A model-independent proof of Dost's law of corresponding areas

Provided that the body is regarded as a linear system and the response to a unit impulse input is Riemann integrable in the interval [0, ), the validity of Dost's law of corresponding areas is demonstrated. No other restrictions are placed on the nature of the blood drug concentration-time curve. The derivation is independent of any drug distribution models. However, the specification of a drug input point is essential for the application of the area relationship. A limit theorem for the improper integration of a convolution integral is presented.     

Inappropriate use of the law of corresponding areas to calculate the time course of absorption for multicompartmental systems

From the law of corresponding areas, Dost has derived a simple method for calculating the percentage absorbed of a drug during an entire period of treatment. The method utilizes a graphical procedure to determine the fraction of a dose absorbed at each time point, when data are available following oral and intravenous administration of the drug. The method has been suggested for use with drugs whose kinetics are described by single and multicompartment systems. The method is valid for single-compartment body systems and can be shown to be the graphical equivalent of the well-known Wagner-Nelson method. However, it can be proved mathematically that the graphical method will not yield correct answers for multicompartment body systems. Here, for identical plasma concentrations following oral and intravenous administration of the same dose, the amount of drug in the peripheral compartment(s) will always be greater following intravenous administration than after oral administration (during the absorption phase). Therefore, areas under the curve calculated from shifted intravenous curves will always overestimate the amount absorbed. Analog and digital computer simulations illustrate the mathematical treatments.Supported in part by Grant GM 16496 from the National Institutes of Health.Presented in part at the Sixth International Congress of Pharmacology, IUPHAR, July 20–25, 1975, Helsinki, Finland.This paper was submitted to a Consulting Editor who served as a Journal Editor during its review process.During the course of this study, Dr. Galeazzi was a Fellow of the Swiss National Science Fund.     

对科技期刊中首位与通信作者标注相关性的分析

目的寻找对通信作者标注较好恰当的定义和定位,规范其使用的方法。方法通过对国内2种期刊2010年全年刊出的论文中的首位与通信作者标注调查与分析,同时与国外的3种期刊作了对比。结果发现国内与国外通信作者标注的定义与规范上有一定的差异性。结论需要进一步规范首位与通信作者在论文中的标注。     

急性心肌梗死合并对应性ST改变的临床特征及预后

目的 :分析急性心肌梗死 (AMI)合并对应性 ST改变的临床特征及预后。方法 :记录 12 6例有 Q波 AMI患者中合并对应性 ST段改变者的临床特征及住院早期并发症 ,行常规 12导联及右胸导联加 V7～ 9导联 ,并与无 ST段改变者比较。结果 :AMI合并 ST段改变组较无 ST段改变组住院早期严重心律失常 (P<0 .0 5 )及泵衰竭 (P<0 .0 5 )发生率高 ,住院病死率也增高 (P<0 .0 5 )。结论 :AMI合并对应性 ST改变者预后差     

Transfer functions obtained by the rule of corresponding fractional areas

Summary The transfer of a drug from the compartment in which it is applied to one from which samples can be taken can be determined from time-concentration curves by simple graphical and numerical procedures. The method requires subdivision of the total transferable amount of the drug into four quantities — occupancy, transit, transfer and availment, which can be obtained by an extension of the rule of corresponding areas. Each of these quantities is represented by a fractional area under the experimental time-concentration curve. Subdivision into fractional areas is possible if an additional experiment is performed in which the drug is placed directly in the reference compartment from which the estimations are made. The principle of the method is explained, and its application is demonstrated in examples of the gastrointestinal absorption of iron in children.     

药物靶标热点领域的共词聚类分析研究

后基因组时代的药物靶标是创新药物开发的源泉,了解药物靶标的热点领域有利于针对性地开展创新药物的研究工作.现对2003-2007年MEDLINE数据库收录的药物靶标文献的高频主题词进行共词聚类统计分析,并通过聚类映射图和战略坐标等分析结果与专业知识相结合,揭示药物靶标的热点领域.研究发现,目前的靶标研究主要聚焦在抗肿瘤领域,尤其是酶的药理学研究;结晶学、计算机模拟、生物模型等药靶开发技术也应值得重点关注.     

