血清、血浆、红细胞内氯氮平浓度测定的临床意义

目的 探讨精神分裂症病人血清、血浆、红细胞内氯氮平浓度与临床效应的关系。方法 59例精神分裂症病人经氯氮平150～600mg/d治疗8周。采用BPRS,PANSS量表评定临床效应,同时测定血清、血浆、红细胞内氯氮平及它的代谢产物去甲氯氮平浓度。结果 血清、血浆、红细胞内的药物浓度呈两两正相关,未发现血浆及红细胞内药物浓度与疗效指标相关(P值均>0.05);按疗程结束时的BPRS减分率≥30％为有效,分别取血浆氯氮平浓度最低有效阈值100ng/ml、350ng/ml、600ng/ml,相应的有效率56.9％、48％、50％均无显著性差异(χ~2=0.61,P>0.05)。结论 血清、红细胞内氯氮平及去甲氯氮平浓度低于血浆浓度,建议检测血浆浓度;去甲氯氮平在红细胞内分布较多,与临床效应间的关系有待进一步探讨;本研究中氯氮平治疗精神分裂症病人的起效血浆浓度范围很宽,推测患者对药物疗效的反应性是影响血药浓度与临床疗效关系的重要因素,采用氯氮平血药浓度指导临床实践时,应分析是否适用于临床实际情况。     

CYP1A2活性、性别、吸烟对氯氮平去甲基代谢的影响

目的探讨精神分裂症患者细胞色素氧化酶P4501A2(CYP1A2)活性、性别、吸烟对氯氮平(clozapine,CLZ)体内去甲基代谢的影响.方法对单一用氯氮平治疗6周的46例精神分裂症患者,用咖啡因试验检测血中CYP1A2活性指数,剂量固定1周后检测血中氯氮平、去甲氯氮平(desmethylclozapine,DCLZ)浓度.分析性别、吸烟对CYP1A2活性及CLZ代谢的影响,以及CYP1A2活性与氯氮平代谢的关系.结果吸烟男性与不吸烟男性比较去甲基代谢率分别为0.71±0.17、0.55±013,差异非常显著(P＜0.01).CYP1A2活性指数分别为0.62±017、0.48±014,亦有显著差异(P＜0.05);女性和男性不吸烟组去甲基代谢率分别为040±016、055±0.13,CYP1A2活性指数分别为0.37±0.14和0.48±0.14,两组间均有显著性差异(P＜0.05).去甲基代谢率与CYP1A2活性指数呈正相关.结论CYP1A2活性、性别、吸烟是影响氯氮平去甲基代谢的主要原因.     

2002年度中华精神科杂志优秀论文礼来奖揭晓

20 0 2年度中华精神科杂志优秀论文礼来奖的评选结果已经揭晓 ,共有 6篇论文获奖。两名一等奖分别为 :上海复旦大学附属华山医院精神医学教研室曹秋云等的《轻度认知功能障碍患者正电子发射计算机体层摄影术和神经心理学测定的初步研究》 ,四川大学华西医院心理卫生研究所邓红等的《精神分裂症同胞家系的 6号染色体基因组扫描研究》 ;两名二等奖分别为 :首都医科大学附属北京安定医院李樱等的《精神分裂症患者血清、血浆、红细胞内氯氮平及其代谢物浓度的研究》 ,南京医科大学附属脑科医院精神科张志等的《精神分裂症患者海马区γ 氨基丁…     

抗结核药与氯氮平的相互作用及临床效应的影响

目的探讨抗结核药对氯氮平血药浓度及临床效应的影响。方法 服氯氮平2周后,连续测3次氯氮平血浓度,取平均值。然后合并抗结核药2周后.再3次测氯氮平血浓度,取其均值进行比较。同时采用BPRS、CGI、TESS对精神症状及药物副反应进行评定。结果 合并抗结核药氯氮平血药浓度(91±57)ng/ml比单用氯氮平血药浓度(284±254)ng/ml显著降低(P<0.05)。BPRS单用氯氮平评分为38±6.2,合并用药评分47±8.6(P=0.01),TESS合并用药前后分别为103±6.4与86±14.7(P=0.01),CGI合并用药前后为2.3±1.4和1.5±O.9,(P=0.2)。结论 抗结核药可降低氯氮平血浓度,并影响其临床效应。     

利培酮对氯氮平血浓度影响的初步研究

目的：了解利培酮对氯氮平血浓度的影响。方法：11例精神分裂症人,单用氯氮平2周后并用利培酮3月,分别测定药前后氯氮平血药浓度,进行自身配对比较分析。结果,加利培酮后,平均氯氮平血浓度和平均N－去甲氯氮平血浓度升高（后者P＜0．05）,单用氯氮平和并用利培酮时,N－去甲氯氮平血浓度与氯氮平浓度呈正相关（P均＜0．01）。结论：利培酮可使氯氮平血浓度升高,如氯氮平剂量偏高时,并利用培酮,有增加氯氮平药物毒副反应的潜在危险性。     

