Başkent Üniversitesi Yayınları

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    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.
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    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, Mohammad
    Objectives: 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.
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    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, Atilla
    Aortic 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.
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    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 Raj
    Objective: 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.
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    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, John
    Objectives: 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.
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    An Unusual Case of Posttransplant Osteoid Osteoma
    (Başkent Üniversitesi, 2009-06) Ossareh, Shahrzad; Naseem, Soubia; Shooshtarizadeh, Tina
    Posttransplant 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.
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    Antioxidant Enzymes and Lipid Peroxidation in Cold Ischemic Lung Preservation
    (Başkent Üniversitesi, 2009-06) Yeginsu, Ali; Ergin, Makbule
    Objectives: 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.
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    Brain Tumor as an Unusual Presentation of Posttransplant Lymphoproliferative Disorder
    (Başkent Üniversitesi, 2009-03) Azarpira, Negar; Rakei, Mohamad; Torabineghad, Simin
    Objectives: Posttransplant lymphoproliferative disorder following solid organ transplant is a life-threatening form of posttransplant malignancy. Its occurrence is typically associated with Epstein-Barr virus and profound immunosuppressive therapy. We describe a case of posttransplant lympho­proliferative disorder in the brain parenchyma, 4 years after renal transplant. Case Report: A 23-year-old man was evaluated for generalized headache 4 years after receiving a deceased donor renal transplant. After initial immuno­suppression with tacrolimus and pred­nisolone, mycophenolate mofetil was added for maintenance immunosuppression. A tumor in the right occipitoparietal lobe was detected by magnetic resonance imaging and excised. Immuno­histo­chemical testing of the tumor revealed B-cell marker and Epstein-Barr virus. After surgery, the dosage of immunosuppressive drugs was reduced, and the patient was treated with chemotherapy and radiotherapy. Our patient is well after treatment. Conclusions: Reduction in immunosuppressive therapy is an important component of treatment for Epstein-Barr virus-positive posttransplant lympho­pro­liferative disorder and may lead to remission in early disease. If reduced immunosuppression fails to control early disease, cytotoxic chemotherapy, surgery and radiotherapy, antiviral therapies, and cell-based therapies are other options for treatment.
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    A Report of Outcomes After Orthotopic Liver Transplant With Allografts From Heparin Antibody-Positive Donors
    (Başkent Üniversitesi, 2009-12) Aloia, Thomas A.; Goss, John A.
    Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition associated with thrombo­cytopenia and thrombotic complications. The condition is increasingly recognized in hospitalized patients including severely injured trauma patients. Because these patients may eventually be considered for organ donation, management of the HIT screen-positive donor has become an important issue in transplant surgery. We describe the recent management of 2 liver allograft donors with relative thrombo­cytopenia and positive HIT antibody screens. In both cases, systemic anticoagulation at the organ recovery operation was accomplished with argatroban, a synthetic thrombin inhibitor. This management strategy resulted in successful transplants for 7 recipients (1 heart, 2 liver, 4 kidney). Neither of the liver recipients demonstrated signs or symptoms of HIT, and neither had any postoperative thrombotic complications. Based on this experience, a treatment algorithm for managing HIT-positive donors is proposed. In addition, the pathophysiology of HIT and various testing modalities for the disorder are discussed.
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    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, Hamid
    Objectives: 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.