冷保存-再灌注损伤对大鼠移植肝胆管上皮细胞凋亡及bcl-2/bax表达的影响

背景：移植肝胆管上皮细胞凋亡是影响肝移植后胆道功能恢复的因素之一，调控基因bcl-2/bax可能对胆管上皮细胞的生存起到决定作用。 目的：观察缺血-再灌注损伤后大鼠肝内胆管上皮细胞的凋亡及调控基因bcl-2/bax mRNA表达的变化。 设计、时间及地点：动物实验，细胞形态学观察，于2008-02/08在解放军第三军医大学西南医院肝胆外科研究所实验室完成。 材料：健康雄性Wistar大鼠100只，随机分为3组：供肝冷保存1 h组40只，冷保存12 h组40只，对照组20只。 方法：供肝冷保存1，12 h组，组内随机配对，体质量相对较轻的大鼠做为供体，供肝置于4 ℃器官保存液中，分别保存1、12 h后行原位肝移植，对照组只行开、关腹手术。在“两套袖法”基础上，以“支架法”建立动脉化大鼠原位肝移植模型，供受体肝总动脉采用改良“支架法”进行端端吻合，重建肝动脉血供。 主要观察指标：分别于移植后1，3，7，14 d检测血清总胆红素、碱性磷酸酶及肝内胆管上皮细胞的凋亡，实时荧光定量RT-PCR法检测胆管上皮细胞内bcl-2 mRNA 和bax mRNA的表达。 结果：保存1 h 组移植后1，3 d可见轻度胆道损伤的血清学及病理学表现，肝内胆管上皮细胞凋亡指数分别为(4.62?0.23)%, (3.42?0.22)%, (2.91?0.23)%，(2.87?0.16)%，且在移植后7 d即与对照组无明显差异。在保存12 h组移植后1，3，7 d，胆汁郁积征象明显，伴有严重的胆管损伤病理学改变，且肝内胆管上皮细胞凋亡指数明显高于保存1 h组和对照组，分别为(6.51?0.33)%, (8.52?0.36)%, (3.51?0.27)%，(2.91?0.28)%。在移植后各时相点，保存1 h组肝内胆管上皮细胞内bcl-2 mRNA/bax mRNA比值分别为(1.12?0.12)%，(1.34?0.13)%，(1.51?0.14)%，(1.60?0.15)%，在移植后7 d即接近对照组水平，而保存12 h组则为(0.90?0.08)%，(0.79?0.02)%，(1.36?0.12)%，(1.59?0.14)%，在移植后7 d仍明显低于保存1 h组和对照组，且与肝内胆管上皮细胞凋亡指数显著负相关（P =0.029）。 结论：冷保存时间延长导致胆道功能严重损伤，导致肝内胆管上皮细胞内bcl-2 mRNA/bax mRNA下调，促进移植后早期肝内胆管上皮细胞的凋亡。     

