Başkent Üniversitesi Makaleler
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Item A Novel Technique for Hepatic Arterial Reconstruction in Living-Donor Liver Transplant(Başkent Üniversitesi, 2007-06) Haberal, Mehmet; Sevmis, Sinasi; Karakayali, Hamdi; Moray, Gokhan; Yilmaz, Ugur; Ozcay, Figen; Torgay, Adnan; Aydogan, Cem; Arslan, GulnazObjectives: Arterial reconstruction in patients undergoing living-donor liver transplant is technically difficult because of the small diameter of the vessels in the partial liver graft. In this study, we present our technique for hepatic arterial reconstruction. Methods: Since December 2005, we have performed 54 living-donor liver transplants, which are analyzed retrospectively in this report. In our technique now used at our institution, native and graft hepatic arteries are spatulated from both the anterior and posterior walls to provide a wide anastomosis. Computed tomographic angiography is used to evaluate the vascular anatomy and to measure the diameter of the graft hepatic arteries. Results: Mean follow-up was 7.2 ± 5.5 months (range, 1-17 months). Nine of the 54 recipients died within 4 months of the surgery. At the time of this writing, the remaining 45 recipients (84%) are alive and demonstrating good graft function. In 2 recipients (3.7%) in this series, hepatic artery thromboses developed, which were treated with an interventional radiologic technique. Conclusions: Our arterial reconstruction technique has enabled reconstruction of smaller arteries and arteries of various diameters without an operating microscope. The rate of complications in our patients is similar to that reported in similar individuals.Item Successful Living-Donor Liver Transplantation and Retransplantation with Cavoportal Hemitransposition: A Case Report(Başkent Üniversitesi, 2006-12) Ozden, Ilgin; Suoglu, Ozlem Durmaz; Aydogan, Aysen; Bilge, Orhan; Yavru, Aysen; Sokucu, Semra; Acarli, KorayAn 11-month-old female infant underwent living-donor liver transplantation for secondary biliary cirrhosis 8 months after Kasai operation. The portal vein was hypoplastic, and its diameter was only 4 mm at the level of the splenomesenteric confluence. End-to-end anastomosis of the recipient suprarenal vena cava to the graft portal vein (a left lateral section from the patient’s mother) was performed. An end-to-side portocaval shunt with the recipient portal vein was constructed to mitigate portal hypertension. The early postoperative course was relatively uneventful. However, persistent hepatitis caused by infection with Cytomegalovirus and chronic rejection resulted in progressive hepatic dysfunction. Nine months after the initial operation, a living-donor retransplantation (a left lateral section from the patient’s grandmother) was performed. One month after retransplantation, severe acute rejection that eventually required OKT3 treatment developed. The patient was in excellent health until 4 months after retransplantation, when another acute rejection episode (for which she was successfully treated) developed. Cavoportal hemitransposition should be included in the armamentarium of the transplant surgeon for the management of extensive portal system thrombosis and portal vein hypoplasia. An additional shunt may be useful in mitigating portal hypertension.Item Quiescent Interplay Between Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-α: Influence on Transplant Graft Vasculopathy in Renal Allograft Dysfunction(Başkent Üniversitesi, 2006-06) Elahi, Maqsood M.; Matata, Bashir M.; Hakim, Nadey S.A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-α in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-α. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-α in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-α interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-a as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.Item Induction Therapy(Başkent Üniversitesi, 2005-06) Bakr, Mohamed A.Transplantation is a suitable option for patients with end-stage organ failure. Many immunosuppressive agents are available, and this may pose difficulty in choosing an appropriate combination for maintenance therapy, treating episodes of acute rejection of varying severities, and tailoring therapies for specific patients. Induction therapy strategies are accomplished either by relatively high doses of conventional immunosuppressants or by using poly- or monoclonal antibodies. These antibodies are an integral part of transplant medicine today. The rationale for antibody therapy aims at augmenting immunosuppression, ensuring that delayed introduction of calcineurin inhibitors is safe, encouraging steroid withdrawal, and facilitating treatment of patients sensitized to human leukocytic antigens in addition to its crucial role in immunologic conditioning either by tolerance induction or alternatively minimizing the immunosuppressive drugs. Different trends in induction therapy initially consisted of anti-thymocyte globulin, then anti-CD3 Orthoclone, and finally anti-CD20, 25, and 52 agents. Induction therapy is associated with beneficial short- and long-term outcomes when increased risk of adverse effects related to immune system suppression are an issue, especially from cytomegalovirus and lymphomas.Item Middle East Society for Organ Transplantation (MESOT) Transplant