围手术期负荷剂量他汀对急性ST段抬高型心肌梗死患者预后的影响

为了探讨围手术期给予阿托伐他汀负荷剂量对急性ST段抬高型心肌梗死（STEMI）患者急诊经皮冠状动脉介入治疗（PCI）后对心血管事件的影响。选取因STEMI行急诊PCI术患者160例,其中80例于PCI术前给予阿托伐他汀负荷剂量40mg,80例术前未给予阿托伐他汀负荷剂量进行研究。分析两组患者住院期间肌酸激酶同工酶与超敏C反应蛋白值,PCI术后与术后1个月心功能情况。结果显示围手术期阿托伐他汀负荷剂量组主要心血管事件发生率优于非阿托伐他汀组（P〈0．05）。因此,围手术期给予负荷剂量的阿托伐他汀可以降低住院期间不良心血管事件的发生率,改善患者预后。     

肖碧莲与中国低剂量口服避孕药的研发

1969年中国通过了1/4剂量口服避孕药的鉴定,进而批量生产和推广使用,是当时世界上临床大量应用的最低剂量。生殖内分泌学家肖碧莲(1923-)是口服避孕药早期研发的重要领导者之一。本文回顾肖碧莲的学术成长经历以及对中国生殖内分泌学的奠基作用,重点梳理其团队的低剂量口服避孕药研发工作,从避孕药的剂量和剂型等变化考察社会经济条件对技术的具体形态的影响,尤其对技术的政治负载加以分析。     

中国医用度量衡发展概况

中医方药剂量离不开计量,研究<伤寒论>本源剂量,必须梳理中国医用度量衡的发展历史.中国古代度量衡的量值,总体看来在逐渐增大.随着度量衡的发展,秦汉以后医用度量衡出现了较大变化.后世应用经方多进行剂量折算,然折算标准不一,造成经方本源剂量的迷失.     

雷公藤多苷对肝脏的双重作用及其思考

文献研究表明,雷公藤多苷既可治疗肝脏疾病,又能引起肝脏毒性.本文对其双重作用从不同角度进行了分析,认为药物均存在治疗作用和毒副作用的双重效应,且与用药剂量、时间密切相关,并从严控剂量时间、加强监测、重视"治未病"、改进剂型等方面提出了应对措施.     

心肺复苏时肾上腺素剂量变迁的思考

肾上腺素是临床上心肺复苏的一线药物,但在最近二十几年以来,其剂量应用方案几经变迁,从20世纪80年代的小剂量,到90年代大剂量方案的兴起,又经历了个体化方案阶段,近几年又重新回归到小剂量给药方案.从唯物辩证法的基本思想出发,阐述心肺复苏时肾上腺素剂量变迁的哲学基础,并运用辩证唯物主义原理来探讨肾上腺素剂量研究的发展方向,这将有助于心肺复苏研究的理论与实践.     

心肺复苏时肾上腺素剂量变迁的思考

肾上腺素是临床上心肺复苏的一线药物,但在最近二十几年以来,其剂量应用方案几经变迁,从20世纪80年代的小剂量,到90年代大剂量方案的兴起,又经历了个体化方案阶段,近几年又重新回归到小剂量给药方案。从唯物辩证法的基本思想出发,阐述心肺复苏时肾上腺素剂量变迁的哲学基础,并运用辩证唯物主义原理来探讨肾上腺素剂量研究的发展方向,这将有助于心肺复苏研究的理论与实践。     

雷公藤多苷对肝脏的双重作用及其思考

文献研究表明,雷公藤多苷既可治疗肝脏疾病,又能引起肝脏毒性。本文对其双重作用从不同角度进行了分析,认为药物均存在治疗作用和毒副作用的双重效应,且与用药剂量、时间密切相关,并从严控剂量时间、加强监测、重视“治未病”、改进剂型等方面提出了应对措施。     

