disease, the lipid lowering therapy with statins had to be stopped 6 years after transplant, and coronary artery disease developed rapidly within 2 years. Off-pump, coronary bypass surgery was performed using a new, multisuction cardiac positioner; a disposable stabilizer; and a proximal seal system to avoid clamping of the aorta. The patient received 3 bypass grafts: the left internal thoracic artery; to the left anterior descending coronary artery; 1 saphenous vein graft to the marginal branch of the circumflex artery; and 1 saphenous vein graft to the right coronary artery. His postoperative course was uneventful.Item Hepatic Abscesses After Liver Transplant: 1997–2008(Başkent Üniversitesi, 2009-12) Malek-Hosseini, Seyed Ali; Janghorban, Parisa; Nikeghbalian, Saman; Salahi, Roohallah; Salahi, Heshmatallah; Bahador, Ali; Kakaie, Farzad; Kazemi, KorushObjectives: Infectious complications (such as liver abscesses) remain one of the major causes of posttransplant morbidity and mortality. Management may be problematic and is often based on experience with hepatic abscess in nontransplant patients. We reviewed our experience with hepatic abscess in liver transplant recipients to assess their presentation, clinical features, treatment, and outcome. Materials and Methods: A retrospective review of all liver transplant in Shiraz transplant center from September 1997 through September 2008 was performed. Hepatic abscess was defined as a parenchymal hepatic lesion consistent with abscess (as described by a radiologist), positive liver or concurrent blood cultures, or both (within 24 hours), and compatible clinical findings. Results: Of 560 liver recipients, we identified 5 patients (23-42 y) who had experienced 7 episodes of hepatic abscess, 30-240 days after transplant. All patients had received liver from deceased donors. Biliary reconstruction was done by duct-to-duct anastomosis in 4 and hepatico-jejunostomy in 1 case. Pretransplant diagnoses included hepatitis B cirrhosis, autoimmune hepatitis (2 cases), Caroli disease, and cryptogenic cirrhosis. Liver aspirates showed E. coli in 4 cases, and Aspergillus in 1 case. The main predisposing factor was bile-to-duct anastomosis stricture in 3, diabetes mellitus in 2, and hepatic artery thrombosis in 1 of the patients. Two patients died owing to liver and multiorgan failure, despite percutaneous and operative drainage with broad spectrum antibiotics and antifungals. Conclusions: Hepatic abscess, a rare complication after liver transplant, was associated with hepatic artery thrombosis, biliary anastomosis stricture, and diabetes mellitus. Mortality was higher than in patients who had not undergone transplant. Prolonged antibiotic therapy and drainage are required to improve the outcome in these patients.Item Peroneal Neuropathy Following Liver Transplantation: Possible Predisposing Factors and Outcome(Başkent Üniversitesi, 2009-12) Singhal, Ashish; Gupta, Subash; Wadhawan, Manav; Vij, Vivek; Goyal, Neerav; Varma, MukulIntroduction: Perioperative peroneal neuropathy is an uncommon complication following operations remote from the leg or in supine position including liver transplant. Materials and Methods: We retrospectively reviewed the medical records of 132 living-donor liver transplant recipients done at our center between September 2006 and December 2008. Various potential preoperative, intraoperative, and postoperative factors were studied in the cases that developed perioperative peroneal neuropathy. Results: Peroneal neuropathy was reported in 7 recipients (5.3%) following liver transplant. Apart from intraoperative positioning, other identifiable predisposing factors appear to be poor nutritional status, tall and slender body shape, alcoholic liver disease, and higher pretransplant model for end-stage liver disease score. All patients were treated conservatively, including nutritionally balanced diet and vitamin supplements combined with physical rehabilitation therapy. The motor power returned to normal within 6 months in all 7 patients. Conclusions: Perioperative peroneal neuropathy may be contributed by various preoperative factors apart from intraoperative nerve compression. It can be effectively prevented by being aware of the predisposing factors and implicating adequate precautions perioperatively.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 Posttransplant Soluble CD30 as a Predictor of Acute Renal Allograft Rejection(Başkent Üniversitesi, 2009-12) Ghadimi, Naime; Rezaie, Alireza R.; Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad HasanBackground: Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. Materials and Methods: In this prospective study, we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Results: Preoperative sCD30 levels of 3 groups were 96.2 ± 32.5, 80.2 ± 28.3, and 76.8 ± 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 ± 5.2, 22.1 ± 3.2, and 19.8 ± 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Conclusions: Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.Item Impact of the Addition of Maintenance Steroids to a Rapid Steroid Discontinuation Immunosuppressive Protocol Following Acute Renal Transplant Rejection(Başkent Üniversitesi, 2009-12) Arora, Swati; Sureshkumar, Kalathil K.; Dikkala, Sudharani; Marcus, Richard J.Objectives: Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. Materials and Methods: The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection × 1 and no maintenance steroids, (ii): acute rejection × 1 and started on maintenance steroids, (iii): acute rejection × 2 and no maintenance steroids (iv): acute rejection × 2 and started on maintenance steroids, and (v): no acute rejection Results: Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes—whether they were started on maintenance steroids (P = .003) or not (P = .006)—but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). Conclusions: More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.