精神病人与正常人戒烟前后焦虑抑郁症状的对照研究

目的　了解精神病人和正常人戒烟前后精神状况的变化及差异性 ,探讨戒烟措施。方法　对 71例精神病人和 5 0例正常人戒烟前及戒烟后 1周分别应用汉密顿焦虑量表 (HAMA)、汉密顿抑郁量表 (HAMD)、焦虑自评量表 (SAS)、抑郁自评量表 (SDS)、简明精神病量表 (BPRS )进行测评。结果　精神病人强制性戒烟前HAMA、HAMD、SAS、SDS、BPRS分值分别为 (8.2 1± 6 .4 1)、(7.6 4± 5 .71)、(36 .81± 7.14 )、(33.71± 7.1)、(2 9.4 5± 8.4 7) ;戒烟后HAMA、HAMD、SAS、SDS、BPRS分值分别为 (16 .4 5± 6 .34)、(19.73± 8.71)、(5 8.1± 12 .12 )、(5 6 .31± 11.4 )、(37.32± 7.95 ) ;戒烟前后 5种量表分值变化与正常人戒烟前后分值变化比较有极显著性差异(P <0 .0 1)。结论　对精神病人强制性戒烟可引起明显的情绪反应 ,应适宜控制病人吸烟 ,建立一个合理的管理制度     

小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Improvement of Decreased Critical Flicker Frequency (CFF) in Headache Patients With Drug Abuse After Successful Withdrawal

A considerable proportion of headache patients fulfill the criteria of "drug abuse" (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis.
The present study deals with the question whether this impairment of vigilance and continuous performance is reversible. Forty-eight headache patients with drug abuse were investigated three times by means of CFF analysis: immediately before (A), immediately after (B), and 3 weeks after having finished (C) inpatient drug withdrawal.
Immediately after withdrawal, a significant decrease of headache intensity was observed. The CFF values, however, remained unchanged at a depressed level, probably due to withdrawal medication and the initial sedative side effects of thymoleptic agents (given as prophylaxis).
Three weeks after withdrawal, however, the CFF values were significantly improved, and were now within a range not far from the normal values known from a healthy general population. Thus, even after many years of drug abuse, headache patients have a good chance to improve their vigilance and continuous performance and to reach normal or close to normal levels.     

鞘内注射吗啡对切口疼痛大鼠脊髓背角蛋白激酶Cγ免疫反应的影响

目的 研究鞘内注射吗啡对切口疼痛大鼠脊髓背角蛋白激酶Cγ(PKCγ)免疫反应的影响。方法 SD雄性大鼠24只,随机分为4组(每组6只):假手术组(Ⅰ组)、对照组(Ⅱ组)术前30 min鞘内注射人工脑脊液20μl,术后吗啡治疗组(Ⅲ组)、术前吗啡治疗组(Ⅳ组)分别于术后和术前30min鞘内注射吗啡5μg(10 μl)。所有大鼠均按Brennan法制成切口疼痛模型,用免疫组织化学方法观察脊髓背角PKCγ的表达。结果 Ⅱ组术侧脊髓背角PKCγ-IR表达高于非术侧及Ⅰ组(P<0.01)。与Ⅱ组比较,Ⅲ组、Ⅳ组脊髓背角PKCγ-IR表达降低(P<0.05或0.01),而Ⅲ组、Ⅳ组比较差异无显著性。结论 在大鼠切口疼痛模型中,鞘内注射吗啡的镇痛作用可能与抑制脊髓背角的PKCγ-IR免疫反应有关。     

Panic Anxiety after Abrupt Discontinuation of Mianserin

Abstract: We observed a case of withdrawal after abrupt discontinuation of mianserin. A 41-year-old woman was treated according to a diagnosis of depression, which was her 6th episode. Mianserin 30 mg/day, etizolam 1 mg/day and flunitrazepam 1 mg/day were administered. When the patient discontinued taking the drugs by herself because of subsiding of these symptoms, severe panic anxiety appeared. This panic anxiety was not relieved by taking etizolam and flunitrazepam again, but subsided rapidly by the re-administration of mianserin 30 mg/day, and because of that the depressive symptom also disappeared.
From these experiences panic anxiety seemed to be a withdrawal symptom, and involvement of the noradrenergic system in panic anxiety as well as serotonergic system was suggested.     

骨外科患者拔尿管时注入药物对排尿的影响

目的探讨提高长时间留置导尿管病人拔管后2h内排尿成功率的方法。方法按入院先后随机将64例导尿的男性骨折病人分两组,单数为观察组,双数为对照组。对照组常规拔尿管,观察组拔尿管时遵医嘱注入地塞米松5mg+2%利多卡因5ml+生理盐水5ml+庆大霉素8万U,比较首次排尿的自觉症状,包括尿痛、排尿困难、排尿障碍等。结果观察组较对照组病人首次排尿出现自觉症状的例数明显减少(P<0.01),有显著性差异。结论拔尿管时注入药物安全有效,明显提高了长期置管病人拔除尿管后首次排尿的成功率,减轻了病人的痛苦,有广泛的应用价值。