Başkent Üniversitesi Yayınları
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Item The Role of Generics in Kidney Transplant: Mycophenolate Mofetil 500 Versus Mycophenolate: 2-Year Results(Başkent Üniversitesi, 2010-12) Abdallah, Taieb Ben; Kheder, Adel; Abderrahim, Ezzeddine; Bacha, Med Mongi; Mhibik, Sonia; Karoui, Cyrine; Helal, Imed; Cherif, Mejda; Ounissi, MondherObjectives: The introduction of mycophenolate mofetil has proven itself effective in preventing acute rejection in renal transplant recipients. However, this cost is ineffective with countries with a limited income. This study sought to compare the clinical and therapeutic profiles of a generic formulation with mycophenolate mofetil. Materials and Methods: This 2-year, single-center, prospective, randomized, open-label study investigated the efficacy and safety of a new mycophenolate mofetil generic formulation compared with mycophenolate renal transplant recipients. The study divided patients in 2 groups: 8 patients in G1 received mycophenolate mofetil 500 and 10 patients in G2 received mycophenolate. Their demographics were similar: mean age, 36.6±7.1 and 33.3±11.7 years; sex M/F: 2/6 and 5/5; mean donor age, 42.6±11.1 and 43.6±13.9 years; mean HLA mismatches, 2.7±1.2 and 3.3±1.5; deceased donors, 25% and 20%; and warm ischemia time, 40.2±11.9 and 38.7±10.5 minutes. All patients received 2 g daily of mycophenolate mofetil 500 or mycophenolate with initial dosage of 0.1 mg/kg/d and prednisolone. Results: One patient of 7 in the mycophenolate mofetil group and 4 of 6 in the mycophenolate group had 1 episode of acute tubular necrosis, and 1 patient in each group had an acute rejection with no significant differences between the groups. The area under the curve of the mycophenolate mofetil did not show any difference between the 2 groups. The values of serum creatinine were also comparable. Patient survival rate at 6, 12, and 24 months was 100% in the groups. The frequencies of digestive and hematologic adverse effects were comparable in the groups with no significant differences. Conclusions: Use of mycophenolate mofetil 500 provided safe and effective immunosuppressive therapy compared with mycophenolate. However, as the duration of the study was short, these results need to be confirmed in a long-term study.Item Proteinuria Among Primarily Sirolimus Treated Live-donor Renal Transplant Recipients' Long-term Experience(Başkent Üniversitesi, 2010-12) Hamdy, Ahmed F.; Ghoneim, Mohamed A.; Bakr, Mohamed A.Objectives: Recent evidence of a high incidence of proteinuria among de novo sirolimus-based regimens has been reported among renal transplant patients at short-term follow-up. We report on long-term evaluation of proteinuria among patients maintained on such regimen. Materials and Methods: Between May 2001 and January 2003, 132 patients received a renal allograft from a living donor and were randomized to 2 groups (steroids/sirolimus/tacrolimus, n=65) and (steroids/sirolimus/mycophenolate mofetil, n=67): Both received basiliximab induction. Retrospective review of those patients was performed, 5 years posttransplant with particular emphasis on the incidence of proteinuria. Results: The 5-year incidence of proteinuria was 29.2% and 38.8% among sirolimus/tacrolimus and sirolimus/mycophenolate mofetil group. Single DR-matched patients (P = .016) and the incidence of acute rejection (P = .039) were associated with significantly higher incidence of proteinuria. Moreover, the presence of mesangial matrix increased (P = .015), and glomerulosclerosis (P = .014), in 1-year protocol biopsies, was found to have a positive predictive value for current and future incidences of proteinuria. Proteinuria was found to be associated with significant inferior graft outcome. Recurrent original kidney disease, de novo glomerulopathy, and acute transplant glomerulopathy were responsible for early cases of nephrotic range proteinuria (first 2 years), while cases presented later were attributed to chronic allograft nephropathy. Conclusions: Proteinuria has become a recognized, serious event of primarily sirolimus-treated renal transplants patients, which is most probably of glomerular origin. It has been shown that proteinuria exerts a bad prognostic effect upon graft function and subsequent graft survival at 5-year follow-up.Item Cutaneous Metastasis of Pancreatic Adenocarcinoma After Kidney Transplant: A Case Report and Review of the Literature(Başkent Üniversitesi, 2010-12) Pontinen, Thomas; Ortiz, Jorge; Zaki, Radi; Kung, Shiang Cheng; Chewaproug, Daranee; Khanmoradi, Kamran; Varadi, Gabor; Melin, AlysonObjectives: Pancreatic cancer is one of the most lethal human cancers. Each year in the United States, about 42 470 individuals are diagnosed with this condition, and 35 240 die, despite advances in imaging, medical treatment, and surgical intervention. Often, 80% to 90% of pancreatic cancers are diagnosed at the locally advanced or metastatic stage. However, cutaneous metastases originating from pancreatic cancer are rare. If cutaneous metastases do indeed occur, it is often near the umbilicus, known as the Sister Mary Joseph’s nodule. Nonumblical cutaneous metastases are rare, with only several cases reported, but none regarding lesions after organ transplant. We introduce the first reported case of a cutaneous metastatic lesion of pancreatic adenocarcinoma after the transplant of an organ. We also performed a literature review and an analysis of reported cases of nonumblical cutaneous metastases of pancreatic adenocarcinoma. Materials and Methods: We performed a MEDLINE and PubMed search of reported nonumblical cutaneous metastases of pancreatic adenocarcinoma since 1980 after a literature review and analysis. Results: Our case involved a 76-year-old woman who developed cutaneous pancreatic adenocarcinoma metastases in her surgical wound 2 years after a bilateral kidney transplant. This is the first case of pancreatic adenocarcinoma cutaneous metastases after an organ transplant. Conclusions: The death rate from cancer