Başkent Üniversitesi Yayınları
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Item Emergency Liver Transplant in Patient with Child-Pugh Class C Cirrhosis and Strangulated Umbilical Hernia(Başkent Üniversitesi, 2013-02) Chaudhary, Abhideep; Ray, Ramdip; Agarwal, Shaleen; Pareek, Shishir; Gupta, Subash; Wadhawan, Manav; Ramaswamy, Vasudevan Karisangal; Goyal, Neerav; Daga, SachinThe authors report the case of a patient who presented with small bowel obstruction while awaiting liver transplant for Child-Pugh class C cirrhosis. He underwent emergency liver transplant with resection of the small bowel after the obstruction did not improve with conservative management. The authors believe this is the first case of successful emergency liver transplant with resection of the small bowel in a patient with decompensated Child-Pugh class C liver cirrhosis and strangulated umbilical hernia. This case suggests the possibility of improved outcomes of emergency hernia repair in patients with liver cirrhosis when small bowel resection is combined with liver transplant.Item Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells(Başkent Üniversitesi, 2013-02) Wang, Xin; Le, Qihua; Hong, Jiaxu; Xu, Jianjiang; Wang, WentaoObjectives: To evaluate the effect of rapamycin pretreatment before allogenic corneal transplant on CD4+CD25+Foxp3+T regulatory cells (Treg) in recipient mice, and analyze its correlation with graft survival. Materials and Methods: Balb/c mice were intraperitoneally injected with rapamycin or control solution for 2 weeks. They then underwent a corneal transplant with C57/BL6 serving as the donor. Graft status was assessed twice a week. Recipient mice were killed 14 days after surgery, and the percentage of CD4+CD25+Foxp3+Treg in peripheral blood, spleen, and draining lymph nodes was analyzed by flow cytometry. Moreover, CD4+CD25+T cells in corneal grafts and conjunctiva were identified, and expression of Foxp3 mRNA in the grafts was tested. Additionally, the concentration of IL-10 and TGF-β1 in serum and aqueous humor was measured. Results: Pretreatment of rapamycin significantly enhanced the percentage of CD4+CD25+Foxp3+Treg in peripheral blood and draining lymph nodes, preoperatively and postoperatively, which had significant negative correlation with graft opacity and neovascularization. Moreover, rapamycin pretreatment led to a larger number of CD4+CD25+T cells infiltrating in corneal grafts and conjunctiva, increased expression of Foxp3 mRNA in grafts, and elevated concentration of TGF-β1 in aqueous humor. Conclusions: Pretreatment with rapamycin for 14 days before an allogenic corneal transplant enhances the percentage of CD4+CD25+Foxp3+Treg cells in peripheral blood, draining lymph nodes, and grafts, thereby inhibiting graft rejection.Item Effect of Positive End-Expiratory Pressure After Porcine Unilateral Left Lung Transplant(Başkent Üniversitesi, 2013-02) Madke, Gabriel Ribeiro; Andrade, Cristiano Feijó; Pereira, Raoni Bins; Felix, Elaine Aparecida; Cardoso, Paulo Francisco Guerreiro; Mariano, Rodrigo; Moraes, Mikael Marcelo de; Fontena, Eduardo; Grün, Gustavo; Forgiarini, Luiz AlbertoObjectives: To evaluate the effects of 2 different levels of positive end-expiratory pressure on pigs who had unilateral lung transplants. Materials and Methods: A left lung transplant was performed in 12 pigs. The animals were randomized into 2 groups based on positive end-expiratory pressure: group 1 (5 cm H2O) and group 2 (10 cm H2O). Hemodynamics, gas exchange, and respiratory mechanics were measured before and after surgery. Cytokines, oxidative stress, and histologic scores were assessed in the lung tissue of each pig. Results: Pigs in group 2 exhibited a significantly higher mean heart rate (P = .006), static compliance (P = .001), lower mean arterial pressure (P = .003), and airway resistance (P = .001) than did pigs in group 1. There were no postoperative differences between the groups in concentrations of thiobarbituric acid reactive substances, superoxide dismutase, and interleukin 8. At the end of the observation period, pigs in group 2 had higher levels of thiobarbituric acid reactive substances (P = .001) and interleukin 8 (P = .05), and pigs in group 1 had higher levels of superoxide dismutase (P = .05) than they did at baseline. Conclusions: After unilateral lung transplant, higher positive end-expiratory pressure was associated with improved respiratory