男性肝豆状核变性下丘脑-垂体-睾丸轴功能研究

目的了解男性肝豆状核变性（ＷＤ）病人下丘脑－垂体－睾丸轴激素分泌功能。方法用放射免疫法测定２６例病人血清垂体、性激素水平。结果孕酮（Ｐ）显著低于正常对照组（Ｐ＜０．０５），生长激素（ＧＨ）、黄体生成素（ＬＨ）、雌二醇（Ｅ２）亦显著降低（Ｐ＜０．０１），性激素结合球蛋白（ＳＨＢＧ）则显著高于正常对照组（Ｐ＜０．００１），２０例患者进行促性腺激素释放激素（ＧｎＲＨ）试验，发现腺垂体对外源性ＧｎＲＨ的刺激反应迟钝。结论ＷＤ垂体、性腺细胞中部分酶的活性降低，使二者激素分泌功能降低；同时肝的铜沉积扰乱了蛋白代谢，使ＳＨＢＧ升高，进一步降低了性激素的生物效应     

Wilson病患者血清氧化物和抗氧化物水平与内脏损伤的关系

目的 探讨Ｗｉｌｓｏｎ病（ＷＤ）患者血清氧化物和抗氧化物水平与内脏损伤的关系。方法 应用化学比色法和反相高效液相色谱法（ＲＰ－ＨＰＬＣ）测定２９例ＷＤ患者和２１名正常人血清丙二醛（ＭＤＡ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、谷胱甘肽（ＧＳＨ）和维生素Ｅ（ＶｉｔＥ）的水平。结果 ＷＤ组与对照组相比ＭＤＡ显著增高（Ｐ〈０．０１）,ＧＳＨ－ＰＸ显著下降（Ｐ〈０．０１）。且两者呈负相关;血清ＶｉｔＥ和ＧＳＨ在肝型ＷＤ患者显著减少（分别Ｐ〈０．０１和Ｐ〈０．０５）。非肝型患者与对照组比,差别无显著性（Ｐ〉０．０５）。结论 ＷＤ患者轿清中存在着自由基系统的代谢紊乱,氧化物水平升高,抗氧化物水平下降,这可能是该病患者内脏损伤的重要原因之一。     

血清ApoE对脑动脉硬化症的诊断价值

本文观察４２例脑动脉硬化症患者与正常对照组４４例，对其血清ＡｐｏＥ和ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＡＩ、ＡｐｏＢ１００２６含量进行测定，并将ＡｐｏＥ与ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＡＩ、ＡｐｏＢ１００逐一进行相关比较，结果发现：脑动脉硬化症病人血清ＡｐｏＥ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＢ１００明显高于正常对照组（Ｐ〈０．０１），ＨＤＬ－Ｃ显著低于正常对照组（Ｐ〈０．０１）     

重症肌无力患者HLA－DRB_1等位基因分析

作者应用ＰＣＲ－ＳＳＰ方法，对３４例重症肌无力（ＭＧ）患者和８６名健康汉人ＨＬＡ－ＤＲＢ１等位基因进行分析、研究，结果发现，ＭＧ病人组ＭＲＢ１区域内０９０１、１３０１两对等位基因的频率明显高于对照组（ＲＲ分别为１６．９４４和５．５１２，Ｐ均＜０．０１）。其中８例伴有胸腺瘤的ＭＧ患者除０９０１、１３０１两对等位基因频率增高外，０４０１基因频率亦明显高于正常对照组（ＲＲ分别为３９．５０３、４．９８０和４．０００．Ｐ均＜０．０１）。作者认为，ＭＧ发病可能与ＨＬＡ－ＤＲＢ１区域内０９０１、１３０１和０４０１三对等住基因相关联。     

缺血性脑卒中患者红细胞膜脂质、微粘度及血清脂质分析

对５３例缺血性脑卒中（ＩＳ）患者红细胞膜胆固醇（膜ＣＨ）、膜磷脂（膜ＰＬ）、膜微粘度（膜）及血清脂质进行测定，并与４１例对照组相比。结果显示：①ＩＳ患者膜ＣＨ、膜ＣＨ与膜ＰＬ比值（膜ＣＨ／膜Ｐｕ及膜显著增高（Ｐ＜０．０１），膜亏与膜ＣＨ及膜ＣＨ／膜ＰＬ呈显著正相关；②ＩＳ组血清胆固醇（ＣＨ）、载脂蛋白Ｂ（ＡＰＯ－Ｂ）均显著增高（Ｐ＜０．０１），高密度脂蛋白胆固醇（ＨＤＬ－ＣＨ）和载脂蛋白Ａ＿１（ＡＰＯ－Ａ＿１）显著降低（Ｐ＜０．０１），膜ＣＨ和膜与ＡＰＯ－Ｂ呈显著正相关，而与ＨＤＬ－ＣＨ、ＡＰＯＡ＿１呈显著负相关。     

