氯氮平与氯丙嗪治疗精神分裂症的对照研究

为进一步验证氯氮平在治疗精神分裂症中的地位。方法对病程＜５年的１２２例首次住院的精神分裂症患者，采用分层随机法分为两组，分别首选氯氮平和氯丙嗪进行８周治疗。以ＢＰＲＳ、ＳＡＰＳ、ＳＡＮＳ评定疗效，以ＴＥＳＳ评定副反应。结果治疗前后比较，两组ＢＰＲＳ、ＳＡＰＳ分均显著下降（Ｐ＜０．０１），ＳＡＮＳ分氯氮平组显著降低（Ｐ＜０．０１），氯丙嗪组无明显差异（Ｐ＞０．０５）；疗后氯氮平组的ＢＰＲＳ、ＳＡＰＳ、ＳＡＮＳ总分均明显低于氯丙嗪组（Ｐ＜０．０１）；ＴＥＳＳ总分氯氮平组亦低于氯丙嗪组，且无锥体外系副反应。结论氯氮平确是一种十分有效且药物副反应并不多见的抗精神病药。在严密监测血象的情况下，氯氮平实际上可作为一个可供选择的治疗精神分裂症的第一线药使用。     

氯氮平药代动力学影响因素及血药浓度与临床效应的关系

为了探讨吸烟与性别对氯氮平药代动力学及稳态浓度的影响，以及氯氮平、去甲氯氮平稳态浓度与疗效、不良反应的关系，对３０例（吸烟男性１０例，不吸烟男性和女性各１０例）精神分裂症病人进行氯氮平药代动力学研究，对５８例精神分裂症病人于治疗第２、４、６、８周测定氯氮平和去甲氯氮平浓度，并评定简明精神病症状评定量表（ＢＰＲＳ）、阳性和阴性症状量表（ＳＡＰＳ、ＳＡＮＳ）及副反应量表（ＴＥＳＳ），分析血药浓度与疗效、不良反应的相关性。结果显示，吸烟者的氯氮平半衰期、达峰浓度和稳态浓度明显低于非吸烟者（Ｐ＜０．０１）。氯氮平、去甲氯氮平浓度和二者总浓度与ＴＥＳＳ呈显著正相关（Ｐ＜０．０１），与ＢＰＲＳ、ＳＡＰＳ和ＳＡＮＳ无显著相关，但有效组血药浓度高于无效组（Ｐ＜０．０５）。认为氯氮平血药浓度监测有一定临床意义，血药浓度以３５０～６００μｇ／Ｌ为宜     

以阴性症状为主的精神分裂症患者认知功能与局部脑血流的 …

目的 动态观察药物对局部脑血流量（ｒＣＢＦ）的影响,探索以阴性症状为主的精神分裂症患者潜隐的局部脑功能异常。方法 对２１例符合Ａｎｄｒｅａｓｏｎ阴性精神分裂症标准的患者（以下简称患者组）于氯氮平治疗前后进行威斯康星卡片分类测验（ＷＣＳＴ）和单光子发射计算机断层扫描（ＳＰＥＣＴ）检查,以４０名正常人为对照组（其中２８名为ＷＣＳＴ对照组,１２名为ＳＰＥＣＴ对照组）。结果 患者组氯氮平治疗前后ＷＣＳＴ的     

氯氮平台并利培酮与氯氮平治疗精神分裂症阴性症状的对照研究

目的 比较氯氮平合并利培酮与氯氮平对精神分裂症阴局限性症状的疗效。方法 ６０例长期住院的精神分裂症患者，分别接受氯氮平合并利培本呼氯氮平治疗，疗程８周，用ＢＰＲＳ，ＳＡＮＳ，ＳＡＰＳ，ＴＥＳＳ评定疗效和副反应。结果 氯氮平合并利培酮组在治疗后４周、８周ＳＡＮＳ评分较治疗前均有显著差异（Ｐ〈０．０１）；氯氮平组在治疗后８周ＳＡＮＳ评分与治疗前比较也有显著差异（Ｐ〈０．０５）。两组在治疗后４周、８周时     

利培酮和氯氮平对精神分裂症阴性症状的疗效及不良反应比较

目的比较利培酮与氯氮平对精神分裂症阴性症状的疗效和不良反应。方法应用利培酮和氯氮平治疗精神分裂症各２０例，其阴性症状评定量表评分≥６５分者入组。用阴性症状评定量表（ＳＡＮＳ）评定疗效，用副反应量表（ＴＥＳＳ）评定药物不良反应。结果利培酮和氯氮平对精神分裂症阴性症状的疗效相当，起效时间为２周。两药的副反应不同，利培酮多见锥体外系反应，而氯氮平多见心动过速、嗜睡、流涎、便秘等。结论利培酮对精神分裂症阴性症状有效、疗效与氯氮平相当。     

