β—淀粉样蛋白对阿尔茨海默病大鼠脑局部神经元超微结构的影响

目的：探讨Meynert核注射β-淀粉样蛋白（Aβ）后对大鼠脑神经细胞超微结构的影响及其可能机制。方法：将1μ1Aβ1-40(10μg/μl)在立体定向仪下注入大鼠右侧Meynert核，分别于1、4周时用透射电镜观察脑组织中神经细胞超微结构。结果：Aβ注射1周后，实验组Meynert核、海马区和皮层区均可见一些神经细胞核染色质浓缩成团块并见边缘现象，神经细胞有发生凋亡的趋势；4周时可见典型的神经细胞凋亡；突触结构数量减少。正常对照组和假手术组超微结构基本正常。结论：Aβ注入Meynert核能引发CNS神经细胞凋亡和突触结构减少，可能是AD记忆障碍和痴呆形成的重要机制之一。     

β淀粉样肽及冈田酸对大鼠脑内突触素和发动蛋白Ⅰ表达的影响

目的:探讨β淀粉样肽(Aβ)及冈田酸(OA)对大鼠学习记忆能力及脑内突触素和发动蛋白Ⅰ的表达影响。方法:采用立体定向方法将Aβ1-42及OA分别注入SD大鼠双侧海马CA1区,2个月后水迷宫实验检测大鼠学习记忆能力,Western印迹及实时聚合酶链反应(real-time PCR)检测大鼠脑组织中突触素和发动蛋白及mRNA表达水平。结果:与对照组相比,Aβ注射组、OA注射组及Aβ+OA共同注射组均能引起大鼠学习记忆能力降低,各组脑组织中突触素、发动蛋白Ⅰ及mRNA表达均降低(P0.01),其中以Aβ+OA共同注射组改变尤为明显。结论:Aβ和OA均可降低大鼠学习记忆能力,降低突触素和发动蛋白Ⅰ的表达,该改变可能与AD发病机制中学习记忆能力减退有关。     

实验性阿尔茨海默模型大鼠海马内病理和PCNAmRNA表达的变化及rLent/NT4-NAP对其的影响

目的探讨实验性阿尔茨海默病模型大鼠脑内海马光镜下的变化和DNA修复蛋白PCNAmRNA表达的变化,进一步探讨神经保护肽慢病毒rLent/NT4-NAP（NAP）对其具有神经保护作用机制。方法选择无菌级雄性大鼠Wister大鼠40只,随机分为对照组,假手术组,阿尔茨海默（AD）模型大鼠组,rLent/NT4-NAP（NAP）组,每组10只。建立Aβ1-40联合应用转移生长因子β1（TGFβ1）注入实验大鼠左侧海马区制备阿尔茨海默动物模型,通过HE染色观察各组大鼠海马区的形态学改变;通过原位杂交的方法检测实验各组大鼠海马区PCNAmRNA表达的变化。结果 HE染色发现痴呆组大鼠左侧海马区神经细胞明显变性、坏死,而NAP组细胞损伤情况较痴呆组大鼠明显减轻;用原位杂交的方法检测痴呆组大鼠左侧海马区神经细胞胞核内PCNAmRNA强阳性表达减少,而NAP组左侧海马区神经细胞胞核内PCNAmRNA表达较痴呆组显著上调与对照组比较无统计学差异。结论 NAP通过诱导DNA修复蛋白PCNA蛋白表达上调,从而促进DNA损伤修复和减少细胞凋亡,对神经细胞有神经保护作用,实现其内源性的保护作用。     

骨髓间充质干细胞对血管性痴呆大鼠海马CA1区突触素表达的影响

目的：观察静脉注射同种异体骨髓间充质干细胞对血管性痴呆（VaD）模型大鼠海马CA1区突触素表达的影响。方法：体外分离、扩增大鼠骨髓间充质干细胞（MSC），并用BrdU标记。大鼠双侧颈总动脉结扎法制备血管性痴呆模型。1周后经尾静脉注射MSCs，观察注射后4周大鼠海马CA1区突触素（SYN）表达的变化。结果：4周后VaD大鼠海马CA1区锥体细胞层内SYN表达较正常对照组减少，差异有显著性（P〈0．01）；MSCs注射后4周，大鼠海马CAl区可见荧光标记的MSCs，SYN表达较未注射组增加，差异有显著性（P〈0．01）。结论：静脉注射MSCs使VaD大鼠海马CA1区突触素表达增加。     