丹参对原位肝移植大鼠供肝冷保存再灌注损伤的保护作用☆

目的: 研究表明，丹参对心、脑、肝等重要器官的缺血再灌注损伤有保护作用。制备大鼠异体原位肝移植模型，验证丹参对大鼠肝移植缺血再灌流损伤的保护作用。 方法：实验于2006-10/2007-08在南方医院中心实验室及动物实验中心完成，动物实验方法符合动物伦理学要求。①实验材料及分组：选用SD大鼠40只，按随机数字表法分为假手术组、模型对照组和丹参注射液组，假手术组8只，模型对照组、丹参注射液组各8对（供体与受体）。②实验方法：建立原位肝移植模型，在供肝灌注冷保存时，以4 ℃ 乳酸林格氏液为基液，丹参注射液组灌注保存液中加60 mL/L丹参注射液；模型对照组不加丹参。③实验评估：移植术后6 h处死各组大鼠取样，检测血清谷草转氨酶、谷丙转氨酶及乳酸脱氢酶活性；测定肝组织中丙二醛含量及超氧化物歧化酶、谷胱甘肽过氧化物酶活性，并对比观察移植肝病理形态学改变。 结果：模型对照组和丹参注射液组16只受体大鼠及假手术组8只大鼠全部进入结果分析，无脱失。①丹参注射液组和模型对照组移植肝再灌注后血清谷丙转氨酶、谷草转氨酶及乳酸脱氢酶活性均高于假手术组(P < 0.01)；丹参注射液组低于模型对照组(P < 0.01)。②丹参注射液组肝组织中丙二醛含量较模型对照组明显下降(P < 0.01)，超氧化物歧化酶和谷胱甘肽过氧化物酶的活性则明显升高 (P < 0.01)。③丹参注射液组较模型对照组肝组织肝细胞坏死程度减轻，炎性细胞浸润减少，肝组织再灌注损害程度减轻。 结论：丹参对原位肝移植肝脏的缺血再灌注损伤有保护作用，从而减轻氧自由基及脂质过氧化，保护细胞膜，改善肝功能。     

供肝冷保存再灌注过程中肝细胞、肝窦内皮细胞及枯否细胞损伤的比较**☆

目的: 冷保存及再灌注损伤是决定移植物功能及受者存活率的重要因素之一，这与供肝冷保存再灌注过程中枯否细胞的活化及肝窦内皮细胞的损伤密切相关。建立大鼠同种异体原位肝脏移植模型，比较不同冷保存再灌注时间下供肝肝细胞、肝窦内皮细胞及枯否细胞的损伤情况。 方法：①实验于2005-12/2006-12在河南省实验动物中心及郑州大学第一附属医院肝移植实验室完成，实验方法符合动物伦理学要求。②选用Wistar大鼠63只，采用随机数字表法取7只大鼠为正常对照组，另外56只平分为供体组与受体组，两两配对后再分为供肝冷保存3 h，6 h，8 h和12 h组（每组供、受体各7只）。各冷保存组用4 ℃ Euro-collins液灌注和保存供肝，之后行同种异体原位肝移植。③于受体门脉复流后15，30，60 min检测各组大鼠肝窦内皮细胞损伤指标血清透明质酸、枯否细胞激活指标肿瘤坏死因子α含量及肝细胞损伤指标丙氨酸氨基转移酶、天冬氨酸氨基转移酶活性；观察受体门脉复流后60 min移植肝肝细胞、肝窦内皮细胞及枯否细胞的超微结构变化。 结果：63只大鼠均顺利完成模型建立，术中无异常死亡。①各冷保存组在门脉复流后15，30，60 min血清透明质酸、肿瘤坏死因子α含量均高于正常对照组（P < 0.05），并且随冷保存时间延长依次升高。②各冷保存组在门脉复流后15 min血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶活性与正常对照组无显著性意义（P > 0.05）；在门脉复流30 min后血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶活性高于正常对照组（P < 0.05）。③冷保存3 h及6 h组肝细胞结构基本正常，冷保存8及12 h组出现结构变化；而各冷保存组中，肝窦内皮细胞均有损伤并较肝细胞为重，枯否细胞均有激活表现。 结论：供肝冷保存再灌注过程中，肝窦内皮细胞的损伤及枯否细胞的激活明显早于并重于肝细胞损伤。     

