精神分裂症患者细胞色素P-450 1A2酶活性及氯氮平稳态血药浓度与治疗效应的关系

目的探讨精神分裂症患者细胞色素P-450 1A2酶(CYP1A2)活性、氯氮平(CLZ)稳态血药浓度与治疗效应间的关系.方法对49例精神分裂症患者单一氯氮平治疗6周,治疗第1～10天调整剂量,至第10天时剂量达5 mg*kg-1*d-1,并固定此剂量到治疗第6周末.检测CYP1A2酶活性指数和氯氮平(CLZ)、去甲氯氮平(DCLZ)稳态血药浓度.同时用阳性和阴性症状评定量表(PANSS)评定临床疗效. 结果 CYP1A2酶活性指数与氯氮平的去甲基代谢率DCLZ/CLZ之间呈显著性正相关(r=0.754,P<0.01);氯氮平血药浓度、氯氮平与去甲氯氮平浓度之和与PANSS减分率之间呈显著性正相关(r=0.309,r=0.293,P<0.05). 结论 CYP1A2活性和氯氮平稳态血药浓度是预测临床疗效的重要指标.     

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。     

奥氮平和氯氮平治疗精神分裂症老年患者的对照研究

目的：对比奥氮平与氯氮平治疗精神分裂症老年患者的疗效和安全性。方法：对64例精神分裂症老年患者分别给予奥氮平、氯氮平治疗，其中奥氮平组30例，氯氮平组34例，疗程8周。以阳性症状和阴性症状量表(PANSS)、临床疗效总评量表(CGI)、简明精神病评定量表(BPRS)评定临床疗效。以副反应量表(TESS)和实验室监测评价安全性。结果：治疗结束时，两组PANSS和BPRS总分较治疗前显著降低，组间差异无显著性。两组间从治疗第1周起各时点PANSS减分率差异有显著性。临床有效率：奥氮平组76．7％，氯氮平组64．7％，两组相仿。奥氮平组不良反应较氯氮平组少，常见不良反应为胆碱能作用、嗜睡、体重增加和一过性肝酶升高等。结论：奥氮平治疗精神分裂症的疗效与氯氮平相似，某些不良反应较氯氮平轻而少；是一种安全有效、服用方便的新型抗精神病药。     

氯丙咪嗪合并氯氮平治疗精神分裂症阴性症状有效

目的探讨氯丙咪嗪合并氯氮平治疗精神分裂阴性症状的作用。方法对78例住院精神分裂症患，用氯氮平或氯氮平合并1种以上抗精神病药治疗2个月以上症状未完全缓解，采用口服氯丙咪嗪合并氯氮平连续治疗3个月。采用简明精神病量表(BPRS)、阴性症状量表(SANS)、副反应量表(TESS)，在治疗前及治疗后1个月、2个月进行评分。结果采用口服氯丙咪嗪合并氯氮平治疗后，BPRS、SANS量表总分和TESS减分与治疗前比较均有显性减低。结论氯丙咪嗪合并氯氮平治疗精神分裂症阴性症状有一定疗效。     

奎的平与氯氮平治疗以阴性症状为主的精神分裂症对照研究

目的　比较奎的平与氯氮平对以阴性症状为主的精神分裂症的疗效和副反应。方法　对 72例以阴性症状为主的精神分裂症住院患者 ,随机分别用奎的平与氯氮平治疗 ,疗程 12周 ;于治疗前及治疗后 1、2、4、8、12周末用阴性症状量表 (SANS)、简明精神病量表 (BPRS)评定临床疗效 ,用副反应量表 (TESS)评定药物副反应。结果　奎的平组与氮氮平组治疗前后SANS、BPRS总分及减分比较差异无显著性 (P >0 0 5 ) ,各组治疗后SANS、BPRS总分与治疗前比较差异有极显著性 (P <0 0 1) ,奎的平在兴趣社交缺乏因子方面的疗效优于氯氮平 (P <0 0 5 ) ;奎的平组的副反应较氯氮平组少而轻。结论　奎的平对以阴性症状为主的精神分裂症有肯定的疗效 ,在某些方面优于氯氮平 ,安全性较高     

