Simulating realistic zero loop pedigrees using a bipartite Prufer code and graphical modelling.

Graph algorithms previously developed by the authors are adapted to simulate pedigrees similar to those used in genetic linkage studies which associate disease phenotypes with specific genomic locations. Pedigrees are chosen uniformly at random from the set of those with specified numbers of individuals and matings and which contain no loops. Summary statistics from pedigrees generated in this way can be used to check real pedigrees for anomalies due to biased sampling or phenotypic effects on the pedigree structure.     

AN-132 block of cardiac sodium channels: A gate-related receptor analysis

Summary Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 μmol/L) blocking were 0.051, 0.038, and 0.034 AF⁻¹ at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.     

头低位模拟失重状态对前庭功能的影响

为研究头低位模拟失重对运动病症状、垂直视动眼震（ＶＯＫＮ）及体液重新分配的影响，在头低位－１０°的模拟失重状态下，采用大视野的垂直视动刺激，观察１８名正常人的运动病症状、ＶＯＫＮ、激素（ＡＶＰ、ＶＩＰ、ＣＯＲＴ、ＡＬＤＯ）的反应特点。结果表明，头低位－１０°状态下的大视野垂直视动刺激可以诱发出明显的运动病症状，头低位－１０°的垂直视动刺激比坐位更容易诱发运动病。坐位状态ＶＯＫＮ慢相速度有明显的方向性不对称，敏感组ＶＯＫＮ方向性不对称有显著差异（Ｐ＜０．０５）。头低位－１０°时ＶＯＫＮ的不对称现象不明显，向下方向运动的ＶＯＫＮ慢相速度显著增加。分析指出，头低位－１０°状态下垂直视动刺激比坐位和秋千刺激的贡献率大。尿中ＣＯＲＴ（皮质醇）在秋千和头低位的垂直视动刺激前后有显著性增加。提示：大视野的垂直视动刺激与头低位－１０°两种刺激的结合可能成为预测空间运动病的方法之一．     

Comparison of Simulated and in-Vivo Plasma Levels of Cilastatin Following Intravenous in-Line Drug Administration

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.     

Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.     

用计算机拟合法制作ALT标准曲线

用赖氏法重复测丙氨酸氨基转移酶（ＡＬＴ）标准曲线１０次，计算机作线性回归和曲线拟合。直线回归结果，酶活性在不高于９７Ｕ的范围内，相关系数（Ｒ）＝０．９９９，斜率（ｂ）＋２．５５×１０＾－３，截距（ａ）＝０．０２８６；而达到２００Ｕ时，Ｒ＝０．０８６，ｂ＝１．９０×１０＾－３，ａ＝０．０６６，，显著性检验两者之间差别为极显著。表明：９７Ｕ以下线性较好但不过原点，大于９７Ｕ之后开始明显偏离该线性。拟合     

现代医院手术室建设中的问题及动态研究

手术室是医学技术与工程技术结合的产物。随着医疗技术和新的手术工具的不断涌现,带动了手术量的迅猛上升。旧的手术室空间布局、实施标准、功能配置等方面已经无法满足新技术的应用要求,同时人们对手术环境和手术质量也提出了更高的标准。而今第四代手术室已开始步入我们的时代。洁净化、数字化和人性化则是其主要代表特征。本文分别从洁净手术室、数字化手术室和人性化手术室三个方面来探讨现代医院手术室建设中应注意的问题及动态研究。层流手术室已经是手术室建设不可逆转的发展趋势,除了按照《医院洁净手术部建筑技术规范》来建造外,其布局、人流、物流、质量监控等等都要进行合理的安排才能达到最优的手术环境。数字化手术室是将温度、湿度、压力、通风量、新风量等一切参数系统的由计算机来分配统筹,从而实现精确高效的手术管理。人性化手术室则是手术室建设的软件部分,是一种“以病人为中心”的服务理念,它打破了传统的生物医学模式,转变为生物—心理—社会模式,这是病人需求与市场竞争的必然选择。     

Numerical method for weights adjustment in minimax multi‐model LQ‐control

The minimax linear quadratic problem, where ‘max’ is taken over a finite set of indices (models) and ‘min’ is taken over the set of admissible controls, is considered. The solution is obtained by the robust optimal control application. The control turns out to be a linear combination of the controls optimal for each individual model. This paper develops a numerical method for the optimal weights adjustment. An example shows a quick convergence of the proposed procedure. Copyright © 2007 John Wiley & Sons, Ltd.     

片剂含量均匀度计量检验新方案的研究

本文通过大量测试工作,查明10批国产小剂量片剂的含量分布,在此基础上提出了计量检验新方案。采用计算机模拟随机抽样的方法,通过计算绘制了USP XX,BP,JP和新方案在正态分布和10批实际分布下的OC曲线。结果表明,当用于测定生产规模的片剂批时,与国外片剂含量均匀度计数检验方案中统计特性最优的USP XX方案相比,新方案NEW能在化验工作量相近的前提下,作出更准确的判断;新方案SMA能在不降低判断准确性的前提下,减少化验工作虽约三分之一。新方案还可减免分析方法误差对判定结果的影响。     

Analysis of Intestinal Perfusion Data for Highly Permeable Drugs Using a Numerical Aqueous Resistance—Nonlinear Regression Method

Purpose. To develop, validate and apply a method for analyzing the intestinal perfusion data of highly permeable compounds using the Numerical Aqueous Resistance (NAR) theory and nonlinear regression (NAR-NLR) and to compare the results with the well-established Modified Boundary Layer (MBL) Analysis. Methods. The NAR-NLR method was validated and the results were compared to the MBL analysis results using previously reported cephradine jejunal perfusion data. Using the Single Pass Intestinal Perfusion (SPIP) method, the concentration dependence of intestinal permeability was investigated for formycin B, proline, and thymidine, three compounds reported to be absorbed by carrier-mediated transport processes. The MBL and NAR-NLR analyses were then applied to the three sets of SPIP data. Results. The results demonstrate that the intrinsic MBL transport parameters were highly variable and, in one case, the analyses failed to give a statistically significant Michaelis constant. The MBL mean dimensionless wall permeabilities (P*_w) were greater than the NAR-NLR P*_w and were also highly variable. In all cases, the NAR-NLR variability was significantly lower than the MBL variability. The extreme variability in the MBL-calculated P*_w is due to the sensitivity of P*_w when the fraction of unabsorbed drug (C_m/C_o) is low or, alternatively, when P*_w approached the aqueous permeability, P*_aq. Conclusions. The NAR-NLR method facilitates the analysis of intestinal perfusion data for highly permeable compounds such as those absorbed by carrier-mediated processes at concentrations below their K_m. The method also allows for the use of a wider range of flow conditions than the MBL analysis resulting in more reliable and less variable estimates of intestinal transport parameters as well as intestinal wall permeabilities.