哮喘控制稳定后如何减停糖皮质激素

糖皮质激素是最有效的抗气道炎症药物,吸入糖皮质激素(ICS)是首选哮喘控制药物.由于治疗后达到哮喘临床控制(症状、肺功能)需要一定时间,ICS达到一定剂量后量效曲线较平坦,而全身不良反应却逐渐增加.因此,达到临床控制后在长期监测下至少维持哮喘控制3个月以上,开始减少50%ICS剂量,直至ICS减至最低维持剂量.如为ICS加另一种控制药(长效β2受体激动剂、白三烯调节剂、缓释茶碱)联合治疗达到控制者,在ICS减至最低剂量时再停用另一种控制药.应用最低剂量ICS维持控制达1年方可考虑停药.     

哮喘控制稳定后如何减停糖皮质激素

糖皮质激素是最有效的抗气道炎症药物,吸入糖皮质激素(ICS)是首选哮喘控制药物。由于治疗后达到哮喘临床控制(症状、肺功能)需要一定时间,ICS达到一定剂量后量效曲线较平坦,而全身不良反应却逐渐增加。因此,达到临床控制后在长期监测下至少维持哮喘控制3个月以上,开始减少50%ICS剂量,直至ICS减至最低维持剂量。如为ICS加另一种控制药(长效β2受体激动剂、白三烯调节剂、缓释茶碱)联合治疗达到控制者,在ICS减至最低剂量时再停用另一种控制药。应用最低剂量ICS维持控制达1年方可考虑停药。     

晚期非小细胞肺癌TKIs治疗：关注与思考

以表皮生长因子受体（EGFR）为靶点的酪氨酸激酶抑制剂（TKIs）对晚期非小细胞肺癌EGFR突变患者的治疗效果令人瞩目。本文分析总结近年国内外相关研究,指出低剂量TKIs的应用虽有待进一步证实,但优于标准剂量组,并从安全性、改善肿瘤血管结构和功能、与细胞毒化疗的关系三方面探讨大剂量TKIs的应用效果。进一步分析指出大剂量联合小剂量TKIs能够最大程度地防止或延迟耐药的发生,进而控制疾病的进展。从而,为晚期非小细胞肺癌EGFR突变患者的TKIs治疗选择提供参考。     

The role of dopamine in reinforcement: changes in reinforcement sensitivity induced by D1-type, D2-type, and nonselective dopamine receptor agonists

Dose-dependent changes in sensitivity to reinforcement were found when rats were treated with low, moderate, and high doses of the partial dopamine D1-type receptor agonist SKF38393 and with the nonselective dopamine agonist apomorphine, but did not change when rats were treated with similar doses of the selective dopamine D2-type receptor agonist quinpirole. Estimates of bias did not differ significantly across exposure to SKF38393 or quinpirole, but did change significantly at the high dose of apomorphine. Estimates of goodness of fit (r2) did not change significantly during quinpirole exposure. Poor goodness of fit was obtained for the high doses of SKF38393 and apomorphine. Decrements in absolute rates of responding were observed at the high dose of quinpirole and at the moderate and high doses of SKF38393 and apomorphine. Changes in r2 and absolute responding may be due to increases in stereotyped behavior during SKF38393 and apomorphine exposure that, in contrast to quinpirole, were distant from the response lever. The present data provide evidence that sensitivity to reward is affected more strongly by dopamine D1-like receptors rather than D2-like receptors, consistent with evidence from other studies investigating consummatory dopamine behavior and the tonic/phasic dopamine hypothesis.     

