基于尿动力学客观指标的神经原性膀胱概率预测模型构建

目的:建立概率预测的Logistic回归模型,分析影响神经原性膀胱尿动力学的主要危险因素和保护因素,并评价模型的灵敏度、特异度和准确性。方法:收集2004-03/2006-03在中山大学附属第一医院尿流动力学室行尿动力学检查的患者80例,对其尿动力学图的客观指标进行回顾性分析。①80例中尿流动力学图正常者29例为对照组,尿流动力学图显示神经原性膀胱者51例为病例组。②将两组资料采用统一的变量指标(包括性别、年龄以及尿流动力学仪器自动采集计算的34个数据)输入SPSS12.0版本数据库,进行主成分分析,将贡献率高的主成分进行单因素分析,取其中有统计学意义的主成分作多因素Logistic回归分析,建立Logistic回归方程,计算各因素的OR值,并计算模型的灵敏度、特异度和准确度。结果:①尿动力学34个客观指标进行主成分分析后得出8个主成分(C1～8),取贡献率高的5个主成分进行单因素分析,结果有2个主成分可以进入多因素Logistic回归分析。获得Logistic回归概率预测模型,此概率预测模型灵敏度为82.4%,特异度75.9%,准确度为80.0%。②主成分C1的OR值=4.606,C1中的首次尿意膀胱压力和逼尿肌压力、正常尿意膀胱压力和逼尿肌压力、强烈尿意膀胱压力和逼尿肌压力、尿急尿意膀胱压力和逼尿肌压力、充盈期最大逼尿肌压力的系数分别是0.823,0.834,0.781,0.913,0.924,0.932,0.883,0.916,0.857,高于C1中其他变量的系数,故可把主成分C1看作是一个“压力型”指标。③C3的OR值=0.183,C3中系数较高的变量是最大流率、平均流率、压力流率中最大流率和平均流率,分别是0.694,0.777,0.768,0.771,因此把C3看作为“流率”变量指标。结论:①成功构建了人神经原性膀胱尿流动力学图的概率预测模型,其中“压力”因子主成分是危险因素,“流率”因子主成分是保护因素。②概率预测模型的灵敏度、特异度和准确性显示其有较好的代表性。     

Can the reading for serologic reactivity following 37 degrees C incubation be omitted?

The need to detect antibodies that agglutinate and/or hemolyze red cells (RBCs) directly at 37 degrees C, but do not react in subsequently performed indirect antiglobulin tests (IATs), is of concern relative to the streamlining and automation of antibody detection methods. To determine incidence and significance of such reactions, data from 87,480 tests, which used low-ionic-strength saline, 10-minute incubation at 37 degrees C, and anti-IgG, were analyzed for unexpected antibodies. There were 3590 positive tests, of which 475 showed reactions at 37 degrees C but not in subsequently performed IATs (37 + IAT-). Of these, 196 reactions were due to autoantibodies or other factors usually considered insignificant with respect to the survival of transfused incompatible RBCs, 176 were due to alloantibodies of questionable clinical significance (M, Lea, P1, etc.), and 103 were associated with alloantibodies of potential clinical significance (63 E, 27 K, 5 Jka, 4 D, 3 cE, and 1 C). This latter reaction was seen in 72 patients, with two 37 + IAT-antibodies occurring in each of 3 patients. Of the 75 potentially significant 37 + IAT-antibodies, 57 were seen in patients recently exposed to homologous RBCs, 13 in patients with a history of transfusion and/or pregnancy, and 5 in patients with no known exposure to homologous RBCs. IAT reactivity was observed in subsequent samples with 27 of these antibodies. The predictive value of a 37 + IAT-test was 21.7 percent for a potentially significant antibody. The incidence was 0.12 percent of all tests for unexpected antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)     