载脂蛋白E与脑动脉硬化症

本文观察７８例脑动脉硬化症患者与对照组４４例，对其血清载脂蛋白Ｅ（ＡＰＯＥ）和高密度脂蛋白（ＨＤＬ－Ｃ）、低密度脂蛋白（ＬＤＬ－Ｃ）、胆固醇（ＴＣ）、甘油三脂（ＴＧ）、载脂蛋白ＡＩ（ＡＰＯＡＩ）、载脂蛋白Ｂ（１００）（ＡＰＯＢ（１００））进行含量测定，并将ＡＰＯＥ与ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＡＩ、ＡＰＯＢ（１００）逐一进行相关比较，结果发现：脑动脉硬化症病人（ＣＡＳ）血清ＡＰＯＥ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＢ（１００）明显高于正常对照组（Ｐ＜０．０１），ＨＤＬ－Ｃ显著低于正常对照组（Ｐ＜０．０１），ＡＰＯＡＩ无明显变化（Ｐ＞０．０５），且ＡＰＯＥ与ＨＤＬ－Ｃ呈负相关；与ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＢ（１００）呈正相关；与ＡＰＯＡＩ无直线相关关系。提示ＡＰＯＥ可做为诊断脑动脉硬化症的重要指标。     

脑血栓患者血脂、高、低密度脂蛋白载脂蛋白A1、B的观察

测定４５例脑血栓患者血胆固醇，甘油三醌，高密度脂蛋白胆固醇，低密度脂蛋白胆固醇，极低密度脂蛋白胆固醇，载脂蛋白Ａ１，载脂蛋白Ｂ，ＡｐｏＡ１／ＡｐｏＢ比值，ＬＤＬ－Ｃ／ＨＤＬ－Ｃ比值与对照组比较，脑血栓患者ＴＣ，ＴＧ，ＬＤＬ－Ｃ，ＶＬＤＬ－Ｃ，ＡｐｏＢ，ＬＤＬ－Ｃ／ＨＤＬ－Ｃ比值较对照组显著升高Ｐ〈０．０１－０．００１，ＨＤＬ－Ｃ，ＡｐｏＡ１／ＡｐｏＢ比值较对照组显著降低，Ｐ〈０．０１，ＡｐｏＡ１脑     

缺血性脑血管病伴OSAS患者的血压和血管舒缩功能观察

目的 观察缺血性脑血管病（ＩＣＶＤ）伴阻塞型睡眠呼吸暂停综合征（ＯＳＡＳ）患者平均动脉压（ＭＡＢＰ）、血浆降钙素基因相关肽（ＣＧＲＰ）和内皮素（ＥＴ）的变化及相互关系。方法 应用放免方法测量３１例患者血浆ＣＧＲＰ和ＥＴ含量,静息状态下测量血压;多元相关分析。结果 ＩＣＶＤ伴ＯＳＡＳ患者组ＭＡＢＰ、ＥＴ均炕于正常对照组（均Ｐ〈０．００１）,ＣＧＲＰ明显低于对照组（Ｐ〈０．００１）;ＣＧＲＰ与ＭＡＢＰ     

脑出血与8项血脂指标的关系探讨

测定了１２５例脑出血病人的血总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白（ＨＤＬ）、低密度脂蛋白（ＬＤＬ）、载脂蛋白Ａ－１、Ｂ－１００（ＡｐｏＡ－１、ＡｐｏＢ－１００）、脂蛋白（ａ）［ＬＰ（ａ）］和氧化修饰低密度脂蛋白（ｏｘＬＤＬ）浓度。结果显示：与对照组比较，ＡｐｏＢ－１００、ｏｘＬＤＬ显著增高，ＨＤＬ、ＡｐｏＡ－１显著降低（Ｐ＜０．０１），ＬＤＬ明显降低（Ｐ＜０．０５），ＴＣ、ＴＧ、ＬＰ（ａ）无明显变化（Ｐ＞０．０５）。提示：血ＬＤＬ、ＡｐｏＢ－１００、ｏｘＬＤＬ浓度增高和ＨＤＬ、ＡｐｏＡ－１浓度降低与脑出血有一定的相关关系，可作为脑出血的危险因素。     

100例肝豆状核变性患者的脑电图监护

对１００例肝豆状核变性（ＨＬＤ）患者及２０例健康对照组行脑电图监护（ＶＥＥＧ）检查，结果发现ＨＬＤ患者ＶＥＥＧ异常率达８０％，明显高于健康对照组的异常率（２０％）（Ｐ〈０．０１）；不同临床类型ＨＬＤ患者ＶＥＥＧ的异常率无显著差异，其ＶＥＥＧ异常主要表现为基本节律慢化，阵发性慢波和痫样放电。     

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.