COMPARING TREATMENT TACTICS WITH A HYPERACTIVE PRESCHOOL CHILD: STIMULANT MEDICATION AND PROGRAMMED TEACHER INTERVENTION1

Two treatment tactics, food and praise contingent on appropriate play and varying doses of methylphenidate (Ritalin), were evaluated for their effects on a preschool child's activity changes. In addition, other social, verbal, and academic behaviors were monitored to examine possible side effects of the two treatment tactics. Fewer free-play activity changes occurred during contingent reinforcement phases while medication had variable effects: increasing attention to tasks but, at higher doses, decreasing intelligibility of speech and responsiveness to mands. The study outlines a replicable model for comparing medication with alternative behavioral strategies to control hyperactivity and enhance skill development.     

Effects of d-amphetamine and caffeine on schedule-controlled and schedule-induced responding.

The effects of d-amphetamine and caffeine were studied on rates and patterns of lever pressing and schedule-induced licking under fixed-interval schedules of food pellet presentation. In addition, the effects of caffeine were studied on lever pressing and licking under a multiple fixed-ratio fixed-interval schedule. Caffeine reduced mean overall rates of licking at lower doses than it reduced mean overall rates of pressing under the fixed-interval schedules, but the effects of caffeine on both licking and lever pressing depended largely on the control rate of responding. d-Amphetamine reduced mean overall rates of lever pressing and licking at about the same dose, but the effects of d-amphetamine also were a function of the control rate of responding.     

Preference in rhesus monkeys given a choice between cocaine and d,l-cathinone

Previous experiments have shown that both cocaine and d,l-cathinone can function as positive reinforces when delivered intravenously to rhesus monkeys. However, the relative reinforcing efficacies of these compounds have not been established. In the present experiment, three rhesus monkeys were allowed to choose between saline and several doses of d,l-cathinone or cocaine as well as between several doses of both drugs in a discrete-trial choice procedure. Sufficient doses (.05 to .2 mg/kg/injection) of either drug maintained self-administration and the higher doses were reliably preferred to saline. Doses of d,l-cathinone that were preferred to saline were then compared to a range of cocaine doses in drug-drug choice. As the dose of d,l-cathinone that was available was increased, an increase in cocaine dose was necessary to maintain cocaine preference. Comparison of drug-drug choice data to dose combinations predicted to be chosen with equal frequency revealed that the reinforcing efficacy of d,l-cathinone was equivalent to that of cocaine.     

Drug effects on repeated acquisition: comparison of cumulative and non-cumulative dosing

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of a sequence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-minute sessions, with a 10-minute inter-session interval. Cumulative dose-effect curves for phencyclidine, pentobarbital, and d-amphetamine were obtained by giving an injection before each of the four sessions; successive injections increased the cumulative dose in equally spaced logarithmic steps. For comparison, non-cumulative doses of each drug (i.e., doses not preceded by other doses on the same day) were also tested. As the cumulative dose of each drug increased, the overall response rate decreased, the percent errors increased, and there was less within-session error reduction (acquisition). With phencyclidine and pentobarbital, the rate-decreasing and error-increasing effects tended to be greater with a non-cumulative dose than with the corresponding cumulative dose. In contrast, with d-amphetamine, the effects were considerably greater with the cumulative doses. The results indicate that although the cumulative-dosing procedure saved a substantial amount of time in determining dose-effect curves, there were quantitative differences in effects between cumulative and non-cumulative doses.     

Antiaggressive and motor effects of the DA release inhibitor CGS 10746B

In the present study the effects of a wide range of doses of the dopamine release inhibitor CGS 10746B were evaluated in spontaneous activity and in aggressive behaviour using the paradigm of isolation‐induced aggression. The two higher doses (8 and 16 mg/kg) produced a decrease in spontaneous motor activity. Antiaggressive effects were observed after administration of doses from 4 mg/kg upwards. At this dose, CGS 10746B diminished threat and attack, and although an increase in immobility was observed, no impairment of other motor behaviours was presented. With higher doses, aggression was practically abolished but with a concomitant effect on many other behaviours. When animals were separated depending on their latency of attack, those that showed a long attack latency (LAL) presented a stronger response to 4 mg/kg than those that had a short attack latency (SAL), which were not affected in their aggression by this dose. We can conclude that presynaptic dopamine function is necessary for the normal expression of aggressive behaviours, since CGS 10746B reduces aggression at doses that do not affect spontaneous motor activity. Aggr. Behav. 27:382–390, 2001. © 2001 Wiley‐Liss, Inc.     

