国产利培酮治疗精神分裂症疗效与安全性的随机双盲对照研究

目的:评价国产利培酮片治疗精神分裂症的疗效及安全性.方法:采用随机双盲多中心对照研究,214例符合中国精神障碍分类与诊断标准第3版的精神分裂症患者随机接受国产利培酮片或进口利培酮片治疗,每组均为107例,平均剂量分别为3.9 mg/d和3.7 mg/d,观察疗程为8周.于入组时(基线)、治疗后第2、4、6、8周,采用阳性与阴性症状量表(Positive and Negative Symptoms Scale,PANSS)和临床总体印象量表(Clinical Global Impression Scale,CGI-S)进行疗效评估.于治疗前和试验结束时,以不良反应症状量表(Treatment Emergent Symptom Scale,TESS)、血生化指标、心电图和体质量改变等进行安全性评估.结果:国产利培酮组患者的有效率为76%,进口利培酮组为68.6%,差异无统计学意义(P>0.05).随着治疗时间的延长,两组的研1性症状分、阴性症状分、一般精神病理症状分以及PANSS总分均显著下降(P<0.01),并且每个访视点PANSS减分率在两组之间差异无统计学意义(P>0.05).国产利培酮组与研究药物有关的不良事件发牛率为40%,进口利培酮组为37.1%,差异无统计学意义(P>0.05).两组在治疗后体质量均有显著增加(P均<0.01).第8周末国产利培酮组TESS总分低于进口利培酮组,差异有统计学意义(P<0.01).结论:国产利培酮治疗精神分裂症的疗效与进口利培酮相当,安全性良好.     

齐拉西酮与利培酮治疗青少年首发精神分裂症的对照研究

目的:比较齐拉西酮与利培酮治疗青少年首发精神分裂症的疗效与安全性。方法:将140例13~18岁首发精神分裂症患者随机分为齐拉西酮组与利培酮组,每组70例,分别给予齐拉西酮与利培酮治疗8周,于治疗前及治疗2、4、8周末采用阳性与阴性量表(PANSS)评定疗效,药物不良反应量表(TESS)评定不良反应,分别在治疗前及治疗药物达到临床最大剂量进行心电图检查,对心电图QT/QTC间期进行对比分析。结果:治疗8周后齐拉西酮组痊愈率34.3%,有效率77.1%,利培酮痊愈率32.9%,有效率75.7%,两组疗效比较差异无统计学意义(P0.05);两组治疗后PANSS评分均明显低于治疗前(P0.01),且两组间PANSS减分率差异无统计学意义;齐拉西酮组不良反应发生率21.3%,利培酮组发生率为38.5%,两组差异有统计学意义(P0.05);齐拉西酮组治疗后QT间期较治疗前显著延长,差异有显著统计学意义(t=-4.330,P=0.000),QTC间期较治疗前虽然延长,但无统计学意义(P0.05),利培酮组治疗后QT/QTC间期变化与治疗前比较,差异无统计学意义(P0.05)。结论:齐拉西酮与利培酮治疗青少年首发精神分裂症的疗效相当,但齐拉西酮不良反应少。     

帕罗西汀合用劳拉西泮治疗广泛性焦虑的随机对照研究

目的 评价帕罗西汀治疗广泛性焦虑早期合用劳拉西泮的临床疗效和副反应.方法 采用随机对照法,对符合CCMD-3诊断标准的64例广泛性焦虑症进行随机入组,其中对照组32例,帕罗西汀治疗8周;研究组32例,帕罗西汀合用劳拉西泮治疗8周(其中劳拉西泮2～4周末停药).采用汉密顿焦虑量表(HAMA)、焦虑自评量表(SAS)和副反应量表(TESS)评定疗效和副反应.结果 研究组在1周末SAS和HAMA总分、SA因子分的减分比较差异有显著性(P＜0.05),治疗2、4、8周末SAS和HAMA总分、SA因子分、PA因子分较治疗前减分显著(P＜0.01);治疗8周末评定总体疗效两组相近,两组间副反应差异无显著性(P＞0.05),主要副反应为口干、头晕或头痛、恶心或食欲下降、嗜睡、乏力.结论 帕罗西汀治疗广泛性焦虑早期合用劳拉西泮症状改善早、起效快、依从性好.     

