奥氮平治疗精神分裂症剂量、血药浓度和临床效应的性别差异

目的　研究奥氮平治疗精神分裂症的剂量、血药浓度和临床效应的性别差异。方法　采用高剂量奥氮平 [0 .36mg/(kg·d) ]治疗男、女性患者各 10例和 5例 ,中剂量奥氮平 [0 .18mg/(kg·d) ]治疗男、女性患者各 2 0例和 10例 ,低剂量奥氮平 [0 .0 9mg/(kg·d) ]治疗男、女性患者各 10例和 5例。疗效和不良反应分别用PANSS和TESS量表评定 ,用HPLC法测定治疗后 2、4、8、周末稳态血药浓度。结果　奥氮平高、中剂量组疗效无性别差异 (P >0 .0 5 ) ,低剂量组女性疗效显著好于男性 (P <0 .0 5) ,奥氮平同等剂量时女性的血药浓度显著高于男性(P <0 .0 5 ) ,尤以高剂量组为甚(P <0 .0 1) ,高剂量组女性不良反应显著高于男性 (P <0 .0 1)。结论　女性精神分裂症患者接受奥氮平治疗以中、低剂量 [0 .0 9～ 0 .18mg/(kg·d) ]为宜     

奥氮平治疗精神分裂症的疗效与其血药浓度的相关性分析

目的　探讨奥氮平治疗精神分裂症的疗效、副反应与血药浓度的关系 ,有效血药浓度的范围。方法　用阴性与阳性症状量表 (PANSS)、简明精神病评定量表 (BPRS)、社会功能缺陷筛选量表 (SDSS)和副反应量表 (TESS)评定疗效和副反应 ;用反相高效液相色谱法测定病人第 1、8周末的奥氮平血药浓度。结果　奥氮平能明显降低精神分裂症病人的阳性和阴性症状评分 (P <0 0 1) ,副反应主要为嗜睡、口干和体重增加。奥氮平的血药浓度个体差异较大 ,最高浓度为 5 9 83ng/mL ,最低浓度为 3 71ng/mL ,在此浓度范围内 ,奥氮平血药浓度与剂量成正相关 (r=0 3 3 ,P =0 0 2 1)。血药浓度大于 9ng/mL的病人疗效较好 (P <0 0 1) ;BPRS和SDSS的减分率与奥氮平血药浓度之间呈正相关 (P <0 0 5 )。结论　奥氮平能有效治疗精神分裂症 ,改善其社会功能障碍 ;其治疗精神分裂症的疗效与血药浓度有相关性 ,9ng/mL是奥氮平治疗精神分裂症适宜血药浓度的下限。     

奥氮平与氯氮平对精神分裂症急性期的治疗研究

目的　比较奥氮平与氯氮平治疗精神分裂症急性期的疗效及安全性。方法　奥氮平组30例 ,剂量范围 10～ 2 0mg/d ;氯氮平组 2 5例 ,剂量范围 15 0～ 4 0 0mg/d ,两组均以PANSS量表 ,TESS量表评定观察 8周。结果　 (1)奥氮平组和氯氮平组治疗精神分裂症急性期的有效率为 76 .6 7%和72 % (P >0 .0 5 )。 (2 )PANSS总分减分在第 1,2周末 (P <0 .0 5 ) ,PANSS阴性因子分减分在第 1,2 ,4周末 (P <0 .0 1)及第 8周末 (P <0 .0 5 )奥氮平组优于氯氮平组。 (3)奥氮平组的药物不良反应少。结论　奥氮平治疗精神分裂症急性期的疗效肯定、安全性好 ,对急性期阴性症状的治疗效果优于氯氮平。     

小剂量阿司匹林对缺血性脑血管病患者血小板聚集功能的影响

目的 :观察小剂量阿司匹林 (ASA)对ICVD患者血小板聚集功能的影响。方法 :用花生四烯酸 (AA ,5 0 0 μmol·L-1)、二磷酸腺苷 (ADP ,5 μmol·L-1)、肾上腺素 (EPN ,5 μmol·L-1)和胶原 (COL ,2 μg·mL-1)做诱导剂检测ICVD患者服用不同剂量ASA组 ( 2 5、5 0和10 0mg·d-1)的血小板聚集率。结果 :各ASA组对AA、COL诱导聚集的变异系数较大。对AA诱导聚集无显著抑制者的比例分别为2 5mg·d-1组 44 4%、5 0mg·d-1组 2 9 6%、10 0mg·d-1组 2 9% ,其中 5 0mg·d-1组中合并糖尿病的例数较显著抑制者中多。结论 :ICVD患者中小剂量ASA作用个体差异较大 ,部分与自身危险因素有关。提示临床中ASA的效果需要实验室检测并应个体化     