Insulin and dextrose effects on fixed-interval behavioral thermoregulation in albino rats

This study is a systematic replication of the effects of insulin doses on operant behavior reinforced (in an earlier study) by fixed-ratio schedules of microwave (MW) reinforcement. In this study, insulin and dextrose doses were administered (ip) prior to fixed-interval 2-min. schedules of MW reinforcement in rats tested in a cold environment. Six Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW radiation (SAR = 0.34 Watts/kg/(mW/cm2) under the FI-2' schedules. Humulin-regular insulin and 50% solutions of dextrose were administered (ip) alternately with saline control sessions for 8-hr. durations. A within-subjects, repeated-measures 4 x 8 x 3 factorial analysis of variance design showed that insulin doses suppressed operant responding for heat, which confirmed the results of the earlier study under a different schedule. In addition, high doses of dextrose had similar suppressing effects on operant responding for heat. The data are interpreted in terms of the discriminative properties of increased thermogenesis produced by the insulin and dextrose doses. The suppressing effects were more pronounced for the first two hours, yet they persisted for approximately six hours of the 8-hr. sessions.     

Effects of amphetamine-CNS depressant combinations and of other CNS stimulants in four-choice drug discriminations

Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine-pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs at these doses, and saline (methamphetamine-morphine group). After 10 to 13 months of training, the pigeons averaged more than 90% of their responses on the appropriate key during training sessions. In subsequent testing, dose-response curves were determined for the individual drugs, for a wide range of dose combinations of the training drugs, and for two drugs to which the pigeons had not been exposed previously (pseudoephedrine and nicotine). After low test doses of the training drugs, pigeons responded on the saline key. As the dose increased, responding on the key associated with that drug during training sessions increased. When training drugs were combined at doses that were not discriminable when given alone, responding occurred on the saline key. When a discriminable dose of one training drug was combined with a nondiscriminable dose of the other training drug, responding occurred on the key associated with the discriminable dose. When both drugs were given at discriminable doses, responding almost always occurred on the drug-combination key. The response-rate decreasing effects of pentobarbital and amphetamine were mutually antagonized when the drugs were combined, but the rate-decreasing effects of morphine and methamphetamine were not. After low doses of pseudoephedrine and nicotine, pigeons in both groups responded on the saline key. After higher doses of pseudoephedrine and nicotine, responding in the amphetamine-pentobarbital group occurred primarily on the amphetamine key. In the methamphetamine-morphine group, higher doses of pseudoephedrine and especially nicotine engendered more responding on the combination key than had occurred in the other group. The four-choice procedure can reveal subtle effects in the discrimination of individual drugs and drug combinations that are not apparent with procedures offering fewer response alternatives.     

Combined action of diazepam and d-amphetamine on fixed-interval performance in cats

Cats trained under a fixed-interval 5-min schedule of milk presentation were injected with diazepam, amphetamine, and combinations of amphetamine and diazepam. Diazepam increased overall response rate as a function of the dose and disrupted the temporal pattern of responding. Low doses of amphetamine (0.5 mg/kg) usually increased the response rate; higher doses (1 to 2 mg/kg) either decreased the response rate or had little effect. Amphetamine always disrupted the temporal pattern of responding, even though it did not affect the overall rate. When doses of amphetamine that increased the response rate or left it unchanged were combined with diazepam, a potentiated increase in response rate occurred. When doses of amphetamine that decreased the response rate were combined with diazepam, the amphetamine-induced rate decreases were reversed at least partially. Less clear potentiation of disruption of the temporal pattern of responding was observed when amphetamine and diazepam were combined.