Effects of repeated doses of benzodiazepines on arterial blood gases and transcutaneous Po2

The effects of repeated doses of benzodiazepines, diazepam and midazolam in combination with meperidine on arterial blood gases and transcutaneous PO2 were studied in eight healthy volunteers. The study was designed to mimic a clinical situation. Initially two doses of either midazolam 0.05 mg/kg or diazepam in fat emulsion 0.15 mg/kg were given in a randomized crossover fashion with a 20-min interval, followed by meperidine 0.5 mg/kg another 20 min later. The opioid effects were then antagonized by naloxone 0.4 mg. The initial doses of benzodiazepines caused an increase in PaCO2 and a decrease in PaO2. The changes in PaO2 were of short duration and recovered to baseline levels between injections. However, they came sooner and were more pronounced after midazolam. The changes in PtcO2 paralleled those in PaO2. The PtcO2 index as a measure of cardiac output and peripheral blood flow adequacy was increased immediately after the first injection of midazolam but was otherwise not different from control. There were no differences between the drugs concerning PtcO2 index. PaCO2 increased after the first benzodiazepine injection and remained so throughout the study. Addition of meperidine caused only small changes in PaO2 and PaCO2. These changes were reversed by naloxone. In spite of different elimination kinetics there was no difference in the duration of respiratory depression between the two benzodiazepines.     

下腹部Joel—Cohen切口术后切口愈合临床观察

目的探讨肥胖患者下腹部手术采用Joel—Cohen切口对预防非感染性切口裂开的临床效果。方法选择切口部位皮下脂肪层厚达4—5cm的妇产科手术患者90例，随机分为观察组44例，采用Joel—Cohen切口；对照组46例，采用下腹正中直切口。观察切口愈合和脂肪液化情况。结果观察组切口甲级愈合率显著高于对照组（P〈0．01）；脂肪液化切口裂开率显著低于对照组（P〈0．05）。结论脂肪组织厚达4—5cm以上下腹部手术切口，采用Joel—Cohen切口可以减少脂肪液化，切口愈合显著优于下腹直切口，值得临床推广应用。     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.     

Ill-health as a household norm: Evidence from other people's health problems

This paper proposes that an individual's self-assessed health (SAH) does not only suffer from systematic reporting bias and adaptation bias but is also biased owing to confounding health norm effects. Using 13 waves of the British Household Panel Survey covering the period 1991–2005, I show that, while there is a negative and statistically significant correlation between SAH and individuals' own health problem index, this negative effect reduces with the average number of health problems per (other) family member. The relative health bias is small, however, which implies that measures of SAH may not suffer seriously from systematic health norm bias. This is an important finding for researchers working with SAH data as it indicates that we do not have to worry too much about controlling for confounding influences from the health of other household members when estimating SAH regression equations.     

纸本与数字的交互：手机阅读的最佳效果

随着全球3G商用的推进和拥有大容量存储能力的智能终端的日益普及,手机正逐步演变成为一个新型的数字阅读终端。利用手机进行电子阅读的全新模式,正以前所未有的普及速度冲击着人们的阅读习惯。而这趋势也逐渐为"阅读"进行重新的定义。对于每一个读者而言,在这样一个信息化的时代里,手机阅读和纸本阅读的交互使用、取长补短,才是获得最佳阅读效果的最有效方式。     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

前列腺癌中PIM-1的表达及其临床意义

目的 探讨PIM-1在前列腺癌中的表达及临床意义。方法 逆转录-聚合酶链反应（RT—PCR）半定量分析2例良性前列腺增生（BPH）和5例前列腺癌（PCa）组织标本中PIM-1mRNA表达，免疫组织化学法检测20例BPH、20例高分级前列腺上皮内瘤（HGPIN）和42例PCa组织标本中PIM-1蛋白表达水平，染色结果分为阴性、弱阳性、阳性和强阳性。结果 5例PCa组织PIM-1mRNA表达相对值分别为0．63、0．55、0．42、0．91、0．76，2例BPH中其相对值为0．26、0．27。BPH、HGPIN和PCa组织中PIM-1蛋白阴性表达率分别为60％（12／20）、20％（4／20）和2％（1／42），弱阳性表达率分别为40％（8／12）、20％（4／20）和12％（5／42），阳性列强阳性表达率分别为0（0／20）、60％（12／20）和86％（36／42），PCa中PIM-1蛋白表达水平高于HGPIN和BPH（P值均〈0．05）。PIM-1蛋白表达水平随PCa的临床分期和病理分级增高而增强，在有和没有淋巴结转移PCa组织中PIM-1强阳性表达率分别为70％（7／10）、25％（8／32），差异有统计学意义（P〈0．05）。结论PIM-1高表达可能与PCa发生和发展相关，PIM-1表达水平与PCa分期、Gleason评分呈正相关，可能成为PCa预后判断的肿瘤标志物。     

Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson's disease patients: the effects of an early therapeutic intervention

To evaluate the long-term effects of entacapone on both mean daily 'on' time and health-related quality of life (QoL) in patients with Parkinson's disease (PD) experiencing 'end-of-dose' motor fluctuations and the benefits of an early therapeutic intervention. A prospective, multicenter, observational, 12-month study was performed with an initial 3-month intervention phase, consisting of a phone call to half of the patients from randomly selected investigators to assess if dose adjustment was necessary. Effectiveness was determined by home diaries ('on' time), subscales II and III of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Parkinson's Disease Questionnaire (PDQ-8). After 3 months of treatment, 4.0% of the intervention group patients discontinued the study, versus 18.4% in the control group ( P  < 0.01). The improvement in 'on' time was significantly increased since the 3-month visit (21%, P  < 0.0001) until the end of the study (23% at 12 months, P  < 0.0001). Entacapone also induced significant reductions in the UPDRS scores for subscales II and III and in the PDQ-8 score. 11.2% of patients experienced at least one adverse reaction. This study confirms the effectiveness of entacapone in reducing motor fluctuations by increasing 'on' time, and in improving QoL of PD patients. An early adjustment of entacapone and levodopa doses reduces the number of treatment discontinuations during the first months of treatment.     

西咪替丁对林可霉素生物利用度的影响

通过8名健康志愿者服药后的对照实验,用微生物法检测血药浓度,按一室模型配置求算药物动力学参数,探讨西咪替丁对林可霉素体内过程的影响。结果表明,西咪替丁不能改变林可霉素的吸收速率(Ka)和消除速率(Ke),但可通过增加其吸收程度或改变其分布容积,使林可霉素的血药浓度和生物利用度分别增加约19％和27％。