E不同冷保存时间热缺血供肝在肝移植中的应用**☆

背景：目前国内临床肝移植供肝的主要来源仍然是无心跳供体供肝,国外近年来也越来越多地使用无心跳供体供肝,但无心跳供体供肝这类经历了热缺血的供肝能够耐受冷保存的安全时限尚没有统一标准,也鲜有这方面的临床报道。 目的：评价不同冷保存时间的热缺血供肝在临床肝移植中的应用安全性及疗效。 设计、时间及地点：随机对照观察,于2006-01/2007-12在中山大学附属第一医院器官移植中心完成。 对象：无心跳供体供肝热缺血时间在10 min内的肝移植病例154例。 方法：根据冷保存时间不同分为3组,8 h内组58例,8~12 h组62例,13~16 h组34例。供肝按供体分配原则按随机数字表法分配给3组患者,移植后采用相同的免疫抑制方案。 主要观察指标：比较3组患者肝移植后谷丙转氨酶峰值、原发性移植肝无功能、急性排斥反应、胆道并发症、血管并发症、感染,以及移植肝存活和受体存活情况的差异。 结果：随访8~32个月,3组患者移植后均未发生原发性移植肝无功能。8~12 h组患者移植后仅谷丙转氨酶峰值高于8 h内组(P < 0.05),其余治疗两组比较差异均无显著性意义(P > 0.05)。与8 h内组患者比较,13~16 h组患者的移植后谷丙转氨酶峰值、感染发生率和胆道并发症发生率显著升高(P < 0.05),移植肝存活率和受体存活率显著降低(P < 0.05)。 结论：热缺血时间在10 min内的无心跳供体供肝能够耐受12 h的冷保存损伤,超过此时限,移植后胆道并发症和感染的发生率明显升高,移植肝存活率和受体存活率明显降低。     

原位肝移植后胆管损伤的病理学改变

背景：肝移植术后胆道损伤引起的并发症是临床上诊治的难点，是抑制肝移植发展的瓶颈。 目的：在成功应用胆道内镜治疗肝移植术后胆道并发症的同时，对胆管的损伤进行观察记录并取活检病理，分析不同胆管损伤、组织病理学类型与肝移植术后胆管并发症的关系。 设计、时间及地点：病例分析，于2001-07/2005-10在大连市肝胆外科研究所，友谊医院肝胆外科完成。 对象：将19例肝移植术后患者根据胆管并发症发生情况分为3组：正常组4例，胆管损伤组12例，肝动脉损伤组3例。 方法：利用内镜技术，分别对3组患者进行胆管观察、记录，内镜下取活检进行病理分析。对于无T管者，应用子母胆道镜观察、取活检。 主要观察指标：应用胆道内镜观察T管造影、肝内外胆管黏膜外观及病理学检查结果、供-受体胆管吻合口的愈合情况。胆管损伤组经内镜取石、狭窄扩张治疗后行上述指标的复查。 结果：①正常组患者肝内外胆管解剖正常，无狭窄、瘢痕，胆管黏膜颜色正常，供-受体胆管吻合口愈合佳。病理学检查均可见修复性的黏膜组织，被覆上皮完整。②胆管损伤组患者胆管内有各种类型的单发、多发及铸型结石，胆管均有不同程度损伤，经内镜取净结石、解除梗阻后，胆管黏膜均有不同程度的修复，造影检查胆树恢复正常。③肝动脉损伤组患者胆管壁缺血坏死，丧失胆管的组织结构，明显充血，胆泥和结石完全灌满供体胆树，Ⅲ级胆管间断具有胆管的组织结构；病理学检查发现胆管壁弥漫坏死，结构不清，大量胆汁渗入，可见增生的肉芽组织和化脓灶。 结论：在原位肝移植中胆管均有不同程度的损伤，冷保存/再灌注损伤是导致胆管树损害最重要的始动因素，胆管周围血管丛的损伤和微循环障碍可能是胆管损伤的途径之一。     

