Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.     

REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART

1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P₂, such that the majority of InsP isomers derive from Ins(1,4,5)P₃. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.     

The stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice

Modafinil is a new drug used in the treatment of narcolepsy. Its administration in mice induced a dose-dependent increase in locomotor activity. The effects of modafinil were compared with those of dexamphetamine on three tests that assessed the anxiety level (drugs were used at doses which induced a roughly similar stimulation of locomotor activity). Dexamphetamine increased the latency of exploration of a white compartment, increased thigmotaxis in an open-field and decreased the time spent in the open arms of an elevated plus-maze. None of these responses was significantly modified by modafinil. We conclude that modafinil does not share the anxiogenic effects of dexamphetamine.     

Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P<0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased form 78.1 to 93.6 bpm on average (P<0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.     

上海市少年儿童住院医疗保险费用分析

本文研究了上海市少年儿童住院医疗保险的费用水平、特点和影响因素。研究结果表明:手术与否、患者年龄、就诊地点、家长医疗保健制度和医院等级的差异造成次均费用的差异;次均费用构成比较合理,药品费比例低于全市水平。病种费用居前三位的是白血病、肺炎和先天性心脏病;特殊病种占总医疗服务人次的4.90％,而医疗费用占总费用的32.57％。     

医院综合效益评价案例分析

运用层次分析法建立了医院综合效益评价指标体系，开发了医院综合效益九型评价图，用于显著评价结果。在此基础上进行了３个案例的评价分析。论述了通过对西南地区２７所医院综合效益４年多的追踪分析所发现的共性问题，并提出了相应的管理对策。     

五所医院特需医疗服务状况调查

通过对上海医科大学附属华山医院、协和医院、北京同仁医院、中山医科大学附属第一医院、浙江医科大学附属第二医院开展的特需医疗服务情况的调查，论述了五所医院的具体做法，在对调查结果进行分析的基础上，就特需医疗服务的管理提出了建议。     

努力推进军队卫生系统的计算机应用

系统地介绍了军队卫生系统计算机应用的概况，总结了军队卫生系统自动化建设的主要经验，并提出了加强军队卫生系统计算机应用的设想。     

Adverse reactions to non-ionic contrast media with special regard to high-risk patients

Non-ionic contrast media (CM) are proven to be significantly safer than the high osmolar ionic contrast media (HOCM). Nevertheless deaths are reported after administration of non-ionic agents. The aim of the study was to investigate the rate of adverse reactions to non-ionic CM with special regard to high-risk patients and the effects of premedication with H1-and H2-receptor antagonists.In a prospective study conducted over about 2 years 12 995 examinations with intravenous or intra-arterial non-ionic CM were evaluated. Premedication with H1-and H2-antagonists was used in 1276 high-risk patients with known adverse reaction to CM, history of allergy or severe cardiac or pulmonary disease. 229 patients received no premedication inspite of known risk factors. In total, there were 143 (1.10%) adverse reactions (mild in 0.58%, moderate in 0.41% and severe in 0.05%). In high-risk patients there were adverse reactions in 4.37% without and in 1.57% with premedication. There were no severe adverse reactions in the high-risk patients after premedication. The age of the patient, CM dosage and CM concentration were not shown to be risk factors in the present study. In conclusion, the additional premedication with H1- and H2-antagonists could be an effective agent to reduce the risk of mild and moderate adverse reactions and to avoid severe adverse reactions in high-risk patients. Correspondence to: U. Fink     

十二烷氮酮氟尿嘧啶凝胶治疗疣及银屑病150例

443例(男225例,女218例;年龄36±14a)皮肤病患者,其中150例(扁平疣52例、寻常疣55例、银屑病43例)外用含1.8％十二烷氮(艹卓)酮的1％氟尿嘧啶(5-FU)凝胶作为治疗组,148例外用1％5-FU凝胶及145例外用2.5％5-FU霜作为2个对照组。经双盲对照临床试验,结果表明含1.8％十二烷氮(艹卓)酮的1％5-FU凝胶的疗效明显优于2个对照组(P<0.01及P<0.005)。证明氮(艹卓)酮对5-FU确有渗透促进作用。