即刻早期基因锌指结构9在肝纤维化大鼠肝脏中的表达

目的：通过研究肝纤维化大鼠肝组织锌指结构9（zinic finger9，ZF9）基因的表达及其变化，初步探讨ZF9在大鼠肝纤维化发生中的作用。方法：雄性SD大鼠，随机分为正常组、1周组、4周组和8周组，皮下注射40％植物油四氯化碳（CCl4），并分别于注射后1、4、8周取肝组织免疫组化检测转化生长因子-β1（TGF-β1）蛋白，RT-PCR检测ZF9 mRNA水平．苦味酸-酸性品红染色观察胶原纤维表达变化。结果：（1）正常大鼠肝组织ZF9基因少量表达，模型组大鼠注射CCl4 1周后其表达增强，注射CCl4 4周后明显增强，8周时仍呈高表达。（2）正常大鼠TGF-β1在少许肝窦周细胞和汇管区部分间质细胞着色，大鼠注射CCl4 1周后，上述着色细胞增多，范围增加，注射CCl4 4周后，TGF-β1表达进一步增加，第8周TGF-β1表达更加丰富，部分肝细胞也可见表达。（3）正常肝组织几乎不表达胶原，模型组注射CCl4 1周后可见胶原有少量着色，到第4和第8周表达明显增多。结论：ZF9基因转录水平在肝纤维化的形成过程中逐渐增加．并与TGF-β1的表达同步，与胶原纤维的增加一致，可能通过活化肝星状细胞促进肝纤维化的发生。     

益智治呆方通过干预神经胶质细胞治疗老年痴呆症的大鼠实验研究

目的观察益智治呆方对β-淀粉样蛋白(Aβ)诱导的大鼠脑组织星形胶质细胞蛋白(GFAP)表达及对乙酰胆碱酯酶、过氧化氢酶活性的影响,分析益智治呆方治疗老年痴呆症患者的具体作用途径。方法选取30只大鼠,平均分成对照组(脑内注射5μl生理盐水)、模型组(脑内注射Aβ1-42,10μg/5μl)以及AD模型联合益智治呆方组(治疗组,脑内注射Aβ1-42,10μg/5μl)。建模成功后治疗组采用益智治呆方0.5 mg/(kg·d)灌胃,对照组和模型组采用等量生理盐水灌胃。持续喂养之后取脑组织分析病理改变状况,使用免疫染色法检测Aβ标记部位与神经细胞毒性,应用Western blot进行GFAP检测。分析三组大鼠行为学结果。结果治疗组大鼠以及模型组大鼠脑组织切片当中的海马中央还有皮质中线旁注射区,存在大小不同的Aβ1-42阳性颗粒;神经细胞标记抗体染色之后,在模型组大鼠以及治疗组大鼠注射使用Aβ的脑组织海马区以及皮质区能够发现神经细胞的大小不够均匀,同时少数神经细胞出现变形,细胞带明显出现损伤,细胞数量显著下降,治疗组大鼠的病变程度与模型组对比要轻,同时对照组大鼠无上述变化(P0.05)。治疗组大鼠在使用益智治呆方进行治疗之后,显著降低了神经元的损伤程度,同时降低GFAP表达水平。造模之后模型组大鼠的反应显著下降,电击次数显著上升(P0 05),治疗组大鼠逃避反应更加敏感,电击次数显著下降(P0 05)。结论通过应用益智治呆方,能够有效降低Aβ模型鼠GFAP表达水平,保护神经细胞,减轻脑组织损伤程度。     

人骨髓间充质干细胞移植老年性痴呆大鼠认知能力和海马超微结构的变化

背景: 因发病机制不明,目前尚无治愈老年性痴呆的有效方法.现临床上主要是采用药物治疗,而骨髓间充质干细胞的替代治疗尚处于基础研究阶段,其海马移植后对老年性痴呆认知能力的影响未见报道.目的: 探讨人骨髓间充质干细胞移植对老年性痴呆大鼠认知能力和海马超微结构的影响.方法: 老年雄性Wistar大鼠30只,制各自然衰老痴呆模型,造模后随机分为3组,选取双侧海马为移植区,分化细胞移植组注射定向神经细胞诱导分化的人骨髓间充质干细胞悬液4 μL(2×105个细胞),干细胞移植组注射等量常规培养的人骨髓间充质干细胞,模型组注射等量生理盐水.通过Y迷宫试验测定大鼠的学习、记忆能力,透射电镜观察海马区超微结构.结果与结论: 与移植前大鼠学习、记忆分数比较,移植后12周模型组均显著下降(P<0.01),干细胞移植组均有所提高(P>0.05),分化细胞移植组均显著提高(P<0.01).移植后12周与模型组比较,干细胞移植组、分化细胞移植组大鼠学习、记忆分数均显著提高(P<0.01).电镜观察模型组大鼠海马区神经细胞可见明显损伤,干细胞移植组损伤减轻,分化细胞移植组多数神经细胞结构正常.证实骨髓间充质干细胞移植可以提高老年性痴呆大鼠的认知能力,且定向神经诱导分化的骨髓间充质干细胞移植治疗效果优于未分化的骨髓间充质干细胞,提示骨髓间充质干细胞减少海马组织神经细胞变性坏死可能是其改善老年性痴呆大鼠认知功能障碍的作用机制之一.     

