A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.     

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with ^99mtechnetium (Tc)-stannous colloid (n=13) or ¹¹¹indium (In)-oxine (n=10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [^99mTc]-stannous colloid, while six [¹¹¹In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4–9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.     

Case-Based Discussion Regarding Challenges in Patient Selection and Procedural Planning in Left Atrial Appendage Occlusion

Atrial fibrillation (AF) accounts for most embolic strokes, especially in elderly individuals. Although anticoagulation is known to reduce the risk of embolic stroke, a significant proportion of patients have relative or absolute contraindications to anticoagulation. The left atrial appendage has been implicated as the major source of emboli in more than 90% of ischemic strokes in nonvalvular AF. Left atrial appendage occlusion offers an alternative for stroke prevention in patients with an elevated stroke risk (CHADS₂ score ≥2 or CHA₂DS₂-VASc score ≥3) who have a rationale for avoiding long-term oral anticoagulation after a shared decision-making process. However, there remain significant challenges in left atrial appendage occlusion therapy related to patient selection, the procedure itself, and postprocedural patient management decisions. In this review article, we discuss some of these challenges in a case discussion–based approach.     

Glomerular basement membrane changes in aging nondiabetic and diabetic guinea pigs

Glomerular hyperplasia and thickening or the glomerular basement membrane increase with age in humans and animals. This glomerulopathy can be enhanced by hyperglycemic conditions such as diabetes mellitus. When diabetic guinea pigs were examined by fluorescent microscopy, deposits of a substance similar to immunoglobulin G (IgG) were seen. Comparison with nondiabetic age-matched control animals suggest that glomerulopathy is related to aging, and can be further enhanced by hyperglycemia.     

682株鲍曼不动杆菌分布及耐药性分析 FREE

目的方法结果结论为了解鲍曼不动杆菌临床分布及其耐药情况,对某院2005-2007年间分离的鲍曼不动杆菌的耐药性进行监测分析。共分离鉴定鲍曼不动杆菌682株,其中674株分离自住院患者：重症监护室（ICU）248株,内科221株,外科205株;8株分离自门诊患者。标本来源以痰为主,共分离443株,占64.95%;其次为分泌物、脓液标本,分离91株,占13.34%。药敏结果显示,鲍曼不动杆菌对头孢他啶和头孢吡肟的耐药率较高,分别为69.17%和58.58%;对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、亚胺培南和美罗培南的耐药率分别为25.85%、66.46%、3.80%和7.10%。提示鲍曼不动杆菌在ICU的分离率高,对常用抗菌药物的耐药率高,必须加强抗菌药物合理使用的管理。     

碘缺乏和甲状腺功能减退对大鼠仔鼠海马钙调磷酸酶表达的影响

目的 观察碘缺乏和甲状腺功能减退对大鼠仔鼠海马钙调磷酸酶蛋白表达的影响.方法 健康2月龄雌性Wistar大鼠,交配妊娠后,取孕鼠28只,按体质量随机分成对照组、甲状腺功能减退组和碘缺乏组,甲状腺功能减退组根据饮水中含丙基硫尿嘧啶剂量分为5 ppm组和15 ppm组.每组7只孕鼠.分别于出生后7 d(PN7)、14 d(PN14)和31 d(PN21)时,每组随机取5只仔鼠,灌流固定大脑,进行组织病理切片和免疫组化染色,观察分析海马钙调磷酸酶的表达.结果 PN14和PN21时,在海马CA1和CA3区15 ppm组和碘缺乏组仔鼠海马钙调磷酸酶表达显著高于对照组(P<0.05),而海马DG区则相反.PN7时,各区均几乎观察不到阳性反应产物,各组间蛋白表达无显著差异.结论 碘缺乏和甲状腺功能减退可增加海马CA1和CA3区钙调磷酸酶的蛋白表达.     

