高血压性脑出血与血管紧张素转换酶基因多态性及血清水平关系的研究

目的：探讨原发性高血压（EH）,高血压性脑出血（CH）与血管紧张素转换酶（ACE）基因I／D多态性及血清ACE水平的相互关系。方法：对正常人（NC组）29例,EH组28例和CH组31例提取白细胞DNA,检测ACE基因型,等位基因和血清水平。结果：88例中不同ACE基因型血清ACE水平有显著性差异（DD＞ID＞II,P＜0．01）,EH组DD基因及D基因频率与NC组比较无显著性差异（P＜0．05）,CH组血清ACE水平和D基因频率显著高于NC组及EH组（P＜0．01）,其DD型的血清ACE水平也高于后二者（P＜0．05）,结论：ACE基因多态性及其血清水平与EH无关,而与CH呈正相关,D基因可能为高血压病患者脑出血发病的相对危险因素。     

丛集性头痛的血小板儿茶酚胺

作者报告33例丛集性头痛(CH)患者的血小板儿茶酚胺(CA)含量。其中男30例,女3例,年龄22～64岁(平均43岁)。在缓解期,丛集期(单一发作除外)和单一发作期测定血小板去甲肾上腺素(NE)、肾上腺素(E)和酪氨酸水平。并与15例(男13、女2)、年龄25～55岁(平均41岁)的对照组进行比较。所有受试者受试前2周内无用药,CH 发作期仅给吸O_2。结果:对照组与CH 病人缓解期或丛集期(C-luster period),血小板酪氨酸水平(nm/10~(10)血小板)无显著差异。单一发作期与缓解期或丛集期以及对照组相比,血小板酪氨酸水平显著增加。12例病人连续研究结果[发作期0.17(0.03)、缓解期0.111     

精神分裂症患者嫉妒妄想与血清睾丸酮和雌二醇水平相关性分析

目的探讨精神分裂症患者嫉妒妄想的形成与患者血清睾丸酮、雌二醇水平变异的内部联系。方法将29例有嫉妒妄想的精神分裂症患者（研究组）、33例无嫉妒妄想的精神分裂症患者（对照组）分别于治疗前及治疗后采用放射免疫法进行男性血清睾丸酮（T）、女性雌二醇（E2）含量的测定并进行统计学比较。结果T及E2水平测量，经药物治疗嫉妒妄想未消失的患者治疗前、后自身比较无差异性（P〉0．05），嫉妒妄想消失的患者治疗前、后自身比较有差异性（P〈0．05），研究组与对照组比较有差异性（P〈0．05），与22例正常人组比较差异有显著性（P〈0．01）。结论精神分裂症患者嫉妒妄想的形成与血清睾丸酮（T）、雌二醇（E2）水平存在一定相关性。     

精神分裂症患者血清催乳素和生长激素水平与奎硫平、氟哌啶醇治疗关系的对照研究

目的研究精神分裂症患者血清催乳素(PRL)、生长激素(GH)的基础水平与正常人的差异,以及奎硫平、氟哌啶醇治疗前后PRL、GH的变化。方法采用放射免疫法检测126例精神分裂症患者(包括奎硫平组62例和氟哌啶醇组64例)治疗前和治疗8周后PRL、GH水平,观察这2种药物对PRL、GH的影响及比较两者的差异,并与65名健康者进行对照分析。结果 126例精神分裂症患者的基础PRL、GH水平与对照组比较无显著性差异(P>0．05),奎硫平组治疗后PRL和GH均无显著改变(P>0．05)。氟哌啶醇组治疗后PRL值为(96．20±41．12)μg/L,较治疗前的(20．39±11．26)μg/L显著升高(P<0．01),女性升高更明显,为男性的 2．6倍。氟哌啶醇组治疗后GH值为(1．72±1．32)μg/L,较治疗前的(2．41±11．26)μg/L显著降低(P<0．01)。结论奎硫平治疗精神分裂症患者,对PRL及GH无明显影响,更适合生长期的青少年患者和药物性溢乳、乳房发育患者。     

性激素水平与脑卒中病情及预后的关系

目的 研究血清性激素水平与脑卒中病情程度及预后的关系。方法 采用放射免疫法测定老年急性脑卒中127例及对照组39例的性激素水平。结果 脑卒中组男性血清雌二醇（E2）明显比对照组高（P＜0．05）,女性血清睾酮（T）比对照组高（P＜0．05）;脑卒中组男性T水平及女性E2水平与对照组比较均无显著性差异。脑卒中患者性激素水平与病情程度无关。但与疾病的预后有关,即预后越好,E2升高、T降低,E2／T值上升越明显。结论 E2对脑卒中患者的受损脑细胞可能具有保护作用,而T具有加重脑损害的可能。E2／T值对预测脑卒中患者的预后具有一定的临床价值。     

绝经期脑梗死垂体—性腺轴变化的临床研究

目的 探讨脑梗死病人垂体－性腺轴功能变化的规律,为小剂量雌激素补充疗法提供理论依据。方法 采用放射免疫法,检测血清促卵泡素（FSH）、黄体生成素（LH）、雌二醇（E2）、催乳素（PRL）浓度。绝经期脑梗死病人68例,皮层动脉梗死（CAIG）26例,穿通动脉腔隙性梗死（PAIG）42例,健康对照组26例。结果 脑梗死组血清FSH、LH及E2显著低于正常组（P＜0．01）,PRL轻度升高（P＜0．05）;CAIG组和PAIG组血清FSH、LH、及PRL比较差异无显著性（P＞0．05）,CAIG组E2轻度升高（P＜0．05）。结论 脑梗死病人垂体－性腺轴功能显著减退,不受脑梗死部位及范围的影响,小剂量补充雌激素将有可能预防脑梗死。     