齐拉西酮对首发精神分裂症患者眼动功能和执行功能的影响

目的:探讨齐拉西酮对首发精神分裂症患者眼动功能和执行功能的影响。方法:将79例首发精神分裂症患者随机分为齐拉西酮组(n=42)和利培酮组(n=37),在基线、治疗4周和8周时进行探究性眼球运动测试和威斯康星卡片分类测验(WCST)。结果:1眼动功能显示,治疗8周时两组的凝视点数显著提高(P0.01);反应性探索评分(RSS分),两组在治疗4周、8周时均显著升高(P0.01),而两组之间差异无统计学意义(P0.05);D分值两组治疗4周时显著下降(P0.01),治疗8周时平均降为负分;2WCST测验治疗前两组均存在执行功能障碍,两组间无统计学差异。与基线时相比,齐拉西酮组治疗4周、8周时总测验次数、持续错误数、随机错误数均明显降低(P均0.01),正确反应数和分类完成数均明显提高(P均0.01);利培酮组治疗4周、8周时总测验次数、持续错误数、随机错误数均明显降低(P均0.01),正确反应数和分类完成数均明显提高(P均0.01)。齐拉西酮组与利培酮组对比,治疗4周时随机错误数齐拉西酮组(29.70±10.66)较利培酮组(35.07±12.36)显著降低(t=2.06,P0.05),治疗8周后齐拉西酮组(20.13±7.08)较利培酮组(23.26±6.28)显著降低(t=2.07,P0.05);其余两组无显著性差异。结论:齐拉西酮对首发精神分裂症患者的眼球轨迹运动有显著影响,改善眼动功能,与对照组利培酮相比差异无统计学意义;首发精神分裂症患者存在执行功能受损,齐拉西酮对执行功能具有显著的改善,较利培酮效果显著;齐拉西酮是一种对认知功能有效的抗精神病药物,值得临床广泛应用与推广。     

利培酮联合碳酸锂治疗分裂情感性精神病的对照研究

目的评价利培酮联合碳酸锂治疗分裂情感性精神病的临床疗效及安全性。方法根据躁狂评定量表(BRMS)总分≥16分,汉密尔顿抑郁量表(HAMD)总分≥17分,阳性与阴性症状量表(PANSS)总分≥65分的82例诊断为分裂情感性精神病的患者随机分成两组,分别口服利培酮联合碳酸锂或氯氮平联合碳酸锂治疗,观察8周。于治疗前及治疗2周、4周和8周末采用PANSS、HAMD、BRMS和副反应量表(TESS)4套量表评定临床疗效和不良反应。结果以PANSS、HAMD、BRMS减分率判定临床疗效,治疗8周末,研究组PANSS总分显效率57.5%,有效率95%,对照组10%,62.5%。两组比较有显著性差异(t1=-2.07,P1=0.04;t2=-29.64,P2<0.01);研究组HAMD显效率85%,有效率95%,对照组60%,77.5%。两组比较有显著性差异(t1=-5.63,P1<0.01;t2=-6.57,P2<0.01);研究组BRMS显效率85%,有效率95%,对照组10%,70%。两组比较有显著性差异(t1=-14.89,P1<0.01;t2=-17.75,P2<0.01)。故利培酮组和氯氮平组在治疗8周末的临床疗效有显著差异,且利培酮组的不良反应发生率低于氯氮平组,差异有显著性(P<0.01)。结论利培酮组治疗分裂情感性精神病疗效显著,安全性高,依从性好,能显著提高患者的生活质量。     

小剂量利培酮口服液对难治性抑郁症的辅助治疗

目的 探讨小剂量利培酮口服液对难治性抑郁症的辅助疗效及安全性.方法 将60例难治性抑郁症患者随机分成研究组和对照组各30例,研究组采用小剂量利培酮口服液联合盐酸舍曲林治疗并与单独采用盐酸舍曲林治疗的对照组进行对照,分别在治疗1、2、4、6、8周以汉密尔顿抑郁量表(HAMD)评定疗效,以副反应量表(TESS)评定不良反应.结果 两组HAMD评分治疗后与治疗前比较均有显著差异性(P＜0.01),两组间HAMD评分在治疗后第4、6、8周均有显著性差异(t分别为5.67,6.75,2.85;P＜0.01).两组间副反应量表评分比较差异不明显.结论 小剂量利培酮口服液联合盐酸舍曲林治疗难治性抑郁症效果好于单独采用盐酸舍曲林,起效快,且耐受性好.     

清心冲剂I号联合利培酮、奥氮平治疗精神分裂症的临床对照研究

目的 观察清心冲剂I号对于利培酮、奥氮平治疗精神分裂症有无增效作用.方法 将清心冲剂I号合并利培酮、奥氮平治疗者作为实验1组,不合并清心冲剂I号的作为对照1组;清心冲剂I号加氯丙嗪、氟哌啶醇、奋乃静治疗者为实验2组,不合并清心冲剂I号的作为对照2组,观察疗程8周.在治疗前及治疗后2、4、8周采用PANSS量表评价疗效.结果 治疗前及治疗后实验组与对照组总体疗效比较差异无显著性(P＞0.05);实验组与对照组治疗8周末PANSS和各症状评分较治疗前差异均有显著性(P＜0.01),8周后实验组与对照组阳性症状分比较差异有显著性(P＜0.05).结论 清心冲剂I号对于抗精神病药物治疗精神分裂症有增效作用,尤其可以改善精神分裂症患者的阳性症状,因此在精神分裂症的治疗中有一定的临床价值.     

