加用阿立哌唑对利培酮所致精神分裂症男性患者高催乳素血症的影响

目的 探讨加用阿立哌唑对利培酮所致的首次发病的男性精神分裂症患者高催乳素血症的影响及安全性.方法 将80例男性精神分裂症首次发病住院患者随机分为研究组(40例)和对照组(40例).使用利培酮治疗4周后催乳素水平≥60 μg/L的患者,在维持原有治疗不变的基础上,研究组加用阿立哌唑5 mg/d,对照组加用安慰剂治疗,总疗程12周,研究周期8周(第4～12周末).于治疗第0,4,8,12周末检测血清催乳素含量,并用阳性和阴性症状评定量表(PANSS)、治疗中需要处理的不良反应量表(TESS)进行评定.结果 研究组治疗第12周末血清催乳素[(25±7)μg/L]较第4周末[(76±17)μg/L]下降,差异有统计学意义(t=15.87;P＜0.01).对照组治疗第12周末催乳素[(79±13)μg/L]与第4周末[(78±15)μg/L]比较,差异无统计学意义(t=0.72;P＞0.05);治疗第12周末催乳素下降率为(66 ±11)%、正常率为67.6%,均高于对照组[分别为(-1±18)%、6.5%](P均＜0.01).两组患者治疗前后比较,PANSS评分总分及分量表分均明显下降(P均＜0.01);在治疗第12周未两组之间各项评分比较,筹异均无统计学意义(t=0.40,0.76,0.22,0.88;P均＞0.05).治疗第12周未研究组TESS评分(4.8±4.3)与对照组(4.5±3.9)的差异无统计学意义(t=0.29;P＞0.05).结论阿立哌唑治疗利培酮所致精神分裂症男性患者高催乳素血症有效,安全.     

阿立哌唑治疗利培酮所致精神分裂症女性患者高催乳素血症的研究

目的 探讨阿立哌唑治疗利培酮所致女性患者高催乳素血症的疗效及安全性.方法 117例利培酮所致高催乳素血症的女性患者,随机分为治疗组(60例)和对照组(57例).维持原有利培酮治疗不变,治疗组加用阿立哌唑5 mg,对照组加用安慰剂治疗,疗程均为6周.于治疗第0,6周末检测催乳素,评定简明精神病量表(BPRS)、治疗中需处理的不良反应症状量表(TESS).结果 (1)治疗第6周末,治疗组催乳素[(26±6)μg/L]较基线[(112±40)μg/L]下降,差异有统计学意义(P=0.000);对照组催乳素[(99±44)μg/L]与基线[(104±34)μg/L]比较,差异无统计学意义(P=0.180).(2)治疗第6周末,治疗组催乳素下降率[(75±8)%]、正常率(82%),均高于对照组[分别为(5+30)%,4%];P均=0.000.(3)治疗第6周末,治疗组[(20.4±2.1)分]、对照组[(20.8±1.9)分]BPRS评分均较基线[分别为(21.1±1.8)分,(21.4±1.9)分]下降,P均=0.045;两组不良反应发生率相近(P=0.553).结论 阿立哌唑治疗利培酮所致精神分裂症女性患者的血高催乳症有效、安全.     

利培酮和氟哌啶醇对精神分裂症患者超氧化物歧化酶及催乳素影响的临床对照研究

目的 探讨经第一、二代抗精神病药治疗的精神分裂症患者体内超氧化物歧化酶(SOD)、催乳素(PRL)与精神症状间的关系.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的78例精神分裂症患者,随机分为利培酮组(41例),剂量为6 mg/d;氟哌啶醇组(37例),剂量为20mg/d;观察疗程均为12周.使用阳性和阴性症状量表(PANSS)评定临床疗效.采用放射免疫法在治疗前后分别测定患者血浆SOD及PRL浓度.以30名正常人为正常对照组.结果 利培酮组(40例)、氟哌啶醇组(33例)患者的基线SOD浓度[(794±126)ng/mg Hb,(750±101)ng/mg Hb]均明显高于正常对照组[(483±110)ng/mg Hb],而PRL浓度[(6±7)μg/L,(6±8)μg/L]均明显低于正常对照组[(18±12)μg/L],差异均有统计学意义(P均＜0.05).利培酮组和氟哌啶醇组患者的治疗前SOD与PRL间存在显著负相关(n=70,P＜0.05).治疗第12周末,利培酮组和氟哌啶醇组的SOD浓度[(499±98)ng/mg Hb,(482±76)ng/mg Hb]明显降低,而PRL浓度[(33±19)μg/L,(25±16)μg/L]则明显升高.利培酮组与氟哌啶醇组间治疗前后的SOD、PRL的差异均无统计学意义(P均＞0.05).治疗前后,阴性症状改善与SOD浓度差值(P＜0.05)、阳性症状改善与PRL浓度差值(n=70,P＜0.01)有相关性.结论 精神分裂症患者SOD及PRL浓度异常,两者间存在着相互作用,且对抗精神病药的临床疗效有影响.     