MECT合并药物与单纯药物治疗精神分裂症疗效比较

目的 探讨无抽搐电休克治疗精神分裂症的疗效.方法 对符合中国精神障碍分类与诊断标准（第三版）（CCMD-3）的精神分裂症住院病例随机分为A组（MECT合并抗精神病药物治疗组）和B组（单纯药物治疗组）各50例,分别于入院前、治疗1,2,4,8,12周末,采用简明精神病量表（BPRS）,阳性症状量表（SAPS）,阴性症状量表（SANS）计算减分率;评定治疗有效率疗效;并用副反应量表（TESS）评定副反应.结果 BPRS减分率,两组治疗4周末差异有统计学意义（P＜0.01）.SAPS减分率,两组4,12周末差异有统计学意义（P＜0.05）,而1,2,8周末差异不大.SANS减分率,两组4,8周末（P＜0.05）、12周末（P＜0.01）,差异均有统计学意义.两组有效率差异有统计学意义（P＜0.05）.两组TESS评分差异无统计学意义.结论 MECT合并药物治疗比单纯药物治疗精神分裂症起效快,对阳性症状、阴性症状控制同样效果明显.尤其对阴性症状较突出者,病情反复小.两组病例副反应均较小.MECT是各类精神分裂症早期治疗的有效方法 ,疗效较为确切.对阴性症状较重者疗效可能更为明显.     

哌泊噻嗪合并氯氮平治疗精神分裂症阴性症状的对照研究

目的 研究呱泊噻嗪合并氯氮平对阴性症状的疗效。方法 将50例以阴性症状为主的精神分裂症患者随机分为氯氮平合并哌泊噻嗪组(26例)和单用氯氮平组(24例),采用临床疗效评定、简明精神病量表(BPRS)、阴性症状量表(SANS)评定疗效。结果哌泊噻嗪合并氯氮平组显效率为58％、SANS减分率为66.0％,氯氮平组显效率为37％、SANS减分率为53.4％。经U检验,两者均有显著性差异(P<0.05)。结论 哌泊噻嗪合并氯氮平治疗精神分裂症阴性症状的疗效较为理想。     

丙戊酸钠对氯氮平血药浓度和疗效的影响

目的:探讨合用丙戊酸钠对氯氮平治疗精神分裂症时的血药浓度和疗效的影响。方法:将80例男性精神分裂症患者随机分为两组,单用组40例患者单服氯氮平,合用组40例患者同时服用氯氮平及丙戊酸钠,分别于治疗前、治疗1周和4周末测定氯氮平的血药浓度,同时评定阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)。结果:合用组治疗1周和4周末有部分患者氯氮平血药浓度升高,部分患者降低,与基线期相比,治疗4周末有显著降低。结论:合用丙戊酸钠后氯氮平血药浓度治疗4周末显著降低;丙戊酸钠可以提高氯氮平对阳性症状的疗效。     

氯氮平、利培酮对精神分裂症患者白细胞介素-2的影响

目的 了解氯氮平、利培酮对首发精神分裂症偏执型患者血清白细胞介素-2(IL-2)的影响,并探讨IL-2与精神病理的关系。方法 对58例首发精神分裂症偏执型患者给予氯氮平或利培酮治疗,分别在治疗前和治疗后第4、8周末、6月末用酶联免疫吸附法检测血清IL-2水平,并用阳性和阴性症状量表(PANSS)评估精神症状及其变化。结果 两组患者治疗后第4、8周末血清IL-2水平均显著低于治疗前;不同药物对IL-2影响差异无显著性;治疗前IL-2水平与SPANSS总分、阳性症状分呈显著正相关;治疗后8周末血清IL-2减分值与阳性症状减分值呈显著正相关;利培酮组患者治疗后第8周末血清IL-2减分值与利培酮日量呈显著相关。结论 氯氮平和利培酮有相似的免疫抑制作用,血清IL-2与精神分裂症精神病理之间有一定的关系。     

齐拉西酮与氯氮平治疗精神分裂症兴奋激越症状的对照研究

目的比较齐拉西酮与氯氮平治疗精神分裂症患者伴有兴奋激越的疗效与不良反应。方法符合CC-MD一3诊断标准的非首发精神分裂症住院患者,共80例,分为齐拉西酮组(试验组)40例,氯氮平组(对照组)40例,采用随机对照、开放性研究治疗两周。并以治疗前后简明精神病量表激越分减分率评定疗效,以副反应量表评估不良反应。结果两组在1周末和2周末BPRS激越分均较治疗前显著下降,2周末试验组有效率为70.0%,对照组有效率为72.5%,两组疗效相仿(P>0.05)。试验组不良反应较对照组少。结论齐拉西酮对精神分裂症兴奋激越症状的疗效与氯氮平相当,不良反应较小,安全性好。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.