冷冻干燥过程中猪主动脉血管形态的变化

背景：冷冻干燥血管是进行血管移植的良好材料，但目前对冷冻干燥工艺的研究不多，同时缺乏对冻干后血管物理学性能变化的分析报道。 目的：利用冷冻干燥的方法对血管的保存作了初步尝试，使用微型CT对冻干过程进行跟踪，以揭示冻干过程中血管形态发生的变化。 设计及地点：单一样本观察，实验在上海理工大学制冷及低温研究所完成。 材料：上海屠宰场生猪新鲜主动脉。冷冻干燥机为美国SP Industries公司生产；TRAPEZIUM LITE 质构仪由岛津(香港)有限公司生产。 方法：使用质构仪对冻干后复水的猪主动脉与新鲜猪主动脉进行力学性能对比分析。 主要观察指标：①冷冻干燥过程温度曲线。②微CT断层扫描猪主动脉冻干过程。③猪主动脉冻干前后拉伸力学性能及穿刺力学性能比较。 结果：试验结果发现猪主动脉血管在冻干过程中会发生分层现象，血管冻干后复水，其力学性能同新鲜血管比最大轴向拉伸应力减少约40%，周向最大拉伸应力增大约45%，最大穿刺应力约是新鲜血管的75%。 结论：冻干复水后的血管基本保持了新鲜血管的力学性能，可望成为一种有效的血管保存手段。     

血管冻干工艺过程中升华界面移动特性的微CT实验

背景：前期实验发现冻干过程中物料内部的孔隙分部、空隙连通度等对内部传热传质影响较大，但对于干燥过程热质迁移的机制未阐明。 目的：在前期实验基础上，以微CT为分析工具，尝试对冷冻干燥过程中升华界面移动特性进行实验观察分析，希望对血管冻干工艺提供参考。 方法：以新鲜猪主动脉为材料使用微CT扫描仪的扫描成像、图像重构及灰度值分析技术对血管在冻干时升华过程进行观察分析。 结果与结论：冻干温度曲线斜率初期较大，升华速率较快，由血管的二维横截面重构图像中可以看出冻干区与冰晶区的灰度值差别较大，升华界面明显，升华是在物料的外表面和内表面同时进行，界面移动明显。随着时间推移，温度曲线斜率变小，升华速率也随之变慢，界面移动逐渐不明显。对于竖直放置的血管在底部进行加热的干燥过程，升华是在外表面和内表面同时进行的。升华界面逐渐向血管壁面中心移动。冻干过程随时间推移热质传递阻力增大，升华速率减慢。     

冻干辐照对猪腹膜体外稳定性的影响

背景：有实验表明60Coγ射线灭菌处理的胶原膜会促使胶原分子产生交联，影响其稳定性。 目的：通过测定冻干辐照处理后猪腹膜胶原酶酶解时间，了解冻干辐照猪腹膜在体外的稳定性。 设计、时间及单位：动物实验观察，于2007-07/2008-06在南昌大学烧伤研究所、南昌大学-新三思公司联合力学实验室、江西中医学院中药固体制剂国家工程研究中心与江西天兆科技发展公司完成。 材料：选用健康活体猪6只，无菌条件下取新鲜猪腹膜。60Coγ射线辐照装置为江西天兆科技发展公司生产。 方法：新鲜猪腹膜按照处理方式分成4组，新鲜组：将新鲜猪腹膜放入含有庆大霉素1×105 U/L的生理盐水中清洗修剪平整后，再放入保护液中浸泡约15 min，最后放入0~4 ℃冰箱中保存、备用。冻干组：将新鲜猪腹膜放入EMDE+10%甘油中的猪腹膜浸泡15 min后，取出放入-78 ℃的冰箱中，使其形成冰晶，再放入真空冷冻干燥机内冻干6 h，取出室温保存、备用。辐照组：在冻干组基础上将猪腹膜放入剂量为25 kGy的 60Coγ辐照装置内，动态辐照72 h后取出，放入0~4 ℃冰箱中保存、备用。冻干+辐照组：在辐照组基础上将猪腹膜放入剂量为25 kGy的60Coγ辐照装置内，动态辐照72 h后取出室温保存、备用。 主要观察指标：同时取直径为5 mm各组猪腹膜圆片用胶原酶Ⅰ型酶解，计算各片材料完全酶解时间。 结果：4组猪腹膜胶原酶酶解时间：(9.6±1.2)，(6.1±1.6)，(29.2±3.0)，(23.5±2.6) mins。辐照组和冻干+辐照组猪腹膜酶解时间比新鲜组和冻干组明显延长(P < 0.05)，但新鲜组和冻干组之间比较及辐照组和冻干+辐照组之间比较，猪硬脑膜酶解时间无明显差别(P > 0.05)。 结论：经60Coγ射线照射后的猪腹膜抗酶解能力增强；辐照均能增加猪腹膜的稳定性，冻干对猪腹膜的稳定性无明显影响。     

