黑质内注射脂多糖对多巴胺能神经元和小胶质细胞活性的影响

目的：观察脂多糖（LPS）对黑质多巴胺能神经元的损毁作用以及对小胶质细胞活性的影响。方法：60只雌性SD大鼠随机分为正常组、1d组、1周组、2周组和2个月组各12只，除正常组外，其余各组采用立体定向技术向大鼠单侧黑质内注入LPS，于注药后1d、1周、2周和2个月时分别经腹腔注射阿朴吗啡诱发动物旋转行为为造模成功；按各组不同时间点观察大鼠黑质酪氨酸羟化酶（TH）阳性细胞数变化和小胶质细胞活化过程、纹状体和黑质部位多巴胺（DA）及其代谢产物含量及黑质变性神经元。结果：单侧黑质内注入LPS后的各组黑质TH＋细胞数分别较对侧减少12％～71．5％；其损伤侧纹状体和黑质DA及其代谢物含量降低28．2％～65．7％（均P〈0．05～0．01）；1周组Fluoro—jadeB染色可见染色阳性神经元；LPS注射的各组黑质均可见活化的小胶质细胞。结论：黑质注入LPS可诱导小胶质细胞活化和黑质多巴胺能神经元变性死亡。     

热休克蛋白70在大鼠黑质多巴胺神经元损伤中的表达

目的 :探讨热休克蛋白 70 (HSP70 )在大鼠黑质多巴胺 (DA)神经元损伤中的表达以及在帕金森病 (PD)诊断中的意义。方法 :将 48只大鼠随机分为黑质DA神经元损毁组 (PD组 )和对照组各 2 4只。PD组注射 6 羟多巴胺 (6 OHDA)损毁大鼠黑质DA神经元 ,对照组仅注射 6 OHDA溶媒。于注射后 1、7、14及 2 1d采用免疫组织化学、尼氏染色、电镜手段动态观察HSP70在损毁的DA神经元中的表达以及DA神经元形态学变化。结果 :在 6 O HDA损毁黑质 1～ 2 1d ,对照组黑质HSP70表达和尼氏细胞计数差异无显著性 (P >0 .0 5 )。PD组HSP70表达在 1d最高 ,7d锐减 ,14和 2 1d则逐渐减少 ,分别为 2 5 %、74%、87%及 88% ;尼氏细胞计数在 4个时间点分别减少1%、13%、35 %及 48% ;超微结构损伤程度呈进行性加重。结论 :PD渐进性发病具有其形态学基础 ,HSP70可作为DA神经元存活的指标和早期诊断PD的指标。     

正常及帕金森病大鼠黑质细胞凋亡与左旋多巴剂量相关性的实验研究

目的 研究左旋多巴对黑质细胞的神经毒性作用。探讨合理应用左旋多巴治疗帕金森病的方法。方法 通过6-羟基多巴胺脑立体定向注射术制作大鼠帕金森病模型。采用TUNEL方法观察左旋多巴小（每天每公斤10mg)，中（每天每公斤50mg)，大（每天每公斤100mg)三种不同剂量，不同的作用时间（1d,3d,5d,7d)对帕金森病大鼠黑质细胞的毒性作用，并观察治疗后7d各项指标的变化。结果 帕金森病大鼠细胞凋亡数随着左旋多巴治疗的时间，剂量增加而增加。结论 左旋多巴能加速帕金森病大鼠黑质细胞凋亡，小剂量，间隔使用左旋多巴能有效减少其神经毒性作用。     

帕金森病大鼠黑质细胞凋亡与Bax蛋白表达相关性的实验研究

目的：观察6-羟基多巴胺（6-OHDA）能否诱发黑质细胞凋亡以及Bax蛋白表达与黑质细胞凋亡的关系。方法：72只Wistar雄性大鼠随机分为对照组36只及通过脑立体定位注射60HDA的方法建立的大鼠帕金森病模型组（PD）组36只，采用TUNEL方法、免疫组织化学、电镜等观察术后l、7、14及21d时2组大鼠脑黑质细胞凋亡的数量及超微结构变化，并检测黑质细胞Bax蛋白的表达。结果：术后TUNEI．法发现，与对照组比较，PD组存在明显的黑质细胞凋亡（P％0．05），且在1—21d时细胞凋亡数逐渐增高；电镜观察显示，PD组黑质细胞存在典型细胞凋亡，Bax蛋白表达在ld为最高，其后很快下降，但仍显著高于对照组。结论：6-羟基多巴胺能诱发大鼠黑质细胞凋亡，Bax蛋白是黑质细胞凋亡的关键启动因素。     

