经DNA测序证实的肝豆状核变性基因突变热区的研究

目的研究我国肝豆状核变性（ＷＤ）基因突变的特征。方法应用聚合酶链反应－单链构像多态（ＰＣＲ－ＳＳＣＰ）技术，结合ＤＮＡ测序技术，筛查４０个ＷＤ家系的５６例患者及无亲缘关系的６０名正常人的ＷＤ基因第５、８、１４号外显子（ｅｘｏｎ５，ｅｘｏｎ８，ｅｘｏｎ１４）的突变及多态。结果２１例患者（来自１５个ＷＤ家系）在ｅｘｏｎ８检出２种错义突变，占３７．５％（１５／４０），其中２例（来自同一家系）发生Ａｒｇ７７８Ｇｌｎ纯合子突变（２．５％），８例（分别来自８个ＷＤ家系）发生Ａｒｇ７７８Ｌｅｕ纯合子突变（２０．０％），余１１例（来自６个ＷＤ家系）发生Ａｒｇ７７８Ｌｅｕ杂合子突变（１５．０％，６／４０）。此外，在第８号外显子区域发现了两种多态；在ｅｘｏｎ５和ｅｘｏｎ１４侧翼的内含子区域各发现了１种新多态。这是我国首次经ＤＮＡ测序证实的ＷＤ基因突变热区。结论ｅｘｏｎ８为我国ＷＤ病人基因突变的热区之一，这对于建立准确快速的ＷＤ直接基因诊断方法具有重要意义，该测序方法对明确基因变异的具体部位和内容的具有一定的重要性。     

肝豆状核变性8号外显子778密码子基因突变的酶切检测

目的应用酶切方法对中国人肝豆状核变性患者ＡＴＰ７Ｂ基因中的高频突变点进行检测，并对家系进行基因诊断分析。方法根据高频突变点所处序列设计合适的内切酶ＭｓｐⅠ，对中国人肝豆状核变性３９个家系４５个患者以及６０例正常人的ＡＴＰ７Ｂ基因８号外显子ＰＣＲ扩增后进行酶切分析。对有异常者进行序列分析（自动测序）。结果正常人组未见异常，患者组有２例突变纯合子，占患者总数４４％，１１例杂合子，占患者总数２４４％。酶切的异常率为２８８％。序列分析证实所有异常表现者均为Ｇ２２７３Ｔ置换，即Ａｒｇ７７８Ｌｅｕ突变。并检测和分析了３个高频突变家系。结论ＡＴＰ７Ｂ基因的８号外显子７７８密码子为中国人肝豆状核变性患者的高频突变点。用ＰＣＲ－酶切的方法可以作为检测中国人肝豆状核变性患者基因突变的快速诊断方法     

高血压合并急性脑血管病的心率变异分析

目的：探讨急性脑组织损害对原发性高血压（ＥＨ）患者心率变异（ＨＲＶ）的影响。方法：对２６例ＥＨ并急性脑血管病（ＡＣＶＤ）患者进行２４ｈ动态心电图ＨＲＶ测定,并与２０例ＥＨ元ＡＣＶＤ患者进行对比。结果：ＥＨ并ＡＣＶＤ组最小心率及平均心率明显高于无ＡＣＶＤ组（Ｐ〈０．０１;Ｐ〈０．０１）;２４ｈ相邻Ｒ－Ｒ间期之差的均方根（ｒＭＳＳＤ）、相邻Ｒ－Ｒ间期之差大于５０ｍｓ的心搏数占心搏总数的百分比（ＰＮＮ５     

阿尔茨海默病患者早老素-1基因5号外显子新突变点的研究

目的探讨早老素－１基因突变在散发性阿尔茨海默病（ＳｐｏｒａｄｉｃＡｌｚｈｅｉｍｅｒ′ｓｄｉｓｅａｓｅ,ＳＡＤ）患者发病机制中的作用。方法应用聚合酶链反应－单链构像多态性（ＰＣＲ－ＳＳＣＰ）及ＤＮＡ直接测序技术检测６８名ＳＡＤ患者、１３名血管性痴呆（ＶＤ）患者和６５名正常老年人的早老素－１基因第５号外显子。结果发现４名ＳＡＤ患者的ＰＣＲ产物ＳＳＣＰ分析发生泳动异常,ＤＮＡ序列分析发现：这４名ＳＡＤ患者的１３０号密码子发生了ＣＴＧ→ＡＴＧ错义突变（３８８位点发生Ｃ→Ａ突变）,使编码的氨基酸由亮氨酸变为蛋氨酸（Ｌｅｕ１３０Ｍｅｔ）;１５７号密码子发生了ＧＴＧ→ＣＴＧ错义突变（４６９位点发生Ｇ→Ｃ突变）,使编码的氨基酸由缬氨酸变为亮氨酸（Ｖａｌ１５７Ｌｅｕ）,另有１１名患者ＳＳＣＰ表现为一条单链增快,其性质待定。结论ＳＡＤ患者也存在早老素－１基因第５号外显子突变,该突变点可能为中国人ＳＡＤ患者早老素基因突变点之一。     

34例肝豆状核变性患者24小时大便微量元素含量的测定

国内尚少有肝豆状核变性（ＨＬＤ）的２４ｈ大便微量元素测定的报道，本文将３４例住院确诊为ＨＬＤ患者的２４ｈ大便中铜、锌、铁、钙含量的测定报告如下。资料一般资料：３４例ＨＬＤ患者中，男２３例，女１１例；年龄８～３０岁，平均（１７４±５５）岁。病程３个...     