has increased as the population has aged. This also holds true for transplant recipients. Some believe that cancer will soon surpass cardiovascular disease as the major cause of mortality after transplant. Therefore, it is incumbent upon us to appropriately screen patients with age-appropriate evidence-based examinations. Additionally, those patients with suspicious presentations should be judiciously evaluated to discover a cure for cancer as quickly as possible.Item Switch From Beta-Thalassemia Major to Beta-Thalassemia Intermedia After Secondary Graft Failure(Başkent Üniversitesi, 2010-09) Mellouli, Fethi; Béjaoui, Mohamed; Othman, Tarek Ben; Hmida, Slama; Ladeb, Saloua; Abdelkefi, Abderrahman; Torjmen, Lamia; Lakhal, Amel; Ksouri, HabibIn this article, we report a switch of β-thalassemia major to intermedia β-thalassemia after allogeneic bone marrow transplant of a 6-year-old girl from her HLA-matched brother. After stable mixed chimerism, the patient had a secondary graft rejection and returned to total recipient chimerism as assessed by real-time polymerase chain reaction assay. Nonetheless, with a medium hemoglobin rate of 89 g/L, she did not need further transfusions for 60 months after rejection. We conclude that complete loss of donor cells after bone marrow transplant for β-thalassemia major is compatible with a stable clinical state, probably due to a γ-globin gene demethylation that enhances γ-globin chain production and further allows constitution of a fetal hemoglobin rate compatible with free transfusion survival.Item Acute Gastric Variceal Bleeding During Orthotopic Liver Transplant(Başkent Üniversitesi, 2010-09) Shapiro, David P.; Aniskevich, Stephen; Shine, Timothy S.We present a case of intraoperative gastric variceal bleeding during liver transplant. After an uneventful induction and surgical dissection, our patient developed hemodynamic instability during the anhepatic phase. We believe that an increase in portal pressures, owing to clamping of the portal system, led to spontaneous variceal rupture; however, placement of an oral gastric tube or transesophageal echocardiography probe may have contributed to this also. After intraoperative banding, the patient was stabilized and surgery proceeded uneventfully. The patient had no long-term sequelae. Anesthesiologists involved in the care of patients with end-stage liver disease should be aware of this infrequent intraoperative complication and be prepared to treat it appropriately.Item Liver Transplant in a Patient with Active Pulmonary Tuberculosis(Başkent Üniversitesi, 2010-09) Yankol, Yucel; Kalayoglu, Munci; Acarli, Koray; Alan, Servet; Kanmaz, Turan; Kocak, Burak; Topaloglu, SerdarObjectives: Immunosuppressive treatment generally increases the severity of active infection. Therefore, liver transplant is contraindicated in the presence of active tuberculosis. Despite the importance of supportive treatment, liver transplant is the only treatment for fulminant hepatic failure. Materials and Methods: We report a case of successful liver transplant for fulminant hepatic failure in the presence of active tuberculosis infection. Results: We immediately performed a liver transplant from a live donor. The patient received low-dose immunosuppressive treatment and antituberculosis treatment. The patient was cured and discharged on the 25th day after surgery. We stopped antituberculosis treatment 10 months after discharge. The patient has been followed for 32 months after transplant with normal graft function and has been free of pulmonary tuberculosis infection. Conclusions: Liver transplant can be performed in cirrhotic patients with active infections, such as tuberculosis, as a life-saving procedure.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 TEST(2025) TESTItem Risk Factors of Long-Term Graft Loss in Renal Transplant Recipients with Chronic Allograft Dysfunction(Başkent Üniversitesi, 2010-12) Khalkhali, Hamid Reza; Kazemnejad, Anoushirvan; Hajizadeh, Ebrahim; Ghafari, AliBackground: Graft loss owing to chronic allograft dysfunction is a major concern in renal transplant recipients. We assessed the affect of immune and nonimmune risk factors on death-censored graft loss in renal transplant recipients with chronic allograft dysfunction. Materials and Methods: We performed a retrospective, single-center study on 214 renal transplant recipients with chronic allograft dysfunction among 1534 renal transplant recipients at the Urmia University Hospital from 1997 to 2005. Data registry includes details from all renal transplants. The renal transplant recipient information is regularly updated to determine current graft function, graft loss, or renal transplant recipient’s death. The selection criteria were a functional renal allograft for at least 1 year and a progressive decline in allograft function. Results: Increasing donor age (RR=1.066; P < .001), recipient age (RR=1.021, P = .0), recipient weight (RR=1.024; P = .029), and waiting time on dialysis to transplant. (RR=1.047; P = .006), pretransplant hypertension (RR=3.126; P < .001), pretransplant diabetes (RR=5.787; P < .001), delayed graft function (RR=6.087; P < .001), proteinuria (RR=2.663; P = .001), posttransplant diabetes (RR=2.285; P = .015), posttransplant hypertension (RR=2.047; P = .017), and AR (RR=3.125; P < .001). Patients in stage 2 at the beginning of chronic allograft dysfunction relative to stage 1 (RR=4.823; P < .001) and patients in stage 3 at the beginning of chronic allograft dysfunction relative to stage 1 (RR=123.06; P < .001) were significant risk factors for death-censored graft loss. Using mycophenolate mofetil versus azathioprine reduced death-censored graft loss (RR=0.499; P ≤ .001). Conclusion: We found that age of donor, pretransplant hypertension, pretransplant diabetes, type of immunosuppression (mycophenolate mofetil vs azathioprine), delayed graft function, proteinuria, and stage of allograft dysfunction at the start of chronic allograft dysfunction are the major risk factors for late renal allograft dysfunction.