2010年欧洲神经病学联盟阿尔茨海默病诊疗指南

一、概述 (一)目的 2008年成立工作组的目的是修改前一版欧洲神经病学联盟(EFNS)的阿尔茨海默病(AD)诊疗指南.前一版指南采用了第4版诊断和统计手册(DSM Ⅳ)及美国国立神经病学、语言障碍和脑卒中研究所-阿尔茨海默病及相关疾病学会(NINCDS-ADRDA)对痴呆综合征和AD的诊断标准.     

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design

Journal of Neuro-Oncology - Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to...     

Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations

Current debate focuses on the relevance of linkage disequilibrium (LD), ethnicity and underlying haplotype structure to the search for genes involved in complex disorders. The recently described association between single nucleotide polymorphisms (SNPs) of the CARD15 (NOD2) gene and Crohn's disease (CD) in populations of north-European descent provides a test case that we have subjected to detailed SNP haplotype based analyses. We examined 23 SNPs spanning 290 kb, including CARD15, in large North-European and Korean samples of patients with Crohn's disease and normal controls. In Europeans we confirmed that the three disease-associated SNPs occur independently but share a common background haplotype. This suggests a common origin and the possibility of an undiscovered more strongly predisposing mutation. Korean CD patients present a phenotype identical to the European patients and have not previously been screened for CARD15. The three disease-associated SNPs were absent and there was no evidence of association between CARD15 and CD. Consequently, the disease-associated mutations in the Europeans, which are rare, have arisen recently (after the Asian-European split). Our results highlight important issues relevant to mapping the genes that predispose to complex disorders. First, although ethnically divergent populations may present identical phenotypes they do not necessarily share the same set of predisposing genes. Second, although single-locus tests of association showed consistent association with markers throughout the gene, pair-wise LD between markers (r(2) and D') yielded very little information about actual disease-association. Third, a population comparative approach allowed refining of the marker set through the examination of shared polymorphisms and common LD-groups. This approach, in conjunction with the examination of the mutational steps in a haplotype network, allows unambiguous identification of the potentially causative mutations.     

Ethyl pyruvate and ethyl lactate down-regulate the production of pro-inflammatory cytokines and modulate expression of immune receptors

Esters of alpha-oxo-carbonic acids such as ethyl pyruvate (EP) have been demonstrated to exert inhibitory effects on the production of anti-inflammatory cytokines. So far, there is no information about effects, if any, of ethyl lactate (EL), an obviously inactive analogue of EP, on inflammatory immune responses. In the present study, we provide evidence that the anti-inflammatory action of alpha-oxo-carbonic acid esters is mediated by inhibition of glyoxalases (Glo), cytosolic enzymes that catalyse the conversion of alpha-oxo-aldehydes such as methylglyoxal (MGO) into the corresponding alpha-hydroxy acids using glutathione as a cofactor. In vitro enzyme activity measurements revealed the inhibition of human Glo1 by alpha-oxo-carbonic acid esters, whilst alpha-hydroxy-carbonic acid esters such as EL were not inhibitory. In contrast, both EP and EL were shown to suppress the Lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and IL-8 from human immunocompetent cells, and modulated the expression of the immune receptors HLA-DR, CD14 and CD91 on human monocytes. Here, we show a crossing link between glyoxalases and the immune system. The results described herein introduce glyoxalases as a possible target for therapeutic approaches of immune suppression.     

CT模拟结肠镜在结肠病灶诊断中的应用

结肠癌是常见的消化道肿瘤,上海等地区的发病率有明显增高的趋势。在发达国家,结肠癌占肿瘤死亡率第二位,且与大肠腺瘤关系密切。如能早期发现有恶变先兆的息肉并切除之,可以预防结肠癌发生。目前,对结肠癌发病高危人群并未作大规模普查,部分由于患者缺乏早期主诉,或是由于现有普查手段不够有效。大便隐血试验只能发现３０％～４０％结肠肿瘤,乙状结肠镜不能进入近端结肠,并有１０％～１５％乙状结肠肿瘤漏诊。钡剂灌肠和结肠镜能检查全结肠,但有１０％～１５％患者行结肠镜检查失败,并且结肠镜可能使１０％～２０％病灶遗漏,尚…     

创伤患者输血与供者白细胞微嵌合的相关性

输血是挽救创伤患者生命而普遍使用的治疗方法,但其又存在着明显和潜在的危险性。当今,经血液传播传染病和输血反应很少发生,但仍然存在。尽管在临床治疗中试图控制创伤患者休克的发展及损伤的严重度,但其输血后细菌感染、多脏器功能衰竭、死亡的发生率仍较高。     

Dishevelled 2 signaling promotes self-renewal and tumorigenicity in human gliomas

Glioblastoma multiforme is the most common glioma variant in adults and is highly malignant. Tumors are thought to harbor a subpopulation of stem-like cancer cells, with the bulk resembling neural progenitor-like cells that are unable to fully differentiate. Although multiple pathways are known to be involved in glioma tumorigenesis, the role of Wnt signaling has been poorly described. Here, we show that Dishevelled 2 (Dvl2), a key component of the Wnt signaling pathway, is overexpressed in human gliomas. RNA interference-mediated depletion of Dvl2 blocked proliferation and promoted the differentiation of cultured human glioma cell lines and primary, patient-derived glioma cells. In addition, Dvl2 depletion inhibited tumor formation after intracranial injection of glioblastoma cells in immunodeficient mice. Inhibition of canonical Wnt/β-catenin signaling also blocked proliferation, but unlike Dvl2 depletion, did not induce differentiation. Finally, Wnt5a, a noncanonical Wnt ligand, was also required for glioma cell proliferation. The data therefore suggest that both canonical and noncanonical Wnt signaling pathways downstream of Dvl2 cooperate to maintain the proliferative capacity of human glioblastomas.     

Socio—cultural factors influencing insecticide treated bed net utilization in a malaria endemic city in north—central Nigeria

ObjectiveTo ascertain the socio-cultural factors influencing the rate of utilization of insecticide treated bed nets (ITNs) in a malaria endemic city of Makurdi, north central Nigeria.MethodsThe study was cross-sectional in nature using systematic sampling method to identify households. Both quantitative and qualitative data was generated from adult women using structured and semi structured questionnaires, and focused group discussions (FGDs) to obtain information on rate and patterns of utilization of ITNs. Information such as age, educational level, marital status, awareness or otherwise of the existence of malaria, and factors influencing rate of ownership and utilization of ITNs were obtained. FGDs were used to obtain qualitative information on rate of utilization of ITNs not captured in the questionnaires. Data obtained was analysed using Epi Info 6 statistical software.ResultsAmong the respondents interviewed, 97.0% (2 013/2 075) were aware of existence of malaria and 87.0% of these (1 751/2 013) would associate it with mosquitoes. The rate of ownership of any bed net, ITNs and untreated bed nets (UTNs) was 25.1%, 17.0% and 8.3%, respectively. Utilization of ITNs among children was 30.0% (112/373) and UTNs 12.9% (48/373). Positive contributors to ITNs utilization were literacy, enhanced economy, experience of marriage, and being gainfully employed (P<0.05); while negative contributors were ignorance, poverty and some cultural beliefs and values.ConclusionsA more synchronized advocacy should be carried out on the potential benefits of ITNs utilization and sustained. Also ITNs should be made available to the people of the community at minimal or no cost.