罗格列酮对乙烯雌酚诱发的大鼠泌乳素腺瘤治疗作用的初步研究

目的采用乙烯雌酚（DES）诱发方法建立垂体催乳素（PRL）腺瘤模型，研究罗格列酮对PRL腺瘤的影响。方法首先将20只雌性Wistar大鼠分为皮下植入含DES硅胶管的DES组（A0组）及皮下植入空白硅胶管的空白对照组（B0组）。8周后处死所有大鼠，观察并比较两组大鼠的血清PRL水平、垂体质量、垂体中PRL蛋白分布及细胞周期素D1（Cyclin D1）的表达。然后取雌性Wistar大鼠40只．皮下均植入含DES的硅胶管．8周时分为空白对照组（A组），溴隐亭组（B组）、大剂量罗格列酮组（C组）、中剂量岁格列酮组（D组）、小剂量罗格列酮组（E组）。药物干预4周后分别处死大鼠．观察各组大鼠血清PRL水平、垂体质量、垂体中PRL蛋白分布及Cyclin D1的表达，结果雌性Wistar大鼠皮下埋植含DES的硅胶管8周后均能形成垂体PRL腺瘤。在B、C组．药物干预后血清PRL值、垂体质量、垂体中PRL蛋门分布均较A、D、E、A0组降低，差异有统计学意义（P〈0．05）：但B、C组间差异无统计学意义（P〉0．05），C组垂体中CyclinD1表达较A、B组及A0组降低，差异有统计学意义（P〈0．05）。结论罗格列刚对DES诱发的大鼠PRL腺瘤有治疗作用。     

sIL-2R、mIL-2R及TNF-α在多发性硬化症免疫学发病机制中的作用

目的探讨可溶性白细胞介素-2受体（sIL－2R）、膜白细胞介素-2受体（mIL－2R）和肿瘤坏死因于-α（TNF－α）与多发性硬化（MS）免疫学发病机制、病程及病情的关系。方法采用ELkA法检测了临床确诊的48例MS患者血清、28例CSF中sIL－ZR水平，用免疫荧光法检测28例MS患者血中mIL－2R的表达，用生物活性测定法检测28例MS患者PBMCs体外诱生TNF－α水平。结果MS患者组激素治疗前血清及CSF中sIL－1R和血中TNF－α水平显著高于对照组（NC组）（P＜0．01），其中急性复发组MS显著高于缓解组（P＜0．01）；治疗后血清SIL－2R及TNF－α水平较治疗前显著下降（P＜0．01），且二者水平仍显著高于NC组（P＜0.01）。而缓解组TNF－α水平低于NC组（P＜0．05）。MS组血中mIL－2R表达，急性复发期MS患者显著高于缓解期（P＜0．01）及NC组（P＜0．01），缓解期MS患者则又显著低于NC组（P＜0．01）。MS患者血中sIL－2R及TNF－α水平与病情显著相关而与病程无关，sIL－2R与TNF－α显著相关。结论sIL－2R，mIL－2R、TNF－α在MS免疫发病中可能起重要作用，为探讨MS免疫发病机制进一步提供了理论依据。     

急性脑梗死患者血清基质金属蛋白酶-2、基质金属蛋白酶组织抑制因子-2的变化及其意义

目的观察急性脑梗死患者血清基质金属蛋白酶-2（MMP-2）及基质金属蛋白酶组织押制因子-2（TIMP-2）水平的变化，探讨其在急性脑梗死的发病机制中的作用及临床意义。方法采用酶联免疫吸附法对56例急性脑梗死患者（CI组）及49例健康时照组（NC组）进行血清MMP-2、TIMP-2测定。结果CI组血清MMP-2水平在发病后呈先增高后降至NC组水平的趋势，病程〈24h、2～5d、28d分别为（46.29±14．37）μg／L、（62．18±12．32）μg／L、（35．72±8．91）μg／L，其中以2～5d时最高，与CI组病程〈24h、28d、NC组比较有显著性差异（P〈0．05）。CI组血清TIMP-2水平在病程〈24h、2～5d、28d分别为（186．14±27．91）μg／L、（160．62±25．49）μg／L、（189．01±33．17）μg／L，其中以2～5d时最低，与CI组病程〈24h、28d、NC组比较有显著性差异（P〈0．05）。结论急性脑梗死患者存在血清MMP-2、TIMP-2水平异常，提示MMP-2、TIMP-2参入脑梗死病理过程。     

血清尿酸与多发性硬化关系的研究

目的 探讨多发性硬化（MS）患者血清尿酸水平的改变与临床的关系。方法 检测88例MS患者（MS组）血清尿酸水平,分析其与临床分期、病程、病情的关系;并与其他神经系统炎症性疾病患者（OIND组）和健康体检人员（正常对照绀）比较。结果 MS组血清尿酸水平明显低于OIND组及正常对照组（均P〈0．05）,处于MS急性复发期患肯的血清尿酸水平低于缓解期患者（P〈0．05）。血清尿酸水平与MS的临床分期独口相关（P〈0．05）,与病橼和扩展后的功能障碍状况量表评分不相关（均P〉0．05）。结论 血清尿酸水平的变化可作为MS诊断及判断MS患者不同临床分期的辅助指标。     

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.