6-羟基多巴胺诱发大鼠黑质细胞凋亡的实验研究

目的：为了解证实细胞凋亡参与了帕金森病（Parkinson disease,PD)的发病和黑质细胞凋亡的调控因素。方法：通过脑立体定位注射6－羟基多巴胺（6－OHDA）建立大鼠PD模型。采用TUNEL法、原位杂交技术、电镜观察等，选择6－DHDA注射术后1、3、5、7、14及21d为研究时点，观察大鼠PD模型形成过程中黑质细胞凋亡的数量及超微结构变化情况，并检测黑质细胞Bcl-2 mRNA、P53 mRNA表达情况及铁的浓度。结果：用TUNEL法发现黑质细胞存在细胞凋亡，与对照组比较差异有显著性（P＜0．05），7d 细胞凋亡数为最高，21d最低；电镜观察在此过程中黑质细胞存在典型的细胞凋良，并逐渐加重;Bcl-2和铁随时间增加而升高，P53则在1d为最高，其后很快下降，但都高于对照组（P＜0．05）。结论：6－OHDA能诱发大鼠黑质细胞凋亡，细胞凋亡参与了PD发病，并受到Bcl-2、P53和铁的影响。     

帕金森病大鼠黑质细胞凋亡与左旋多巴剂量的关系

目的 研究左旋多巴对黑质细胞的神经毒性作用，探讨左旋多巴治疗帕金森病(PD)的最佳方案。方法 选用Wistar大鼠，采用改良的Thomas方法，用6-OHDA行脑立体定向注射术制作大鼠帕金森病(PD)模型100只，随机分为两大组：PD模型组(n=25)、L-dopa治疗组(n=75)，采用TUNEI。方法 观察左旋多巴小、中、大3种不同剂量[10，50，100mg／(k&;#183;d)]、不同的作用时间(1，3，5，7d)对帕金森病大鼠黑质细胞的毒性作用，并观察治疗后7d各项指标的变化。结果 同一时点PD大鼠黑质细胞凋亡数随着左旋多巴治疗的时间、剂量增加而增加；1～7d小剂量组：从(412&;#177;35)个／mm^2减少到(403&;#177;22)个／mm^2，中剂量组从(468&;#177;33)个／mm^2增加到(605&;#177;37)个／mm^2．大剂量组从(759&;#177;61)个／mm^2减少到(486&;#177;37)个／mm^2；7～14d各时点减少。结论 左旋多巴能加速PD大鼠黑质细胞凋亡，小剂量、间隔使用左旋多巴能有效减少其神经毒性作用。     

烟草成份保护多巴胺神经元作用的研究

目的：探讨烟草成份保护多巴胺神经元对抗6－羟基多巴胺（6－OHDA）的神经毒性作用。方法：采用大鼠脑内立体注射6－OHDA建立帕金森病模型，连续观察术前4周开始分别给予被动吸烟和腹腔注射尼古丁（每次0.1mg/kg或0.4mg/kg,bid，持续6周）对阿朴吗啡诱发的旋转行为，纹状体多巴胺（dopamine,DA)的含量和黑质酪氨酸羟化酶（Tyrosine Hydroxylase,TH）阳性神经细胞数目的影响。结果：被动吸烟和腹腔注射尼古丁的大鼠旋转行为明显减少，受损侧纹状体DA含量和黑质TH阳性神经元的数目较对照组增高（P＜0．01），高剂量尼古丁作为更为显著。结论：烟草成份可减轻6－OHDA对黑质DA神经元的损伤。     

颞叶癫痫模型中黑质多巴胺能神经元变化的实验研究

目的：建立颞叶癫痫模型．探讨颞叶癫痫模型中黑质多巴胺能神经元的改变。方法：实验于2004—05／09在解放军第一军医大学珠江医院进行。取SD大鼠43只，设空白对照组，生理盐水组，红藻氨酸组。生理盐水组及红藻氨酸组大鼠于右侧侧脑室分别注射生理盐水(2mL)和红藻氨酸(5μg)，于给药后第0．5，2．0，12．0，24．0和72．0h处死；取黑质部切片作免疫组织化学检测，根据记录阳性细胞数作半定量检测。结果：对照组及生理盐水组无癫痫发作。红藻氨酸组大鼠均出现癫痫发作，发作于脑室注射红藻氨酸后10min开始，1h达高峰，3—6h后停止。癫痫发作后0.5h开始伴随有黑质多巴胺能神经元阳性细胞数[(80.00&;#177;9．15)个]减少，与生理盐水组【(119．02&;#177;12．02)个】相比其差异有显著性意义(t=4．93l，P=0．003)，2—6h持续下降，3d后细胞数接近正常，与生理盐水组相比其差值没有统计学意义(P&;gt;0.05)。结论：一侧侧脑室注入红藻氨酸，可成功建立癫痫模型。红藻氨酸致痫后伴有黑质多巴胺阳性细胞数的改变，提示黑质多巴胺能神经元可能在颞叶癫痫活动中参与了调节作用。     

