Tegaserod does not alter fasting or meal-induced biliary tract motility

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.     

粮食中微量元素锌与大骨节病的关系

本文就西南大骨节病区粮食中微量元素锌、铁、锰、铜、铬测定作了初步分析。其中较有规律的是锌,并对锌在大骨节病发病过程中的作用进行了试探性讨论。认为锌在发病中占有重要的地位,很可能是硒对大骨节病作用的重要复合因子之一。     

72例鼻咽结核的临床分析

目的 探讨鼻咽结核的诊断与治疗。方法 对72例经活检病理证实的鼻咽结核进行回顾性分析。结果 72例患者中男性31例，女性41例，男女比例为1：1．32，平均年龄为30．7岁；鼻咽结核以局部症状为特征，颈淋巴结肿大发生率为79．2％（57／72）；鼻咽结核在临床上误诊率较高；抗结核治疗9～12个月治愈，随访1～5年，未见复发。结论 近年来鼻咽结核有增加的趋势，尤以原发性病例居多。鼻咽镜活检可确诊，规则抗结核治疗可治愈。     

Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans

The Caenorhabditis elegans defecation motor program (DMP) is a highly coordinated rhythmic behavior that requires two GABAergic neurons that synapse onto the enteric muscles. One class of DMP mutants, called anterior body wall muscle contraction and expulsion defective (aex) mutants, exhibits similar defects to those caused by the loss of these two neurons. Here, we demonstrate that aex-2 encodes a G-protein-coupled receptor (GPCR) and aex-4 encodes an exocytic SNAP25 homologue. We found that aex-2 functions in the nervous system and activates a G(s)alpha signaling pathway to regulate defecation. aex-4, on the other hand, functions in the intestinal epithelial cells. Furthermore, we show that aex-5, which encodes a pro-protein convertase, functions in the intestine to regulate the DMP and that its secretion from the intestine is impaired in aex-4 mutants. Activation of the G(s)alpha GPCR pathway in GABAergic neurons can suppress the defecation defect of the intestinal mutants aex-4 and aex-5. Lastly, we demonstrate that activation of GABAergic neurons using the light-gated cation channel channelrhodopsin-2 is sufficient to suppress the behavioral defects of aex-2, aex-4, and aex-5. These results genetically place intestinal genes aex-4 and aex-5 upstream of GABAergic GPCR signaling. We propose a model whereby the intestinal genes aex-4 and aex-5 control the DMP by regulating the secretion of a signal, which activates the neuronal receptor aex-2.     

Modulation of platelet and leucocyte function by a Chinese herbal formulation as compared with conventional antiplatelet agents

Platelet and leucocyte activity are important in the acute development of thrombosis and in the pathogenesis of ischaemic vascular disease. Dan Shen Di Wan (DS, Cardiotonic Pill or Dantonic(R) Pill) is one of the most commonly used Chinese herbal formulations for treating patients with atherosclerotic disease in China and several Asian countries. We studied the effect of DS on platelet and leucocyte function and compared the effects with conventional antiplatelet agents, cangrelor (ADP P2Y(12) receptor antagonist) and aspirin (acetyl salicylic acid, ASA). Measurements were made by platelet aggregation (%) and activation (CD62P %), platelet-monocyte conjugate formation (P/M, CD42a median fluorescence, mf), platelet-neutrophil conjugate formation (P/N, mf), and leucocyte activation (CD11b median fluorescence on monocytes and neutrophils, mf) in response to 3.3 micromol/L adenosine diphosphate (ADP), 1.0 micromol/L platelet activating factor (PAF), 5.0 micromol/L adrenaline and 0.5 microg/mL collagen. We also evaluated the effect of its main component, water soluble extract of salvia miltiorrhiza (SME) on intracellular calcium mobilization in platelets triggered by 10 micromol/L ADP, 10 micromol/L PAF, 2 microg/mL collagen and 15 micromol/L thrombin receptor activating peptide (TRAP). Overall DS showed inhibition of platelet aggregation, platelet activation, platelet-leucocyte conjugate formation and leucocyte activation in response to all the agonists apart from adrenaline (all p < 0.01). DS showed inhibition of platelet aggregation and leucocyte activation equivalent to cangrelor 100 nmol/L and ASA 100 micromol/L. SME dose-dependently inhibited intracellular calcium mobilization in platelets following stimulation with all the platelet agonists with maximum effective at 0.36 mg/mL (all p < 0.01). When used at 0.18 mg/mL its inhibitory effect was equivalent to cangrelor and ASA. We conclude that DS is a potential inhibitor of both platelet and leucocyte activation.     

Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II 'reactive site' deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation.     