异烟肼对氯氮平血药浓度及疗效的影响

目的　探讨异烟肼对氯氮平血药浓度及疗效的影响。方法　采用自身对照的方法 ,对 2 0例伴肺结核的精神分裂症患者在原来氯氮平治疗的基础上合用异烟肼 ( 0 3g/d)治疗 10周。分别于合用前、合用后 2、6、10周末测定氯氮平稳态血药浓度 ,并采用阳性与阴性症状量表 (PANSS)评定疗效 ,同时采用副反应量表 (TESS)评定两药合用前后的副作用。结果　合用异烟肼前与合用后第 2、6、10周末的氯氮平血药浓度分别为 ( 4 2 0± 14 3 )g/L、( 5 2 9± 2 5 5 )g/L、( 5 3 0± 2 83 )g/L和 ( 5 10± 3 2 9)g/L ,合用前后氯氮平血浓度无显著性差异 (F =0 80 ,P >0 0 5 ) ;合用异烟肼前后患者PANSS及TESS评分比较无显著性差异 (P均大于 0 0 5 )。结论　异烟肼合用氯氮平虽能提高部分精神分裂症患者的氯氮平血药浓度 ,但对患者合用前的精神症状无明显影响 ,两药合用早期应监测氯氮平血药浓度。     

利培酮对精神分裂症患者血浆高香草酸的影响

目的　探讨利培酮对精神分裂症患者中枢多巴胺代谢产物血浆高香草酸 (pHVA)的影响。方法　 30例精神分裂症住院患者 (患者组 )纳入研究 ,利培酮治疗平均剂量为 (3 2± 1 1)mg/d ,共观察 6周。以阳性和阴性症状量表 (PANSS)评定疗效 ,以高效液相库仑阵列电化学检测法测定患者治疗前后的 pHVA含量。 30例健康志愿者作为对照组 ,检测pHVA水平。 结果　 (1)患者组治疗前 pHVA含量 [(7 9± 4 0 ) μg /L]与对照组含量 [(8 8± 4 1) μg /L]的差异无显著性 (P >0 0 5 ) ,而患者组治疗后 pHVA含量 [(5 3± 2 7) μg/L]明显低于治疗前 (P <0 0 1) ;(2 )治疗前患者组 pHVA与PANSS阳性症状评分 [(2 0 7± 4 1)分 ]存在正相关 (r =0 39,P <0 0 0 1) ,与基线PANSS阴性症状评分 [(19 7± 5 1)分 ]存在负相关 (r =- 0 35 ,P <0 0 1) ;(3)基础pHVA含量及其治疗前后差值[(2 6± 1 3) μg/L]与PANSS阳性症状评分减分值 [(10 8± 4 1)分 ]均分别呈正相关 (r =0 4 8,P <0 0 1;r=0 6 0 ,P <0 0 0 1)。结论　患者组治疗前pHVA可部分反映精神分裂症症状 (尤其是阳性症状 )的严重程度 ,基础 pHVA含量及治疗前后pHVA水平的变化与利培酮治疗阳性症状的疗效相关。     

利福平对氯氮平血药浓度及疗效的影响

目的 :探讨利福平对氯氮平血药浓度及疗效的影响。　方法 :采用自身对照的方法 ,对 30例伴肺结核的精神分裂症患者在原氯氮平治疗的基础上合用利福平 (4 5 0mg/d) ,治疗 6周。以阳性症状与阴性症状量表 (PANSS)评定疗效 ,用高效液相色谱法 (HPLC)测定氯氮平稳态血药浓度。　结果 :合用利福平前与合用后 2、6周末的氯氮平血药浓度分别为 (4 38± 183) μg/L、(10 2± 4 1) μg/L和 (91± 30 ) μg/L ,差异有非常显著性 (F =87 32 ,P <0 0 1)。 30 % (8例 )患者阳性精神症状加重。　结论 :利福平可显著降低氯氮平血药浓度和疗效 ,导致精神分裂症患者阳性症状加重     

氟伏沙明抑制奥氮平体内代谢的药代动力学研究

目的　探讨细胞色素P450 1A2酶 (CYP1A2 )抑制剂氟伏沙明对奥氮平在体内代谢的影响。方法　 1 2名男性健康志愿者 ,采用自身前后对照设计 ,两次服药间隔 4周 ,口服单剂奥氮平 1 0mg;对照部分采用单剂量奥氮平 ,试验部分是在氟伏沙明连续 9天服用过程中的第 4天合用单剂量奥氮平。高效液相色谱电化学法测定奥氮平血浆浓度。结果　合用氟伏沙明后 ,奥氮平各时点的平均浓度增高 ;奥氮平的峰浓度由 1 9 5μg/L增至 2 9 1 μg/L(1 52倍 ,P <0 0 0 1 ) ,消除半衰期由 32 2h延长为46 1h(1 48倍 ,P <0 0 1 ) ,0～ 1 2 0h药时曲线下面积由 647 5μg·h 1 ·L 1 增至 1 0 55 0 μg·h 1 ·L 1 (1 65倍 ,P <0 0 0 1 ) ;而达峰时间由 3 8h缩短为 2 6h(0 69倍 ,P <0 0 1 ) ,系统清除率由 1 6 4L/h减至 8 5L/h(0 59倍 ,P <0 0 0 1 ) ,表观分布容积由 435 5L降为 2 99 2L(0 70倍 ,P <0 0 1 )。结论　氟伏沙明能明显抑制奥氮平在体内的代谢。CYP1A2可能是催化奥氮平体内代谢的主要氧化酶之一。奥氮平与涉及CYP1A2的药物合用时应注意密切观察、趋利避害     

