Başkent Üniversitesi Yayınları
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Item Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α(Başkent Üniversitesi, 2013-02) Blank, Gregor; Königsrainer, Alfred; Nadalin, Silvio; Handgretinger, Rupert; Kratt, Thomas; Li, JunAcute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graft-versus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.Item Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity(Başkent Üniversitesi, 2013-02) Sato, Toshikazu; Homma, Yukio; Ishikawa, AkiraObjectives: Cyclosporine, a potent immunosuppressant, has nephrotoxic adverse effects that may be mediated by oxidative stress. The reduced form of coenzyme Q10 has antioxidant effects. The aim of the present study was to evaluate the effect of the reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. Materials and Methods: Six-week-old male Wistar rats were divided into 3 groups (10 animals each). Group 1 (control) received olive oil only. Group 2 received cyclosporine (30 mg/kg/d, which is an experimentally nephrotoxic dose). Group 3 received cyclosporine (30 mg/kg/d) and the reduced form of coenzyme Q10 (600 mg/kg/d). The cyclosporine and the reduced form of coenzyme Q10 were given orally for 4 weeks. Daily urinary albumin excretion, serum creatinine level, and urinary 8-hydroxydeoxyguanosine level were measured, and renal tissue was evaluated by immunohistochemistry. Results: In rats treated with cyclosporine and the reduced form of coenzyme Q10 (group 3), there were significantly less abnormalities in mean urinary albumin excretion (group 1: 2.8 ± 0.5; group 2: 41 ± 7; group 3: 21 ± 4 µg/d), serum creatinine (group 1: 1.0 ± 0.2; group 2: 1.8 ± 0.4; group 3: 1.4 ± 0.3 mg/dL), and urine 8-hydroxydeoxyguanosine levels (group 1: 7 ± 3; group 2: 10 ± 3; group 3: 7 ± 1 mg/mL creatinine) than rats treated with cyclosporine alone (group 2). There were 8-hydroxydeoxyguanosine deposits seen in the proximal tubular cells of group 2 that were not present in rats treated with the reduced form of coenzyme Q10 (group 3). Conclusions: The reduced form of coenzyme Q10 may prevent or minimize cyclosporine nephrotoxicity by an antioxidant effect.Item Rhinomaxillary Mucormycosis in a Renal Transplant Recipient: Case Report(Başkent Üniversitesi, 2012-12) Azarpira, Negar; Khademi, Bighan; Kazemi, Kourosh; Ashraf, Mohamd JavadObjectives: Rhinomaxillary mucormycosis is a clinical manifestation of zygomycosis in solid-organ transplant recipients. Without proper diagnosis and treatment, rhino-orbital-cerebral zygomycosis, particularly a central nervous system disease, will develop with substantial complications. Case report: A 42-year-old man who had undergone renal transplant was admitted to our otolaryngology department with unilateral bloody nasal discharge. Mucormycosis was detected in the necrotic tissue of the maxillary sinus. Surgical ablation of the infected parts, along with antifungal treatment, restricted extension of the infection. Conclusions: Early detection of opportunistic infections in transplant recipients plays an important role in preventing dissemination. Fungal infections, including zygomycosis, should be considered in all solid-organ recipients, especially in persons with local unusual manifestations. Early diagnosis and successful treatment reduce mortality.Item Reduction of Transplant Arteriosclerosis After Treatment With Mycophenolate Mofetil and Ganciclovir in a Mouse Aortic Allograft Model(Başkent Üniversitesi, 2012-12) Hoffmann, Julia; Steinkasserer, Alexander; Ensminger, Stephan M.; Weyand, Michael; Zinser, Elisabeth; Spriewald, Bernd M.; Ramsperger-Gleixner, Martina; Abele-Ohl, Silke; Böhm, MartinObjectives: Transplant arteriosclerosis is a major obstacle for long-term allograft survival in heart transplant. The aim of this study was to investigate potential synergistic effects of combined treatment with mycophenolate mofetil and ganciclovir on the development of transplant arteriosclerosis, presence of regulatory T cells, and expression of donor specific alloantibodies. Materials