血管紧张素I转换酶基因多态性与急性脑血管病的关系

目的 研究血管紧张素转换酶（ＡＣＥ）基因多态性和急性脑血管病（ＡＣＶＤ）的发病关系。方法 应用ＰＣＲ方法检测１５０例ＡＣＶＤ患者和１１７名正常人ＡＣＥ基因的缺失／插入多态性，同时测定血浆血管紧张素ＩＩ（ＡｎｇⅡ）水平。结果 ＡＣＶＤ患者的ＡＣＥ基因型及等位基因频率和正常对照组比较差异无显著意义，脑卒中和高血压家族阳性患者的ＤＤ型及Ｄ等位基因频率明显高于阴性家族史的患者，ＡＣＶＤ患者血浆ＡｎｇⅡ水平     

脑卒中患者血管紧张素转换酶基因多态性分析

目的：研究血管紧张素转换酶（ＡＣＥ）基因多态性和脑卒中的发病关系。方法：应用ＰＣＲ方法检测１０５例脑卒中患者、１０６例原发性高血压（ＥＨＴ）患者及６４例正常人的 ＡＣＥ基因的缺失／插人（Ｄ／Ｉ）多态性。结果：脑卒中组ＡＣＥ基因型及等位基因频率与ＥＨＴ组及正常对照组比较差异无显著意义,脑卒中组中脑梗死组和脑出血组分别与正常对照组比较ＡＣＥ基因型均无显著差异。脑卒中伴ＥＨＴ组与无伴ＥＨＴ组比较,Ⅱ基因型频率明显升高,而ＤＤ基因型频率则明显降低;脑卒中伴 ＥＨＴ组Ⅱ基因型频率明显高于 ＥＨＴ组,而 ＤＤ基因型频率远低于 ＥＨＴ组和正常对照组,同时脑卒中伴ＥＨＴ组的平均年龄较其它组明显高。结论：原发性高血压患者中Ⅱ基因型携带者可能具有卒中易感性,ＤＤ基因型携带者有随年龄增加而减少的趋势。     

血管紧张素转换酶基因多态性与高血压合并脑血管病的关系

目的　研究血管紧张素转换酶 (ACE)基因多态性和高血压合并脑血管病的关系。方法　应用PCR方法检测正常对照者 (6 6人 )、高血压 (4 0例 )、高血压脑梗死 (5 4例 )、腔隙性脑梗死 (4 5例 )、高血压合并脑出血 (33例 )患者的ACE基因插入 /缺失 (I/D)多态性 ,同时测定 6例脑梗死患者急性期和恢复期血浆血管紧张素Ⅱ (AngⅡ )水平。结果　高血压患者的ACE基因型及等位基因频率和正常对照组及高血压合并不同脑血管病患者比较无显著差异 (P >0 0 5 ) ,高血压合并不同脑血管病患者的ACE基因型及等位基因频率和正常对照组比较无显著差异 ,但高血压合并脑出血组的ACE基因型及等位基因频率较其他组高 ;脑梗死患者急性期血浆AngⅡ水平显著高于恢复期 (P <0 0 5 )。结论　高血压合并脑出血的发病可能与ACE基因I/D多态性有关 ,血浆AngⅡ水平升高可能是脑梗死患者急性期血压升高的因素之一     

脑梗死患者血管紧张素转换酶基因多态性的研究

目的 研究肾素－血管紧张素转换酶（ＡＣＥ）基因多态性与脑梗死的关系。方法 通过ＰＣＥ方法研究７６例脑梗死患者（其中高血压患者５１例）及３０例健康对照者的ＡＣＥ基因。结果 脑梗死组ＤＤ／ＩＩ基因型显著增高／降低（Ｐ〈０．０５,Ｐ〈０．０１）,尤其伴设备在压的脑梗死患者这种趋势更为明显。结论 ＡＣＥ基因多态性和高血压脑梗死患者有关联性,ＤＤ基因型提示可能与高血压患者发生脑梗死有关,而ＩＩ型为保护型基因     

动脉粥样硬化性脑梗塞患者ACE基因与AT1R基因多态性分析

目的探讨在动脉粥样硬化性脑梗塞（ＡＣＩ）发生中血管紧张素转换酶（ＡＣＥ）基因与血管紧张素Ⅱ受体１型（ＡＴ１Ｒ）基因多态性的关系。方法采用聚合酶链反应－限制性片段长度多态性技术分别检测８１例ＡＣＩ患者和１０２例健康对照的ＡＣＥ和ＡＴ１Ｒ基因型。结果ＡＣＥ基因ＤＤ型与ＡＣＩ的发生显著相关（Ｐ＜０．０５）。在携带有ＡＣＥ基因ＤＤ型的群体中，ＡＴ１Ｒ基因型ＡＡ的个体患ＡＣＩ的比数比为１．３９，ＡＴ１Ｒ基因型ＡＣ患ＡＣＩ的比数比为３．６６，ＡＴ１Ｒ基因型ＣＣ患ＡＣＩ的比数比为５．８４。结论在ＡＣＩ发生中ＡＣＥ基因和ＡＴ１Ｒ基因多态性具有协同作用。     