广州地区呼吸道疾病患儿16种常见变应原检测分析

目的 了解广州地区呼吸道疾病患儿对16种常见变应原的过敏情况,同时探讨不同年龄组之间的变应原阳性率差异,并比较致敏程度.方法 选择2007年8月至2008年3月广州医学院第一附属医院呼吸科门诊和儿科门诊初诊为支气管哮喘、过敏性鼻炎、呼吸道感染等患儿320例为研究对象,其中婴幼儿组(≤3岁)214例,儿童组(>3岁)106例.采用德国FOOKE ALLERG-O-LIQ-SYSTEM变应原检测系统,通过免疫捕获法检测血清中常见的16种变应原特异性免疫球蛋白E(SIgE)抗体.结果 在所有患儿中,其中261例(81.56%)SIgE呈阳性.59例(18.44%)呈阴性.16种变应原SIgE阳性率为屋尘螨(36.88%)、粉尘螨(35.31%)、热带螨(24.06%)、狗毛(6.56%)、猫毛(8.75%)、德国小蠊(16.56%)、蜜蜂毒素(0.94%)、屋尘(45.63%)、全蛋(45.94%)、牛奶(46.25%)、小麦面粉(6.88%)、玉米粉(1.25%)、花生(9.06%)、大豆(5.94%)、螃蟹(2.81%)、虾(4.38%).婴幼儿组SIgE的阳性率为81.78%,以食物性变应原(牛奶、全蛋)为主;儿童组的阳性率为81.13%,以吸人性变应原(尘螨)为主(X2=0.02,P=0.89).儿童组尘螨的过敏阳性率均高于婴幼儿组(P<0.05),且儿童组屋尘螨和粉尘螨的过敏程度多在3级以上.婴幼儿组各级阳性率比较平均.两组对热带螨的过敏程度均较低,多在3级以下.婴幼儿组牛奶和全蛋过敏阳性率高于儿童组(P<0.05),两组的过敏程度均在3级以下.结论 儿童组与婴幼儿组对常见变应原的总阳性率差异无统计学意义,只是对不同变应原阳性率及过敏程度的差异.儿童组主要是对吸人性变应原产生过敏,婴幼儿组主要是对食物性变应原产生过敏,应以不同年龄段来分析儿童变应原检测结果.     

The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ?-amyloid peptide

Background and purpose:

β-Amyloid peptide (Aβ) is implicated in the pathogenesis of Alzheimer''s disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress.

Experimental approach:

We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Aβ-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Aβ and on neurite outgrowth in PC12 cells were investigated.

Key results:

Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Aβ_1-42. Similar protective effects against Aβ_1-42 were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Aβ load was markedly diminished in the brain of those animals after treatment with piracetam. Aβ production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Aβ-induced mitochondrial dysfunction and Aβ-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam.

Conclusion and implications:

Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Aβ on brain function.This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers by Pravdic et al. and Puerta et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j.1476-5381.2010.00663.x     

漂浮导管技术在监测指导急性心力衰竭患者临床治疗的价值

目的评估漂浮导管技术在监测指导急性心力衰竭（HF）患者临床治疗的价值。方法以48例经常规处理效果不佳的急诊心力衰竭患者为研究对象,尽早留置漂浮导管,留置漂浮导管后0．5h和48h,记录心率（HR）、中心静脉乐（CVP）、肺毛细血管楔压（PCWP）、心排血量（CO）,并计算心脏指数（CI）、左心室每搏做功指数（LVSWI）、右心室每搏做功指数（RVSWI）、体循环阻力（SVR）、肺循环阻力（PVR）,然后根据情况选用各种药物治疗。HF患者根据出院时预后分为病情好转组和病情恶化组,对两组患者留置漂浮导管后0．5h和48hHR、CVP、PCWP、CO、CI、LVSWI、RVSWI、SVR、PVR变化进行比较。结果33例病情好转患者应用监测漂浮导管治疗后与治疗前比较,心率、PCWP、CVP明显下降（均P〈0．01）,SVR、PVR明显下降（P〈0．05）,CO、CI、RVSWI明显升高（均P〈0．05）,LVSWI明显升高（P〈0．01）;与治疗前比较,15例病情恶化患者应用监测漂浮导管治疗后HR、CVP、PCWP、CO、CI、LVSWI、RVSWI、SVR、PVR均无明显改变（均P〉0．05）。结论漂浮导管技术在血流动力学不稳定的急性心力衰竭患者的评估病情、指导临床治疗和预后评估中有再要的价值。