精神分裂症d－芬氟拉明激发的神经内分泌反应与临床症状的关系

目的探讨ｄ－芬氟拉明（ｄ－ＦＦ）激发的神经内分泌反应与精神分裂症临床症状的关系。方法把１５例精神分裂症患者在氯氮平治疗前、后行ｄ－ＦＦ激发试验，同时以简明精神病评定量表（ＢＰＲＳ）、阳性症状量表（ＳＡＰＳ）、阴性症状量表（ＳＡＮＳ）评定精神症状。结果混合型患者治疗前基础皮质醇（ＣＯＲ）值、治疗后ｄ－ＦＦ激发的ＣＯＲ值及治疗前、后ｄ－ＦＦ激发的催乳素（ＰＲＬ）值均显著高于阳性型。症状评分与激素反应有一定的相关关系。结论提示精神分裂症的发生可能与中枢５－羟色胺／多巴胺（５－ＨＴ／ＤＡ）功能失平衡有关。     

精神分裂症治疗前后脑脊液5-羟色胺代谢变化的对比研究

目的　观察精神分裂症患者脑脊液５羟色胺（５ Ｈ Ｔ） 及其代谢产物５羟吲哚醋酸（５ Ｈ Ｉ Ａ Ａ） 和其前体物质色 氨酸（ Ｔ Ｒ Ｐ）的功能状态，以及经氯丙嗪治疗后上述物质的代谢变化。方法　应用 Ｈ Ｐ Ｌ Ｃ 法对４０ 例未经治疗的精神分裂症（ 阳性症状为主） 患者与１５ 例非中枢神经系统疾病对照者作上述物质的比较，其中２７ 例精神分裂症患者在接受氯丙嗪治疗８ 周后复查了上述物质。结果　精神分裂症组疗前脑脊液５ Ｈ Ｉ Ａ Ａ 浓度比对照组显著为低，治疗后各物质浓度均显著降低。结论　支持有关精神分裂症５ － Ｈ Ｔ 代谢障碍的假说，认为５ － Ｈ Ｔ 功能低下可能系阳性症状为主精神分裂症的易感标志，该型的症状发生与转归主要与多巴胺的代谢障碍有关。     

急性一氧化碳中毒后迟发性脑病甲状腺激素代谢的初步研究

目的探讨急性一氧化碳中毒后迟发性脑病（ＤＥＡＣＭＰ）的甲状腺激素代谢的特点及其临床意义。方法采用放射免疫分析法测定３８例ＤＥＡＣＭＰ患者入院初、出院前三碘甲状腺原氨酸（Ｔ３）、甲状腺素（Ｔ４）、促甲状腺素（ＴＳＨ）、反三碘甲状腺原氨酸（Ｒ－Ｔ３）的含量,并与３０例正常对照组作比较。结果患者组入院时血清Ｔ３、Ｔ４、ＴＳＨ、Ｒ－Ｔ３和脑脊液Ｔ３、ＴＳＨ、Ｒ－Ｔ３值与正常对照组比较差异均有显著意义（Ｐ＜０．０５）,并随病情的恢复,此种变化逐渐恢复,与入院时比较差异有显著意义（Ｐ＜０．０５）。结论ＤＥＡＣＭＰ急性期患者呈现典型的低Ｔ３、Ｔ４综合征变化,动态监测血清和脑脊液甲状腺激素水平变化对判断ＤＥＡＣＭＰ患者的病情和预后具有重要的临床意义。     

氯氮平的早期副作用治疗窗

寻找氯氮平早期副作用治疗窗。方法 给６６例精神分裂症患者单服氯氮平,并且评价了０周ＰＡＮＳＳ、２周ＴＥＳＳ和血清氯氮平浓度、４周ＰＡＮＳＳ和ＴＥＳＳ。结果 ２周ＴＥＳＳ总分和诸因子分与４周ＰＡＮＳＳ总分减分率均无显著相关性,２周抗α１－肾上腺素因子分在窗内（０～５分）的显效率４７％比窗外的２２％显著为高（Ｐ〈０．０５）,２周氯氮平血清浓度在内（２３０～３３０μｇ／Ｌ）的显效率５１％比窗外的１９％显     