Drugs, alcohol and the law

While other aspects of the relationship between the law and intoxicants are mentioned briefly, this paper focuses upon doctrinal aspects of the criminal law relevant to the grossly intoxicated offender. It is generally true to say that the criminal law requires proof of individual fault before an accused can be convicted of a serious criminal offence. The accused must be judged on the facts, not as they are, but as he or she actually believes them to be. This causes difficulty where the accused is grossly intoxicated. The fair and correct doctrinal response to this problem has been the subject of controversy for over fifty years. The common law jurisdictions have come to different conclusions. In 1979, the High Court of Australia decided that if an accused was found to have lacked the intention to commit the crime required by law, then the fact that the lack of intention arose by reason of his or her voluntary ingestion of an intoxicant was irrelevant. If the accused is found to have lacked the intention, then the crime has not been proven and an acquittal must result. This decision caused some controversy at the time. The Victorian Law Reform Commission has been looking into the matter. The policy conflict is in one sense clear: on the one hand, the basic principle that a person should not be found guilty of a criminal offence except on the basis of personal fault, on the other hand the idea that those who, for example, kill when so under the influence of intoxicants as to be unable to form the intention to perform the killing should not escape the net of the criminal law.     

贫困地区综合医院网络报告肺结核患者追踪现状分析

目的了解综合医院传染病网络报告肺结核患者追踪现状,分析追踪不到位相关因素。方法对我省52个贫困县各一所县级综合医院2007年传染病网络报告转诊未到位5833例肺结核患者中经专业结核防治机构追踪仍未到位的2100例患者进行相关因素分析。结果追踪5833例患者,其中69.3%通过电话和家访追踪,30.7%通过电话追踪。追踪到位3733例,两种追踪方式追踪到位率分别为76.12%和35.29%,追踪到位率差异有统计学意义（χ2=924.65,P〈0.01）,总追踪到位率64.00%。不到位2100例（36.00%）,追踪不到位主要原因依次是查无此人630例,地址不详589例,返乡362例,住院231例,拒绝195例,死亡26,其他67例。结论采取电话和家访相结合方式追踪到位率高于单纯电话追踪到位率。诸多影响因素导致患者追踪不到位,其中以地址不详、查无此人、流动人口返乡为主要影响因素。     

Reduction of stilbene oxide and styrene oxide to the corresponding alkenes by intestinal bacteria

1. This study provides the first evidence that stilbene oxide and styrene oxide are reductively metabolized to the corresponding alkenes by intestinal bacteria in animals. 2. When trans- or cis-stilbene oxide were incubated with the caecal contents of rat under anaerobic conditions, both trans- and cis-stilbene were isolated from the incubation mixture. Styrene oxide was also reduced to styrene by rat caecal contents. 3. Caecal contents of mouse, hamster and guinea pig also exhibited alkene oxide reductase activities toward cis- and trans-stilbene oxides, and styrene oxide. In contrast, liver microsomes or cytosol exhibited no epoxide reductase activities toward these substrates. 4. Seven pure strains of intestinal bacteria exhibited alkene oxide reductase activities of varying degrees under anaerobic conditions, with the highest activity being observed in Clostridium sporogenes. 5. Cell-free extracts of either the intestinal bacteria in rat caecal contents or C. sporogenes exhibited reductase activity when supplemented with both NAD(P)H and FMN under anaerobic conditions. Reductase activity was also observed on addition of the photochemically reduced form of FMN instead of both NAD(P)H and FMN.     