碱性磷酸酶对大鼠自体原位肝移植后急性肺损伤的保护作用★

目的: 肝移植术后并发症不仅包括肝脏本身的损害，亦能导致肝外多个器官功能衰竭，其中肺脏是较易且较早受累的器官。文章通过建立大鼠自体原位肝移植模型，观察肝移植术后肺部急性损伤情况及碱性磷酸酶的干预作用。 方法:①实验于2007-05/10在南方医科大学附属南方医院实验动物中心、消化内科实验室完成，动物实验方法符合动物伦理学要求。②选用SD大鼠24只，按随机数字表法分为对照组、自体原位肝移植组和碱性磷酸酶组，每组8只。后两组建立大鼠自体原位肝移植模型，对照组开腹后游离肝叶后即关腹，碱性磷酸酶组于肝脏恢复血供前5 min自舌静脉注入碱性磷酸酶。③手术结束后2 h检测肺组织髓过氧化物酶活性、丙二醛含量、肺组织表面活性蛋白A含量及肺组织干湿重比值，并行肝脏、肺脏病理检查。 结果:大鼠24只全部进入结果分析。①自体原位肝移植组、碱性磷酸酶组肺组织中髓过氧化物酶活性、丙二醛含量均高于对照组（P﹤0.01），碱性磷酸酶组肺组织中髓过氧化物酶活性、丙二醛含量均低于自体原位肝移植组（P﹤0.01）。②碱性磷酸酶组、自体原位肝移植组肺组织表面活性蛋白A含量较对照组低，而碱性磷酸酶组较自体原位肝移植组有所升高。③自体原位肝移植组、碱性磷酸酶组肺组织干湿重比值均低于对照组（P﹤0.01），碱性磷酸酶组肺组织干湿重比值高于自体原位肝移植组（P﹤0.05）。④病理结果显示，肝移植后大鼠肝、肺组织受到明显损害，而碱性磷酸酶能减轻损伤程度。 结论:肝移植术后肺部确实存在急性损伤，而碱性磷酸酶对其具有保护作用。     

缺血预处理减轻大鼠减体积肝移植损伤并促进肝再生

背景：近年来,肝移植技术迅速发展,如何预防缺血再灌注损伤并有效保护肝再生成为研究的热点。缺血预处理是保护肝缺血损伤的有效方法,但其确切机制尚存争议。 目的：研究缺血预处理在大鼠减体积肝移植肝损伤和肝再生中的作用及机制。 方法：动物随机分为3组,肝移植组建立大鼠减体积肝移植模型。缺血预处理+肝移植组在供肝灌注前阻断第1肝门行缺血预处理10 min,再灌注15 min。假手术组在开腹后游离肝周韧带,然后关腹。分别于术后0.5,2,6,24 h取材。通过血清谷丙转氨酶水平和移植肝组织病理检查评估肝损伤。半定量免疫组织化学和western blot法测定氧化还原蛋白1表达水平,检测移植肝细胞增殖细胞核抗原评估肝再生情况。 结果与结论：与肝移植组相比,缺血预处 理+肝移植组术后6,24 h受体血清谷丙转氨酶明显降低(P < 0.05;P < 0.01)。病理学分析显示肝移植组术后24 h可见到门脉周围大量炎细胞浸润,肝窦扩张明显,肝组织损伤较重;而缺血预处理+肝移植组则损伤较轻。半定量免疫组织化学显示缺血预处 理+肝移植组移植肝中Ref-1蛋白表达明显增加,这一结果同样在westernblot检测中得到验证：缺血预处理+肝移植组移植肝术后24 h Ref-1蛋白表达较肝移植组明显增强 (P < 0.05)。同时,术后2,6和24 h 缺血预处理+肝移植组增殖细胞核抗原阳性细胞数较肝移植组明显增加(P < 0.05)。结果提示缺血预处理可减轻大鼠减体积肝移植术后早期移植物肝损伤并促进肝再生,这与Ref-1蛋白高表达密切相关。     

大鼠近交系间原位肝移植急性排斥模型的建立与评价

背景：目前国内常用的封闭群品系大鼠(SD与Wistar大鼠)所建立肝移植急性排斥模型并不理想,易产生肝移植耐受。 目的：通过二袖套法建立稳定的DA-Lewis大鼠原位肝移植急性排斥模型。 方法：实验分为两组：同基因组：Lewis-Lewis 24例;异基因组：DA-Lewis 24例。观察移植后一般情况及移植后存活时间,两组受体分别于移植后3,5,7,10 d随机取3只处死取标本,观察肝脏组织病理变化,测定天冬氨酸转氨酶、总胆红素、细胞因子水平变化。 结果与结论：同基因组大鼠无急性排斥反应表现,中位生存时间超过100 d,肝脏组织发生轻度形态学改变。异基因组大鼠移植后黄疸明显,中位生存时间为11 d,移植后第7天肝脏组织病理表现典型急性排斥反应(Banff国际标准)。同期相比异基因组天冬氨酸转氨酶、总胆红素、细胞因子水平均高于同基因组(P < 0.001)。提示,DA-Lewis是稳定的大鼠肝移植急性排斥模型,是研究肝移植排斥反应及免疫耐受的理想动物模型。     