以阳性或阴性症状为主的精神分裂症患者的单类神经递质代谢

目的 探讨以阳性症状为主（以下简称阳性）或以阴性症状为主（以下简称阴性）的精神分裂症患者在氯氮平治疗前后脑脊（ＣＳＦ）中高香草酸（ＨＶＡ）和５－羟吲哚乙酸（５－ＨＩＡＡ）浓度的动态变化。方法 对２８例阳性患者和１８例阴性患者进行８周的氯氮平治疗。用高效液相色谱－电化学方法测定患者的ＨＶＡ和５－ＨＩＡＡ浓度。以精神分裂症阳性症状量表（ＳＡＰＳ）和阴性症状表（ＳＡＮＳ）为评定工具。以１２例非中枢神经系     

Coexpression of junctophilin type 3 and type 4 in brain

Recent studies indicated that junctophilins (JPs) contribute to the formation of junctional membrane structures in excitable cells by interacting with the plasma membrane and spanning the endoplasmic/sarcoplasmic reticulum (ER/SR) membrane. In the brain, functional crosstalk between cell-surface and intracellular channels is proposed in the "subsurface cistern" as the junctional membrane complex observed in neurons. So far, three JPs have been identified as tissue-specific subtypes derived from different genes; JP-1 is specifically expressed in skeletal muscle, JP-2 is detected throughout muscle cell types, and JP-3 is predominantly expressed in the brain. In this paper, we report a novel JP subtype, JP-4, encoded in the human (chromosome 14q11.1) and mouse (chromosome 14C1-2) genomes. Cloning the cDNA showed that JP-4 shares characteristic structural features with other JP subtypes, and Northern and Western blot analyses demonstrated its brain-specific expression. In situ hybridization analysis revealed that both JP-3 and JP-4 mRNAs are expressed in discrete neuronal sites, and their overall regional distribution patterns were similar in the brain. Furthermore, both the JP mRNAs and subsurface cistern showed somatodendritic localization in hippocampal pyramidal neurons. The results obtained suggest the collaborative contribution of JP-3 and JP-4 to the subsurface cistern formation in neurons.     

Scaled-down genetic analysis of myotonic dystrophy type 1 and type 2

Types 1 and 2 myotonic dystrophy are neuromuscular disorders caused by genomic expansions of simple sequence repeats. These mutations are unstable in somatic cells, which leads to an age-dependent increase of expansion length. Studies to determine whether changes in repeat size may influence disease severity are limited by the small amount of DNA that can be recovered from tissue biopsies samples. Here we used locked nucleic acid oligonucleotide probes and rolling circle amplification to determine length of the expanded repeat in sub-microgram quantities of genomic DNA. These methods can facilitate genetic analysis in cells and tissues obtained from individuals with myotonic dystrophy.     

精神分裂症免疫功能与血清5-羟色胺的研究

目的:研究阴性型和阳性型精神分裂症患者免疫功能和神经生化物质改变情况及其变化规律.方法:选择阴性型和阳性型精神分裂症患者各20例以及20名正常对照者,抽取静脉血检测T细胞亚群,主要免疫球蛋白和补体C3、C4水平,和血清5-羟色胺(5-HT)水平.结果:阴性型精神分裂症患者CD 3下降,阳性型CD 3、CD 4则升高;IgG、IgA水平2种类型精神分裂症患者均显著降低;5-HT水平阳性型精神分裂症患者显著升高,阴性型精神分裂症患者显著降低.结论:精神分裂症患者伴随有免疫功能的改变,不同类型的精神分裂症其免疫应答参与机制也有不同.     

Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy

To characterize and compare electrical myotonia in myotonic dystrophy type 1 (DM1) and type 2 (DM2), 16 patients with genetically confirmed DM1 and 17 patients with DM2 underwent standardized concentric needle electromyography of deltoid, biceps, extensor digitorum communis, first dorsal interosseous, tensor fascia lata (TFL), vastus lateralis (VL), tibialis anterior, and thoracic paraspinal muscles. Eight needle insertions per muscle were made by electromyographers blinded to DM type who recorded the presence and type of myotonia (e.g., classic waxing-waning or less specific waning discharges). Manual muscle testing was performed by a physical therapist. Overall, myotonia was more elicitable in DM1 than DM2; only in VL and TFL was myotonia more elicitable in DM2 than DM1. The major type of myotonia was waxing-waning in DM1, and waning in DM2. Four DM2 (24%), but no DM1 patients had only waning myotonia. In the arms, myotonia was distally predominant in both DM1 and DM2. In the legs, it was distally predominant in DM1, but both proximal and distal in DM2. The severity of myotonia was positively correlated with muscle weakness and with the presence of waxing and waning discharges in DM1, but with neither in DM2. Thus, myotonia is qualitatively and quantitatively different in DM1 than DM2. Except for proximal leg muscles, myotonia is more evocable in DM1 than DM2. It tends to be waxing-waning in DM1 but waning in DM2, thus making electrodiagnosis of DM2 more challenging. Its severity correlates with muscle weakness and the presence of waxing-waning discharges in DM1 but not DM2.     