缺血性脑血管病患者ACE基因缺失多态性分析

目的研究血管紧张素转换酶（ＡＣＥ）基因插入／缺失多态性与ＩＣＶＤ的关系。方法应用聚合酶链式反应（ＰＣＲ）技术，对８８例缺血性脑血管病（ＩＣＶＤ）组患者和８２例对照组人群分别检测其基因频率和基因型频率。结果ＤＩ等位基因频率之比脑血管病组为０．５９０．４１，对照组为０．４２０．５８（Ｐ＜０．０５）；ＤＤ基因型在ＩＣＶＤ组更多见（３１／８８例），对照组１５／８２例（Ｐ＜０．０５）；ＤＤ基因型对各种类型ＩＣＶＤ的相对危险性为２．４３，进一步分析表明，其危险性增高主要是由腔隙性梗塞和脑栓塞所致。结论ＡＣＥ基因缺失多态性与ＩＣＶＤ的发生显著相关，ＡＣＥ基因的缺失多态性对腔隙性梗塞和脑栓塞均可能是独立的危险因素。     

缺血性脑血管病患者载脂蛋白E基因多态性分布

为研究中国汉族缺血性脑血管病（ＩＶＣＤ）患者ＡｐｏＥ基因主等位基因分布状况、随机选择ＩＶＣＤ患者９３例，平均年龄６３．９岁；并选择同龄非ＩＣＶＤ受检者１００例进退这构象多态性（ＳＳＣＰ）技术检测ＡｐｏＥ基因型。主要结果如下：（１）ＩＣＶＤ患者组ＡｐｏＥε３／３频率明显低于同龄对照组，（２）中年组ＩＣＶＤ患者中ε３／３为５６．７８％，明显低且之７３．０７％，ε４／２频率（３１．３７％）较同龄对照组（     

血管紧张素转换酶基因多态性与高血压并脑梗死的关系

目的：探讨中国人中血管紧张素转换酶（ＡＣＥ）基因插入／缺失（Ｉ／Ｄ）与脑梗死的关系。方法：原发性高血压患者８９例,其中并发脑梗死４１例,正常对照组３０例,应用ＰＣＲ技术检测ＡＣＥ基因１６内含子的Ｉ／Ｄ多态性片段可分为三种基因型：纯合子缺失型（ＤＤ）、纯合子插入型（Ⅱ）,杂合子型（ＩＤ）。结果：显示,高血压并发脑梗死患者的Ｄ等位基因频率（０．６４）高于单纯ＥＨ（０．４２）和正常对照组（０．４５）。结     

ACE基因多态性与脑出血的相关性研究

目的　探讨血管紧张素转换酶 (ACE)基因多态性和脑出血发病的关系。方法　应用 PCR方法检测82例脑出血患者和 86例健康者 ACE基因的缺失 /插入多态性。结果　脑出血患者的 DD基因型及 D等位基因频率和正常对照组比较差异有显著意义 ;伴高血压的脑出血患者的 DD基因型和 D等位基因频率明显高于无高血压的脑出血患者 ;无高血压史的脑出血患者的 DD基因型和 D等位基因频率明显高于正常对照组 ;DD基因型和 D等位基因频率与性别、有无糖尿病、高脂血症及吸烟无关。结论　 DD基因型和 D等位基因携带者具有脑出血易感性 ,这种易感性不依赖于高血压     

急性脑血管病与糖耐量,胰岛素水平,肾素,血管紧张素—醛固酮？…

目的：探讨糖耐量（ＯＧＴＴ）胰岛素水平（ＦＩＮＳ）肾素（ＰＲＡ）、血管紧张素（ＡＩＩ）一醛固酮（ＰＡ）与急性脑血管病（ＡＣＶＤ）的关系。方法：随机收集既往无尿辣的脑出血和脑梗死及正常对照者各３１例，用放射免疫计数法测定ＰＲＡ、ＡＩＩ、ＰＡ的血浆含量；用放射免疫顺序饱和法测定血浆ＦＩＮＳ，及ＯＧＴＴ的测定。结果：糖耐量低下者脑出血１６例，脑梗死１５例；ＦＩＮＳ病例组均高于对照组；ＰＲＡ、ＡＩＩ、ＰＡ     

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.     

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.     

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.     

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.     

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.     

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.