大鼠胫骨骨折愈合过程中Ⅰ，Ⅱ型胶原蛋白的表达：失神经状态下Western blot方法测定

背景: 近年来大量的实验及临床观察均证实神经因素对骨折愈合有调节和支配作用。Ⅰ型胶原是促成骨细胞分化和增强成骨细胞黏附能力主要因素，是组成骨构架的基质蛋白；而Ⅱ型胶原由软骨细胞产生。 目的：观察失神经状态下骨折愈合过程中Ⅰ，Ⅱ型胶原蛋白表达的变化规律。 设计、时间及地点：随机对照动物实验，于2005-05/12在解放军第二军医大学动物实验室及细胞生物教研究室完成。 材料：选用3月龄健康雄性SD大鼠40只，采用随机数字表法分为2组，单纯胫骨骨折组与脊髓损伤并胫骨骨折组各20只。 方法：单纯胫骨骨折组大鼠于从左胫骨平台前缘插入1根φ0.8 mm克氏针，制成胫骨骨折模型。脊髓损伤并胫骨骨折组在植备上述模型的基础上，横断切除T10 段脊髓约0.3 cm，制成T10脊髓完全性损伤大鼠胫骨骨折模型。 主要观察指标：分别于伤后1，2，4，5周采用Western blot法检测两组大鼠骨折断端骨痂中Ⅰ，Ⅱ型胶原的蛋白表达。 结果：伤后第1周两组大鼠骨折断端骨痂中Ⅰ，Ⅱ型胶原均有表达，脊髓损伤并胫骨骨折组两种胶原的表达程度均高于单纯胫骨骨折组(P < 0.05)；伤后第2周脊髓损伤并胫骨骨折组Ⅱ型胶原的表达量达到峰值，高于单纯胫骨骨折组(P < 0.05)；伤后第4周单纯胫骨骨折组Ⅰ型胶原表达量达峰值，高于脊髓损伤并胫骨骨折组(P < 0.05)，脊髓损伤并胫骨骨折组Ⅱ型胶原仍有高表达；伤后第5周两组Ⅰ，Ⅱ型胶原表达量均下降。 结论：失神经状态下骨折愈合过程中Ⅰ、Ⅱ胶原的分泌规律与正常骨折愈合一致，区别在于各时间点尤其是在峰值点上表达量有明显差异。     

毛囊单位移植促进创面愈合

背景：皮肤创伤后毛囊真皮鞘细胞可能直接参与真皮损伤的修复或者转化为成纤维细胞参与皮肤修复。 目的：建立大鼠毛囊单位创面移植模型，对创面愈合过程中真皮成分的生长进行组织学和超微结构观察和分析，拟探索毛囊组织参与创面真皮愈合的潜力。 设计、时间及地点：对照动物实验，于2007-09/2008-04在复旦大学附属中山医院完成。 材料：体质量为200~250 g的18只SD大鼠用于制备毛囊单位创面移植模型及微粒表皮移植模型。 方法：剪取毛囊单位创面移植组大鼠单侧鼠须垫皮肤，伤口原位缝合，用锐器分割鼠须垫毛囊，切取带有毛囊乳头、毛囊周围组织及部分表皮的毛囊单位复合组织。将毛囊单位植入制备好的创面上，每个创面放入5~7个毛囊单位；切取微粒表皮移植组大鼠全层皮肤中剪切取表皮和部分真皮层皮肤，并修剪成约3 mm×3 mm大小，原位植入创面中，每个创面放入5~7个微粒皮片。 主要观察指标：第2，3，4，5周取创面标本，行苏木精-伊红染色、苦味酸天狼猩红染色，制作碱性水处理的扫描电镜标本，在偏振光显微镜和扫描电镜下观察，用图像软件处理并分析。 结果：创面愈合的初期，两组的创面分泌的胶原基质的类型与量均无明显差异。但随着创面愈合的进行，创面中胶原基质发生重塑性的改变，两者创面中基质的Ⅲ型胶原开始减少，Ⅰ型胶原相应增加。在创面形成后第5周时观察到毛囊单位移植组与微粒表皮移植组的Ⅰ型和Ⅲ型胶原的比值均有不同程度增加，对照组增加更明显，二者差异显著（P < 0.05）。用碱性水处理的扫描电镜方法对晚期创面基质的观察也发现毛囊单位移植的创面基质中胶原纤维由粗细不等的纤维交织而成，胶原纤维的排列较致密有序，仍保持了一定的方向性。 结论：在创面形成后期毛囊单位移植的愈合创面中胶原比值更接近正常皮肤，胶原排列更整齐有序，提示毛囊单位创面移植提高创面愈合的长期效果好。     