Coping styles of type I and type II alcohol-dependent men undergoing treatment

The purpose of this study was to investigate the ways by which individuals with alcohol dependence, who were subgrouped into type I and type II according to the typology criteria of von Knorring et al, (J. Study Alcohol. 1987;48:523-527), cope with life events. One hundred male alcohol-dependent individuals participating in a therapeutic program composed the study sample. Of the 100, 61 subjects were categorized as type I and 39 subjects as type II. Coping styles were measured using a self-administered questionnaire that includes 8 subscales of coping styles. The type II subgroup scored significantly lower on the suppression subscale and significantly higher on the replacement, mapping, and substitution subscales as compared with the type I subgroup, of which the latter difference was at a tendency level. As regards the remaining 4 coping style subscales, minimization, help seeking, blame, and reversal, no significant differences were found between the 2 patient subgroups. The differences found may be taken into account in the development of therapeutic programs for the 2 subgroups.     

Characteristics of subthalamic oscillatory activity in parkinsonian akinetic-rigid type and mixed type

Objective: To explore neurons with β oscillatory activity in the subthalamic nucleus (STN) in relation to parkinsonian motor signs. Methods: We studied 27 patients with Parkinson's disease (PD) who underwent electrode implantation for STN deep brain stimulation. Thirteen patients were classified as akinetic-rigid (AR) type and 14 patients were classified as mixed type. Microelectrode recording was performed in the STN and the electromyogram (EMG) was simultaneously recorded. Single-unit and spectral analyses were performed. Coherence analysis was used to explore the relationship between β oscillatory activity and EMG activity. Unpaired t-test and chi-square were used to compare the differences between the two PD types. Results: Of 130 neurons identified in the AR type, 43.8% were β oscillatory neurons (mean: 21.3 ± 6.87 Hz, βFB) and 0.8% were tremor frequency oscillatory neurons (4–6 Hz, TFB). Of 102 neurons identified in the mixed type, 19.6% were β oscillatory neurons and 26.5% were TFB oscillatory neurons. There was a significant difference in proportion of neurons with βFB and TFB oscillations between the two PD groups. Additionally, 12% of the βFB oscillatory neurons were coherent with limb EMG of the AR type, but there was no coherence in the mixed type. Most oscillatory neurons were localized in the dorsal portion of the STN. Conclusion: The STN βFB oscillatory neurons correlate with parkinsonian rigidity-bradykinesia. The high proportion of βFB oscillatory neurons found in the AR type of PD is indirect evidence for their importance in generating motor impairment.     

Reduced thrombogenicity of type VI collagen as compared to type I collagen

Type VI collagen has been recently identified as a major constituent of vascular subendothelium where it serves as a binding site for von Willebrand factor. The present study compares the functional characteristics of type VI collagen with those of type I collagen with respect to platelet aggregating and secretory activities. The differences between the two collagens in platelet aggregation and serotonin and betathromboglobulin release were found to be highly significant (p<0.001,p<0.0007, p<0.005 respectively). Our results indicate that under in vitro conditions, type VI collagen stimulates a significantly lesser platelet activation and aggregation response than collagen I, suggesting that type VI collagen may play a role in vivo to limit the platelet thrombotic response following injury to the vascular subendothelium.     

Comprehension of emotions: comparison between Alzheimer type and vascular type dementias

This study investigated the ability of recognizing emotion in dementia. Twenty-five patients with dementia of the Alzheimer type (DAT), 25 patients with vascular dementia (VD), and 12 normal control subjects were evaluated as to general cognition, visuoperception and emotion recognition. The score on the emotion recognition task significantly correlated with that of the Mini-Mental State Examination for VD patients while this was not the case for DAT patients. Moreover, VD patients performed significantly worse than DAT patients on the emotion recognition task in spite of the fact that there was no difference in the general cognitive and visuoperceptual abilities between them. The result of this study coupled with the past studies led to the hypothesis that the relationship between intellectual deficits and the deterioration in recognizing emotions differs according to type of dementia. Caregivers in nursing homes and hospitals need to take into account their patients' intellectual deficits but also their deteriorating ability of identifying emotions.