帕罗西汀对海洛因依赖者的抑郁焦虑症状的治疗研究

目的:评价帕罗西汀对海洛因依赖者的抑郁及焦虑症状的治疗效果.方法:对103例符合诊断标准的海洛因依赖并伴焦虑抑郁者,分别应用帕罗西汀和丁螺环酮进行治疗,疗程为4周.采用HAMA及HAMD两种量表进行评定疗效 ,用TESS量表对不良反应进行评定.结果:帕罗西汀组治疗后与治疗前的HAMA及HAMD评分比较,有显著性差异(P＜0.01);两组间从治疗第1周末起,各时点HAMD评分有显著性差异(P＜0.05);两组间HAMA评分在治疗第1、2周末有显著性差异(P＜0.05),在第3、4周末无显著性差异(P＞0.05);两组间各时点TESS评分无显著性差异(P＞0.05).结论:帕罗西汀在显著改善海洛因依赖者抑郁症状的同时,其改善焦虑症状的疗效与抗焦虑药物丁螺环酮相当,疗效显著,副作用小.     

帕罗西汀治疗咽异感症患者抑郁、焦虑症状的临床观察

目的 探讨帕罗西汀对咽异感症的疗效及安全性.方法 选自门诊咽异感症病人共66例,随机分为帕罗西汀组(33例)和丁螺环酮组(33例),疗程6周.采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定临床疗效,副反应量表(TESS)评定副反应.结果 帕罗西汀组治疗前后的HAMD及HAMA评分比较有显著性差异(P＜0.01),两组问从治疗第2周末起,各时点HAMD评分有显著性差异(P＜0.05);两组问HAMA评分在治疗第2周末有显著性差异(P＜0.05);在第4、6周末无显著性差异(P＞0.05);两组间备时点TESS评分显著性差异(P＞0.05).结论 帕罗西汀在显著改善咽异感症患者抑郁症状的同时,其改善焦虑症状的疗效与抗焦虑药物丁螺环酮相当,疗效较好,副作用小.     

利培酮与氯丙嗪治疗精神分裂症疗效及依从性比较

目的评价利培酮与氯丙嗪治疗精神分裂症的疗效及依从性.方法 98例精神分裂症患者随机分为2组,分别给予利培酮和氯丙嗪治疗,均治疗48周,于治疗前、8周末、48周末采用阳性症状阴性症状量表(PANSS)、药物副反应量表TESS评价其疗效、副反应及依从性.结果 8周后利培酮组有效率91.9%,氯丙嗪组有效率89.8%,2组治疗前后比较有非常显著性的疗效(p<0.01),但两组间比较差异无显著性(p>0.05);48周后利培酮组有效率91.9%,氯丙嗪组有效率69.4%.利组疗效有显著性(p<0.01),氯丙嗪组疗效有显著性(p<0.05),利组优于氯组(p<0.05).利培酮组的不良反应发生率远低于氯丙嗪组.结论精神分裂症患者对利培酮的依从性高主要是因疗效好和副反应轻.     

Asymmetry of the internal connections of the striate cortex of the cat in the projection zone of the center of the field of vision

Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field. Laboratory of Visual Physiology and Laboratory of Central Nervous System Morphology, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 12, pp. 23–29, December, 1996.     

Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.     

The development of the ligament of the head of the femur

The hip joints of 30 human male and female fetuses and stillborns between 20 mm and 350 mm crown-rump length were studied by light microscopy. The ligament of the head of the femur developed in situ as a condensation of mesenchyme at the end of the second month of intra-uterine life (IUL), and was vascularized by branches of acetabular vessels early in the fourth month. In the majority of fetuses older than 5.5 months IUL, vessels in the ligament passed a short way into the femoral head within cartilage canals, to supply a small region around the fovea capitis. The remainder of the head was supplied by vessels in canals from around the upper part of the neck. The ligament changed from predominantly cellular to fibrous during the last 4 months of IUL. This increase in strength suggested significant mechanical functions in utero: limitation of adduction-flexion and opposition to postero-superior dislocation were the most likely.     

