Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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Item Successful Treatment With Third Stem Cell Transplant From an Allogeneic Donor for a Patient With Relapsed Diffuse Large B-Cell Lymphoma(Başkent Üniversitesi, 2013-04) Takasaki, Hirotaka; Tomita, Naoto; Motomura, Shigeki; Sakai, Rika; Ishigatsubo, Yoshiaki; Tsuchihashi, Hitoshi; Yamamoto, Wataru; Ishii, YoshimiHigh-dose chemotherapy with autologous stem cell transplant is commonly used for diffuse large B-cell lymphoma that recurs after successful salvage chemotherapy. However, in patients in whom the disease recurs again, the prognosis is poor. A 40-year-old woman who underwent allogeneic stem cell transplant 4 years after autologous stem cell transplant developed recurrent diffuse large B-cell lymphoma 3 years after the initial autologous stem cell transplant. She then underwent reduced-intensity hematopoietic stem cell transplant from a human leukocyte antigen-matched, unrelated donor who was not the previous autologous stem cell transplant donor. She achieved a long survival (328 days after the reduced-intensity hematopoietic stem cell transplant and 1844 days after the first allogeneic transplant). A second allogenic transplant may provide survival benefits in a proportion of patients with malignant lymphoma recurring after allogeneic transplant, although careful consideration is required because of the high risk of treatment-related mortality with second allogenic transplant.Item Plasma Cell-Rich Acute Rejection With Monoclonal Gammopathy in a Renal Transplant Recipient(Başkent Üniversitesi, 2013-04) Sun, In O; Yang, Chul Woo; Choi, Yeong Jin; Kim, Yong Soo; Park, Cheol Whee; Park, Gyeong Sin; Choi, Bum Soon; Chung, Byung Ha; Hong, Yu Ah; Cho, Yul HeePlasma cell infiltration into a renal allograft comprises a spectrum of lesions from acute rejection to posttransplant lymphoproliferative disease. We report an unusual case of plasma cell infiltration into a renal allograft with monoclonal gammopathy. A 42-year-old woman was admitted because of graft dysfunction after noncompliance with immunosuppressive therapy for 5 months. A graft biopsy showed acute T-cell–mediated rejection and massive plasma cell infiltration. Despite initial treatment with steroids and antithymocyte globulin, there was persistence of graft dysfunction, monoclonal gammopathy, and plasma cell infiltration. Subsequent treatment with bortezomib improved graft function and caused the monoclonal gammopathy to resolve. Immunohistochemical evaluation of markers of B cells (CD20 and CD138) and the ratio of kappa-to-lambda light chain (15:1) showed that infiltrating cells were plasma cells producing kappa light chain. This suggested that plasma cell-rich acute rejection with monoclonal gammopathy in this patient might have been in an early stage of kappa light chain-producing posttransplant lymphoproliferative disease confined to the renal allograft, and that bortezomib may be effective in treating a patient with this condition.Item Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant(Başkent Üniversitesi, 2013-04) Honarbakhsh, Nazanin; Gholami, Kheirollah; Mohebbi, Niayesh; Javadi, Mohammad Reza; Lesan-Pezeshki, Mahboob; Rouini, Mohammad Reza; Karimzadeh, ImanObjectives: To determine the mycophenolic acid pharmacokinetic profile early after transplant in Iranian kidney graft recipients. Materials and Methods: A cross-sectional study was performed during 6 months in 31 patients who recently had kidney transplant and received fixed doses of mycophenolate mofetil (2 g/d). The plasma levels of mycophenolic acid were determined by high performance liquid chromatography. Results: The mean first mycophenolic acid peak level was 10 ± 5 mg/L. The mean mycophenolic acid area under the curve was 26 ± 19 mgh/L and apparent clearance was 57 ± 55 L/h. The mycophenolic acid area under the curve values of only 8 patients (26%) were within the therapeutic range (30-60 mgh/L). The first, second, and third mycophenolic acid peak levels correlated significantly with mycophenolic acid area under the curve (P < .05). Mycophenolic acid concentration at 10 hours had the highest correlation with mycophenolic acid area under the curve (r=0.962; P < .05). No statistically significant differences were evident in the mean mycophenolic acid area under the curve between men and women. Conclusions: There was a high degree of variation between different patients in mycophenolic acid pharmacokinetics early after kidney transplant.Item Posttransplant Hypertension: Multipathogenic Disease Process(Başkent Üniversitesi, 2013-04) Barbari, AntoineArterial hypertension is prevalent among kidney transplant recipients. The multifactorial pathogenesis involves the interaction of the donor and the recipient’s genetic backgrounds with several environmental parameters that may precede or follow the transplant procedure (eg, the nature of the renal disease, the duration of the chronic kidney disease phase and maintenance dialytic therapy, the commonly associated cardiovascular disease with atherosclerosis and arteriosclerosis, the renal mass at implantation, the immunosuppressive regimen used, life of the graft, and de novo medical and surgical complications that may occur after a transplant). Among calcineurin inhibitors, tacrolimus seems to have a better cardiovascular profile. Steroid-free protocols and calcineurin inhibitor-free regimens seem to be associated with better blood pressure control. Posttransplant hypertension is a major amplifier of the chronic kidney disease-cardiovascular disease continuum. Despite the adverse effects of hypertension on graft and patient survival, blood pressure control remains poor because of the high cardiovascular risk profile of the donor-recipient pair. Although the optimal blood pressure level remains unknown, it is recommended to maintain the blood pressure at < 130/80 mm Hg and < 125/75 mm Hg in the absence or presence of proteinuria.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.