直视下单人操作大鼠原位肝移植手术技巧探讨

背景：大鼠原位肝移植模型(rat orthotopic liver transplantation,ROLT)是一种非常有价值的模型,适用于肝脏移植器官保存、组织缺血再灌注损伤、移植免疫排斥反应及免疫耐受机制等方面的实验研究,稳定的肝移植动物模型是肝移植实验研究的基础。 目的：探讨直视下单人操作建立稳定大鼠原位肝移植模型的手术操作技巧。 设计、时间及地点：观察实验,于2008-12/2009-03在福州总医院动物实验中心完成。 材料：成年雄性Sprague-Dawley (SD)大鼠100只,体重200～250g,供体体重小于受体约20 g。 方法：采用“二袖套法”行大鼠原位肝移植,充分暴露腹腔,不翻动肝脏先行经腹主动脉供肝灌注;在体一步法离断肝上下腔静脉,不带膈肌环;吻合肝上下腔静脉采用单线连续缝合;橡皮泥固定法安装门静脉袖套,肝动脉不重建。术后充分补液维持大鼠血液动力学稳定。 主要观察指标：供体手术时间、供肝修整时间、受体手术时间、肝上下腔静脉吻合时间、门静脉袖套时间、肝下下腔静脉袖套时间、无肝期时间,受体1周、1月存活率,评价模型稳定性。 结果：供体手术时间(36.2 ± 2.5)min,供肝修整时间(12.2 ± 1.5)min、受体手术时间(45.6 ± 3.5)min、肝上下腔静脉吻合时间(10.1 ± 2.1)min、门静脉袖套时间(1.5 ± 0.9)min、肝下下腔静脉袖套时间(1.1 ± 0.6)min、无肝期(15.1 ± 2.2) min,手术成功率100％,1周存活率100％,1月存活率100%。 结论：稳定的麻醉、良好的供肝灌注、充分的暴露,熟练的显微外科操作及血管吻合技术,是确保模型成功的关键因素。     

丹参对大鼠移植肝血红素氧合酶1表达的影响*

背景：器官移植前使用丹参预处理能够保护组织缺血-再灌注损伤,改善移植器官存活率。 目的：观察含丹参的冷灌注液对同种异体大鼠移植肝脏中血红素氧合酶1表达的影响,以及对供体肝脏缺血-再灌注损伤的保护作用。 方法：将SD雄性大鼠随机分成UW液组(术中使用UW液灌注保存)、丹参+UW液组(术中使用丹参+UW液灌注保存)、ZnPP预处理组(移植前24 h腹腔内注射ZnPP,术中使用丹参+UW液灌注保存),建立稳定的大鼠同种异体肝移植模型。同时取10只正常大鼠作为正常对照。 结果与结论：丹参+UW液组和UW液组血清总胆红素、谷丙转氨酶、谷草转氨酶水平明显低于ZnPP预处理组(P < 0.01)。血红素氧合酶1mRNA及其蛋白在丹参+UW液组中较UW组表达更明显,在ZnPP预处理组中表达明显受到抑制(P < 0.05)。丹参+UW液组肝脏Suzuki标准评分明显低于ZnPP预处理组及UW液组(P < 0.05)。表明丹参能上调同种异体的大鼠移植肝脏中血红素氧合酶1 mRNA及其蛋白的表达,减轻供肝缺血-再灌注损伤,保护移植大鼠肝脏。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.