烧伤创面愈合过程中胶原代谢与针刺作用的影响

背景：针刺可促进烧伤创面愈合，但对创面组织胶原代谢的影响尚不清楚。 目的：观察针刺对烧伤创面愈合过程中胶原代谢的影响。 设计、时间及地点：随机对照动物实验，于1997-01/2005-12在广州市创伤外科研究所完成。 材料：雌性新西兰大白兔27只，体质量2.0~2.5 kg，用于制备深Ⅱ度烧伤模型。 方法：每个兔背部脊柱两旁造成10个创面。实验分为3组，正常组(n=3)：只背部剃毛备用；常规治疗组：伤后自由进食，创面外用25 g/L的碘伏暴露；针刺组：在常规治疗的基础上，伤后24 h内开始针刺治疗，取双侧“足三里 (ST36)”穴，针刺后接电针仪，频率20 Hz，时间30 min，1次/d。伤后3，7，13，21 d常规治疗组和针刺组各取3只动物处死，取组织待测。 主要观察指标：各组动物不同时间点创面组织中羟脯氨酸水平。 结果：27只大白兔均进入结果分析。烧伤后13 d常规治疗组和针刺组创面组织中羟脯氨酸水平均低于正常皮肤组织(P < 0.05)。伤后21 d 常规治疗组创面组织中羟脯氨酸达到正常皮肤组织水平，两组相比差异无显著性意义(P > 0.05)。而针刺组创面组织中羟脯氨酸水平高于常规治疗组和正常皮肤组织 (P < 0.05)。 结论：针刺可促进烧伤创面胶原的合成。     

皮肤全层缺损真皮修复不同阶段对表皮再生的影响

背景：当前组织工程研究多着重表皮干细胞和真皮支架材料的研究,而少有真皮新生速度和真皮修复不同时期组织结构对表皮新生和重建影响的报道。 目的：观察真皮修复过程中对表皮修复和重建的影响以及是否有促进表皮修复速度的最佳阶段。 方法：新西兰大耳白兔10只分别于第0,7,14天在背部制成3个直径约为3 cm的创面,随机分为0,7,14 d组,每组计10个创面,3组创面分别于皮肤全层损伤修复后21,14,7 d植入自体表皮细胞羊膜载体复合膜。7 d后取材,采用大体观察、常规组织学观察(苏木精-伊红染色,Mallory PTAH染色)、Ⅰ型胶原免疫组织化学观察等化学染色动态观察创面愈合情况。 结果与结论：0 d组创面与周边正常有毛皮肤齐平,与周边组织连接明显较7 d组及14 d组紧密,7 d组尚有凹面,而14 d组创面凹陷明显较7 d组大而深,与周边组织分界明显,这表明0 d组皮肤缺损的修复效果明显优于其他2组(P < 0.05)。 0 d组Ⅰ型胶原阳性的成纤维细胞、血管及胶原纤维等组成的真皮网状层和乳头层较其他2组明显(P < 0.05),创面愈合率高(P < 0.05)。真皮修复的不同时期,对表皮再生的促进作用存在不同,全层皮肤缺损处于真皮修复的增生晚期与重建初期是促进表皮新生的最佳阶段。 关键词：表皮再生;羊膜;碱性成纤维生长因子;维生素C;皮肤缺损;皮肤组织工程     

骨质疏松性骨折愈合过程中Ⅰ，Ⅱ型胶原蛋白表达与其力学性能*☆

背景：研究显示骨质疏松症是涉及Ⅰ型胶原数量及理化性质改变的一种复杂病理生理过程，但有关骨质疏松与Ⅰ，Ⅱ型胶原间的相关性，至今少有报道。 目的：观察骨质疏松性骨折愈合中Ⅰ，Ⅱ型胶原蛋白表达的变化规律，及其与生物力学性能的相关性。 方法：将大鼠随机分为骨质疏松性骨折组与一般性骨折组。骨质疏松性骨折组切除卵巢建立骨质疏松模型。分别于骨折损伤后1，2，4，5，8，12 周采用Western blot 方法检测骨痂中Ⅰ，Ⅱ型胶原的蛋白表达，于损伤后4，8，12，16 周进行骨密度测定与生物力学性能测试。 结果与结论：骨质疏松性骨折组Ⅰ，Ⅱ型胶原的表达及骨密度值在损伤后各时间点与一般性骨折组相比均差异有显著性意义(P < 0.05)，且随着损伤时间的延长，下降趋势更明显。骨质疏松性骨折组中Ⅰ，Ⅱ型胶原与最大转矩、弹性模量、最大扭转角均有相关性(P < 0.05)。结果显示，骨质疏松性骨折愈合过程中Ⅰ，Ⅱ型胶原的分泌异常改变导致了其力学强度乃至骨折愈合质量的降低，影响骨折愈合，是再次骨折发生的主要原因。     