三种化学物质诱发大鼠认知障碍:优化阿尔茨海默病模型的研究

目的:根据正交试验原理,应用3种化学物质诱发大鼠认知障碍模型,判定模型质量,试图优化出建立阿尔茨海默病(AD)模型的方法。方法:健康雌性Wistar大鼠16只,按L16(215)正交试验设计分组观察,依二水平三因素的方法制备模型。三因素为:A因素:一水平为鹅膏蕈氨酸(IBA)一次性微量(1μL,120mmol/L)注入大鼠Meynert基底核;二水平为注射等量人工脑脊液。B因素:一水平为β淀粉样肽1～40(Aβ1～40,20μL)左侧脑室注射,1次/d,连续1周;二水平注射等量人工脑脊液。C因素:一水平为D-半乳糖(D-gal,48mg/kg)皮下注射,1次/d,连用56d;二水平注射等量生理盐水。在处理前后用MG-2迷宫观察大鼠学习记忆成绩。苏木精-伊红染色观察神经细胞形态和数量,Bielschowsky染色观察神经元纤维缠结(NFT)和老年斑等病理改变。结果:应用三因素150d后,IBA,Aβ1～40,D-gal联合应用可致大鼠记忆障碍(均方:7.5625;F=8.067;P<0.05);海马皮层锥体细胞数量明显减少(P<0.01),Alzheimer细胞增多及卫星现象。IBA致大鼠学习记忆障碍(均方:915.0625,10.5625,F=10.602,11.267;P<0.05,0.05);D-gal致大鼠学习障碍(均方:495.0625,F=5.736;P<0.05)。3种化学物质及其交互效用分别可致海马皮质锥体细胞数量明显减少(1.4±0.28,2.2±0.85,1.7±0.14,1.8±0,0.8±0     

糖基化终产物对大鼠视网膜超微结构及凋亡的影响

目的观察外源性非酶糖基化终产物(AGEs)对大鼠视网膜超微结构以及细胞凋亡的影响。方法应用鼠血清白蛋白(RSA)体外孵育AGEs修饰蛋白,并将其注入健康大鼠体内,每日一次,连续两周。TUNEL法检测大鼠视网膜凋亡细胞,透射电镜下观察内核层神经细胞的超微变化。结果AGEs组大鼠视网膜内核层可见凋亡阳性细胞,透射电镜下深染细胞明显增多,细胞核缩小、不规则,染色质形成大小不等的团块凝结、边聚于核膜处。胞质深染,细胞器损害。结论AGEs可使大鼠视网膜内核层神经细胞凋亡,超微结构改变。     

β淀粉样前体蛋白17肽对糖尿病大鼠海马神经细胞线粒体膜电位和凋亡的干预

背景糖尿病大鼠存在学习和记忆障碍,β淀粉样前体蛋白17肽具有改善这一行为的作用.糖尿病是否通过影响海马区神经细胞的膜电位及凋亡导致学习和记忆障碍以及β淀粉样前体蛋白17肽的相关作用机制尚不清楚.目的观察糖尿病大鼠海马区神经细胞的线粒体膜电位和凋亡以及β淀粉样肽前体蛋白干预对其影响.设计完全随机分组设计,对照实验.单位首都医科大学宣武医院北京脑老化研究实验室和河北保定市第一中心医院内分泌科.材料实验中指标测定部分于2002-05/2002-08在解放军总医院仪器测试中心完成.动物造模及干预阶段在首都医科大学附属宣武医院动物室完成.选用Wistar雄性大鼠18只.将大鼠按随机抽签法分为3组,正常对照组,糖尿病模型组,β淀粉样前体蛋白17肽治疗组,每组6只.方法①糖尿病模型组和β淀粉样前体蛋白17肽治疗组大鼠禁食12 h后用pH值4.4链脲佐菌素按60mg/kg腹腔注射诱发糖尿病模型.3 d后测尾静脉血糖＞15 mmol/L为造模成功.正常对照组大鼠不造模.β淀粉样前体蛋白17肽治疗组于背部皮下注射β淀粉样前体蛋白17肽,3.4μg/只,每周3次,共10周.正常对照组及糖尿病组给予等量的生理盐水相同部位注射,每周3次,共10周.②满10周时,将大鼠麻醉,断头取脑后冰浴下取海马组织制备单细胞悬液,采用线粒体膜电位特异性荧光探针JC-1标记线粒体及Annexin-V-FITC&PI双染色技术,进行流式细胞仪上机检测线粒体膜电位和凋亡发生率.③数据间差异比较采用单因素方差分析.主要观察指标各组大鼠海马神经细胞线粒体膜电位和海马单细胞凋亡率比较结果.结果进入结果分析大鼠18只,每组6只.①海马神经细胞线粒体膜电位糖尿病模型组明显低于正常对照组[(551.91±53.36),(809.88±82.41)道,P＜0.01],β淀粉样前体蛋白17肽治疗组高于糖尿病模型组[(705.99±89.92)道,P＜0.05],与正常对照组相近(P=0.146).②海马单细胞凋亡率糖尿病模型组明显高于正常对照组和β淀粉样前体蛋白17肽治疗组[(5.32±1.37)%,(1.03±0.55)%,(2.80±0.92)%,P＜0.01,0.05].结论海马线粒体膜电位下降和细胞的凋亡可能参与糖尿病脑病的发生发展;β淀粉样前体蛋白17肽具有改善这一病理过程的作用.     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.