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Myths about heroin abound. They are now the basis of internationaland national policies and of widespread misery. This book tracestheir development and carefully deconstructs them, aiming primarilyto give accurate informationnot to 相似文献
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Joyce Toral William Hu Donald Critchett Andrew J. Solomon James E. Barrett Patricia T. Sokol M. Reza Ziai 《The Journal of pharmacy and pharmacology》1995,47(7):618-622
The 5-HT3-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an 86Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT3-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT3 agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT3 receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission. 相似文献
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Kay Teschke Susan M. Kennedy Andrew F. Olshan 《American journal of industrial medicine》1994,26(3):327-337
During an exposure monitoring study, 78 saw maintenance tradesmen were randomly assigned to be interviewed about their exposures using one of two questionnaire formats: open-ended and partly prompted questions about five categories of materials; and detailed prompting about 75 agents. The more open-ended questionnaire elicited fewer exposure responses overall, but more responses about agents not included on the detailed questionnaire. Composite materials and trade name products were more frequently cited as exposures than individual metals or compounds. Validity of responses was ascertained using air measurements (individual metals) or observations of the employees (composite materials). Sums of sensitivities and specificities were very low (near 1.0) for most of the metals for both types of questionnaire. For composite materials, validity improved substantially. Sensitivities with the partly prompted format (0.44–0.85) were always lower than with detailed prompting (0.80–1.00). Specificities were usually, but not always, higher with partial prompting (0.66–0.92) than with detailed prompting (0.18–0.86). Selection of questionnaire format for an epidemiologic study would depend on the likely prevalence of exposure in controls and the effects of trade-offs in sensitivity and specificity. 相似文献
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Eric M Cheng Andrew Siderowf Kari Swarztrauber Mahmood Eisa Martin Lee Barbara G Vickrey 《Movement disorders》2004,19(2):136-150
Parkinson's disease (PD) is a major cause of disability. To date, there have been no large-scale efforts to measure the quality of PD care because of a lack of quality indicators for conducting an explicit review of PD care processes. We present a set of quality indicators for PD care. Based on a structured review of the medical literature, 79 potential indicators were drafted. Through a two-round modified Delphi process, an expert panel of seven movement disorders specialists rated each indicator on criteria of validity, feasibility, impact on outcomes, room for improvement, and overall utility. Seventy-one quality indicators met validity and feasibility thresholds. Applying thresholds for impact on outcomes, room for improvement, and overall utility, a subset of 29 indicators was identified, spanning dopaminergic therapy, assessment of functional status, assessment and treatment of depression, coordination of care, and medication use. Multivariable analysis showed that overall utility ratings were driven by validity and impact on outcomes (P < 0.01). An expert panel can reach consensus on a set of highly rated quality indicators for PD care, which can be used to assess quality of PD care and guide the design of quality improvement projects. 相似文献