and Methods: Donor aortas from C57BL/6 (H2b) mice that were fully mismatched to the major histocompatibility complex were transplanted into CBA (H2k) mouse recipients. Groups of mice received mycophenolate mofetil (100 or 300 mg/kg, oral), ganciclovir (10 or 72 mg/kg, intraperitoneal), or a mycophenolate mofetil and ganciclovir combination. Grafts were analyzed by histology and morphometry on day 30 after transplant. Numbers of regulatory T cells and donor-specific alloantibodies were examined by fluorescence- activated cell sorting analysis of splenic tissue and peripheral blood. Results: Mycophenolate mofetil (100 mg/kg) and ganciclovir (10 mg/kg and 72 mg/kg) did not show effects on transplant arteriosclerosis formation or alloantibody production. However, groups treated with mycophenolate mofetil (300 mg/kg) or a low- or high-dose mycophenolate mofetil and ganciclovir combination had significantly reduced transplant arteriosclerosis and alloantibody levels. Expression of regulatory T cells within the spleen was similar between all experimental groups and untreated controls. Conclusions: The combination of mycophenolate mofetil and ganciclovir significantly reduced the development of transplant arteriosclerosis in a mouse abdominal aortic allograft model. This effect may be a result of decreased alloantibody production.Item Mycophenolate Mofetil-related Pancolitis in a Kidney Transplant Recipient(Başkent Üniversitesi, 2012-10) Hamouda, Mouna; Elmay, Mezri; Skhiri, Habib; Mahmoudi, HoudaGastrointestinal adverse effects are common with mycophenolate mofetil administration, especially diarrhea. We report a case of mycophenolate mofetil-related colitis in a kidney transplant recipient. Colonoscopy revealed an ulcerative diffuse colitis. The colonoscopic biopsy specimen showed mild crypt distortion, accompanied by cryptitis and focal graft-versus-host disease like changes. The patient’s symptoms improved after we discontinued the mycophenolate mofetil. A repeat colonoscopy 2 months after we discontinued the mycophenolate mofetil showed reparative changes. Mycophenolate mofetil is an important drug in organ transplant immune-suppression regimens; however, with its widespread use, additional adverse effects continue to be recognized.Item Soft Tissue Sarcoma at a Dialysis Access Site in a Transplant Recipient(Başkent Üniversitesi, 2012-08) Andre, Jason; Campos, Stalin; Ortiz, Jorge; Zaki, Radi; Khanmoradi, Kamran; Minimo, Corrado; Parsikia, AfshinSoft tissue sarcomas typically present as soft, painless masses on an extremity. Here, we present a patient with metastatic soft tissue sarcomas at his dialysis access site. This association with dialysis access has not been documented previously. A 62-year-old man presented with a nonhealing wound on his left upper extremity after excision of a pseudoaneurysmal arteriovenous fistula. The patient had received a second kidney transplant that was functioning well. Immunosuppression included tacrolimus, mycophenolate mofetil, and prednisone. He was induced with thymoglobulin twice. A biopsy was performed showing a high-grade pleomorphic sarcoma. A magnetic resonance image of his left upper extremity showed an 11 × 5.5 × 3 cm mass abutting the biceps and brachialis muscles. Also, we discovered several lesions in the axilla and the left side of the neck, which were suspicious for metastases. A positron emission tomography-computed tomography scan confirmed a left upper extremity soft tissue mass, with marked fluorodeoxyglucose uptake, in abnormally enlarged axillary, and supraclavicular lymph nodes of the left thorax, consistent with metastases. The patient underwent chemotherapy and radiation therapy.Item Everolimus-induced Lymphedema in a Renal Transplant Recipient: A Case Report(Başkent Üniversitesi, 2012-06) Ersoy, Alparslan; Koca, NizameddinThe mammalian target of rapamycin inhibitors is commonly preferred for solid organs for transplantation. Although these drugs have various adverse effects, sirolimus-related lymphedema has been rarely reported. We report a case of lymphedema