The logical structure and validity of experimental designs in pharmacokinetics and clinical pharmacology

Much of the literature on research design in clinical pharmacology and pharmacokinetics emphasizes statistical concerns, thus suggesting that a primary ingredient of a valid research design is an appropriate plan for statistical analysis of data. However, statistical validity is only one of several ways to evaluate an experimental study. The present paper reviews the underlying logic and sources of invalidity of experimental drug research suggesting influences and factors which may deceive or lure an experimenter into erroneous conclusions.     

Polynomial matrix solution of H2 optimal control problem for state‐space systems

A polynomial matrix solution to the H₂ output feedback optimal control problems is obtained for systems represented in state‐equation form. The proof does not invoke the separation principle but is obtained in the z‐domain. The cost function includes weighted states, which allows the so‐called standard system model problem to be solved. This encompasses the class of inferential control problems. The results also enable the two‐degree‐of‐freedom optimal control solution properties to be explored. Copyright © 2002 John Wiley & Sons, Ltd.     

维胺酯-β-环糊精包合物的研究

应用３因素８水平的均匀设计方法，优化出维胺酯－β－环糊精包合物最佳制备条件，所得包合物的包合率为９９．３％，其表观稳定常数为１３９４Ｍ－１．     

有效中药复方研究的方法学探讨

从化学的角度探讨了临床有效中药复方研究的四个过程 ,简述了直接试验设计在全方药味筛选及化学模式识别中药质量控制中的应用 ,论述了复方有效部位和有效部位中主要有效成分的确定及化学计量学的应用和主要药效物质化学结构信息的计算机模拟方法 ,为中药复方研究提供一个范例。     

自行下体负压训练器的研制

目的 研制一种自行下体负压训练器。方法 自行下体负压训练器由若干环形钢圈及涂胶布材料构成的密闭完整的空腔壳体，可上下随意伸缩。上表面安装有单向排气阀门、可调进气阀门、把手及肩带。沿筒体纵轴进行屈／伸膝关节运动，使之被动扩张产生负压。结果 进气阀门完全关闭、打开1／4、1／2至完全打开时，训练器负压峰值逐渐降低，分别为-58、-46、-38和-26mmHg。结论 自行下体负压训练器集体育锻炼和下体负压于一体，安全可靠，使用方便，可望应用于对抗失重生理影响和飞行员抗荷生理训练。     

用正交试验法探讨芸杞补肾口服液的生产工艺

作者采用正文试验法，以水提醇沉法提取和分离酚戒类有效成分，并以苯乙醇成含量作为含量测定指标，考察了乙醇浓度、提取温度及煎煮时间三个因素对有效成分提取量的影响，从而筛选出芸杞补肾口服液的是佳生产工艺。     

Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Summary: Some of the properties of 4–bromobenzalde-hyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of γ-aminobu-tyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 μM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABA_A receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.     

Prognostic factors in clinical trials

Summary Prognostic factors define the study population, help formulate the study objectives, and influence the treatment strategies. They must be accounted for in the study analysis to obtain valid estimates of the treatment differences and to evaluate results across studies. The causal relationship between a prognostic factor and the study endpoint can only be established through prospective randomized study designs. Potential factors discovered through retrospective analysis must be verified to establish their validity. Using such factors prematurely to select patient population and treatment strategy for a new study will not establish the validity of the potentially important factor.Supported by NCI 5 PO1 CA53996-15 and NCI 5 U10 CA38926-08.     

The spherical aberration of aphakic eyes corrected with intra-ocular lenses

The spherical aberration of eyes corrected with intra-ocular lenses is investigated using a model eye with realistic levels of corneal asphericity. The results indicate that the aberration is intermediate between that of paraxial schematic eyes and real eyes. By using standard optical aberration theory, it is shown that for a plano-convex lens with the curved surface facing the cornea, the aberration is similar to that of normal phakic eyes and therefore probably too low to be of any clinical significance. However, for other lens orientations or designs, the level of aberration is usually higher and may lead to a refractive error varying with pupil size and a loss of acuity with large pupil diameters.