高血压合并急性离出血管病的心率变异性改变

对原发性高血压（ＥＨ）合并急性脑血管病（ＡＣＶＤ）患者３０例进行２４小时动态心电图心率变异性（ＨＲＶ）测定，并与３０例无ＡＣＶＤ的ＥＨ患者进行对比。结果显示，合并ＡＣＶＤ组最小心率及平均心率明显高于对照组（Ｐ〈０．０１、〈０．００１）；ＳＤＮＮ、ｒＭＳＳＤ、ＰＮＮ５０比对照组明显减低（Ｐ〈０．００１、〈０．０１、〈０．００１）。提示合并ＡＣＶＤ的ＥＨ患者ＨＲＶ减低，其主要原因可能是自主神经中枢损害     

高血压合并急性脑血管病的心率变异性改变

对原发性高血压（ＥＨ）合并急性脑血管病（ＡＣＶＤ）患者３０例进行２４小时动态心电图心率变异性（ＨＲＶ）测定，并与３０例无ＡＣＶＤ的ＥＨ患者进行对比。结果显示，合并ＡＣＶＤ组最小心率及平均心率明显高于对照组（Ｐ＜０．０１、＜０．００１）；ＳＤＮＮ、ｒＭＳＳＤ、ＰＮＮ５０比对照组明显减低（Ｐ＜０．００１、＜０．０１、＜０．００１）。提示合并ＡＣＶＤ的ＥＨ患者ＨＲＶ减低，其主要原因可能是自主神经中枢损害。     

注意缺陷/多动障碍与注意缺陷障碍对照分析

儿童多动症又名注意缺陷障碍,在中国精神疾病分类方案与诊断标准（ＣＣＭＤ－２－Ｒ）中,必须同时具备显著的注意力不集中和活动过度［１］。我们在临床工作中发现部分患儿并无多动、冲动表现。为了探讨他们的差异,本文将伴与不伴多动的儿童多动症分别定名为注意缺陷／多动障碍（ＡＤ／ＨＤ）和注意缺陷障碍（ＡＤＤ）,对照分析两者的有关资料。１ 资料病人均来源于南京儿童中心１９９８年６～８月门诊咨询患儿,其中ＡＤ／ＨＤ７２例,ＡＤＤ ７４例。１．１ 性别与发病年龄;ＡＤ／ＨＤ组男６６例,女６例;ＡＤＤ组男５０例,女２４…     

伴与不伴注意缺陷多动障碍的抽动秽语综合征患儿动态脑电图的 …

目的 探讨与不伴注意缺陷多动障碍（ＡＤＨＤ）的抽动微语综合征（ＴＳ）患儿间脑电图的差异。方法 对８６例伴与不伴ＡＤＨＤ的ＴＳ患儿进行２４ｈ动态脑电图（ＡＥＥＧ）监测。结果 伴ＡＤＨＤ的ＴＳ组（４０例）ＡＥＥＧ异常率为７５％,单纯ＴＳ组（４６例）异常率为３０％,２组差异有显著性（Ｐ〈０．０５）;ＡＥＥＧ异常的主要表现为慢波异常以及癫痫样波,伴ＡＤＨＤ的ＴＳ组的ＡＥＥＧ局部异常多于广泛异常,且以额叶受     

载脂蛋白B基因信号肽插入／缺失多态性与动脉粥样硬化性脑梗塞关系的研究

应用聚合酶链反应（ＰＣＲ）技术检测了４０例动脉粥样硬化性脑梗塞（ＡＣＩ）患者和４２名正常人ａｐｏＢ基因信号肽插入／缺失（Ｉｎｓ／Ｄｅｌ）长度多态性。结果ＡＣＩ组中Ｉｎｓ等位基因频率为０．８５，高于对照组的０．７４，但差别无显著性。正常对照组ＩＤ＋ＤＤ基因型个体其Ｔ－ｃｈ、ＬＤＬ－ｃｈ水平，ＡＣＩ组ＩＤ基因型个体ＬＤＬ－ｃｈ水平均明显高于相应的Ⅱ型个体。本研究结果表明ａｐｏ－Ｂ基因信号肽插入／缺失多态性单独可能并不能作为中国汉族人群ＡＣＩ易感个体的遗传标记。     

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.