related to everolimus after a kidney transplant. A 60-year-old woman successfully received a deceased-donor kidney. Everolimus was added to the treatment in postoperative month 3 owing to other immunosuppressive drugs’ adverse effects. Edema occurred first on her feet in the first year after the transplant. During 3 months’ follow-up, with no immunosuppressive adjustment, the edema progressed. Diagnosis of lymphedema was established. Several weeks after discontinuing everolimus, the patient’s lymphedema began to resolve itself and completely disappeared in 3 months. The mammalian target of rapamycin inhibitors rarely causes lymphedema by inhibiting different subtypes of vascular endothelial growth factors, which results in impaired lymphangiogenesis. While there are few reports about sirolimus-related lymphedema, this case represents the first everolimus-related case of lymphedema. Further studies are warranted to explain the underlying mechanisms.Item Twenty-Four Hour Steroid Avoidance Immunosuppressive Regimen in Liver Transplant Recipients(Başkent Üniversitesi, 2012-06) Ju, Wei-qiang; Zhu, Xiao-feng; Tai, Qiang; Han, Ming; Hu, An-bin; Wu, Lin-wei; He, Xiao-shun; Ling, Xiaoting; Guo, Zhi-yongObjectives: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. Materials and Methods: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24-hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. Results: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). Conclusions: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.Item Neurologic Complications of Renal Transplant(Başkent Üniversitesi, 2012-06) Ce, Pinar; Uslu, Adam; Nart, Ahmet; Gedizlioglu, Muhtesem; Coban, Gokmen; Koskderelioglu, AsliObjectives: Neurologic problems have a major effect on the survival and quality of life in renal transplant recipients. This study sought to review the incidence and character of neurologic complications after renal transplant. Materials and Methods: Medical records of 319 renal transplant recipients admitted to the Transplant Outpatient Clinic were reviewed retrospectively for neurologic complications. Results: Of the 319 transplant recipient patients reviewed, 124 patients (39%) were women and 193 patients (61%) were men. The mean patient age was 41 ± 11 years, and the transplanted kidney was received from deceased donors in 161 patients (51%) and living donors in 158 patients (49%). There were 50 patients (16%) who had neurologic complications, most commonly herpes zoster infection associated with immunosuppressive medication. Only 1 patient, who had glioblastoma multiforme, died. Treatment included corticosteroids in 296 patients (93%) and calcineurin inhibitors (including tacrolimus) in 111 patients (35%). Conclusions: Neurologic complications are common after renal transplant. Most complications are associated with immunosuppressive medications.Item Chronic Myeloid Leukemia Within a Year of Kidney Transplant With Elevated Alkaline Phosphatase Correlated With Imatinib Therapy(Başkent Üniversitesi, 2011-10) Sayar, Hamid; Mehta, Rakesh; Taber, Tim E.; Sharfuddin, Asif A.The incidence of certain malignancies is significantly higher after organ transplant. However, there are rare reports of chronic myeloid leukemia in the posttransplant setting. The average reported interval between a transplant and the diagnosis of chronic myeloid leukemia is 44 months (range, 10-96 mo). We report 2 patients with chronic myeloid leukemia within 1 year of a kidney transplant, which is significantly shorter than those previously reported. Both patients were receiving mycophenolate mofetil and tacrolimus for immunosuppression. They were treated with imatinib for chronic myeloid leukemia, and both patients demonstrated an isolated elevation of serum alkaline phosphatase that was directly correlated with imatinib. Despite a potential interaction between the 2 drugs, blood levels of tacrolimus and imatinib were not elevated during the course of treatment. Isolated elevation of alkaline phosphatase in this particular setting has not been reported previously.