转染血管紧张素Ⅰ骨髓间充质干细胞复合胶原构建组织工程皮肤修复烫伤后的创面

背景：组织工程皮肤作为可行的皮肤替代物,近年来已成为研究和开发的热点,为烧伤、皮肤溃疡等病变的创面治疗提供了新的解决途径。 目的：观察转染血管紧张素Ⅰ基因的骨髓间充质干细胞复合胶原构建的组织工程皮肤对烫伤后创面的修复及促血管形成作用。 设计、时间及地点：随机对照动物实验,于2008-03/11在中山大学第一附属医院实验动物中心完成。 材料：鼠龄4周的雄性SD大鼠45只,体质量120~150 g,用于制备烫伤模型;牛Ⅰ型胶原为美国Sigma公司产品。 方法：脂质体介导质粒pEGFP-N1-hAng-Ⅰ转染大鼠骨髓间充质干细胞,转染后与牛Ⅰ型胶原复合,体外构建组织工程皮肤,修复大鼠烫伤模型创面。45只SD大鼠按随机抽签法分为3组：血管紧张素Ⅰ/胶原移植组、骨髓间充质干细胞/胶原移植组和空白对照组,每组15只。在烫伤创面分别植入复合骨髓间充质干细胞/转血管紧张素Ⅰ的组织工程皮肤、单纯骨髓间充质干细胞复合的组织工程皮肤。空白对照组不移植任何组织和细胞,其他处理与实验组相同。 主要观察指标：分别在移植后3,7,14,28 d取材,以扫描电镜、组织学、免疫组织化学分析等方法检测构建的组织工程皮肤结构、创面修复及血管再生情况。 结果：pEGFP-N1-hAng-Ⅰ在阳离子脂质体的作用下,成功地进入大鼠骨髓间充质干细胞,转录出相应mRNA。蛋白免疫印迹分析显示转染细胞有与目的基因相对分子质量相符的血管紧张素Ⅰ抗体结合蛋白印迹条带。实验所构建的组织工程皮肤结构完整,细胞状态良好。血管紧张素Ⅰ/胶原移植组、骨髓间充质干细胞/胶原移植组和空白对照组创面的愈合时间分别为(12.6±1.9),(15.4±2.3),(26.4±3.6) d,P < 0.05。组织学检查见转染细胞组毛细血管生长及新形成活跃,移植后7,14,28 d骨髓间充质干细胞/胶原移植组和血管紧张素Ⅰ/胶原移植组微血管密度分别为(22.8±1.4),(34.3±2.6),(57.4±6.1)条/mm2;(38.2±3.4),(53.2±5.8),(74.2±6.9)条/mm2,P < 0.05。 结论：血管紧张素Ⅰ转染细胞组较对照组血供加强,创面修复加速,与细胞因子局部定向释放,加强血管形成有关。     

生肌玉红胶原海绵修复创面损伤

背景：生肌玉红胶原海绵能显著促进创面愈合。 目的：观察生肌玉红胶原海绵对兔皮肤创面愈合的影响。 方法：在新西兰白兔背部制造3处全层皮肤缺损创面,分别以生肌玉红胶原海绵、贝复剂(重组碱性成纤维细胞生长因子外用溶液)、生理盐水修复。观察各组创面愈合时间、创面愈合率,检测创面修复组织内成纤维细胞数、血红素氧化酶1、转化生长因子β1 mRNA与蛋白及增殖细胞核抗原蛋白表达。 结果与结论：与贝复剂、生理盐水比较,生肌玉红胶原海绵可显著促进成纤维细胞增殖(P < 0.05),增加创面血红素氧化酶1、转化生子因子β1及增殖细胞核抗原的表达(P < 0.05),提高创面愈合率(P < 0.05),缩短创面愈合时间(P < 0.05)。证实生肌玉红胶原海绵能够促进创面修复,其作用机制可能是通过提高创面血红素氧化酶1、转化生长因子β1表达促进细胞增殖,增加成纤维细胞等创面修复细胞。     

自体富血小板血浆凝胶修复儿童面部Ⅱ度烧伤创面

背景：富血小板血浆可用凝血酶凝固成胶冻状，不仅可以黏合组织缺损处，还可以防止血小板流失，使血小板在局部长时间分泌生长因子，避免了目前广泛应用于临床的液态重组生长因子试剂在伤口及移植区易流失易蒸发的缺点。 目的：观察外用自体富血小板血浆在儿童面部Ⅱ度烧伤创面修复过程中的治疗作用。 方法：选择2008-01/2010-01在广西昭平县人民医院外科收治的14岁以下面部浅Ⅱ度烧伤、深Ⅱ度烧伤儿童各30例。均以左侧面部为治疗组，右侧为对照组。伤后第3天，治疗组将自体富血小板血浆凝胶直接湿敷于创面上半暴露，换药1次/d；对照组创面单用等渗盐水纱布覆盖半暴露，换药1次/d。干预7，14 d观察两组患者创面愈合率、愈合时间、疼痛与瘢痕情况及不良反应。采用目测类比评分法评估疼痛情况，改良温哥华瘢痕测量法测定深Ⅱ度创面瘢痕增生情况。 结果与结论：在浅Ⅱ度烧伤创面患者中，治疗组7 d愈合率明显高于对照组(P < 0.05)，愈合时间明显短于对照组(P < 0.05)；在深Ⅱ度烧伤创面患者中，治疗组14 d愈合率明显高于对照组(P < 0.05)，愈合时间显短于对照组(P < 0.05)，瘢痕指数明显低于对照组(P < 0.05)；两组患者创面疼痛评分无明显差别。说明外用自体富血小板血浆凝胶能显著加快儿童面部Ⅱ度烧伤创面愈合速度，缩短愈合时间，提高愈合质量，减少瘢痕形成，无明显不良反应。     

经皮电刺激大鼠骨骼肌失神经肌萎缩时成肌调节因子基因的表达

背景：在去神经早期大鼠骨骼肌成肌调节因子(MyoD)表达明显上调,有明显延缓骨骼肌肌萎缩的作用。临床实验证实电刺激是治疗失神经肌萎缩的有效方法。尚未有实验证实电刺激对失神经肌萎缩MyoD表达的影响。 目的：验证电刺激对大鼠骨骼肌MyoD基因表达的影响。 设计、时间及地点：随机对照动物实验,于2008-07/11在山西医科大学动物实验中心完成。 材料：健康的SD大鼠36只,雌雄不限。随机分成3组,即空白对照组、去神经组、电刺激组,每组12只。 方法：空白对照组不做任何处理;去神经组和电刺激组大鼠制作右侧坐骨神经离断,腓肠肌失神经支配模型。用电刺激对电刺激组进行刺激,1次/d,30 min/次。分别于去神经第2,7,14,28天,处死大鼠,取小腿的腓肠肌肉标本。 主要观察指标：用反转录聚合酶链式反应技术检测MyoD mRNA的表达变化,免疫组织化学检测MyoD蛋白表达的变化。 结果：在去神经支配后第2,7,14,28天,去神经组和电刺激组标本中MyoDmRNA和蛋白含量表达上调,与空白对照组比较差异有显著性意义(P < 0.05),电刺激组表达高于去神经组(P < 0.05)。 结论：通过电刺激可以上调大鼠腓肠肌失神经模型MyoD的表达,说明电刺激是延缓骨骼失神经肌萎缩的有效方法。     

偏光显微镜观察发育性髋关节脱位圆韧带组织的病理变化

背景：发育性髋关节脱位与关节囊、韧带等致密结缔组织细胞外基质中的胶原蛋白有密切关系。 目的：观察发育性髋关节脱位与正常儿的髋关节圆韧带的形态学特点，分析Ⅰ型和Ⅲ型胶原含量及二者比例(Ⅰ/Ⅲ)变化规律。 设计、时间及地点：分组对照观察，于2006-10/2007-03卫生部先天畸形实验室完成。 对象：选择2005-06/2006-08在中国医科大学附属盛京医院儿童骨科住院并第1次手术发育性髋关节脱位患儿21例。根据术前X射线片按Tönnis标准分3组，髋臼发育不良组3例、髋关节半脱位组12例、髋关节脱位组6例。选择因其他疾病第1次行髋关节手术及尸检患儿13例为对照组。标本取自患者股骨头相连接部位圆韧带。 方法：将各组标本行苦味酸-天狼猩红染色。 主要观察指标：分别在普通显微镜和偏振光显微镜下并测量Ⅰ型和Ⅲ型胶原含量及计算比例(Ⅰ/Ⅲ)。 结果：Ⅰ型和Ⅲ型胶原含量随年龄增加而增加；对照组Ⅰ型胶原明显高于各病例组(P < 0.01)， Ⅲ型胶原稍低于病例组(P < 0.05)。胶原含量比例(Ⅰ/Ⅲ)随着年龄增加没有明显变化 (P > 0.05)；各病例组胶原含量比例明显低于对照组(P < 0.05)。 结论：发育性髋关节脱位患儿和对照组间圆韧带Ⅰ和Ⅲ型胶原含量及比例(Ⅰ/Ⅲ)有较大差别，发育性髋关节脱位发生可能与关节囊中胶原紊乱有关。     

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.