精神分裂症帕罗西汀激发试验及其与疗效的关系

目的探讨精神分裂症中枢5-羟色胺（5－HT）、多巴胺（DA）功能,以及非典型、典型抗精神病药对它们的影响。方法采用随机、双盲法应用固定剂量利培酮6mg/d、氟哌啶醇20mg／d治疗78例精神分裂症患者,共12周。治疗前后测定皮质醇、催乳素对帕罗西汀激发试验的反应,并以18名正常人为对照组。结果治疗前患者组基础皮质醇[（106±41）μg/L]、皮质醇对帕罗西汀激发试验的反应（曲线下面积AUC为717±229）高于对照组[（73±25）μg／L及AUC585±163],而基础催乳素[（5±7）μg/L]低于对照组[（9±5）μg／L]、催乳素对帕罗西汀激发试验的应答比对照组呈降低趋势（AUC49±41对68±43,P＞0．05）。治疗后,两组患者的催乳素基础值比治疗前均增高（P均＜0.05）;两组之间帕罗西汀介导的催乳素反应差异无显著性。治疗后,两组皮质醇的基础值[（74±32）μg/L及（82±27）μg/L]均较治疗前降低,其中利培酮治疗后降低更为明显。利培酮治疗后皮质醇对帕罗西汀激发试验的反应（AUC518±213）降低,并与对照组差异无显著性,而氟哌啶醇组皮质醇反应与治疗前差异光显著性（P＞0．05）。结论精神分裂症患者治疗前可能有中枢DA功能亢进和5－HT功能增高。利培酮治疗使患者原来过高的中枢5－HT功能接近正常,而氟哌啶醇     

重复经颅磁刺激对催乳素及事件相关电位P300的影响

目的:探讨重复经颅磁刺激(rTMS)对男性精神分裂症患者血清催乳素(PRL)水平及事件相关电位P300的影响。方法:将43例男性精神分裂症患者随机分为rTMS组(21例)和对照组(22例)。rTMS组在稳定剂量的利培酮3～6 mg/d治疗的同时给予连续5 d的高频rTMS刺激,对照组采用假rTMS刺激。刺激前后对两组分别进行血清PRL测定、P300检查及阳性和阴性症状量表(PANSS)、17项汉密尔顿抑郁量表(HAMD)评定。结果:刺激前两组PRL水平差异无统计学意义(P>0.05);治疗后,rTMS组PRL水平高于治疗前,差异有统计学意义(P<0.01);与治疗前比较,治疗后在CZ点,rTMS组P300的P2、P3波幅升高(P均<0.01)。而对照组P300各项指标治疗前后变化均无统计学意义(P均>0.05)。与治疗前比较,治疗后rTMS组及对照组PANSS总分及各因子分变化均无统计学意义(P均>0.05)。rTMS组治疗后HAMD评分下降(P<0.05)。结论:高频rTMS可使男性精神分裂症患者P300的P2、P3波幅升高,改善患者的认知功能及抑郁情绪。但同时会使血清PRL水平增高。     

阿立哌唑治疗奋乃静所致高催乳素血症的临床研究

目的探讨阿立哌唑治疗奋乃静所致高催乳素血症的疗效及安全性。方法将60例奋乃静所致高催乳素血症的精神分裂症患者,随机分为两组,在维持原奋乃静治疗的同时,分别加阿立哌唑（30例）及安慰剂（30例）治疗,疗程6周。分别于治疗前、治疗6周末检测血清催乳素（PRL）水平、评定简明精神病量表（BPRS）及副反应量表（TESS）,同时观察高催乳素血症临床症状变化情况。结果（1）治疗6周末,阿立哌唑组PRL（26.1±6.9）μg/L较治疗前（79.5±19.8）μg/L下降（P=0.000）,安慰剂组PRL（76.0±24.1）μg/L与治疗前（80.2±17.6）μg/L无显著性差异（P=0.227）;（2）治疗6周末,阿立哌唑组PRL下降值（53.4±16.8）μg/L高于安慰剂组（4.2±18.5）μg/L,差异有显著性（P=0.000）;（3）两组不良反应总体发生率均低,对原有奋乃静治疗的疗效均无不良影响。结论阿立哌唑可安全、有效治疗奋乃静所致的高催乳素血症。     