药物自我处置和症状自我监控技能训练对预防精神分裂症复发的作用初探

目的探讨药物自我处置和症状自我监控技能训练对降低精神分裂症患者复发和提高其药物依从性的作用.方法将133例痊愈的精神分裂症患者随机分为技能训练组(以下简称训练组;66例)和对照组(67例).对训练组患者分组进行技能训练,共20周,两组均有64例完成1年随访.每月评定1次简明精神病量表(BPRS),每天以自制的监护人及患者药物依从性评分表进行评分;每2个月测定1次氯氮平血浓度.结果(1)入组时与随访末次评定差值的比较,训练组的BPRS总分[(3.3±13.7)分]、漏服药次数[(-0.9±3.0)次]、监护人药物依从性评分[(-53.0±31.2)分]和氯氮平血浓度[(85.5±44.8)ng/ml],均优于对照组,分别为[(-19.2±21.7)分]、[(-9.5±5.9)次]、[(26.5±24.3)分]和[(199.1±85.0)ng/ml],均P＜0.001;(2)训练组的复发率(12%)和再住院率(3%)低于对照组(分别为52%和38%;P＜0.001);(3)Kaplan-Meier生存分析显示,训练组的复发和再住院累计生存率优于对照组(复发的log-rankx2=25.62,再住院的log-rankx2=25.49,均P＜0.001).结论两种技能训练能降低精神分裂症患者的复发并提高其药物依从性.     

上海精神医学1989～1990年目录索引

1.精神医学总论及基础理论 中国精神病学四十年 1(1):7 我国精神病院的发展现状 2(4):196 精神分裂症的病毒假说和特殊脑损害假 说 2(1):33 心理防御机制的研究与应用2(4):209 决策与精神障碍 2(2):9l 高发精神分裂症的遗传效应2(4):177 生物精神医学八十年代新进展l(1):1 放射受体结合分析法测定氯丙嗪血浓度 ’ :l(1):23 用HPLC测定血中氯氮平及其N一去甲 基代谢产物 2(1):2d 精神疾病患者血浆DBH活性的初步探 讨 2(3)::138 褪黑激素与季节性情感性精神病 2(4):206 氯氮平与HVA 2(2):65 精神分裂症外周血T淋巴细胞亚群及 免疫蛋白测…     

锂盐治疗精神病人导致红细胞内乙酰胆碱的积累研究

本文应用对乙酰胆碱(Ach)敏感的离子选择微电极,在研究服用碳酸锂的8位躁狂症病人红细胞内(Ach)值中发现,其值为:98.2±41.3μmol/L,对照17例正常健康人红细胞内Ach活度值(22.8±1.6μmol/L),经统计学处理有显著性差异,是正常人的5倍(P<0.001)。而服用舒必利和氯氮平精神分裂症患者的(Ach)(31.1±18.9μmol/L),和正常人比较没有差异。     

三唑仑对失眠症患者睡眠脑电的影响

目的应用多导睡眠图(PSG)探讨三唑仑对失眠症患者睡眠脑电活动的影响.方法对28例失眠症患者连续进行4夜PSG描记,其中第3、4晚上睡前予0.5mg三唑仑,观察用药后PSG的变化.正常对照组33名,作2夜适应和基础PSG监测.结果失眠症患者服用三唑仑后夜间PSG显示睡眠效率提高[基线睡眠值(86±9)%,第3晚服药后(91±8)%,第4晚服药后(92±4)%,F值6.143,P＜0.01],觉醒时间减少[同前,(39±17)min,(29±8)min,(23±7)min,F值13.211,P＜0.01],S1减少[同前,(31±18)%,(23±11)%,(16±6)%,F值9.707,P＜0.01],S2增加[同前,(45±17)%,(59±18)%,(60±6)%,F值10.104,P＜0.01],睡眠潜伏期缩短[同前,(35±18)min,(28±17)min,(21±11)min,t值4.947,P＜0.05].结论短半衰期催眠药三唑仑不仅能改善患者对睡眠的主观评价,还对夜间睡眠脑电有影响.     

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。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Satellite cells and myonuclei in young and elderly women and men

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

Retrospective and prospective design and data

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.     

Cortisol levels and depression in men and women using heroin and cocaine

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.     

Dissociation and Counterdissociation: Nuanced and Binary Perceptions of Good and Evil

Dissociated experiences are often communicated to analysts. Clinicians may absorb patients' dissociation, thereby creating “counterdissociated” states. Counterdissociation contributes to binary thinking in the analyst similar to black- and-white thinking commonly seen in patients' dissociated states. This can have both positive and negative effects: Counterdissociation may help therapists identify with patients' experience, thereby cementing the therapeutic bond. If analysts remain counterdissociated, however, patients may remain dissociated. As analysts identify their counterdissociation, they may gain insight into patients' needs for dissociation. As they overcome counterdissociation, patients may concurrently overcome dissociation. This allows both to have a more nuanced view of inner experience. With two extended case studies of sexually abused men, this article tracks how an analyst deals with counterdissociation created through intimate contact with dissociated positive and negative introjects of victimizers, thus forming identifications or overidentifications with the patients' abused parts.     

Necdin蛋白与神经元的生长分化

在神经系统,Necdin只在成熟神经元的细胞核中表达,可能与成熟神经元分裂静止状态的保持有关.近年的研究表明,Necdin是一种生长抑制蛋白,能与多种因子如SV40大T抗原,腺病毒E1A,转录因子E2F1以及肿瘤抑制蛋白p53等结合,在功能上类似于成视网膜瘤蛋白Rb.necdin基因缺陷时,会引起脑内,特别是下丘脑神经元分化障碍.人类necdin基因位于PWS综合征的基因缺失区,可能与PWS的一些症状有关.本文从Necdin蛋白的基本概况,生物功能以及Necdin与疾病三个方面进行了综述.     

Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan and the V(2) antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and V(2) antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.