氟哌啶醇的药代动力学研究

为给临床合理用药提供参考依据，作者对２７例精神分裂症病人和正常志愿者分别口服、肌注５ｍｇ氟哌啶醇和５０ｍｇ氟哌啶醇癸酸酯（ＨＤ），用放射免疫法测定血中氟哌啶醇浓度，所得药代动力学参数如下：（１）口服组达峰时（Ｔｐｅａｋ）３．０±１．３小时，峰浓度（Ｃｍａｘ）１２．７±６．４μｇ／Ｌ，消除相半衰期（Ｔ）１８．２±５．１小时，清除率（ＣＬ）０．４０±０．１３Ｌ／ｍｉｎ；（２）肌注组达峰时１．０±０．９小时，峰浓度１４．１±７．５μｇ／Ｌ，消除相半衰期１８．３±１０．１小时，清除率０．５０±０．２５Ｌ／ｍｉｎ；（３）肌注ＨＤ组达峰时７．６５±３．３１天；峰浓度９．８９±．３９μｇ／Ｌ；消除相半衰期１９．２３±１２．９２天；清除率０．４７±０．４８（ｍｇ／天）／（μｇ／Ｌ）；药时曲线下面积（ＡＵＣ）２０８±３９３μｇ／Ｌ·天。     

高效液相色谱检测血中氟西汀浓度

以氯丙咪嗪为内标，用ＨＰＬＣ方法测定抗抑郁剂氟西汀的血药浓度。血清经碱化，用１．５％异丙醇的正庚烷抽提，使用Ｃ１８柱，在２３０ｎｍ进行色谱分析。批内批间的相对标准偏差小于４．３２％，最低检测３０ｎｍｏｌ／Ｌ．对４例服用氟丁汀的病人进行血浓检测，表明本法灵敏，快速，适于血浓监测和药动学研究。     

甲状腺机能亢进并发脑梗死3例报告

甲状腺机能亢进（简称甲亢）并发神经系统损害以肌肉和周围神经症状多见,而并发脑梗死者甚少。本文报道甲亢并发脑梗死３例如下。１　病例１．１　例１　男,１８岁。多食、消瘦、乏力、心悸伴甲状腺肿大２年,于１９９６年５月３日入院。查体：Ｔ３８．２℃,Ｐ１４２次／分,ＢＰ１８／８ｋＰａ,表情亢奋,双眼球略突出,双侧甲状腺Ⅱ°肿大,无结节,双上极闻及血管杂音,双肺（－）,心率１４２次／分,心律不齐,未闻及病理性杂音。实验室检查：Ｔ３８．６μｇ／Ｌ（参考值０．８～２．２μｇ／Ｌ）,Ｔ４１５２．４μｇ／Ｌ（参考值…     

注意缺陷多动障碍患儿血清儿茶酚胺类递质的测定

目的探讨注意缺陷多动障碍（ＡＤＨＤ）可能的精神生化机制。方法采用高效液相色谱法，测定了经哌醋甲酯治疗后的６４例ＡＤＨＤ男性患儿和３０名正常男性儿童的血清儿茶酚胺类递质及其代谢产物水平。结果ＡＤＨＤ患儿血清去甲肾上腺素（ＮＥ）水平和ＮＥ／３－甲氧－４－羟苯乙二醇（ＭＨＰＧ）比值（２７±１８）低于正常儿童（１５２±５７），血清高香草酸水平（３．９±２．９μｇ／Ｌ）高于正常儿童（０．８±０．３μｇ／Ｌ）；经哌醋甲酯治疗有效者血清ＭＨＰＧ水平（１３±１０μｇ／Ｌ）高于无效者（８±５μｇ／Ｌ）；智力发育不平衡组血清ＮＥ水平（８４±４３μｇ／Ｌ）低于智力发育平衡组（８９±５８μｇ／Ｌ）；根据美国精神障碍诊断统计手册第３版修订本，将病情分为轻度、中度和重度，重度ＡＤＨＤ患儿血清ＮＥ水平（８２±４５μｇ／Ｌ）明显低于轻度（１０５±５９μｇ／Ｌ）。结论ＡＤＨＤ可能是多巴胺能和去甲肾上腺素能两种递质系统失调或失衡的结果。     

脑脊液肿瘤坏死因子及白细胞介素6的检测对感染性脑膜炎鉴别诊断的临床意义

目的探讨脑脊液肿瘤坏死因子及白细胞介素６的检测对感染性脑膜炎鉴别诊断的价值。方法留取２７例各型脑膜炎（化脓性脑膜炎９例、结核性脑膜炎７例、隐球菌性脑膜炎４例及病毒性脑膜炎７例）患者脑脊液,检测肿瘤坏死因子及白细胞介素６的含量。同时设正常脑脊液对照组３０例。结果脑膜炎组肿瘤坏死因子浓度为２６４．２４±７８．９４ｎｇ／Ｌ;白细胞介素６浓度为３．１８±０．６３μｇ／Ｌ,两者均明显高于对照组（Ｐ＜０．０１）。但各型脑膜炎间肿瘤坏死因子及白细胞介素６的浓度相比较,相差不显著（Ｐ＞０．０５）。结论检测脑膜炎患者脑脊液中肿瘤坏死因子及白细胞介素６对感染性脑膜炎患者鉴别诊断无临床意义。     