Registry(Başkent Üniversitesi, 2004-12) Haberal, Mehmet A.; Shaheen, Faissal A. M.; Stephan, Antoine; Ghods, Ahad J.; Al-Rohani, Muhamed; Mousawi, Mustafa Al; Mohsin, Nabil; Ben, Taieb; Bakr, Adel; Rizvi, Adibul HasanDuring the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors. Based on this and similar declarations, all Middle Eastern countries except Egypt passed laws that allow cadaveric transplantation and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan, and Lebanon all have current active cadaveric programs and perform liver, heart, pancreas, and lung transplants. More than 5088 renal transplants/year are performed in the region with Iran leading with 1600. The cumulative number of renal transplant patients is now nearly 60,000. With a 2003 population of 600,682,175, the rate/million for renal transplantation in the MESOT region is a mere 9/million. Rates of renal transplantation range from 31/million in some countries to 0 in others. The major obstacle in establishing an accurate number of transplants is “tourist transplantation,” in which the same transplanted patients are registered in different countries. Although cadaveric programs have been active for more than 10 years, live-related and nonrelated transplants account for nearly 85% of the total transplants. The data presented were collected from MESOT representatives in the region and from publications. For proper compilation of the registry, a format is being proposed that will be presented at the Congress for review and adaptation. Even with the limited resources in the region, immunosuppressive drugs for induction and maintenance therapy are available and are used. Costs for transplantation and immunosuppressive therapy are either totally or heavily supported by governmental agencies.Item Ten-Year Follow-Up of Recipients of a Kidney or Heart Transplant Who Received Induction Therapy with a Monoclonal Antibody Against the Interleukin-2 Receptor(Başkent Üniversitesi, 2004-06) Wabbijn, Marike; Balk, Aggie HMM; Domburg, Ron T van; Vantrimpont, Pascal JMJ; Riemsdijk, Iza C van; Baan, Carla C; Weimar, Willem; Gelder, Teun vanObjective: Twelve years ago, we performed two randomized clinical trials to investigate safety and efficacy of induction therapy with BT563, a highly potent murine monoclonal antibody against the interleukin-2 receptor after kidney and heart transplantation. We analyzed the long-term safety and efficacy data from all 120 patients who participated in the two randomized trials after kidney and heart transplantation 10 years ago. Materials and Methods: One of these two trials was a randomized, double-blind, placebo-controlled trial, with 60 primary and secondary kidney allograft recipients (cadaveric and living-related donors). The control group was treated with the standard regimen at that time, consisting of cyclosporin and prednisone. In the study group, BT563 was added for 10 days. The second trial was a randomized, double-blind trial, with 60 recipients of a primary heart transplant. In that study, we compared induction therapy with BT563 with the standard regimen at that time, consisting of cyclosporin, prednisone, and OKT3 (both induction agents were given for 7 days). Results: Patient survival in the kidney trial was excellent: in the BT563 group, 24 patients were alive (80%), and in the placebo, group 21 (70%) 10 years after transplantation. Also, graft survival was good: in the BT563 group, 63.3% of the kidneys (19/30) were functioning, in the placebo group, 72.4% (21/29) were functioning (P = 0.455). Also, in the heart study, patient (and graft) survival was excellent: 18 patients were alive in the BT563 group (58%), and in the OKT3 group, 21 (72%) patients were alive (P = ns). No increase in the incidence of malignancies was observed between patients treated with BT563 compared with the control groups. Patients following heart transplantation more often suffered from a malignancy than did patients after kidney transplantation (20/60 vs 10/59). Conclusion:We report follow-up data on all patients participating in the two randomized trials, and our data reflect a total of 932 years of patient follow-up. Patient and graft survival appear to be excellent in both the BT563-treated patients and the control groups. BT563 treatment was not associated with an increased likelihood of developing infections or malignancies.Item The Science of Stem Cells: Ethical, Legal and Social Issues(Başkent Üniversitesi, 2003-12)Stem cells are exciting to physicians, scientists and patients because of their potential to develop into many different cell types, tissues and perhaps even organs that can possibly be used to treat large numbers of patients with a variety of diseases. Scientific research, while it is still at a very early stage, is developing rapidly and creating enormous challenges for ethicists and policy-makers, especially in relation to embryonic stem cells. An understanding of the scientific facts of stem cell science and technology per se, the embryology and the associated terminology is critically important to making ethically sound policy judgments. The facts, definitions and terminology are confusing and are liable to misuse by those who seek to further a particular position. In this paper we provide a concise overview of the important scientific facts related to embryology and embryonic