大鼠皮肤的冷冻干燥保存

背景：细胞干燥保存的研究报道较多,组织器官是否适用于干燥保存,尚缺乏证据。 目的：用海藻糖作为干燥保护剂,优化海藻糖载入大鼠皮肤的条件,探索皮肤干燥保存的可行性。 设计、时间及地点：观察性实验,于2007-11/2008-11在西北大学生命科学学院组织工程实验室完成。 材料：体质量150 g左右成年SD大鼠。海藻糖由Sigma公司提供。 方法：通过控制海藻糖浓度(50,300,500,800,1 000 mmol/L)、负载时间(0.5,4,7,9 h)和温度[4 ℃、4~37 ℃(相转变)和37 ℃],优化海藻糖导入大鼠皮肤的条件。将负载海藻糖的皮肤置于含100 g/L二甲基亚砜的DMEM冷冻液中孵育,程序冷冻仪以1 ℃/min的速率降温至-80 ℃后移入冷冻干燥机中进行冻干。将冻干皮肤水化复苏后分别用双醋酸羧基荧光素(CFDA)、四甲基偶氮唑盐(MTT)检测皮肤活性,并以新鲜和甲醛固定皮肤的吸光度值作为阳性和阴性对照。以苏木精-伊红染色和观察皮肤组织结构,并进行自体移植。 主要观察指标：海藻糖在不同加载浓度、孵育温度和时间载入大鼠皮肤的情况。冻干皮肤水化后的形态学、组织学变化及其自体移植后存活情况。 结果：海藻糖浓度小于800 mmol/L,皮肤的海藻糖载入量随海藻糖浓度的升高而明显增(P < 0.05),浓度大于800 mmol/L,海藻糖载入量差异不显著。孵育温度为37 ℃组和相转变组皮肤海藻糖载入量明显高于4 ℃组(P < 0.05),相转变组与37 ℃组差异无统计学意义。皮肤孵育4,7,9 h的海藻糖载入量明显高于孵育0.5 h的载入量(P < 0.05),孵育时间为4,7,9 h之间的海藻糖载入量差异不显著,但孵育7 h后皮肤的海藻糖载入量不再增加。实验以海藻糖浓度为800 mmol/L,孵育温度为37 ℃,孵育时间为7 h为优化的负载条件处理大鼠皮肤。冻干皮肤玻璃化状态良好,呈半透明状。水化后能够恢复到新鲜皮肤的大小和色泽,组织结构和细胞形态与新鲜皮肤组织无差别。冷冻干燥皮肤的活性明显高于甲醛固定的大鼠皮肤 (P < 0.05)。冻干保存的皮肤水化后移植回自体大鼠,可存活长达13 d。 结论：海藻糖可作为干燥保护剂进行大鼠皮肤冷冻干燥保存,海藻糖浓度为800 mmol/L,孵育温度为37 ℃,孵育时间为 7 h是海藻糖载入大鼠皮肤的最佳条件。     

新鲜羊膜及几种保存羊膜移植治疗角膜碱烧伤★

目的：近年来羊膜移植成为治疗角膜碱烧伤较为有效的手段之一，但其生物学基础尚不完全清楚。观察不同活性羊膜移植对兔眼角膜碱烧伤的治疗效果，并分析其生物活性成分作用。 方法：实验于2004-01/07于重庆医科大学动物实验中心实验室完成，动物实验方法符合动物伦理学要求。①实验材料及分组：健康产妇剖宫产胎盘由重庆医科大学附属第一医院产科提供。选用新西兰大白兔45只，按随机数字表法分为5组（n =9）：新鲜羊膜组、甘油保存羊膜组、乙醇保存羊膜组、真空干燥羊膜组及对照组。②实验方法：于新鲜羊膜制备后24 h内，保存羊膜保存1个月后行羊膜移植。③实验评估：术后2~21 d每日、21 d后每3日观察眼表角膜透明度及新生血管生长情况；术后14，30，60 d行荧光素染色，观察角膜上皮的修复情况；术后2周、1个月、2个月行组织病理和透射电镜观察。 结果：白兔43只进入结果分析。①在角膜透明性及角膜上皮修复速度上新鲜羊膜组、甘油保存羊膜组和真空干燥羊膜组无明显差异，均明显优于乙醇保存羊膜组和对照组，乙醇保存羊膜组与对照组无明显差异。②在抑制新生血管方面，新鲜羊膜组明显优于甘油保存羊膜组及真空干燥羊膜组。 结论：真空干燥羊膜、甘油保存羊膜和新鲜羊膜移植后均能减轻眼表碱烧伤的炎症反应，促进角膜上皮修复。其中新鲜羊膜效果最好，可能与其较其他羊膜含有更多的生物活性物质有关。     