Counterpointing the functional role of the forebrain and of the brainstem in the control of the sleep-waking system

This paper reviews the lifetime contributions of the author to the field of sleep-wakefulness (S-W), reinterprets results of the early studies, and suggests new conclusions and perspectives. Long-term cats with mesencephalic transection show behavioral/polygraphic rapid eye movement sleep (REMS), including the typical oculo-pupillary behavior, even when the section is performed in kittens prior to S-W maturation. REMS can be induced as a reflex. Typical non-rapid eye movement S (NREMS) is absent and full W/arousal is present only after a precollicular section. The isolated forebrain (IF) rostral to the transection exhibits all features of W/arousal and NREMS [with electroencephalographic (EEG) spindles and delta waves], arousal to olfactory stimuli, and including the appropriate oculo-pupillary behaviors. These features also mature normally after neonatal transection. REMS is absent from the IF. After deprivation there is NREMS pressure and rebound in the IF, but the decerebrate cat only shows pressure for REMS. Most IF reactions to pharmacologic agents are within expectations, except for the tolerance/withdrawal effects of long-term morphine use which are absent. In contrast, these effects are supported by the brainstem (i.e. seen in the decerebrate cat). In cats with ablation of the telencephalon, or diencephalic cats, delta waves are absent in the thalamus. EEG thalamic spindle waves are seen triggering S for only 4-5 days after ablation. Therefore, true NREMS is absent in chronic diencephalic cats although pre- and postsomniac behaviors persist. These animals are hyperactive and show a pronounced, permanent insomnia; however, a low dose of barbiturate triggers a dramatic REMS/atypical NREMS rebound. Cats without the thalamus (athalamic cats), initially show a dissociation between behavioral hyperactivity/insomnia and the neocortical EEG, which for 15-20 days exhibits only delta and slower oscillations. Fast, low-voltage W rhythms appear later on, first during REMS, but spindle waves and S postures are absent from the start, such that these cats also display only atypical NREMS. Athalamic cats also show barbiturate-sensitive insomnia. Cats with ablation of the frontal cortices or the caudate nuclei remain permanently hyperactive. They also show a mild, but significant hyposomnia, which is permanent in afrontal cats, but lasts for about a month in acaudates. The polygraphic/behavioral features of their S-W states remain normal. We conclude and propose that: (a) the control of the S-W system is highly complex and distributed, but is organized hierarchically in a well-defined rostro-caudal manner; the rostral-most or highest level (telencephalon), is the most functionally complex/adaptative and regulates the lower levels; the diencephalic/basal forebrain, or middle level, has a pivotal role in inducing switching between S and W and in coordinating the lowest (brainstem) and highest levels; (b) W can occur independently in both the forebrain and brainstem, but true NREMS- and REMS-generating mechanisms exist exclusively in the forebrain and brainstem, respectively; (c) forebrain and brainstem S-W processes can operate independently from each other and are preprogrammed at birth; this helps understanding normal and abnormal polygraphic/behavioral dissociations in humans and normal dissociations/splitting in aquatic mammals; (d) NREMS homeostasis is present in the IF, but only REMS pressure after deprivation persists in the decerebrate cat; (e) the thalamus engages in both NREMS and W; (f) insomnia in diencephalic cats is the result of an imbalance between antagonistic W- and S-promoting cellular groups in the ventral brain (normally modulated by the telencephalon); (g) the EEG waves, which are signature for each S-W state, appear to truly drive the concomitant behaviors, e.g. a hypothetical human IF could alternate between behavioral NREMS and W/arousal/awareness; (h) a role for REMS is to keep the individual sleeping at the end of the self-limiting NREMS periods. The need for accelerating research on telencephaling NREMS periods. The need for accelerating research on telencephalic S-W processes and downstream control of the lower S-W system levels is emphasized.     

Topical organization of the projections of neurons of the substantia nigra and the ventral field of the tegmentum of the midbrain to the head of the caudate nucleus of the cat

Neuroscience and Behavioral Physiology -     

Involvement of the striatum in the central regulation of the hormonal functions of the gonads

Studies reported here show that intrastriatal administration of corticoliberin to rats decreases the blood testosterone level. However, in conditions of chemical deficiency of dopaminergic transmission in the dorsal striatum induced by injection of 6-hydroxydopamine, the effect of this neurohormone did not appear. It is concluded that extrahypothalamic corticoliberin is involved in regulating the hormonal reproductive system acting via dopaminergic mechanisms. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 4, pp. 594–597, April, 1999.     

Ultrastructure of the endothelium of the drainage system of the eye

The endothelium of the ocular drainage system (Schlemm’s canal, collector tubules, and aqueous veins) in primary juvenile glaucoma undergoes degenerative dystrophic changes with compensatory hypertrophy and proliferation at the initial stages of the glaucomatous process and atrophy and desquamation at advanced and terminal stages. Progressive decrease in the pinocytous function of endotheliocytes, reduction of the protein-synthesizing and mitochondrial compartments of the cytoplasm, and formation of autophagosomes reflect the process of endotheliocyte degeneration in general. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 574–577, May, 2008