脂多糖诱导帕金森病模型中炎症因子的机制

目的：探讨脂多糖诱导帕金森病大鼠模型过程中肿瘤坏死因子α、白细胞介素1β、诱导型一氧化氮合酶等细胞毒性因子的作用。方法：实验于2003-07／2004-07在中山大学附属第一医院神经科实验室进行,取35只雄性SD大鼠随机分为4组：7，14，30d组，每组10只，对照组5只。对照组不做任何处理，3个不同时间点组立体定位注射脂多糖(20μg，质量浓度5g／L)入大鼠黑质。于注射后不同时间点观察大鼠行为学改变，并采用免疫组织化学及原位杂交等方法动态观察酪氨酸羟化酶神经元、肿瘤坏死因子a、白细胞介素1B、诱导型一氧化氮合酶等的表达。结果：29只动物进入结果分析。①行为学改变：脂多糖术后7d仅表现为轻度的旋转，每30min旋转(85&;#177;13)r，至14d时旋转次数增多，每30min旋转(121&;#177;17)r，30d时达高峰，每30min旋转(295&;#177;21)r。②7，14，30d组术侧黑质酪氨酸羟化酶阳性神经元数量较正常组明显下降(P&;lt;0．001)，30d组下降达高峰；正常组仅有少量或无肿瘤坏死因子α、白细胞介素1β、诱导型一氧化氮合酶的表达，术后7d各阳性神经元表达较正常组显著增多(P&;lt;0．05)，术后14d表达至高峰，术后30d较14d明显下降但仍高于正常对照组，其中诱导型一氧化氮合酶阳性神经元表达于术后30d仍维持较高水平。③各组均检测到酪氨酸羟化酶mRNA表达，7，14，30d组表达数量较正常组明显下降(P&;lt;0．01)，30d组其表达下降达高峰(P&;lt;0．001)。正常组有少量肿瘤坏死因子d、白细胞介素1B、诱导型一氧化氮合酶mRNA表达，术后7d表达明显增加，术后14d达高峰，术后30d组肿瘤坏死因子d、白细胞介素1BmRNA表达明显降低，诱导型一氧化氮合酶mRNA表达仍维持较高水平。结论：脂多糖可诱导肿瘤坏死因子α、白细胞介素1β、诱导型一氧化氮合酶等细胞毒性因子的释放，其表达高峰期明显早于多巴胺能神经元显著减少期，提示这些细胞毒性因子在多巴胺能神经元变性过程中起协调作用，加重神经元的损害，促进帕金森病的发展，提示抑制免疫和炎症过程可能有效阻断或减轻这种恶性循环的病理过程。     

胆红素脑病仔兔黑质-纹状体系神经元计数及超微结构的研究

目的 探讨胆红素对黑质—纹状体系神经元的毒性作用及损伤程度。方法 30只纯系日产大耳白仔兔随机分为3组：对照组(C组，6只)腹腔注射生理盐水1m1，注射后6小时灌杀；模型1组(N1组，12只)腹腔注射胆红素100mg／kg，分别于给药后6小时(N1α组，6只)、16小时(N1b组，6只)灌杀；模型2组(N2组，12只)腹腔注射胆红素200mg／kg，分别于给药后6小时(N2a组，6只)、16小时(N2b组，6只)灌杀。用图像分析仪进行细胞计数，电镜分析超微结构变化。结果 N1b组黑质神经元数少于C组、N1a组(P＜0．05)，N2b组黑质神经元数明显少于N1b、N2a组(P＜0．05)的黑质—纹状体系神经元数量减少，神经元超微结构有不同程度的改变。结论 胆红素能减少黑质—纹状体系神经元数量，且剂量越大、时间越长，减少越明显；胆红素脑病时黑质、纹状体系神经元超微结构改变明显，且剂量越大、时间越长损伤越重；黑质、纹状体系的形态、计量学变化呈现一致性。     

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.     

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.