冻干辐照猪硬脑膜胶原酶酶解时间与生物力学的测定*★

背景：理想的硬脑膜替代材料要求其自身具有一定的韧性与弹性。 目的：通过对经冻干辐照处理后猪硬脑膜胶原酶Ⅰ型酶解时间、最大负荷及抗张强度进行测定，验证经冻干、辐照处理过的猪硬脑膜是否符合硬脑膜移植对生物力学的要求。 设计、时间及地点：对比分析实验，于2007-07/2008-06在南昌大学烧伤研究所、南昌大学-新三思公司联合力学实验室、江西中医学院中药固体制剂国家工程研究中心与江西天兆科技发展公司完成。 材料：选用健康活体猪6只，无菌条件下取新鲜猪硬脑膜。 方法：猪硬脑膜经过冲洗、预冻、冻干、60Coγ射线照射等处理，按照处理方式分成新鲜猪硬脑膜组、冻干猪硬脑膜组、辐照猪硬脑膜组及冻干+辐照猪硬脑膜组。 主要观察指标：取5 mm各组猪硬脑膜圆片用胶原酶Ⅰ型酶解计算其完全酶解时间；用EMT彩屏电子拉力试验机分别测出各组替代材料的最大负荷、抗张强度。 结果：新鲜猪硬脑膜组、冻干猪硬脑膜组、辐照猪硬脑膜组及冻干+辐照猪硬脑膜组硬脑膜胶原酶酶解时间分别为 （8.3±2.5），（7.6±1.8），（23.6±5.7） 与（21.1±5.3）min，最大负荷和抗张强度分别为（79.93±4.36），（70.50±5.97），（96.97±4.84） N和（93.59±4.61），（7.98±0.44），(7.05±0.60)，（9.70±0.48）和（9.40±0.46）N/mm，与新鲜猪硬脑膜组和冻干猪硬脑膜组比较，辐照猪硬脑膜组和冻干+辐照猪硬脑膜组时间明显延长，差异有显著性意义（P < 0.05），但辐照猪硬脑膜组及冻干+辐照猪硬脑膜组结果无明显差别（P > 0.05）。 结论：经60Coγ射线照射后的硬脑膜抗酶解能力、生物力学特性增强；辐照与冻干+辐照猪硬脑膜均能满足硬脑膜移植对其生物力学方面的要求。     

正常国人升主动脉、腹主动脉、肾动脉血管的松弛函数及力学性质

背景：主动脉损伤都需要进行吻接修复。国内外学者对主动脉血管的粘弹性力学性质已作了一些研究。作者未检索到关于人主动脉单向拉伸破坏实验及构建松弛函数的报道。 目的：对正常国人急性外伤致死的成人新鲜尸体升主动脉、腹主动脉、肾动脉进行一维拉伸试验，测量分析血管的力学性质。 设计、时间及地点：以函数为描述方式的对比分析，实验于2007-08-10/20在吉林大学力学实验中心完成。 材料：实验标本取自正常国人因急性外伤至死的5具男性尸体的升主动脉、腹主动脉、肾动脉，由白求恩医科大学解剖教研室提供，年龄23~30岁。 方法：死后1 h之内解剖取死者出升主动脉、腹主动脉、肾动脉，将标本沿纵向切成长25 mm的试样共26个。以一维拉伸的方法对升主动脉、腹主动脉、肾动脉进行拉伸实验。在模拟正常人体温在(36.5±0.5) ℃的温度场下进行，以20 mm/min的速度对试样施加拉应力，试样破坏后，计算机自动输出应力-应变曲线和数据。 主要观察指标：①升主动脉、腹主动脉、肾动脉一维拉伸实验结果。②升主动脉、腹主动脉、肾动脉一维拉伸实验中的应力-应变关系。③升主动脉、腹主动脉、肾动脉松弛函数构建。 结果：①拉伸实验结果显示，肾动脉的破坏应力大于腹主动脉和升主动脉(P < 0.05)，腹主动脉的伸长比和应变大于肾动脉和升主动脉(P < 0.05)。②应力松弛蠕变试验结果表明：肾动脉和腹主动脉7 200 s应力松弛量比较接近，升主动脉7 200 s应力松弛量小于腹主动脉和肾动脉，差异显著(P < 0.05)。腹主动脉7 200 s蠕变量大于肾动脉大于升主动脉，差异显著(P < 0.05)。根据冯元桢教授的准线性理论得出升主动脉、腹主动脉、肾动脉松弛函数κ(λt)=G(t)T(e)(λ)的表达式。 结论：肾动脉的最大应力大于腹主动脉及升主动脉，腹主动脉伸长比和应变大于肾动脉及升主动脉。主动脉升部、腹部、肾部随其生理解剖位置不同具有不同的力学性质。     