stem cells and highlight some recent scientific developments that are salient for the purpose of understanding the ethical, legal and social issues that have arisen and will continue to arise and be debated.Item Important Social Factors that Affect Organ Transplantation in Islamic Countries(Başkent Üniversitesi, 2003-12) AAAl-Khader; Shaheen, F A M.; Al-Jondeby, M S.Social attitudes and beliefs have direct and strong impact on people’s acceptance of organ donation and brain death, and therefore affect the entire practice of organ transplantation. The views differ from one society to another, and they at least partially explain regional variations in the world with respect to success of organ transplantation. Social attitudes and ethics in Islamic countries are closely intertwined with Islamic tradition, teachings and heritage. These positions are strongly adhered to in many Islamic countries, and by Moslems who live in countries that are not predominantly Islamic. We feel that transplant physicians and transplant coordinators should be aware of these factors when dealing with potential donors and recipients. Decision-making can be facilitated if these issues are considered prior to consulting with a donor’s family and if an appropriate compassionate explanation of need for transplantation and basis of brain death diagnosis is provided based on a knowledge of underlying social constraints. Such steps can make the donation process smoother for both health care workers and the family.Item Induction of Immunosuppression with Polyclonal Antithymocyte Globulins: An Overview(Başkent Üniversitesi, 2003-12) Beiras-Fernandez, A.; Thein, E.; Hammer, C.The induction of immunological tolerance to solid organ allograft is currently a subject of major investigation due to the morbidity and mortality related to immunosuppressive therapy. Immunosuppression induction by recipient treatment may allow to tailoring the timing and dosage of standard therapy not only reducing adverse reactions but also improving the graft outcome. Depletion of recipient T cells with polyclonal antithymocyte globulins is one of the methods nowadays investigated both in experimental and clinical procedures, demonstrating a better outcome of organ engraftment. Our intention is to give an overview of the literature about the mechanisms of action of polyclonal ATGs, the status of induction treatment in clinical and experimental transplantation as well as of the possible pathophysiological relationships with acquired tolerance, delayed graft failure and ischemia-reperfusion injury.Item Organ Transplantasyonu ve Nörolojik Komplikasyonlar(Başkent Üniversitesi, 2006-09) G. Çileker,; S. Benli,; M. Kılınç,; T. ZileliOrgan transplantasyonu son yıllarda gelişmekte olan bir alan olup, immünsüpresan tedavilerin giderek gelişmesiyle başarısı daha da artmaktadır. Bununla birlikte transplant alıcıları sinir sistemini de ilgilendiren çok sayıda komplikasyonla karşılaşmaktadır. Nörolojik komplikasyonlar bütün organ transplantasyonlarında ortak olarak görülen komplikasyonlar ve belli bir organ transplantasyonuna özgü nörolojik komplikasyonlar olmak üzere ikiye ayrılabilir. Nöbetler, santral sinir sistemi enfeksiyonları, inme, ensefalopati ve kullanılan immünsüpresanlara bağlı yan etkiler daha sık görülürken, diğer ilaçların yan etkileri, maligniteler, hareket bozuklukları, nöromusküler ve nörooftalmik komplikasyonlar daha az sıklıkta görülmektedir. Komplikasyonlar ortaya çıktığında her vakanın ayrıntılı sistemik ve nörolojik değerlendirilmeden geçirilmesi esastır. Fırsatçı enfeksiyonlar yönünden dikkatli değerlendirme yapılmalı, kullanılan immünsüpresan ilaçların seviyelerinin değerlendirilmesi ve normal ilaç seviyelerinde de nörotoksisite ihtimali olabileceği göz önünde bulundurulmalıdır. Nörolojik komplikasyonların erken tanısı, tedavi edilebilir ve geri dönüşümlü nedenlerin belirlenmesi, transplantasyonun mortalite ve morbiditesini azaltmaktadır. Neurologic Complications After Organ Transplantation In recent years, there has been an exponential increase in successful organ transplantation that is in part due to recent advances in immunosuppressive regimens. However, some transplant patients continue to experience severe complications, especially those involving the central nervous system (CNS). The neurologic complications of organ transplantation are frequently associated with all types of allografts and can also be specific to a particular type of organ transplantation. Seizures, CNS infection, stroke, encephalopathy, and adverse effects caused by treatment with immunosuppressive drugs are the most common complications. Malignancy, movement disorders, neuroophthalmic and neuromuscular complications, and adverse effects caused by other types of drugs occur less frequently. When such complications do appear, the patient must undergo thorough systemic and neurologic examinations and an equally thorough evaluation for the presence of opportunistic infections. Neurotoxicity caused by treatment with immunosuppressive agents is also a frequent cause of neurologic complications and may experienced with normal serum drug levels. The early diagnosis of neurologic complications and the identification of their reversible and treatable causes can significantly decrease morbidity and mortality rates in patients who undergo organ transplantation.