利培酮对女性精神分裂症患者神经内分泌的影响

目的 探讨利培酮对女性精神分裂症患者神经内分泌的影响。方法 对58例女性精神分裂症患者存利培酮治疗至少6个月后,检测性激素水平及利培酮血药浓度。并与30名健康女性进行对照分析。结果 研究组催乳素(PRL)、睾酮水平均显著高于对照组(P<0.01),而雌二醇、孕酮水平则显著低于对照组(P<0.01)。溢乳组PRL水平显著高于无溢乳组(P<0.01),ROC曲线显示,当PRL≥98.0μg/L时溢乳的危险性升高。结论 ①利培酮治疗后可见血催乳素、睾酮水平升高,雌二醇、孕酮水平降低;②催乳素≥98.0μg/L时发生溢乳的危险性升高。探讨利培酮对神经内分泌的影响还需进一步做前瞻性研究。     

利培酮与舒必利对精神分裂症男性老年患者血清催乳素水平影响的对照研究

目的 探讨利培酮和舒必利对精神分裂症男性老年患者血清催乳素（PRL）水平的影响。方法 将51例精神分裂症男性老年患者随机分为利培酮组[（3．7±0、9）mg／d，24例]和舒必利组[（800±156）mg／d，27例]，采用酶联免疫方法测定两组治疗前后的PRL水平，并与25名正常男性老年人（对照组）进行对照。结果 （1）治疗前，患者组PRL水平[（26±11）彬L]与对照组[（24±14）μg／L]的差异无统计学意义，利培酮组[（26±11）μg/L]与舒必利组[（28±12）μg/L]的差异亦无统计学意义（均P〉0．05）。（2）治疗后，患者组PRL水平[（149±59）μg/L]高于治疗前（t=14．53，P〈0．01）；利培酮组[（118±47）μg/L]和舒必利组[（196±73）μg/L]亦均高于治疗前，其中舒必利组高于利培酮组（均P〈0．01）。结论 利培酮和舒必利均能升高精神分裂症男性老年患者的PRL水平，其中以舒必利更为显著。     

阿立哌唑治疗利培酮所致高催乳素血症效果的性别差异

目的探讨阿立哌唑治疗利培酮所致高催乳素血症的效果是否存在性别差异。方法采用分层随机方法将116例利培酮所致高催乳素血症的精神分裂症患者分为研究组(男性28例,女性31例)和对照组(男性26例,女性31例)。维持原有利培酮治疗方案不变,研究组合并用阿立哌唑20mg·d-1,对照组合并安慰剂治疗。于基线期、治疗第2、4、8周末检测血清催乳素水平,于基线期、治疗8周末采用UKU副作用评定量表(UKU)评定药物不良反应。结果在治疗后第2、4、8周末,研究组男性、女性分别与对照组男性、女性血清催乳素水平比较差异均有统计学意义(P均0.01)。研究组男性、女性在治疗后第2、4、8周末血清催乳素水平分别与其基线期比较,差异均有统计学意义(P0.01),而在第2周、第4周、第8周末同组内两两比较,差异无统计学意义(P0.05)。对照组男性、女性血清催乳素水平治疗前后差异无统计学意义(P0.05)。8周末,研究组男性、女性催乳素水平下降率[(79.61±17.81)%vs.(75.54±12.96)%]差异无统计学意义(P0.05),研究组男性高催乳素血症治愈率(92.9%)高于女性(58.1%)(χ2=9.39,P0.001)。结论合并阿立哌唑对利培酮所致的高催乳素血症在治疗第2周显效。在相同剂量下,对男性患者的疗效可能优于女性。     

低频重复经颅磁刺激对酒依赖患者急性戒断后焦虑、抑郁和复饮的效果

目的探讨低频重复经颅磁刺激(rTMS)对酒依赖急性戒断后焦虑、抑郁和复饮的疗效,为改善酒依赖患者预后提供参考。方法选取在绵阳市第三人民医院住院的、符合《国际疾病分类(第10版)》(ICD-10)酒精依赖诊断标准的急性戒断后的102例患者为研究对象。采用随机数字表法分为研究组(n=50)和对照组(n=52)。两组患者均接受常规治疗,研究组加用rTMS,对照组应用伪刺激,治疗共8周。于治疗前和治疗第2、4、8周末进行汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表17项版(HAMD-17)评定,在患者出院后3、6月末评定其复饮情况。结果治疗第2、4、8周末,研究组HAMA和HAMD-17评分均低于治疗前(P均0. 01),且研究组均低于对照组,差异均有统计学意义(P均0. 01);在患者出院后3、6月末,研究组复饮率均低于对照组(P均0. 05)。结论低频rTMS可能有助于改善酒依赖患者急性戒断后的焦虑、抑郁情绪和复饮情况。     

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.     

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.