淀粉/聚乙烯醇复合生物膜的制备及其表征

背景：目前还没有将淀粉/聚乙烯醇膜应用于引导组织再生技术的研究，实验结合天然高分子和合成高分子的优点制备成多孔结构的引导组织再生膜。 目的：不同制备工艺条件对淀粉/聚乙烯醇膜性能的影响。 方法：以聚乙烯醇和淀粉为主要原料，通过溶液浇注、冷冻干燥法制备具有多孔结构的引导组织再生膜，考察原料配比、溶液浓度和预冻温度对多孔薄膜性能的影响。对薄膜的表面形貌、孔隙率、吸水率、力学性能及细胞毒性进行了表征。 结果与结论：不同工艺条件下制备膜的孔径在1~50 μm，孔隙率在60%~70%，拉伸强度在12~26 MPa，并且该膜具有良好的生物相容性和亲水性。当溶液浓度为5%，预冻温度为-30 ℃时该膜表面孔的分布比较均匀，淀粉含量越多，孔径越大。 关键词：引导组织再生膜；聚乙烯醇；淀粉；多孔结构；功能复合生物材料；组织诱导性生物材料 doi:10.3969/j.issn.1673-8225.2010.08.020     

鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察*★

目的：制备含有不同冻干保护剂的鬼臼毒素固体脂质纳米粒(POD-SLN)冻干粉，并考察其理化性质，筛选出最佳配方。 方法：实验于2006-12/2007-11在南方医科大学药学部实验室完成。冻干配方为15%海藻糖、15％甘露醇和二者联用各取 5％，冷冻干燥制作冻干粉制剂。扫描电镜下观察冻干粉复溶后粒子形态，Image -Pro Plus 6.0软件计算粒径大小，高效液相考察固体脂质纳米粒的药物包封率，并考察冻干粉的外观、复溶和4 ℃保存对其影响，评价不同辅料对冻干品的影响。 结果：①外观和复溶情况：海藻糖冻干粉、海藻糖联用甘露醇冻干粉表面均松脆多孔，疏松，复溶较快，约需20 s，甘露醇冻干粉表面较光滑，结构致密，饼状，复溶较慢，需借助外力。冻干粉样品4 ℃冰箱放置24 h、1，3，6个月其外观和复溶均无明显变化。②电镜下粒子形态：呈圆形或椭圆形，分布较均匀，冻干前后无明显差异。③粒径：未加冻干保护剂时为（82.65± 18.43）nm，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为（94.78±21.94），（109.26±16.15），（114.63±21.42）nm。④包封率：未加冻干保护剂时为 87.4%，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为86.2%，80.3%，79.6%。 结论：以15%海藻糖为冻干保护剂制备的鬼臼毒素固体脂质纳米粒冻干粉粒径较小，包封率高，稳定性好，其制备工艺合理可行。     

碱性成纤维细胞生长因子促进冻干肌腱移植重建前交叉韧带的早期血管生成：组织学表现

背景：以往实验已证实碱性成纤维细胞生长因子在体内外均有促新生血管形成的作用。冻干法可以减低移植物的抗原性，经冻干处理后的移植物保存时间长并且运输方便，更容易商品化。冻干肌腱补充活性细胞生长因子有望加速新血管的生成。 目的：拟验证碱性成纤维细胞生长因子促进冻干肌腱移植重建前交叉韧带后早期血管的生成作用。 设计、时间及地点：对照观察动物实验，于2006-06/2007-06在解放军第四军医大学西京医院骨科研究所完成。 材料：选用健康成年家犬14只。 方法：取2只犬，无菌手术取其双下肢伸趾长肌腱16条，冻干处理后供实验用。将其余12只犬左、右侧膝关节分别移植单纯冻干肌腱和复合100 μg/L碱性成纤维细胞生长因子后冻干肌腱重建前交叉韧带。 主要观察指标：分别于移植后1，2，3，4，5，6周取材，每次取2只。进行苏木精-伊红染色，通过图像分析仪定性观察新生血管的生成情况。 结果：复合碱性成纤维细胞生长因子冻干肌腱组移植后两三周出现新生血管，四五周达到高峰；单纯冻干肌腱组移植后四五周出现新生血管。复合碱性成纤维细胞生长因子冻干肌腱组新血管长入肌腱的时间先于对照组，深度深于对照组。 结论：复合100 μg/L碱性成纤维细胞生长因子的冻干肌腱移植重建前交叉韧带后，在新血管形成的时间及长入肌腱的深度方面均优于单纯冻干肌腱。     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.