运动训练对实验性脑出血大鼠血肿周围组织细胞凋亡及海马CA1区超微结构的影响

目的观察运动训练后血肿周围组织细胞凋亡情况和组织学改变，以及海马CA1区超微结构方面的表现，以研究运动对出血性脑损伤细胞凋亡的影响及其改善神经功能的机制。 方法88只SD大鼠被随机分为3组，实验组（40只，出血并运动）、对照组（40只，出血不运动）和假手术组（8只，无出血，不运动），前两组又分为术后24 h、7 d、14 d、21 d、28 d等5个时相点，每个时相点取5只用于TUNEL检测及光镜观察，3只用于电镜观察。 结果实验组和对照组血肿周围、大脑皮质、海马等脑组织在ICH后24h出现典型的细胞凋亡特征（电镜及TUNEL染色），实验组不同时相点凋亡细胞数明显较对照组和假手术组减少（P<0.05），而血管增生却较对照组和假手术组更明显（光镜）。 结论运动训练可以通过抑制脑出血后血肿周围及海马区的神经细胞凋亡，增加血管再生，从而改善神经功能。     

脑出血周围组织细胞凋亡与bcl-2及bax蛋白表达的关系

目的：探讨脑出血灶周围组织中bcl-2，bax蛋白表达和细胞凋亡的关系。方法：SD大鼠70只。随机分为两组（实验组和对照组）。实验组采用胶原酶诱导大脑尾状核脑出血模型，分别于术后第6h、12h、24h、48h、72h、7d、14d，7个时相点（每个时相点5只）处死大鼠，运用TUNEL法、免疫组化SP技术，检测血肿周围脑组织中细胞凋亡及bcl-2．bax蛋白表达。结果：实验组细胞凋亡、bcl-2，bax蛋白表达与对照组有非常显著性差异（P〈0．01）．高峰期分别为脑出血术后第6h、48h。bcl-2蛋白表达与凋亡阳性细胞数呈负相关（r=-0．7628，P〈0．05），bax蛋白表达与凋亡阳性细胞呈正相关（r=0.8438，P〈0．01）。结论：脑出血灶周围脑组织中存在细胞凋亡，bcl-2，bax蛋白对凋亡具有调控作用。     

运动训练对出血性脑损伤细胞凋亡基因caspase-3及其蛋白表达的影响

目的： 观察运动训练对脑出血大鼠神经细胞凋亡基因caspase-3 及其蛋白表达的影响。方法：实验动物用健康雄性SD大鼠120只。随机分为3组，实验组（出血后运动，40只）、对照组（出血后不运动，40只）、假手术组（无出血不运动，40只）。各组又分为术后7d，14d，21d，28d共4个时相点，每个时相点5只用于免疫组化检测，5只用于RT-PCR 和Western印迹法检测。实验组于术后24h开始跑笼训练，其余大鼠在标准笼内自由活动。结果：①免疫组化结果：caspase-3阳性细胞表达为细胞胞浆着棕黄色，阳性细胞主要分布于血肿周围和大脑皮质的神经元。实验组随运动训练时间延长似乎有表达上调趋势，28d时表达虽有下降迹象，但仍处于较高水平。对照组表达水平较实验组更明显，但两组差异无显著性意义（P>0.05），实验组和对照组与假手术组相比差异有非常显著性意义（P<0.01）。②Western blotting和RT-PCR 结果与免疫组化一致。结论：caspase-3参与了脑出血后细胞凋亡的发生，但运动训练对caspase-3基因及其蛋白表达的抑制作用不明显。     

实验性脑出血血肿周围组织细胞凋亡的研究

目的探讨脑出血大鼠血肿周围组织细胞凋亡的发生、发展情况。方法64只SD大鼠被随机分为2组,实验组（56只）采用胶原酶诱导大脑尾状核脑出血模型,对照组（8只）为假手术组,实验组分为术后6h、12h、24h、48h、72h、7d、14d7个时相点,运用TUNEL、SP技术和电子显微镜检测血肿周围组织中细胞凋亡及caspase-3蛋白表达。结果TUNEL阳性细胞数在实验组6h时可见,24～48h表达明显,与对照组相比有显著性差异（P〈0.05）。caspase-3蛋白表达规律与TUNEL一致,但高峰时间早于TUNEL。透射电镜可见细胞凋亡形态学改变。结论脑出血后血肿周围组织存在神经细胞凋亡,且与caspase-3蛋白表达有关。     