奥氮平与氯丙嗪治疗精神分裂症急性期的对照研究

目的 比较奥氮平与氯丙嗪治疗精神分裂症急性期的疗效和安全性。方法 奥氮平组36例，剂量5—20mg／d；氯丙嗪组32例，剂量100-400mg／d。两组均以PANSS、CGI及TESS量表评定2周。结果两组总体疗效相当，奥氮平组PANSS兴奋激越因子减分在第5天（t=3．47，P〈0．05）、1周末（t=3．21，P〈0．05）及2周末（t=3．64，P〈0．05）优于氯丙嗪组。结论奥氮平治疗精神分裂症急性期的疗效肯定，起效较快，不良反应较小，且安全性良好。     

奥氮平与氯氮平治疗精神分裂症对照研究

目的　研究奥氮平治疗精神分裂症的疗效及安全性。方法　分析 6 1例用奥氮平治疗 6周的精神分裂症病例 ,并与 6 1例用氯氮平治疗的精神分裂症病例作对照 ,采用阳性及阴性症状量表 (PANSS)的减分率评价疗效 ,用副作用量表 (TESS)评价 6周末的副作用。结果　 6周末PANSS量表总分、阳性症状分、阴性症状分和一般病理分与治疗前比较 ,两组差异均有非常显著性 (P <0 .0 1) ,但两组间差异无显著性 (P >0 .0 5 )。于 2周末两组间除一般病理分外 ,余差异均有极显著性 (P <0 .0 1) ;于第四周末一般病理分差异也有非常显著性 (P <0 .0 1) ;副作用两组间比较 ,奥氮平组明显小于氯氮平组。结论　奥氮平治疗精神分裂症疗效好、起效快、副作用小。     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

Sudanophilic lipid accumulation in astrocytes in periventricular leukomalacia in monkeys

Summary Sudanophilic lipid accumulation is a characteristic feature of periventricular leukomalacia (PVL) of infants. At least two types of lipid-containing cells have been identified, one being the macrophage, the other the pre-myelin glial cell. A third type of lipid-containing cell has been seen in two monkeys with spontaneous PVL. Electron microscopically this cell appears to be an astrocyte. This probably represents a reaction of the astrocyte to hypoxia and may be the equivalent of the hypertrophic astrocytes found in human infants.Supported in part by NIH grant HDO 8633 and the Regional Primate Research Center Grant RR-00166     

Increase in cathepsin D activity in rat brain in aging

Cathepsin D-like activity in homogenates of five brain areas of 3-month-old and 24-month-old Fischer 344 rats was measured. With hemoglobin as substrate at pH 3.2, more than 90% of the activity was inhibited by pepstatin. In each area studied, activity was more than twice as high in the old rat brain: 140-160% higher in the cortex, cerebellum, pons-medulla, and striatum and 90-100% higher in the hippocampus and spinal cord. The greatly increased metabolic capacity in the absence of an increase in protein turnover may have a role in age-related pathological degeneration in the brain.     

Issues in evaluation of cognition in the elderly in developing countries

Background:

Developing regions of the world host the majority of elderly subjects who are at risk for dementia. Reliable epidemiological data from these countries is invaluable in tackling this global problem. Scarcity of such data in literature is largely attributable to problems that are unique to developing communities worldwide.

Objective:

To classify and describe the problems that interfere with the collection of reliable epidemiological data on cognitive impairment in the elderly in developing communities, and to suggest practical solutions for some of them.

Methods:

Inferring from the experiences of a large, ongoing, population-based study on the cognitive impairments in the elderly in South India and from the review of literature.

Conclusion:

A fatalistic attitude regarding aging in the communities, significant heterogeneity in educational abilities and activities of daily living, high illiteracy among rural subjects, and lack of an organized health care system and updated demographic figures are some of the major factors that contribute to technical, namely, methodology-related problems and practical, namely, subject-related problems in such epidemiological studies.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Defects in Bioenergetic Coupling in Schizophrenia

Synaptic neurotransmission relies on maintenance of the synapse and meeting the energy demands of neurons. Defects in excitatory and inhibitory synapses have been implicated in schizophrenia, likely contributing to positive and negative symptoms as well as impaired cognition. Recently, accumulating evidence has suggested that bioenergetic systems, important in both synaptic function and cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as well as bioenergetic abnormalities. We report findings on the bioenergetic interplay of astrocytes and neurons and discuss how dysregulation of these pathways may contribute to the pathogenesis of schizophrenia, highlighting metabolic systems as important therapeutic targets.     

Gender in Voice Perception in Autism

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.