mechanics, a negative effect on hemodynamics, a stronger inflammatory response, and increased production of reactive oxygen species, but no effect on gas exchange.Item Ischemic Postconditioning Reduces Ischemic Reperfusion Injury of Non–Heart-Beating Donor Grafts in a Rat Lung Transplant(Başkent Üniversitesi, 2013-02) Hu, Qing-hua; Wang, Lin; Luo, Wan-jun; Luo, Fan-yanObjectives: This study was designed to see if ischemic postconditioning could attenuate ischemic reperfusion injury of transplanted lungs recovered from non–heart-beating donors. Materials and Methods: Forty Sprague-Dawley rats were randomized into 2 groups: the control group and the ischemic postconditioning group, with 10 donor rats paired with 10 recipient rats in each group. Twenty rats underwent a left lung transplant from non–heart-beating donors with a warm ischemia time of 36.7 ± 5.62 minutes. In the ischemic postconditioning group, 5 cycles of 1-minute reperfusion and 1-minute reocclusion at the onset of reperfusion were applied as postconditioning. Arterial blood gas, wet-to-dry lung weight ratio, activities of malondialdehyde and superoxide dismutase, and expressions of apoptosis and ICAM-1 mRNA were compared. Results: When compared with the control group 4 hours after reperfusion, PaO2 was higher, and wet-to-dry lung weight ratio was lower, in the ischemic postconditioning group, and expression of apoptosis and ICAM-1 mRNA as well as activity of malondialdehyde were lower, while superoxide dismutase activity was higher in the ischemic postconditioning group. Conclusions: Ischemic postconditioning can reduce ischemic reperfusion injury of lungs recovered from non–heart-beating donors and preserve lung function by reducing reactive oxygen species and inhibiting apoptosis and inflammation.Item Proinflammatory and Anti-Inflammatory Cytokine Balance in Patients With Cirrhotic Hepatitis During Live-Donor Liver Transplant(Başkent Üniversitesi, 2013-02) Koh, Hyun-Jung; Lee, Jaemin; Hwang, Ji-Eun; Her, Yang-Mi; Cho, Mi-La; Joo, JinObjectives: The immune system releases cytokines during the stress response, and the balance between proinflammatory and anti-inflammatory cytokines is important. This prospective study was done to determine which cytokines are responsible for maintaining cytokine balance during live-donor liver transplant surgery. Materials and Methods: Recipients undergoing live-donor liver transplant surgery due to cirrhotic hepatitis were allocated to a recipient group (n=44), and healthy donors were placed in the donor group (n=45). In donors, blood sampling for cytokine level analysis was performed after anesthetic induction (before the start of surgery, time point 1). In recipients, blood samples were collected before the start of surgery (time point 1), 60 minutes after the start of the anhepatic period (time point 2), and 60 minutes after reperfusion (time point 3). The proinflammatory cytokines measured were interleukin-1β, interleukin-6, and tumor necrosis factor-α; the anti-inflammatory cytokines were interleukin-10 and interleukin-4. Cytokines were quantified using sandwich enzyme-linked immunoassays. The time course of proinflammatory and anti-inflammatory cytokine concentrations during surgery in the recipient group was evaluated. Results: Interleukin-6, interleukin-10 and tumor necrosis factor-α showed significant changes in concentration during surgery, with interleukin-6 reaching levels 40 times higher than the preoperative value at the anhepatic stage. Interleukin-10 reached a peak at the neohepatic phase, with values 60 times higher than the preoperative value. The preoperative concentrations of interleukin-6 and interleukin-10 in the recipient group were higher than those in the donor group with a median of 4.48 vs 1.98 pg/mL (P < .001) and 2.98 vs 1.22 (P = .026). Conclusions: Interleukin-6 and interleukin-10 play a major role in cytokine balance before and during live-donor liver transplant surgery.Item Immunosuppressant-Related Hip Pain After Orthotopic Liver Transplant(Başkent Üniversitesi, 2013-02) Li, Hua; Chen, Gui-hua; Wang, Gen-shu; Yang, Yang; Zhang, Jian; Wang, Guo-ying; Jiang, Nan; Wang, Kun; Fu, Bin-sheng; He, Ji-wenObjectives: Immunosuppressant-related hip pain can greatly affect a patient’s mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant. Materials and Methods: The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant. Results: A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurin-inhibitor–induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitor–induced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007). Conclusions: Calcineurin-inhibitor–induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor–induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients’ survival.Item Mean Platelet Volume as a Potential Predictor of Renovascular Thrombosis After Renal Transplant(Başkent Üniversitesi, 2013-02) Sakallı, Hale; Haberal, Mehmet; Moray, Gökhan; Gülleroğlu, Kaan Savaş; Bayrakçı, Umut Selda; Baskın, EsraObjectives: We sought to evaluate the importance of mean platelet volume as a marker to follow-up, the tendency for hemorrhagic diatheses, and/or thrombotic complications in patients before and after renal transplant. Materials and Methods: Thirty-four patients (aged, 5 to 18 y) were included. Demographics of the patients, cause of chronic renal failure, dialysis modality, duration of dialysis, arterio-venous fistula thrombosis, and posttransplant immunosuppressive regimens were recorded and laboratory variables were evaluated. Results: At the end of the first posttransplant month, mean platelet volume level was decreased significantly when compared with pretransplant levels (8.3 ± 1.5 vs 7.7 ± 0.9; P = .04). A significant increase was observed in platelet levels during posttransplant measures (273.750 ± 97.700 vs 318.740 ± 84.586; P = .02). Prothrombin time and partial thromboplastin time levels did not differ before and after transplant. None of the patients had any thrombotic events and/or renal allograft loss. A negative correlation was observed between mean platelet volume and C-reactive protein (r=-0.53). Mean platelet volume level was not found to be related to the cause of renal failure, pretransplant dialysis modality, or posttransplant immunosuppressive regimens. Conclusions: Platelet numbers increased and mean platelet volume decreased after pediatric renal transplant, but the potential for increased thrombosis was not observed.Item Influence of Endothelial Nitric Oxide Synthase Gene Polymorphisms (-786T/C, 4a4b, 894G/T) on Iranian Kidney Transplant Recipients(Başkent Üniversitesi, 2013-02) Azarpira, Negar; Ayatolahi, Maryam; Darai, Masumeh; Bahador, Ali; Geramizadeh, Bita; Aghdai, Mahdokht H.Objectives: Nitric oxide is a major mediator in vascular biology and regulator of regional blood flow. Its production is catalyzed by the enzyme endothelial nitric oxide synthase. Protective actions of nitric oxide in ischemia and reperfusion are due to its potential as an antioxidant and anti-inflammatory agent, along with its inhibitory effects on cell signaling pathways of nuclear proteins, such as NF-κB. The endothelial nitric oxide synthase gene polymorphisms affect endothelial nitric oxide synthase activity and are associated with endothelial dysfunction. This study sought to examine the association between single nucleotide polymorphisms in endothelial nitric oxide synthase gene (rs 2070744, 27VNTR, and rs1799983) and the development of acute rejection in renal transplant patients. Materials and Methods: Sixty-six renal transplant recipients (33 patients with an episode of acute rejection and 33 recipients an episode of acute rejection), between June 2010 and March 2011, were included. The polymorphism was determined by simple polymerase chain reaction and polymerase chain reaction-restriction fragment-length polymorphism analysis. Results: There was only a significant association of endothelial nitric oxide synthase -786T allele and acute rejection (P = .03). Recessive model of T-786C alleles (TT vs TC+CC) and acute rejection confirmed a significant association (odds ratio: 3.12; 95% CI: 0.01-9.83; P = .025). Haplotype CbG was higher in recipients without rejection as compared to rejection group (OR: 0.42, 95% CI: 0.16-1.13; P < .05). Respecting the endothelial nitric oxide synthase gene 894G/T single nucleotide polymorphisms and 27VNTR, no significant association between the allele/genotype and acute rejection was seen. Conclusion: Recipient endothelial nitric oxide synthase gene polymorphisms do not alter the risk of acute rejection after a renal transplant. Rejection is a complex immunologic event. Therefore, finding associated genetic variants demands a multicentric larger sample size.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 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.