运动训练对大鼠出血性脑损伤BDNF基因及其蛋白表达的影响

目的：观察运动训练对脑出血（ICH）大鼠脑源性神经营养因子（BDNF）及其蛋白表达的影响。方法：实验动物用健康雄性SD大鼠155只。其中120只随机分为3组：实验组（出血后运动n=40）、对照组（出血后不运动 n=40）、假手术组（无出血不运动n=40只）。各组又分为术后第7天、第14天、第21天、第28天共4个时相点，每个时相点5只用于免疫组化检测，5只用于RT-PCR检测。实验组大鼠于术后第72h开始跑笼训练，其余大鼠在标准笼内自由活动。另外35只随机分为脑出血后第6小时、 第12小时、 第24小时、 第48小时、第72小时，假手术和正常组，每组5只，用于免疫组化和RT-PCR检测。结果：①免疫组化结果：BDNF阳性细胞表达为细胞浆着棕黄色，阳性细胞主要分布于血肿周围和大脑皮质的神经元。脑出血后第12h BDNF曾一度升高，第72h基本恢复正常。实验组随运动训练时间延长表达有上调趋势，第28d达高峰，较对照组相比有差异有显著性（P<0.05），实验组和对照组与假手术组相比差异有显著性（P<0.05）。②RT-PCR 结果：实验组与对照组和假手术组的BDNFmRNA表达（第21—28d）相比差异有显著意义（P<0.05），但对照组与假手术组相比无显著性意义（P>0.05）。结论：BDNF参与了脑出血后神经可塑性的发生，运动训练可促进BDNF基因及其蛋白表达，从而改善神经功能。     

实验性脑出血后细胞凋亡与神经损伤的关系

目的 探讨脑出血后血肿周嗣组织细胞凋亡、Bcl-2和Bax蛋白表达与神经功能损伤的关系。方法 SD大鼠70只，随机分为实验组和对照组，每组各35只。实验组采用胶原酶诱导尾状核脑出血模型，分别于术后6h、12h、24h、48h、72h、7d、14d共7个时相点（每个时相点5只）评测其神经功能缺损情况。之后处死大鼠，采用TUNEL法、免疫组化SP技术，检测血肿周嗣脑组织细胞凋亡及Bcl-2，Bax蛋白的表达。结果脑出血后大鼠出现不同程度的神经功能缺损，以术后48h左右损害严重．出血后6h血肿周嗣组织出现TUNEL阳性细胞，48h达高峰。Bcl-2和Bax蛋白表达高峰期分别是脑出血术后6h和48h。结论 脑出血后细胞凋亡与神经损伤程度一致，细胞凋亡在脑出血后神经功能损伤中起重要作用。     

运动训练对出血性脑损伤微管相关蛋白-2基因表达的影响

目的观察运动训练对脑出血大鼠微管相关蛋白-2（MAP-2）基因表达的影响。 方法健康雄性SD大鼠160只。将其中96只随机分为实验组（出血后运动）、对照组（出血后不运动）、假手术组（无出血，不运动），每组32只，各组又分为术后7，14，21，28 d共4个时相点，每个时相点4只用于免疫组化检测，4只用于反转录聚合酶链反应（RT-PCR）检测。实验组大鼠于术后72 h开始跑笼训练，其余组大鼠在标准笼内自由活动。另外64只随机分为脑出血组（48只）、无出血组（8只）和正常组（8只），脑出血组又分为术后6,12,24,48,72 h和7 d共6个时相点，每个时相点8只，无出血组、正常组及脑出血组各时相点的4只大鼠用于免疫组化检测，4只用于RT-PCR检测。 结果①免疫组化结果：MAP-2阳性细胞表达为细胞胞浆着棕黄色，阳性细胞主要分布于血肿周围和大脑皮质的神经元。脑出血后24 h MAP-2开始上调，持续到7 d，与正常组和无出血组相比，差异有统计学意义（P<0.05）。实验组和对照组于术后14 d出现表达上调，28 d表达达高峰，但实验组表达上调更显著，2组间差异有统计学意义（P<0.05），2组与假手术组相比，差异有统计学意义（P<0.01）。②RT-PCR结果：脑出血后12~24 h MAP-2 mRNA有一短暂表达上调，与无出血组和正常组相比，差异有统计学意义（P<0.05），之后恢复接近正常。实验组术后14～28 d表达上调，与对照组和假手术组相比，差异有统计学意义（P<0.05，P<0.01），对照组在相同时间点同样有上调表现，与假手术组相比，差异有统计学意义（P<0.05）。 结论MAP-2参与了脑出血后神经可塑性的发生，且运动训练可促进MAP-2的表达，从而改善神经功能。     

