成纤维细胞生长因子23在血液透析患者磷和维生素D代谢中的作用

目的 探讨成纤维细胞生长因子23（FGF-23）在维持性血液透析（MHD）患者磷和维生素D代谢中的作用及相关调控机制。 方法 采用酶联免疫分析法（ELISA）对59例MHD患者（血透组）及20例健康志愿者（对照组）进行血清全段FGF-23测定，同时应用放免法测定血清1，25-二羟维生素D（1,25(OH)2VitD）水平。血透组患者测定血清白蛋白（Alb）、血红蛋白（Hb）、血肌酐（Scr）、尿素氮（BUN）、钙（Ca）、磷（P）及全段甲状旁腺激素（iPTH）等指标。 结果 血透组血清FGF-23水平明显高于对照组[（215.23±123.55）比（28.72±11.49） ng/L，P < 0.01]，而血清1,25(OH)2VitD水平明显低于对照组[（13.25±8.73）比（42.24±12.45） μg/L，P < 0.01]。Pearson相关分析显示，血透组血清FGF-23水平与血清P、Scr、Ca、iPTH及透析疗程时间呈正相关（P < 0.05）；与血清1,25(OH)2VitD水平和年龄呈负相关（P < 0.05）；而与性别、血压、血清Alb、Hb、BUN等指标无相关。多元回归分析显示，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23的主要变量，5者组成的模型解释了总变异的约62%（R2=0.623，P < 0.01）。 结论 MHD患者血清全段FGF-23水平明显增高，而1,25(OH)2VitD水平明显降低。FGF-23的调控是由复杂的多种因素共同作用的结果，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23水平的主要调控因子。     

Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.

BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.     

EBV+ B Lymphoma Cell Lines from Patients with Post-Transplant Lymphoproliferative Disease Are Resistant to TRAIL-Induced Apoptosis

Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV⁺ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV⁺ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

Parallel image reconstruction using B-spline approximation (PROBER).

A new reconstruction method for parallel MRI called PROBER is proposed. The method PROBER works in an image domain similar to methods based on Sensitivity Encoding (SENSE). However, unlike SENSE, which first estimates the spatial sensitivity maps, PROBER approximates the reconstruction coefficients directly by B-splines. Also, B-spline coefficients are estimated at once in order to minimize the reconstruction error instead of estimating the reconstruction in each pixel independently (as in SENSE). This makes the method robust to noise in reference images. No presmoothing of reference images is necessary. The number of estimated parameters is reduced, which speeds up the estimation process. PROBER was tested on simulated, phantom, and in vivo data. The results are compared with commercial implementations of the algorithms SENSE and GRAPPA (Generalized Autocalibrating Partially Parallel Acquisitions) in terms of elapsed time and reconstruction quality. The experiments showed that PROBER is faster than GRAPPA and SENSE for images wider than 150x150 pixels for comparable reconstruction quality. With more basis functions, PROBER outperforms both SENSE and GRAPPA in reconstruction quality at the cost of slightly increased computational time.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

血清乙型肝炎病毒标志物不同表现模式及肝功能异常对肾移植受者存活率的影响

目的　探讨血清乙型肝炎病毒标志物不同表现模式对肾移植受者长期存活的影响。方法　对 62例血清乙型肝炎病毒标志物阳性者及 1 96例血清乙型肝炎病毒标志物全阴性者肾移植术后的肝功能、人肾均存活的存活率等指标进行随访和回顾性分析。结果　术后早期血清乙型肝炎病毒标志物阳性组与血清乙型肝炎病毒标志物阴性组比较 ,肝功能异常发生率的差异无显著性 (P >0 .0 5) ;术后中远期 ,HBsAg、HBeAg及抗 HBc阳性者的肝功能受损率明显高于血清乙型肝炎病毒标志物阴性组及HBsAg、抗 HBe、抗 HBc阳性者 (P <0 .0 5) ,其人肾均存活的存活率也最低 (P <0 .0 5)。结论　对HBsAg、抗 HBe及抗 HBc阳性者进行肾移植应慎重 ,而HBsAg、HBeAg及抗 HBc阳性者则不适宜接受肾移植     

Fumonisins as a possible contributory risk factor for primary liver cancer: A 3-year study of corn harvested in Haimen, China, by HPLC and ELISA

Employing HPLC fluorometry, gas-liquid chromatography (GLC) and a novel enzymelinked immunosorbent assay (ELISA) based on a monoclonal antibody, 40 corn samples, each collected in 1993 from agricultural stocks for human consumption in Haimen (Jiangsu County) and Penlai (Shandong Province), high- and low-risk areas for primary liver cancer (PLC) in China, respectively, were analysed for fumonisins (FBs), aflatoxins (AFs) and trichothecenes. Levels and positive rates of FBs and deoxynivalenol (DON) were significantly higher in Haimen than in Penlai. ELISA of the 40 corn samples harvested in the two areas in 1994 revealed that FB contamination levels and rates in these areas were comparable to those observed in 1993 in Haimen. ELISA analysis of 1993 and 1994 products revealed a wide occurrence of AFB₁ but the positive rates as well as levels were not significantly different between these areas. ELISA of the same sample number of corn harvested in 1995 revealed that FB contamination in Haimen was significantly higher than in Penlai. These 3-yearly surveys of corn samples (240 in total) demonstrated that corn harvested in Haimen was highly contaminated with FBs and that the contamination level, as well as positive rate in 1993 and 1995, were 10–50-fold higher than those in Penlai, suggesting FBs as a risk factor for promotion of PLC in endemic areas, along with the trichothecene DON. Co-contamination with AFs, potent hepatocarcinogens, was assumed to play an important role in the initiation of hepatocarcinogenesis.     

High-density lipoprotein subfractions,apolipoproteins and antipyrine clearance in normal subjects

Summary Serum high density lipoprotein (HDL) subfractions HDL₂ and HDL₃, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL₂ cholesterol concentrations and HDL cholesterol/cholesterol and HDL₂/HDL₃ cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL.     

非放射性HBV－DNA探针在乙型肝炎病毒检测中的应用

以地高辛甙元随机引物法标记ＨＢＶ－ＤＮＡ探针，以此探针检测慢性乙型肝炎患者的血清、肝组织，同时以ＥＬＩＳＡ法检测血清ＨＢｅＡｇ、ＨＢｃＡｂ。结果：血清ＮＢｅＡｇ阳性率２７％（１０／３７），血清ＨＢＶ－ＤＮＡ检出率５７．１％（２０／３５），两者有显著性差异。血清ＨＢｃＡｂ阳性率７８．４％（２９／３７），肝组织ＨＢＶ－ＤＮＡ检出率８３．８％（３１／３７），两者无显著性差异。血清与肝组织ＨＢＶ－ＤＮＡ检出率有显著性差异。提示：血清ＨＢＶ－ＤＮＡ检测是较ＨＢｅＡｇ更为准确客观反映血液带毒状况的指标。而准确反映肝脏带毒状况的指标是肝组织ＨＢＶ－ＤＮＡ检测。当ＨＢｅＡｇ阴转，血清ＨＢＶ－ＤＮＡ阴性而肝组织ＨＢＶ－ＤＮＡ阳性时，需注意肝硬化及肝癌的发生。