基于法经济学的药品质量风险规制研究

文章通过对法经济学思想和理论基础的研究,利用执法的边际成本等于边际收益这一主旨,分析了法经济学理论应用于药品质量风险规制中的方法,为药品质量风险的规制提供了理论依据,为今后制药业的健康成长提供了借鉴意义。     

A general model of metabolite kinetics following intravenous and oral administration of the parent drug

A model of metabolite pharmacokinetics is developed in terms of residence time distributions and derived non-compartmental measures. It provides quantitative insight into factors determining the concentration-time curve of metabolite following intravenous and oral administration of the precursor drug. The AUCs and higher curve moments (mean residence times and relative dispersions) are calculated/predicted and their dependence on mean absorption time, fraction of first-pass metabolism and intrinsic disposition residence times of the parent drug and metabolite, respectively, is discussed. An AUC-based method for the determination of the first-pass effect is proposed which is not influenced by drug absorption. The approach is valid for linear pharmacokinetic systems exhibiting hepatic and renal elimination of the precursor drug; it is not restricted to specific compartmental models. Limitations of previous concepts of metabolite kinetics are defined. Criteria are presented for the appearance of concave metabolite curves in a semi-logarithmic scale.     

医疗纠纷在法律中的体现

随着社会经济和医疗改革的发展,群众法律意识增强,医疗纠纷不断上演,成为现代社会争论的焦点之一。因此,正确处理医患双方法律关系成为解决医疗纠纷的首要前提;然而,作为解决医疗纠纷的法律条文《医疗事故处理条例》在处理医疗实践过程中也存在一些不完善的方面。同时,本文也进一步讨论了由医疗纠纷引起的三种法律责任分别为民事责任、刑事责任和行政责任。今后工作的重点应在于推进医疗服务的法制建设,医疗诊治工作要遵循法律法规,医患双方应加强沟通,形成良性互动,共同创造一个良好的医疗卫生环境。     

不同产地穿山龙薯蓣皂苷元含量的比较研究

目的：考察不同产地穿山龙薯蓣皂苷元含量，确定穿山龙薯蓣皂苷元的最佳产地。方法：用RP—HPLC测定穿山龙薯蓣皂苷元的含量。结果：不同产地的穿山龙薯蓣皂苷元含量差异很大，以黑龙江、内蒙、辽宁，所产含量较高，其中黑龙江最高，为1．49％。结论：黑龙江可以定为穿山龙薯蓣皂苷元的最佳产地。     

昌图县基层农村计划免疫接种现状分析

目的分析昌图县基层农村计划免疫接种现状。方法将昌图县基层分为村级、县级、乡级,依照县卫生局制订的调查方案,全县采用同步调查方式,由随机分组进行盲法调查,分析基层计划免疫工作人员分布情况、各接种点注射器使用情况、上级对于安全注射态度及措施、各级单位对接种安全知识的掌握度与服务态度、接种者对接种服务满意度及对接种目的认识情况、注射器来源与一次性注射器使用后处理方式。结果本次调查共包含40个接种点,全部使用一次性注射器,占比100.00%。县级、乡级、村级单位服务态度对比差异无统计学意义(P>0.05);县级单位对于接种安全知识的掌握度优于村级、乡级,差异有统计学意义(P<0.05)。县级对接种服务满意度100.0%、对接种目的认识度100.0%高于乡级的92.4%、92.4%与村级的86.4%、88.8%,差异有统计学意义(P<0.05)。40个接种点中注射器由上级配发40个;所有应用一次性注射器的接种点,其中10.8%乡镇级卫生院与33.3%村级接种点存在使用后为规范化处理,存在随意丢弃现象。结论通过对基层农村人民采取有效针对性的接种政策,可解决当前农村计划免疫各种问题,预防昌图县传染病发病率,保护本地居民健康,是卫生防疫部门重点关注并落实的工作。     