运动训练对脑出血大鼠出血灶周围组织突触素表达的影响

目的观察运动训练对脑出血大鼠出血灶周围组织突触素（SYP）表达的影响。 方法健康雄性SD大鼠95只，其中60只随机分为实验组（出血后运动）、对照组（出血后不运动）、假手术组（无出血、不运动），每组20只，各组又分为术后7，14，21，28 d共4个时相点。实验组大鼠于术后72 h开始跑笼训练，其余大鼠在标准笼内自由活动。剩余35只随机分为脑出血后6,12,24,48,72 h组、无出血组和正常组，每组5只，用于免疫组化检测。 结果突触素阳性细胞主要分布于血肿周围和大脑皮质的神经元。突触素阳性物表达为细胞胞浆着棕黄色，在神经细胞表面排列呈环状或半弧形，在神经纤维间排列成大小不一、不规则团块状，少数神经纤维两侧排列成线状。出血灶中心无明显突触素阳性染色。对照组6~24 h表达减少，48 h后回升，7 d后表达增加，28 d时达高峰。实验组突触素阳性细胞表达更加显著，与对照组相比，差异有统计学意义（P<0.05）；实验组、对照组突触素阳性细胞表达与假手术组相比，差异有统计学意义（P<0.01）。 结论突触素参与了脑出血后神经可塑性的发生，运动训练可促进突触素蛋白表达，从而改善神经功能。     

氟桂利嗪干预后脑出血大鼠血肿周围神经元凋亡的变化

目的：观察大鼠脑出血后血肿周围神经元凋亡表达的变化规律及钙拮抗剂一氟桂利嗪的干预作用。 方法：实验于2003-03／09在解放军第三军医大学西南医院中心实验室完成。①取66只成年健康Wistar大鼠，随机分为正常组6只、脑出血组30只，氟桂利嗪治疗组30只；脑出血组及氟桂利嗪治疗组又分别于出血后0．5h，6h，24h，72h，120h5个时间点进行观察，每个时间点6只。②造模及给药：运用胶原酶法建立大鼠脑出血模型。氟桂利嗪药粉用生理盐水配成1g/L混悬液，出血前ld及出血后连续5d，氟桂利嗪治疗组大鼠1mg／kg腹腔内注射给药，1次／d。③观察指标：经末端脱氧核糖核苷转移酶介导的DUTP缺口末端标记法和二氨基联苯胺染色，测定脑出血后各时点血肿周围神经元凋亡表达。 结果：66只大鼠均进入结果分析。①脑出血后血肿周围凋亡细胞增多，0．5h开始升高（100．88&;#177;9．43）个／视野，6h明显增多（171．83&;#177;19．07）个／视野，24h达高峰（217．88&;#177;22．56）个／视野，72h血肿周围凋亡细胞数逐渐减少（164．50&;#177;14．07）个／视野，120h基本接近正常（54．00&;#177;12．46）个／视野。出血后各时间点与正常组（27．5&;#177;6．95）个／视野1比较差异有显著性意义（P〈0．01）。②氟桂利嗪治疗后0．5h，6h，24h，72h，120h TUNEL阳性细胞明显减少，分别为（81．17&;#177;11．29）个／视野，（101．67&;#177;10．54）个／视野，（129．83&;#177;9．28）个／视野，（71．5&;#177;16．27）个／视野，（30.67&;#177;8．09）个／视野，与脑出血组相应时点比较差异有显著性意义（P〈0．01）。结论：氟桂利嗪明显抑制脑出血后各时点血肿周围凋亡表达，对实验性脑出血神经元损伤起保护作用。     

大鼠脑出血后脑组织线粒体ATPase-6基因表达及TUNEL阳性细胞变化研究

凋亡参与了脑出血后的神经损伤机制，凋亡是一个需要能量的过程。但目前尚缺乏足够的直接证据证实脑出血后能量供应变化与凋亡发生的相关性。目的：研究脑出血后脑组织线粒体ATPase-6基因表达变化与细胞凋亡的相关性。设计：完全随机对照实验。地点和对象：实验在解放军第三军医大学野战外科研究所神经内科实验室完成，对象为Wister大鼠40只。干预：以50μL鼠尾血注入大鼠尾状核制作大鼠脑出血模型，注血后分别于12h,1,3,7d处死大鼠，断头取血肿周围脑组织；对照组仅进针不注血。用RT-PCR方法测定以上不同时相点大鼠脑出血后血肿周围水肿组织线粒体ATPase-6基因表达情况。TdT介导的dUTP缺口末端标记法检测TUNEL阳性细胞的表达。主要观察指标：各组大鼠线粒体ATPase-6基因表达，TUNEL阳性细胞表达。结果：出血后2h,1,3d线粒体ATPase-6基因表达较对照组下降，但差异不显著（P&;gt;0.05)。至第7天时表达明显下降（P&;lt;0.01)。TUNE阳性细胞在出血后12h开始表达[(24.33&;#177;2.50)个],3d达到高峰[(214.17&;#177;21.45)个，7d时仍持续较高水平（124.88&;#177;18.94)个].结论：脑出血早期血肿周围水肿组织线粒体ATPase-6基因表达无明显减少，晚期表达明显下降，在出血早期存在凋亡发生的能量基础。     

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.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

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.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.