A new and highly sensitive method for measuring 3-methoxytyramine using HPLC with electrochemical detection. Studies with drugs which alter dopamine metabolism in the brain

3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D₂ antagonist, BRL 34778 (5 mg/kg i.p.) or -DOPA (50 mg/kg i.p.). The selective D₁ antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors.     

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

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。     

The use of experimental studies to reveal suspected neurotoxic chemicals as occupational hazards: acute and chronic exposures to organic solvents.

The nervous system differs from many other body organs by its central control of vital functions and its low regeneration capacity. Organic solvents have, as a group, been suspected to have neurotoxic effects. Because of their similar physical properties and the fact that in industrial uses, they are often present in various mixtures, organic solvents have also been regarded, unfortunately, to induce common neurotoxic effects. However, it is evident from experimental studies using specified exposure conditions that different organic solvents have very diverse neurotoxic effects and also that the toxic mechanism may differ between acute and chronic exposure. No specific method used to describe a neurotoxic effect or single toxic response can be used for the overall occupational risk assessment of all organic solvents. Each solvent has to be considered as having its own unique toxic effects.     

河南省地方性高碘甲状腺肿的发现、流行特征及其干预研究

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Video assisted thoracoscopic surgery (VATS) in Asia - its impact and implications

Abstract Background: Within a short period of time, video assisted thoracoscopic surgery (VATS) has revolutionised the practice of thoracic surgery. Most of the existing literature, however, is concentrated on the technical aspects.
Aims: We examined the impact of VATS on our practice and its implications.
Methods: We reviewed our thoracic case load two years before and two years after the introduction of VATS in our hospital.
Results: We have witnessed a rapid and progressive increase in our thoracic case load since the introduction of VATS. With increased experience, proportionally more cases were performed using VATS compared to conventional surgical access. The increased case load covered a wide range of thoracic diseases with the majority for spontaneous pneumothorax and pleural diseases.
Conclusion: The higher case load is due to increased referrals which at least partly reflect earlier acceptance by both the patients and their physicians for surgical intervention. The changing indications for surgery and the high cost associated with VATS, however, could place extra demand on the healthcare, especially for some countries in Asia. Cost containment is therefore a high priority here. More research is greatly needed in this area.     

中西医结合治疗缺血性脑血管病临床疗效观察

目的 回顾性分析中西医结合治疗缺血性脑血管病的疗效。方法 对126例缺血性脑血管病患者，在早期西医溶栓、抗凝、降低血液粘度、扩张血管和促进脑细胞代谢等治疗基础上，结合中医辩证施治治疗。结果 42例瘫肢肌力恢复达V级；48例肌力≥Ⅳ级，言语流畅；27例生活能基本自理，可依杖散步，肌力≥Ⅲ级：9例与治疗前对比肌力提高Ⅰ～Ⅱ级，但生活仍不能自理。结论 在西药治疗基础上，结合益气活血中药调理可显著提高患者的疗效。     

弹性义齿修复的临床效果观察

目的：了解弹性义齿修复的临床效果，为临床应用提供参考。方法：152例门诊缺牙患者，制作弹性义齿修复体188件，上颌130件，下颌58件。Kennedy一类缺损修复6件，Kennedy二类缺损修复4件，Kennedy三类缺损修复102件，Kennedy四类缺损修复76件。通过1－4年的观察，从形态和功能、固定和稳定、颜色和美观以及对组织保健判断对义齿的满意程度，并进行临床效果评价。结果：79例95件弹性义齿具有良好的美观效果，颜色满意，感觉舒适，满意和较满意率达100％，Kennedy三、四类缺损修复率为94．74％。弹性义齿对Kennedy一类缺损修复的满意和比较满意率为66．67％；对Kennedy二类缺损修复的满意和比较满意率为50．00％；对Kennedy三类缺损修复的满意和比较满意率为96．15％；对Kennedy四类缺损修复的满意和比较满意率为84．21％。结论：(1)弹性义齿是一种美观、舒适、对基牙预备甚少的可摘局部义齿修复形式。（2）弹性义齿较适合咀嚼压力小而缺牙数目不多的前牙和前磨牙缺失的修复。     

股骨干骨折扩髓腔髓内钉固定对凝血机能和肺换气功能的影响

【目的】探讨股骨干骨折扩髓与不扩髓髓内钉固定对凝血机能和肺换气功能的影响。【方法】 38例股骨干骨折分别采用扩髓 (RFN)和不扩髓 (UFN)髓内钉固定 ,在手术开始前至术后 4 8h内 7个不同时间段监测血小板、纤维蛋白原、凝血酶原时间 (PT)和部分凝血活酶激活时间 (APTT)的变化 ,并动脉血气分析 ,计算肺泡 动脉血氧分压递差 [P(A aDO2 ) ]。【结果】RFN组 ,扩髓后血小板开始减少 ,P(A aDO2 )升高 (P<0 0 5 ) ;髓钉插入后 30min纤维蛋白原减少 ,PT、APTT延长 (P <0 0 5 ) ;UFN组表现出同样的趋势 ;两组中各项指标均在 2 4～ 4 8h内恢复正常 ;动脉血气分析各时间段和组间差异无显著性 (P >0 0 5 )。【结论】扩大髓腔的髓内钉固定 ,和不扩髓相比 ,并不影响肺换气功能 ,对凝血机能的影响是一个自限过程 ,单纯股骨干骨折 ,可耐受扩髓固定手术。     

The discriminative stimulus and subjective effects of d-amphetamine,phenmetrazine and fenfluramine in humans

The discriminative stimulus (DS) and subjective effects of d-amphetamine (AMP), phenmetrazine (PMT) and fenfluramine (FFL) were studied in a group of normal healthy adults. Subjects (N=27) were trained to discriminate between placebo and 10 mg AMP (PO). Fourteen of the subjects (discriminators) reliably learned the discrimination, whereas the other 13 did not. Nearly all discriminators labelled AMP as a stimulant, and AMP, relative to placebo, increased ratings of drug liking and general activity level, and produced typical stimulant-like subjective effects, as measured by the Profile of Mood States, the Addiction Research Center Inventory, and a series of visual analog scales. The discrimination accuracy of discriminators increased as a function of hour after drug ingestion, as did analog ratings of how certain subjects were that their discrimination responses were correct. Discriminators were tested with doses of PMT (25 and 50 mg) and FFL (20 and 40 mg) to determine whether the DS properties of these drugs would substitute for those of AMP. Both doses of PMT consistently substituted for AMP, and PMT produced subjective effects very similar to those of AMP. Conversely, neither dose of FFL consistently substituted for AMP, and FFL produced essentially no subjective effects. These findings are consistent with results from discrimination studies with other species, and provide further evidence of the validity of this procedure for studying the DS properties of drugs in humans. Offprint requests to: L.D. Chait