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41.
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 相似文献
42.
Graves甲亢多种治疗方法对Graves眼病影响的系统评价 总被引:1,自引:0,他引:1
目的 通过榆索、分析文献系统评价131I、手术、抗甲状腺药物(ATD)治疗Graves病(GD)对Graves眼病(GO)的影响.方法 检索了MEDIJNE(1966年-2006年3月)、EMBASE(1984-2005年)、The Cochrane Library(2006年第1期)、中国生物医学文献光盘数据库(EBMdisc,1978年1月-2006年4月)和中国学术期刊全文数据库(CNKI,1994-2006年)所收录的有关不同GD治疗方法对GO影响的文献,同时从参考文献中追溯文献.对纳入研究的方法学质量进行评价,根据是否采取预防甲状腺功能低下(简称甲低)发生的措施对纳入研究进行亚组分析,结果采用RevMan4.2软件进行统计学分析.结果 最终纳入随机对照研究5项,非随机对照研究2项,病例对照研究1项,共1625例患者.Meta分析显示:如GD治疗后早期未采取措施预防甲低,131I与手术治疗、131I与ATD治疗GD在诱发或加重GO以及减轻GO症状方面莘异有统计学意义[检验值分别为2.31,5.97,3.70,5.55;P均<0.05];如GD治疗后早期采取措施预防甲低,手术与ATD治疗GD在诱发或加重GO以及减轻GO症状方面差异无统计学意义(检验值分别为0.27,0.99;P均>0.05),尚无研究涉及131I治疗GD后早期采取甲低预防措施时131I对GO的影响.结论 若未及时采取甲低预防措施,131I较ATD、手术治疗GD更容易诱发或加重GO,减轻GO的症状却不如后两者,对于治疗前已有活动性GO的患者,应慎用131I. 相似文献
43.
低剂量奥沙利铂并氟脲嘧啶对晚期复发直肠癌放疗增敏作用的临床观察 总被引:2,自引:0,他引:2
目的:观察奥沙利铂(L-OHP)并5-氟脲嘧啶、甲酰四氢叶酸钙(5-Fu/LV)配合放疗治疗晚期复发直肠癌患者的增效作用与毒性反应。方法:23例无法手术的晚期复发直肠癌患者进行盆腔放疗,在放疗的第1、5同前一天开始给予L-OHP30mg/m。静滴0.5h,LV100mg/m^2和5-Fu375mg/m^2静滴4h,连用4d。25例单纯放疗者为对照组。结果:放疗结束时,观察组局部症状缓解率较对照组高,尤其对会阴区下坠疼的改善明显(P〈0.05),且转移症状亦有所缓解。两组有效率分别为78.3%、48%(P〈0.05),完全缓解分别为8.7%、4.0%。主要毒副反应是消化道反应、神经毒性、静脉炎,骨髓抑制。结论:利用低剂量L-OHP并5-Fu/LV的增敏作用配合放疗治疗晚期、复发直肠癌可提高近期疗效,改善症状,尤其对于伴远外转移者,为理想、安全的治疗手段。 相似文献
44.
RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature 总被引:12,自引:0,他引:12
Kai Temming Raymond M. Schiffelers Grietje Molema Robbert J. Kok 《Drug Resistance Updates》2005,8(6):381-402
During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed. 相似文献
45.
目的:分析儿童呼吸道苛养菌的感染率及常用抗生素的耐药状况。方法:采用儿童呼吸道2050份咽拭子及痰标本进行苛养菌分离培养与鉴定,并对其中617株苛养菌做了药敏试验,结果:显示275株肺炎链球菌,耐药率较高的有红霉素81.1%,苯唑西林76.9%,复方磺胺甲恶唑76.9%,四环素65.4%;104株流感嗜血杆菌、184株副流感嗜血杆菌、54株卡他莫拉菌对氨苄西林耐药率分别为17.6%,28.9%,64.9%,对亚胺培南/西司他丁耐药率分别为16.4%,16.5%,0,同时复方磺胺甲恶唑的耐药率也分别高达56.7%,56.7%,64.9%。结论:提示苛养菌在儿童呼吸道感染中占有重要的地位,及时掌握这类细菌的耐药动态,对合理使用抗生素,延缓耐药株的产生有极其重要的临床意义。 相似文献
46.
全雄激素阻断治疗晚期前列腺癌 总被引:5,自引:0,他引:5
为了评价全雄激素阻断治疗晚期前列腺癌的疗效,采用双侧睾丸切除、Flutamide和Finasterid联合治疗D2期前列腺癌病人5例。随访15~20个月,结果PSA均正常,前列腺体积缩小61.2%~69.3%,有显著性差异(P<0.01),骨转移灶缩小、部分消失,积水肾脏完全恢复正常,所有病人治疗后全部有效。表明全雄激素阻断对晚期前列腺癌有良好的治疗效果。提出在三个层次上阻断雄激素治疗晚期前列腺癌的策略。 相似文献
47.
48.
J. Boldt H. A. Adams B. Zickmann D. Kling G. Hempelmann 《European journal of clinical pharmacology》1990,38(5):431-436
Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were
not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st
min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation
period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index
(CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV
and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an
increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%),
and RVEF (−15%) fell significantly.
It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse
cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline. 相似文献
49.
Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were
subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received
ICV infusions with 100 μg corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at
the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene, glycol)
did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (≈0.5 g/kg per day), also showed a
robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (≈3.0 g/kg per
day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular
mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol
consumption by acting in the brain, probably by way of neuronal membrane mechanisms. 相似文献
50.
Purpose. Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies.
Methods. The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters.
Results. Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time.
Conclusions. The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process. 相似文献