转化生长因子β细胞内信号转导负调控蛋白Smad6，7在肾间质纤维化大鼠肾脏表达与益气活血法的影响

目的:观察肾间质纤维化大鼠肾组织中转化生长因子β细胞内信号转导负调控蛋白Smad6,7表达变化与益气活血法中药制剂的影响。方法:实验于2006-12/2007-06在首都医科大学解剖与组织胚胎学系实验室完成。①实验动物:Wistar雄性大鼠30只,采用随机数字法随机分为模型组、中药大剂量组、中药中剂量组、中药小剂量组、西药蒙诺组、假手术组,每组5只。益气活血法中药提取液(生黄芪15g,当归10g,赤白芍10g,丹参30g,黄芩10g,车前草15g,牛膝15g等)经水提醇沉得4.4kg/L生药提取液。实验过程中对动物处置符合动物伦理学要求。②实验方法:其中前5组行单侧输尿管梗阻致肾小管间质纤维化模型手术。假手术组打开大鼠腹腔后分离左侧输尿管,并不结扎即关闭腹腔。中药大剂量组、中药中剂量组、中药小剂量组、西药蒙诺组,于手术前2d给予灌胃给药0.072mL/(kg·d),0.036mL/(kg·d),0.018mL/(kg·d),10mg/(kg·d),1次/d,连续2周。模型组及假手术组用相同体积的生理盐水灌胃。③实验评估:6组大鼠于术后14d麻醉后处死,观察梗阻肾组织病理改变,用免疫组化方法检测肾组织Smad6,7蛋白表达,通过医学病理图像分析系统对Smad6,7蛋白的积分光密度进行统计学分析。结果:30只大鼠全部进入结果分析。苏木精-伊红染色显示模型组肾小管上皮细胞萎缩,大部分肾小管管腔扩张,间质纤维组织增生,大量炎性细胞浸润,肾小球数目明显减少。中药大剂量组、中剂量组、西药蒙诺组较模型组肾间质炎性细胞浸润、纤维组织增生、肾小管扩张情况明显减轻。Smad6,7蛋白主要在肾皮质肾小管上皮细胞内表达,在模型组它们的表达较假手术组明显减弱且分布面积减少,两组间积分光密度差异具有统计学意义(P<0.05);中药中剂量组、大剂量组、西药蒙诺组Smad6,7蛋白的表达较模型组明显增强、面积增加,积分光密度差异具有统计学意义(P<0.05)。结论:益气活血法可以通过诱导肾组织Smad6,7蛋白表达而抑制肾间质纤维化。     

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.     

Fractionation of Spatial Memory in GRM2/3 (mGlu2/mGlu3) Double Knockout Mice Reveals a Role for Group II Metabotropic Glutamate Receptors at the Interface Between Arousal and Cognition

Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3^−/−) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals'' exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3^−/− mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive and exploratory spatial memory tasks may be absent in aversive tasks because the latter induce higher levels of arousal, which rescue spatial learning. Consistent with an altered arousal–cognition relationship in GRM2/3^−/− mice, injection stress worsened appetitively motivated, spatial working memory in wild-types, but enhanced performance in GRM2/3^−/− mice. GRM2/3^−/− mice were also hypoactive in response to amphetamine. This fractionation of hippocampus-dependent memory depending on the appetitive-aversive context is to our knowledge unique, and suggests a role for group II mGluRs at the interface of arousal and cognition. These arousal-dependent effects may explain apparently conflicting data from previous studies, and have translational relevance for the involvement of these receptors in schizophrenia and other disorders.     

Preparation,physicochemical characterization and biological evaluation of cefodizime metal ion complexes

Objectives Cefodizime is a broad spectrum cephalosporin belonging to the third generation agents. In this study, attention has been paid to the preparation, physicochemical characterization and biological evaluation of new Cu²⁺, Zn²⁺, Fe³⁺, Co²⁺ and Al³⁺ complexes of cefodizime. Methods The stoichiometrics and the mode of bonding of the complexes were deduced from their elemental and metal analysis, electrical conductivity measurements, UV‐vis, infrared and Raman spectroscopic investigations. Study of the stoichiometry of these complexes referred to the formation of 1: 1 ratios of metal to ligand. Antimicrobial activity of the complexes was determined using two strains of Gram‐positive (Bacillus subtilis and Proteus vulgaris) and two strains of Gram‐negative (Escherichia coli W3110 and Pseudomonas putida) bacteria. The minimal inhibitory concentration was determined as the lowest concentration inhibiting bacterial growth on solid Luria Bertani medium. Key findings The spectra gave evidence as to the position of binding. In addition, the aqueous solubility of cefodizime was strongly reduced by complexation. Conclusions The antibacterial activity of cefodizime was not affected by complexation with Al³⁺ but it was reduced by complexation with the other tested metal ions against the bacteria under study.     

Effects of L-histidine depletion and L-tyrosine/L-phenylalanine depletion on sensory and motor processes in healthy volunteers

Background and purpose:

Animal studies show that histamine plays a role in cognitive functioning and that histamine H₃-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H₁-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.

Experimental approach:

Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.

Key results:

Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.

Conclusions and implications:

L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H₁-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies.