自制羊膜载体复合物植入表皮细胞修复全层皮肤缺损

摘要 背景：利用组织工程和细胞培养技术研制的复合皮肤距理想的人工皮肤尚有一定的差距,如局部皮肤薄弱、抗拉及抗摩擦能力差、无皮肤附属器等。 目的：观察含碱性成纤维细胞生长因子和维生素C的羊膜载体复合物对皮肤缺损局部真皮组织的修复作用,寻找真皮组织修复重建促进表皮生长的最佳时期。 方法：取新西兰大耳白兔36只,在每只背部建立皮肤全层缺损模型3处,分别植入含有缓释碱性成纤维细胞生长因子和维生素C羊膜载体复合物、单纯羊膜载体复合物及油纱覆盖。随机分为3组,分别于术后21,14,7 d植入自体表皮细胞混合液,1周后行大体、组织学、免疫组织化学、墨汁灌注等观察。 结果与结论：术后21 d植入表皮细胞组皮肤缺损局部新生皮肤瘢痕轻、形态结构较满意,创面愈合速度和质量均优于术后14,7 d 植入表皮细胞组,并且植入含碱性成纤维细胞生长因子和维生素C羊膜载体复合物组创面皮肤新生真皮组织完全被新生的表皮覆盖,而且表皮几乎均变为复层,其生长速度及质量优于单纯羊膜载体复合物移植组和油纱覆盖组。说明含有碱性成纤维细胞生长因子和维生素C的羊膜载体复合物植入皮肤全层缺损后,能加速真皮的修复和重建;真皮组织修复增生晚期和重建初期为促进表皮生长的最佳时期。 关键词：羊膜载体复合物;表皮细胞;碱性成纤维细胞生长因子;皮肤创伤愈合;真皮 doi:10.3969/j.issn.1673-8225.2011.16.003     

组织工程皮肤移植过程中白细胞介素10和肿瘤坏死因子α的表达

背景：白细胞介素10和肿瘤坏死因子α在异体异种皮肤移植局部免疫与排斥反应中发挥了重要作用。但在组织工程人工皮肤移植过程中局部皮肤组织内白细胞介素10和肿瘤坏死因子α的表达情况目前尚不清楚。 目的：采用表皮干细胞联合脱细胞真皮构建人工皮肤并移植修复兔全层皮肤缺损创面,观察创面修复效果和局部皮肤组织白介素10与肿瘤坏死因子α的表达变化。 方法：将体外培养的人表皮干细胞或角质细胞接种到脱细胞真皮支架中,构建组织工程人工皮肤;取新西兰白兔常规制作背部全层皮肤缺损创面随机分为4组,表皮干细胞组、角质细胞组用含表皮干细胞或角质细胞的组织工程皮肤移植于皮肤缺损创面;脱细胞真皮组移植单纯脱细胞真皮;对照组创面空置。观察创面修复情况,局部炎症反应,创面愈合时间。各组分别于术后7d在部分创面取材观察组织形态和白细胞介素10与肿瘤坏死因子α表达。 结果与结论：含表皮干细胞的人工皮肤移植后创面愈合良好,局部炎症反应轻微,无出血、积脓、坏死,创面愈合时间较角质细胞组明显缩短。白细胞介素10在各组均有表达,其中表皮干细胞组表达最强,角质细胞组次之,脱细胞真皮组和对照组最弱。肿瘤坏死因子α在各组也均有表达,其中角质细胞组表达最强,表皮干细胞组次之,脱细胞真皮组和对照组较弱。说明以表皮干细胞作为种子细胞联合脱细胞真皮构建人工皮肤可用有效促进皮肤缺损创面的修复治疗,创面修复过程中局部皮肤组织内白细胞介素10和肿瘤坏死因子的表达变化可能是其取得较好效果的主要机制之一。     

羊膜负载表皮干细胞促进糖尿病大鼠创面的愈合

背景：表皮干细胞作为皮肤组织的特异性干细胞,具有强大增殖及多向分化潜能,与创面修复紧密相关。近期研究表明糖尿病皮肤创面愈合过程中表皮干细胞数量减少、活性降低是导致其创面难愈的重要原因。 目的：观察表皮干细胞在糖尿病大鼠创面愈合中的作用。 方法：分离培养及鉴定SD大鼠表皮干细胞,并以BrdU标记。建立糖尿病SD大鼠创面模型,抽签法随机分为3组：表皮干细胞组创面移植羊膜负载BrdU标记的表皮干细胞;羊膜组创面移植羊膜;空白对照组创面未给予干预。 观察创面愈合情况、计算创面愈合率,苏木精-伊红及免疫组织化学SP法检测创面愈合组织中BrdU及增殖细胞核抗原表达。用图像分析软件测量阳性细胞积分吸光度平均值。 结果与结论：表皮干细胞组治疗后7d创面缩小明显,治疗后14 d创面基本愈合,创面愈合率明显高于羊膜组、空白对照组 (P < 0.01)。表皮干细胞组创面及新生表皮中可见BrdU阳性细胞,而另两组皮肤创面组织中始终未见BrdU阳性细胞。各组创面组织中可见增殖细胞核抗原阳性细胞表达,但表皮干细胞组的阳性细胞积分吸光度平均值与羊膜组、空白对照组比较差异有显著性意义(P < 0.01)。结果证实糖尿病大鼠创面愈合过程中表皮干细胞与创缘表皮移行、创面的上皮化有直接关联,可有效促进其创面愈合。     

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。     

含有生肌液的组织工程皮肤修复兔皮肤缺损

背景：在皮肤开放创面上进行缺损修复与重建是组织修复领域的研究焦点。构建含有中药的组织工程皮肤修复创面缺损的研究并不多见。 目的：将含有生肌液的皮肤支架与自体皮肤细胞复合，构建含药组织工程皮肤，修复兔皮肤缺损。 设计：自体对照动物实验。 单位：实验于2005-02/08在天津市天津医院骨科研究所细胞工程室完成。 材料：同窝大耳白兔8只，体质量1.6~1.8 kg。自行提取生肌液(1 500 g/L)，成分为当归、生地、龟板、象皮、血余、生石膏、炉甘石；明胶-壳聚糖支架材为料天津大学提供，分别修剪成1.3 cm直径的圆片，60Co照射灭菌；DR无细胞真皮基质由江苏省启动市医疗用品研究所提供。 方法：分离培养兔皮肤细胞，获取第3代角质形成细胞与成纤维细胞。延兔脊柱两侧制作直径1.5 cm的圆形全层皮肤缺损创面4个。分为4组，阴性对照组（明胶-壳聚糖支架贴附于创面后滴加生理盐水），人工真皮组（DR无细胞真皮基质贴附于创面后接种细胞悬液），非含药组织工程皮肤组（明胶-壳聚糖支架贴附于创面后接种细胞悬液），含药组织工程皮肤组（生肌液-明胶-壳聚糖支架贴附于创面后接种细胞悬液）。 主要观察指标：①术后13 d测量剩余创面面积。②术后7 d、10 d取材行组织学与免疫组织化学染色检测。 结果：①术后13 d各组创面面积均有不同程度的缩小，剩余面积阴性对照组>人工真皮组>非含药组织工程皮肤组>含药组织工程皮肤组，非含药组织工程皮肤组、含药组织工程皮肤组与阴性对照组比较差异有显著性意义（P < 0.05)。②术后10 d，阴性对照组、人工真皮组、非含药组织工程皮肤组均有炎性肉芽组织增生，无表皮组织形成；含药组织工程皮肤组形成接近正常的上皮组织及幼稚的真皮组织。非含药组织工程皮肤组与人工真皮组BrdU标记弱阳性，含药组织工程皮肤组BrdU标记强阳性。 结论：实验采用的方法使种子细胞在含有生肌液的明胶-壳聚糖支架上增殖，在体修复皮肤损伤，能够有效扩展皮肤缺损处的覆盖面积，缩短皮肤缺损的愈合时间。     

羊膜负载骨髓干细胞与角朊细胞对放创性全厚皮肤缺损创面胶原合成的影响*◆

背景：人羊膜含胶原、糖蛋白、蛋白多糖和整合素等多种成分,它表达多种生长因子mRNA及其相关蛋白,有利于细胞的生长繁殖,能负载猪骨髓间充质干细胞与角朊细胞良好生长。 目的：拟验证人羊膜负载骨髓间充质干细胞与角朊细胞对放创性全厚皮肤缺损创面胶原合成的影响。 设计、时间及地点：同体对比观察。实验于2007-06/12在解放军第三军医大学预防医学院全军复合伤研究所,创伤、烧伤与复合伤国家重点实验室完成。 材料：贵州小香猪8只,3~6月龄;雌雄不限,体质量7~16 kg。 方法：贵州小香猪8只,每只背部脊柱两侧均有放创性全层皮肤缺损圆形创面(Ф3.67 cm)各3个,共48个创面。将经处理的人羊膜分别负载自体骨髓骨髓间充质干细胞和角朊细胞,移植到其左侧24个创面作为实验组(人羊膜负载两种细胞移植组);右侧前16个创面用单纯无种植细胞的人羊膜敷盖;后8个创面用单纯油纱布敷盖。单纯人羊膜处理组和油纱布敷盖组作为对照组。 主要观察指标：用图像分析法测算7~21 d各组创面活检组织胶原含量。 结果：移植15~21 d,3组创面胶原均增加,以人羊膜负载两种细胞移植组创面胶原沉积明显,与单纯人羊膜处理组和油纱布敷盖组创面相比,差异均有显著性意义(P < 0.01)。 结论：人羊膜负载自体骨髓间充质干细胞和角朊细胞植入可明显促进放创性全厚皮肤缺损创面愈合过程中胶原的合成。     

人工真皮修复急性创伤后足背皮肤软组织缺损14例

背景：人工真皮具有硅胶膜和胶原海绵双层结构,是最早开发和应用于临床的组织工程化皮肤替代物,主要应用于皮肤软组织缺损修复。 目的：评价人工真皮在足背严重皮肤软组织缺损中的应用。 方法：选择北京积水潭医院烧伤科于2009-06/2010-12收治的14例急性外伤后足背严重皮肤软组织缺损患者,均有肌腱或骨外露。所有患者经清创后,以人工真皮移植,待人工真皮成活后以自体断层皮片移植,观察人工真皮和自体皮的成活情况。 结果与结论：所有植皮成活,创面愈合良好,供区未见明显瘢痕增生。提示人工真皮联合自体断层皮片移植可以有效修复足背严重皮肤缺损创面,减少供区损伤。     

转基因骨髓间充质干细胞移植与组织工程皮肤的血管化

背景：组织工程化皮肤移植后常因缺乏足够的血管化而导致低灌注和缺血损伤。利用转基因技术,可将血管生成调控因子基因导入目的细胞,使其表达某些调控因子,进而利于血管生成。 目的：观察转基因骨髓间充质干细胞移植促进组织工程皮肤血管化基因治疗的可行性。 设计、时间及地点：随机对照动物实验,于2008-03/11在江西省南昌大学第一附属医院烧伤研究所完成。 材料：人骨髓间充质干细胞由试验者取自临床骨髓穿刺检查骨髓正常的患者。pShuttle-CMV/VEGF165 质粒转化大肠杆菌菌种由武汉协和医院郜勇博士惠赠。16只新西兰大白兔用于皮肤缺损模型的制作,分为基因转染骨髓间充质干细胞组、骨髓间充质干细胞组、真皮支架材料组进行移植。 方法: 采用密度梯度离心结合贴壁法分离培养人骨髓间充质干细胞,以pShuttle-CMV/VEGF165质粒转染骨髓间充质干细胞。于兔背部两侧制备2 cm×2 cm 的正方形全层皮肤缺损3个,并分别以人血管内皮细胞生长因子165转染骨髓间充质干细胞、骨髓间充质干细胞、不含细胞的真皮支架材料植入全层皮肤缺损创面。 主要观察指标：观察局部组织微血管密度变化及移植物成活率。 结果：术后7 d,3组创口周围皮肤均无明显红肿及炎症反应,移植物与创面接触紧密,基因转染骨髓间充质干细胞组、骨髓间充质干细胞组可见部分真皮泛红, 真皮支架材料组不明显,术后3周创面基本愈合,基因转染骨髓间充质干细胞组创面的毛细血管密度较骨髓间充质干细胞组、真皮支架材料组明显增高(P < 0.01),14 d时3组中基因转染骨髓间充质干细胞组血管密度仍最高,但3组数据无统计学差异。术后二三周基因转染骨髓间充质干细胞组移植物成活率最高(P < 0.01)。 结论：血管内皮细胞生长因子转染骨髓间充质干细胞移植可改善和促进局部血管再生,促使新的毛细血管从创面长入移植的组织工程皮肤,从而促进组织工程皮肤的早期血管化及创面愈合。     

应用人工真皮联合自体薄层皮片移植修复深度皮肤软组织缺损11例

背景：深度皮肤软组织缺损创面积极的治疗方法往往以皮瓣修复为主，但对患者身体状况要求较高，且代价较大。人工真皮是最早开发和成功应用于临床的组织工程化皮肤替代物，主要用于皮肤软组织缺损的修复。 目的：拟观察人工真皮联合自体薄层皮片移植对深度皮肤软组织缺损创面的修复效果。 设计、时间及地点：病例分析，于2006-01/2008-03在北京大学第三医院成形科、北京积水潭医院烧伤整形科完成。 对象：11例患者均存在由于手术或外伤导致不同程度和部位的皮肤软组织缺损创面，部分病例伴有骨质外露、骨膜缺损。 方法：手术中一期扩创，需要时凿骨，移植人工真皮，经2~4周创面被类真皮组织覆盖后，二期进行自体薄层皮片移植。 主要观察指标：观察创面愈合及植皮存活情况，供皮区有无明显瘢痕。 结果：11例创面均得到良好覆盖。创面愈合后1个月复查，植皮后愈合良好，供皮区均没有明显瘢痕。 结论：人工真皮联合自体薄层皮片移植对深度皮肤软组织缺损创面具有良好的修复效果，供区损伤小。人工真皮的应用为修复包含骨外露创面在内的深度皮肤软组织创面提供了一种新方法。     

异体异种脱细胞真皮与自体刃厚皮复合移植的比较

背景：尽管真皮基质的生物模板作用可减少瘢痕形成, 改善创面愈合质量已得到共识,但不同种属脱细胞真皮基质作为真皮添充物的成活机制和重建过程等生物学性能是否有差异仍需进一步探讨。 目的：对比分析异体及异种脱细胞真皮基质与自体刃厚皮复合移植的近期效果。 设计、时间及地点：随机分组,自身对照观察实验,于2008-01/06在海南省人民医院医学动物实验中心完成。 材料：J-1 型人脱细胞异体真皮基质由北京桀亚莱福生物技术有限公司提供。小型香猪1只以低含量胰蛋白酶消化加反复冻融法制备制备猪脱细胞真皮基质。 方法：选取近交系小型香猪15 只,在每头猪脊背两侧制作6 cm×6 cm全层皮肤缺损创面各3处,共6处,按移植物的不同将创面随机分为3组：猪脱细胞真皮基质与猪刃厚自体皮复合移植组与人脱细胞真皮基质与猪刃厚皮复合移植组在脱细胞真皮基质植入后,在其表面重叠覆盖自体刃厚皮,对照组单纯行猪薄皮片移植。 主要观察指标：移植后9 d、21 d及3个月各组移植物成活情况、创面收缩率和组织学变化。 结果：移植后第9,21天各组移植皮片大部分均成活良好,局部无红肿,3个月时两复合移植组皮肤外观相似,均光滑、柔软、丰满、有弹性,与周围正常组织结合部平坦, 对照组创面收缩凹陷明显,皮片薄弱,韧性也较复合移植组差,3组移植物成活率差异无显著性意义(P > 0.05),自体刃厚皮移植创面收缩率高于其他两组(P < 0.05)。移植后8 d,2个复合移植组脱细胞真皮基质引导形成丰富的毛细血管结构, 复合皮表皮层形成且分化良好;移植后21 d,已有完整的皮肤结构, 真皮层内可见胶原纤维排列规整,表皮-真皮连接区“钉突”结构明显,移植后3个月结构更加接近正常真皮,对照组组织致密,胶原排列紊乱,与瘢痕组织结构相似。 结论：与自体皮复合移植时, 异体及异种脱细胞真皮基质具有相近的生物学性能,且效果优于单纯刃厚自体皮移植。     

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.