Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

多巴胺或多巴胺复合去甲肾上腺素对肝移植术中患者血液动力学、氧代谢及肾功能的影响

目的评价原位肝脏移植术(OLT)中持续输注多巴胺或多巴胺复合去甲肾上腺素对血液动力学、组织氧代谢和肾功能的影响。方法拟行OLT的患者30例,ASAⅢ或Ⅳ级,随机分为2组 (n=15)。A组:术中持续输注多巴胺,初始输注速率为1-3μg·kg-1·min-1;B组:术中持续输注多巴胺复合去甲肾上腺素,初始输注速率分别为1-3μg·kg-1·min-1和0．03μg·kg-1·min-1,多巴胺输注速率不超过5μg·kg-1·min-1;术中两组均调节输注速率维持MAP 60-80 mm Hg。分别于切皮前即刻、切肝期1 h、无肝期1 h、新肝期1h和术毕测定血液动力学、组织代谢和肾功能指标。结果两组HR、 MAP均维持较平稳。无肝期两组CVP、MPAP、PAWP、CO、CI、DO2、VO2降低(P<0．05);SVR和SVRI升高(P<0．05),但均在正常范围内。术中PVR、PVRI、pH及SvO2均较平稳。乳酸浓度增高并持续到术毕。两组术中Cr和BUN均在正常范围,B组总尿量高于A组(P相似文献   

Surgical Complications and Long-Term Outcome of Different Biliary Reconstructions in Liver Transplantation for Primary Sclerosing Cholangitis—Choledochoduodenostomy versus Choledochojejunostomy

Choledochojejunostomy (CJS) is commonly used for biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC). We alternatively performed choledochoduodenostomy (CDS) and side-to-side choledochodocholedochstomy in a large cohort of patients. Fifty-one patients with PSC, transplanted between 1988 and 2000, were analyzed retrospectively. Biliary reconstruction was CDS in 25 (49%), CJS in 20 (39%) and CC in 6 transplantations (12%). Biliary leaks occurred in the early follow-up (< or =41 days) only in CDS patients (20%). However, in the late follow-up (>4 months), stricturing of anastomosis was found once in CDS (4%) and CJS (5%). Later (>9 months), intrahepatic bile duct strictures were diagnosed in four CDS (16%), one CJS (5%) and one CC (17%) patient(s). In 48% of CDS (12/25), 60% of CJS (12/20) and 17% of CC (1/6) at least one incidence of cholangitis was observed. Overall, biliary complication rates were significantly higher in CDS (40%) than CJS (10%) and CC (17%); of those none in CC and 12% in CDS were anastomosis-related. Graft/patient survival showed no significant differences among groups. Based on our results we consider CJS the standard method for biliary reconstruction in PSC; however, in selected cases where CJS is difficult to accomplish because of previous surgery or for retransplantation, CDS may present an alternative technique.     

原位肝移植术后缺血型胆道病变20例

目的探讨原位肝移植术后缺血型胆道病变（ITBL）的病因及预防、诊断和治疗的措施。方法回顾性分析1999年2月至2005年4月间291例次原位肝移植后发生ITBL患者的临床资料。结果291例次原位肝移植术后共发生ITBL 20例（6．9％）。术后发生ITBL的高危因素为：原发病为重型乙型肝炎、供受者ABO血型不符、供肝冷保存时间超过12h和术后肝动脉病变。其发生率分别为12．5％（9／71）、20．0％（2／10）、11．1％（9／81）和60％（3／5）。采用药物、经内镜逆行胰胆管造影（ERCP）介入、胆道外科手术及再次肝移植等方法治疗，有效率为80．0％（16／20）、治愈率为50．0％（10／20），与ITBL相关的病死率为10．0％（2／20），与ITBL相关的移植物功能丧失发生率为20．0％（4／20）。结论针对ITBL的高危因素进行相应处理是预防ITBL的有效措施。胆道造影和核磁共振胆胰管成像对诊断ITBL有很高的敏感性和特异性。根据不同的病因和病变程度采用适当的方法治疗ITBL，可获得良好的疗效。     