射频消蚀术并发症及其防治

３４４例射频消蚀术中出现并发症９例（２．６％），其中心脏破裂致死１例（０．３％），ＩＩＩ度房室传导阻滞３例（０．９％），心室颤动２例（０．６％），主动脉瓣损伤、大头导管误入冠状动脉引起冠状动脉一过性缺血及股动脉术后出血形成巨大皮下血肿各１例。对各种并发症的防治进行了分析讨论。提出经验不足是产生并发症的主要原因。     

A cardiac hydatid cyst involving the basal interventricular septum causing biventricular outflow tract obstruction

We report a case of a 37-year-old sheep-raising man with a cardiac hydatid cyst involving the basal interventricular septum causing biventricular outflow obstruction. He suffered from multi-organ hydatidosis and underwent cerebral hydatid cyst extirpation and right nephrectomy for renal echinococcosis. The diagnosis of the cyst was obtained by echocardiography and magnetic resonance imaging. The diagnosis was confirmed by positive hemagglutination test. He was operated on for cardiac hydatid cyst using enucleation and capitonnage procedure under extracorporeal circulation. The morbidity was complete atrioventricular block, necessitating VDD pacemaker implantation. This was followed by medical treatment with albendazole (400 mg/day).     

中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值在重症肺炎支原体肺炎中的诊断价值北大核心CSCD

目的研究中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)在重症肺炎支原体肺炎(MPP)中的诊断价值。方法回顾性分析2015年1月至2017年12月苏州大学附属儿童医院住院的616例MPP患儿(MPP组)的临床资料和实验室数据,选取同期100例健康体检儿童为健康对照组。采用t检验或秩和检验比较MPP组与健康对照组、重症MPP组与普通MPP组间的NLR及PLR的差异。筛选出影响重症MPP的危险因素,描绘受试者工作特征曲线(ROC)并寻找最佳截断点。结果1.MPP组患儿白细胞计数(WBC)、中性粒细胞数(N)、血小板计数(PLT)、NLR、PLR、免疫球蛋白(Ig)M的中位数及CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均高于健康对照组[8.36×10^(9)/L比7.49×10^(9)/L、4.41×10^(9)/L比3.11×10^(9)/L、340.92×10^(9)/L比234.00×10^(9)/L、1.70比0.91、112.99比70.34、1.33 g/L比1.29 g/L、20.95%比17.10%、11.25%比9.70%];淋巴细胞数(L)、IgA的中位数及CD3^(+)、CD3^(+)CD8^(+)、CD3^(-)CD_((16+56))^(+)百分比的中位数均低于健康对照组[2.64×10^(9)/L比3.37×10^(9)/L、0.86 g/L比1.30 g/L、64.55%比68.00%、23.65%比24.90%、10.50%比12.20%],差异均有统计学意义(Z=-3.074、-2.413、-2.972、-1.357、-1.863、-2.251、-4.282、-3.420、-2.221、-4.181、-2.784、-2.024、-2.791,均P<0.05)。2.重症MPP组患儿N、NLR、PLR、IgA、IgG、IgM的中位数及CD3^(+)、CD3^(+)CD8^(+)百分比均高于普通MPP组[5.18×10^(9)/L比3.52×10^(9)/L、2.39比1.03、149.32比94.23、1.29 g/L比0.71 g/L、9.63 g/L比8.19 g/L、1.40 g/L比1.29 g/L、(65.53±9.75)%比(62.81±9.89)%、(25.35±6.65)%比(23.38±6.91)%];L的中位数、CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均低于普通MPP组(2.02×10^(9)/L比3.25×10^(9)/L、17.40%比21.50%、9.00%比11.70%),差异均有统计学意义(Z/t=-7.807、-11.313、-10.452、-8.819、-6.162、-3.047、-3.128、-3.270、-9.402、-5.191、-5.214,均P<0.05)。3.通过单因素和多因素的Logistic回归分析发现,CD3^(-)CD_(19)^(+)是患儿发生重症MPP的保护因素;N、NLR、PLR是患重症MPP的危险因素(均P<0.05),且相对危险度由高到低依次为NLR>PLR>N。4.NLR、PLR诊断重症MPP的ROC曲线下面积(AUC)分别为:NLR(AUC=0.789,95%CI:0.754~0.823,P<0.001);PLR(AUC=0.767,95%CI:0.730~0.804,P<0.001)。当NLR的截断值为1.09时,敏感性为98.9%,特异性为70.6%;当PLR的截断值为97.47时,敏感性为88.5%,特异性为69.4%。结论NLR、PLR可作为发生重症MPP的独立影响因素,对诊断重症MPP有一定价值。