基于第三代头孢菌素药动学相关研究的可视化分析

目的 梳理Web of Science数据库中关于第三代头孢菌素药动学(Pharmacokinetics, PK)研究,通过文献计量学和可视化分析方法,评价该领域的研究方向、研究热点以及发展趋势,为今后研究提供经验和借鉴。方法 使用Web of Science数据库进行检索,检索式为“Theme=("Third-Generation Cephalosporin"OR Cefoperazone) OR Ceftazidime) OR Cefixime) OR Cefodizime) OR Ceftriaxone) OR Cefotaxime) AND (pharmacokinetics OR PK OR"Population pharmacokinetics")”,检索时间为2009-2020年。利用VOS-viewer软件进行合著分析(作者、机构、国家)、共现分析和共引分析;通过GraphPadPrism8软件进行第三代头孢菌素药动学研究的趋势分析。结果 对纳入的818篇文献进行可视化分析,结果显示发文量呈现逐年上涨趋势,其中发文量最多的国家是美国(288篇,35.21%),最多的期刊...     

边远地区雷达官兵心理健康状况调查

目的调查和分析某部边远地区雷达官兵的心理健康状况。方法随机整群抽取某部雷达官兵465例,分为边远地区组和平原地区组,运用SCL-90症状自评量表（symptomchecklist90,SCL-90）进行测评,并与军人常模进行统计学比较。结果边远地区组人际关系敏感、抑郁和焦虑3项因子分值较平原地区组和军人常模组显著升高（P〈0．01）,敌对因子分值显著高于军人常模组（P〈0．01）,而平原地区组与军人常模组相比差异无统计学意义（P〉0．05）。结论边远地区雷达官兵的心理健康状况低于全军官兵的整体水平,部队基层医务工作者应有针对性地进行心理干预。     

不同产地萝芙木药材质量评价

目的 对不同产地萝芙木药材进行质量评价,为萝芙木药材质量标准修订提供依据.方法 收集市场上不同产地萝芙木药材,应用RP-HPLC法测定不同产地萝芙木药材样本中利血平含量.结果 不同产地萝芙木药材中利血平含量差异显著,入药部位为主要因素,以云南萝芙木根部含量最高.结论 市场上不同产地萝芙木药材在质量上存在差异.     

游离骨骼肌自体移植两型肌纤维横切面积的变化研究

目的 为明确同型肌纤维与不同型肌纤维骨骼肌自体游离移植的肌纤维横切面积和直径变化。方法 成年猫17只,自身对照实验。肌肉移植分为两期:第一期去除支配移植肌的神经;第二期3周后行肌肉移植。肌肉标本取材是在手术时及移植术后6周、10周,以肌球蛋白ATP酶染色(pH9.4)将肌纤维分为Ⅰ型和Ⅱ型,用图像分析仪Mias99与Biomas测量两型肌纤维在不同时期的横切面积和直径。结果 骨骼肌移植后6周再生肌纤维平均横切面积范围在1248～3699μm~2之间、平均直径为16.48±33.71μm,10周时再生肌纤维平均横切面积为2212～4865μm~2、平均直径为27.49～42.38μm。骨骼肌去神经后肌纤维均萎缩,肌肉移植后再生纤维10周比6周粗大。同一肌肉同一时期Ⅱ型肌纤维比Ⅰ型肌纤维粗大,同型肌纤维骨骼肌自体移植后再生肌纤维比不同型肌纤维骨骼肌移植的再生纤维粗大,10周时差异有极其显著意义(P<0.01)。结论 骨骼肌两型肌纤维横切面积的大小与肌的功能适应密切相关,同型肌纤维骨骼肌自体移植后再生肌纤维比不同型肌纤维骨骼肌移植的再生纤维粗大。因此,同型肌纤维游离骨骼肌自体移植在肌功能适应方面是优于不同型肌纤维骨骼肌移植的。     

运用矛盾定律分析查新委托技术资料存在的问题

为履行查新人的职业道德,规范查新委托人的学术行为,笔者应用矛盾定律评判问题,应用逻辑推理分析问题;从而分析出查新委托技术资料存在问题的症结。笔者最后提醒科研人员在填报查新委托技术资料中要实事求是,科学严谨。