肝移植术后糖尿病危险因素分析

目的 探讨肝移植术后糖尿病（PTDM）的发生及发展的危险因素。方法 回顾性分析98例肝移植受者的临床资料。根据其肝移植术后是否发生糖尿病，分为糖尿病组（36例）和非糖尿病组（62例）。以术前和术后可能的9个危险因素作为分析指标，进行这些指标的单因素分析和χ^2检验。结果 在对两组患者的年龄、乙型肝炎病毒（HBV）感染情况、有无肝硬化及肝硬化的程度、术前糖耐量情况、免疫抑制剂的选择及其血药浓度、激素的使用时间的比较分析中发现：术前肝硬化患者PTDM的发生率明显高于无肝硬化者；肝硬化失代偿期患者PTDM的发生率高于代偿期。术前糖耐量异常的患者PTDM的发生率明显高于糖耐量正常者。激素半年内撤离的患者PTDM的发生率明显低于半年内未撤离者。而两组患者的年龄、HBV的感染情况、免疫抑制剂的选择及其血药浓度相比较，差异均无统计学差异。结论 肝硬化、尤其是肝硬化失代偿期，糖耐量异常，长期使用激素是PTDM发生的危险因素。     

Renal function and 25-hydroxyvitamin D concentrations predict parathyroid hormone levels in renal transplant patients.

BACKGROUND: Recent guidelines suggest supplementation with ergocalciferol (vitamin D(2)) in chronic kidney disease stages 3 and 4 patients with elevated parathyroid hormone (PTH) levels and 25-hydroxyvitamin D (25OHD) levels <75 nmol/l. These guidelines are also applied to renal transplant patients. However, the prevalence rates of 25OHD deficiency and its association with PTH levels in renal transplant populations have not been extensively examined. We aimed to document the prevalence rates of 25OHD deficiency [defined by serum levels <40 nmol/l (<16 ng/ml)] and insufficiency [<75 nmol/l (<30 ng/ml)] in a single renal transplant centre, and examine its relationship with PTH levels. METHODS: Serum 25OHD and PTH concentrations were measured in 419 transplant patients attending a single renal transplant clinic over a 4-month period. Demographic and biochemical data were also collected, including serum creatinine, calcium, phosphate and albumin. Simple and multiple linear regression analysis were performed. RESULTS: In 27.3% of the patients, 25OHD deficiency was present, and 75.5% had insufficiency. On univariate analysis, 25OHD, serum albumin and estimated glomerular filtration rate (eGFR) were significantly associated with PTH levels (P < 0.0001, P = 0.004 and P < 0.0001, respectively). Multiple linear regression demonstrated that only 25OHD, eGFR and serum phosphate were significantly predictive of PTH levels (R(2) = 0.19, P < 0.0001). In this model, a 75 nmol/l increase in 25OHD will only result in a maximal reduction in PTH of 2.0 pmol/l. CONCLUSIONS: We conclude that 25OHD deficiency and insufficiency are common in renal transplant patients and may exacerbate secondary hyperparathyroidism. However, 25OHD, eGFR and phosphate only account for 19% of the variability in PTH levels. In addition, even a large increase in serum 25OHD levels is likely to result in only a small reduction in PTH. Therefore, alternative approaches to managing hyperparathyroidism in renal transplant recipients rather than supplementation with ergocalciferol are warranted.     

Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

Smart Prep技术在肾动脉CTA中的临床应用

目的:探讨Smart Prep技术在肾动脉多层螺旋CT血管造影中的应用。方法:20例行同层动态增强扫描,通过时间-密度曲线获得肾动脉的有效浓度阈值。65例行肾动脉CTA造影,经肘静脉团注370mgI/ml优维显1.5ml/kg后,应用Smart Prep软件实时监控靶血管浓度,当感兴趣区对比剂浓度达有效浓度阈值时触发增强扫描完成数据采集,重组和重建图像显示肾动脉。结果:65例肾动脉CTA造影均获成功,58例(89.2%)增强时相处于最佳扫描时期。增强扫描的延迟时间15~38s不等,个体差异明显,而肾动脉CT值持续位于有效浓度阈值(100HU)以上。结论:Smart Prep技术实时监控肾动脉对比剂浓度变化并及时触发增强扫描,它不受个体差异影响即可确保增强扫描的实施,优于小剂量试验。