反复发作抑郁症甲状腺激素水平对照观察

目的　了解反复发作抑郁症患者的甲状腺激素水平。方法　按性别、年龄１∶１ 匹配选取序贯就诊的患者和体检健康者各２８例，采用放射免疫法测定患者组治疗前后和对照组血清 Ｔ３ 、 Ｔ４ 、ｒ Ｔ３ 和 Ｔ Ｓ Ｈ 浓度。结果　患者组治疗前、后血 Ｔ４ 水平（１３５４ ±２２ ．０） μｇ／ Ｌ和（１１３１ ±２０ ．３）μｇ／ Ｌ ，明显高于对照组（１０３９ ±１０ ．３）μｇ／ Ｌ ，治疗后 Ｔ４ 明显下降；治疗前 Ｔ４ 与 Ｈ Ａ Ｍ Ｄ 评分呈显著性正相关（ｒ ＝ ０４１ ， Ｐ＜００５） 。结论　反复发作抑郁症 Ｔ４ 升高继发于情绪障碍，治疗前血清 Ｔ４ 水平能预测患者的抑郁严重度。     

MPTP对小鼠纹状体多巴胺的影响

用高效液相色谱法检测Ｃ（５７）ＢＬ／６Ｊｏｌａ型老龄及幼龄鼠注射１－甲基－４－苯基－１、２、３、６四氢吡啶（ＭＰＴＰ）两周及两个月后纹状体多巴胺含量，发现幼龄鼠两个月后多巴胺含量由两周时的１．９±０．４μｇ／ｇ（以与对照组比较减少８２％）升高至５１．１±０．５μｇ／ｇ（与对照组比较减少５２％）；而老龄鼠则无明显改变。这说明龄鼠多巴胺神经元损害修复的功能减退，这可能是帕金森氏病多发于老年人的原因之一。     

海洛因对人体细胞免疫的影响及其机理

目的探讨长期静脉注射海洛因对人体细胞免疫功能的影响。方法以Ｔ细胞亚群、白细胞介素２（ＩＬ２）、白细胞介素６（ＩＬ６）及一氧化氮（ＮＯ）为指标，检测２２例长期静脉注射海洛因患者的细胞免疫功能改变，并与正常人相对照。结果海洛因依赖者外周血中的ＣＤ＋４Ｔ细胞数（２９．１±１２．７）较对照组（５３．０±１０．１）降低，ＣＤ＋４／ＣＤ＋８比值倒置，有丝分裂原诱导的ＩＬ２水平（３７．８±１１．４μｇ／Ｌ）较对照组（３．８±０．６μｇ／Ｌ）降低，ＩＬ６水平（５５．０±１０．４ｍｇ／Ｌ）较对照组（２．９±０．５ｍｇ／Ｌ）增高，ＮＯ含量（７１．１±１３．３μｍｏｌ／Ｌ）较对照组（５４．６±１７．７μｍｏｌ／Ｌ）增高。结论长期使用海洛因可抑制人体的细胞免疫功能，辅助性Ｔ淋巴细胞１和辅助性Ｔ淋巴细胞２之间的功能失调可能是其细胞免疫功能抑制的中介因素之一。     

L—NAME加强麻醉大鼠低血压诱发的催产素释放作用

取戊巴比妥麻醉大鼠向侧脑室内分别注射一氧化氮合酶的底物Ｌ－精氨酸和ＮＯ合酶抑制剂Ｎ＾Ｇ－硝基－Ｌ－精氨酸甲酯,用放射免疫法测定血浆中催产素水平。结果：侧脑室内注射Ｌ－精氨酸（１００ｇ／Ｌ,１０μＬ,ｎ＝８）和Ｌ－ＮＡＭＥ（５４．０ｔ／Ｌ,５μＬ,ｎ＝１２）,对Ｏ物基础分泌无明显的影响;侧脑室内注射５μＬ Ｌ－ＮＡＭＥ（剂量（１：２７,ｇ／Ｌ,ｎ＝９;剂量２：５４。０ｇ／Ｌｎ＝９）可进一步增强静脉输     

一氧化氮与帕金森病小鼠模型神经损害的研究

目的　研究一氧化氮（ＮＯ） 在帕金森病（ＰＤ）小鼠模型神经损害中的作用。方法　用比色分析、高效液相色谱电化学及免疫组化法检测１甲基４苯基四氢吡啶（ＭＰＴＰ）和７硝基吲唑（７ＮＩ）对Ｃ５７ＢＬ小鼠纹状体一氧化氮合酶（ＮＯＳ） 活性,多巴胺（ＤＡ）、二羟基苯乙酸（ＤＯＰＡＣ）、高香草酸（ＨＶＡ） 水平和酪氨酸羟化酶（ＴＨ） 免疫阳性神经纤维的影响。结果　注射ＭＰＴＰ后Ｃ５７ＢＬ小鼠纹状体ＮＯＳ活性增加,７ＮＩ能明显抑制ＭＰＴＰ引起的ＮＯＳ活性的升高（ 分别为０ ．９３ ±０．２４ 和０．５４ ±０．１６,ｎｍｏｌ·ｍｉｎ－１·ｇ－１ 组织,Ｐ＜０．０１） 。７ＮＩ能明显减轻ＭＰＴＰ引起的Ｃ５７ＢＬ小鼠纹状体ＤＡ（ 分别为０ ．８ ±０ ．２ 和６．８±０．５,μｇ／ｇ 组织,Ｐ＜０．０１） 、ＤＰＯＡＣ（ 分别为０．３ ±０．１ 和０ ．９ ±０ ．３ ,μｇ／ｇ 组织,Ｐ＜ ０ ．０１）、ＨＶＡ（分别为０．４±０．２ 和０．９ ±０ ．２,μｇ／ｇ 湿组织,Ｐ＜ ０．０１） 的降低及ＴＨ 阳性神经纤维损害。结论神经元来源的ＮＯ 参与了ＭＰＴＰ的毒性机制,神经元型ＮＯＳ抑制剂可能有益于ＰＤ的治疗。     

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.