The importance of employing stringent methods to recruit fertile male controls

Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for "fertile" men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion.     

Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver

Summary After perfusion of mouse livers with A₁₄-¹²⁵I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (X_s) and intracellular (X_i) A₁₄-¹²⁵I-insulin, as well as intracellular degradation products (X_deg) of labelled insulin. From the perfusate concentrations (C_p) of A₁₄-¹²⁵I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of C_p, X_s, X_i and X_deg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to receptor-recycling and non-receptor-recycling models, using a computer-aided optimization procedure. The receptor-recycling model could not only adequately explain the C_p, X_s, X_i and X_deg at the low dose, but also predict the C_p at the high dose. On the other hand, a non-receptor-recycling model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the C_p at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes.     

美托洛尔两种光学异构体代谢的酶动力学研究

目的：建立一种用AUC对酶动力学模型参数进行估算的方法，用酶动力学模型对美托洛尔（Met）两种光学异构体在大鼠肝脏的药物代谢进行研究。方法：用数学方法推导参数估算法公式；用大鼠肝切片孵育技术，对Met两种光学异构体的三种不同剂量（5、10、30μmol.L^-1）的药物浓度进行分析。并用本的参数估算法求出各自的酶动力学参数。结果：两种异构体，三种不同剂量的AUC有显性的统计学意义（P＜0．01），R－（＋）－Met的Vm,Km值分别为5．7471μmol.L^-1.h^-1和6．7724μmol.L^-1，S－（－）－Met的Vm,Km值分别为6．4350μmol.L^-1.h^-1和18．3404μmol.L^-1。结论：酶动力学模型适用于脏代谢的药动学研究。两种异构体的代谢具有明显差异。存在代谢的右旋异构体选择性。     

Pharmacokinetics of paclitaxel-containing liposomes in rats

In animal models, liposomal formulations of paclitaxel possess lower toxicity and equal antitumor efficacy compared with the clinical formulation, Taxol. The goal of this study was to determine the formulation dependence of paclitaxel pharmacokinetics in rats, in order to test the hypothesis that altered biodistribution of paclitaxel modifies the exposure of critical normal tissues. Paclitaxel was administered intravenously in either multilamellar (MLV) liposomes composed of phosphatidylglycerol/phosphatidylcholine (L-pac) or in the Cremophor EL/ethanol vehicle used for the Taxol formulation (Cre-pac). The dose was 40 mg/kg, and the infusion time was 8 to 9 minutes. Animals were killed at various times, and pharmacokinetic parameters were determined from the blood and tissue distribution of paclitaxel. The area under the concentration vs time curve (AUC) for blood was similar for the 2 formulations (L-pac: 38.1±3.32 μg-h/mL; Cre-pac: 34.5±0.994 μg-h/mL), however, the AUC for various tissues was formulation-dependent. For bone marrow, skin, kidney, brain, adipose, and muscle tissue, the AUC was statistically higher for Cre-pac. For spleen, a tissue of the reticuloendothelial system that is important in the clearance of liposomes, the AUC was statistically higher for L-pac. Apparent tissue partition coefficients (K_p) also were calculated. For bone marrow, a tissue in which paclitaxel exerts significant toxicity, K_p was 5-fold greater for paclitaxel in Cre-pac. The data are consistent with paclitaxel release from circulating liposomes, but with efflux delayed sufficiently to retain drug to a greater extent in the central (blood) compartment and reduce penetration into peripheral tissues. These effects may contribute to the reduced toxicity of liposomal formulations of paclitaxel.     

大肠癌巨─微血管构筑的临床研究

为了探讨大肠癌和其间质血管的关系，我们研究了48例大肠癌标本不同部位的巨─-微血管构筑。方法：用癌瘤标本造影摄X线片、立体显微镜和微机图象定量分析。结果显示：癌中心血管稀疏或为无血管的坏死区及血管破坏；癌远近端瘤组织内血管增多增粗，畸形及紊乱；其血管定量参数与癌中心和癌远近端肠粘膜相比有显著差异（P＜O．05，P＜0．01）。结论：①大肠癌的发生发展依赖于血管形成和细胞增殖。②在理论上解释了大肠癌的临床病理过程。③大肠癌的恶性程度与其血管密度间似有负相关的趋势。④探讨了其临床应用价值。     

一类单调似然比分布族

该文给出了一类分布族为单调似然比分布族的条件,从而可知非中心的分布族和非中心的分布族均为单调似然比分布族.     

不同血细胞分析系统间检测结果的偏差评估及应用

目的 分析同一临床实验室不同型号的血细胞分析仪的性能特点，并对其检测结果进行评估，对有偏差的项目进行调整，使同一实验室不同型号的血细胞分析仪的检测结果具有可比性。方法 对本实验室所使用的Sysmex KX-21、Sysmex SE-9500和Beckman Coulter Ac．T 5diff三台血细胞分析仪的准确度、精密度、线性度分别进行评价，选定其中一台指标最优的仪器作为比对仪器，将另外两台仪器的血细胞参数进行调整。结果 因Sysmex KX-21的WBC、RBC、HGB及PLT四项指标的准确度、精密度、线性度均较理想，故选为比对仪器。Sysmex SE-6500和Beckman Coulter Ac．T 5diff有部分指标的部分评价项目与Svsmex KX-21有偏差。对有偏差的项目进行调整后，三台仪器的四项指标的相关系数的平方均不低于0．95。结论 同一实验室在使用不同型号的血细胞分析仪时，应对其进行相互校准。校准后，保证三台仪器的检测结果具有可比性。     

基于蓝牙技术的便携式微电脑多参数生理监护仪的研制

介绍了一种基于蓝牙技术的便携式微电脑多参数生理监护仪的工作原理、系统构成。该系统由2个Intel—196单片机构成双CPU系统，通过蓝牙发送、接收模块对信号进行无线传送，最终完成数据的采集、处理、显示，对病人进行实时监控。并可采用串行通讯的方式将数据送给PC机，对数据进行进一步的分析处理。     

高原单兵生理参数监测系统的研制

为了给平、战时伤员急救提供更为可靠的监测手段,同时为高原广大官兵平时的科学训练提供依据,研制了一套具有遥测功能的高原单兵生理参数监测系统。可在高原、高寒等恶劣环境下实时监测人体运动状态的血氧饱和度、脉搏和体温。     

新生儿缺氧缺血性脑病血小板参数的变化及意义

为探讨新生儿缺氧缺血性脑病(HIE)血小板参数的变化及临床意义。对1t2例HIE患儿进行临床分度,于急性期进行血小板参数测定,并于恢复期复查,了解其动态变化情况。并以60例正常足月新生儿作为对照。(l)HIE患儿急性期血小板总数(PLT)较正常儿明显降低(P<0.01),平均血小板体积(MPV)和血小板体积分布宽度(PDW)较正常儿明显增高(P<0.01)。恢复期PLT、MPV、PDW与正常组之间无明显差异(P>0.05)。(2)HIE患儿PLT随HIE病情加重而降低(P<0.01)。而MPV、PDW则随病情加重而增大(P<0.01,P>0.05)。结果提示,动态观察HIE患儿血小板参数,可作为判断HIE病情严重程度的指标。