他汀类药物对心血管的保护作用

他汀类药物(statins)被研制出来的最初目的是降低血脂,但是现在发现它不仅具有降低血脂的作用,还具有很多其他的作用包括改善内皮细胞功能的紊乱,提高内皮源性一氧化氮合成酶的生物活性,抑制血管平滑肌细胞的增殖,抗氧化作用,抗炎作用,降低血压,逆转心血管系统的重构。充分理解statins的多效性作用及机制有利于它更好的在临床中被应用于心血管系统的预防和治疗。     

产科危重患者多器官功能障碍综合征的临床分析

目的 :分析产科危重患者多器官功能障碍综合征 (MODS)的发病特点及诱因 ,以及与急性生理与慢性健康状况评分II(APACHEII)的关系。方法 :回顾分析 2 0 0 0年1月至 2 0 0 4年 4月转入GICU产科危重患者中发生MODS 6 6例的临床资料 ,并计算其A PACHEII评分。结果 :产科MODS患者诱因主要是产科因素 ,共 4 8例 (72 .73% ) ,死亡 7例 (14 .5 8% ) ,以重度子痫前期或子痫及产后出血为主 ;诱因 18例妊娠合并内外科疾病 ,死亡 11例 ,死亡率为 6 1.11% ,以妊娠合并心脏病和妊娠合并重症肝炎为主。产科MODS患者死亡率随着器官损害数的增多而上升 ,差异有显著性 (P <0 .0 5 ) ;随着器官损害数的增多 ,APACHEII评分逐渐升高 ,差异有显著性 (P <0 .0 5 ) ;APACHEII评分用于预测MODS死亡阳性率 ,2 ,3,4 ,5个器官受损害 ,其阳性率分别为 33.4 5 % ,5 7.12 % ,97.0 9% ,10 0 %。结论 :产科多器官功能障碍 /衰竭的产科主要诱因是重度子痫前期 /子痫 ,产后出血 ;产科MODS患者死亡率也随着器官损害数的增多而上升 ;APACHEII评分可在一定程度上作为评定产科MODS患者病情危重程度和预测预后的指标。     

623例慢性前列腺炎患者的性功能状况调查

目的:了解慢性前列腺炎对早泄(PE)和勃起功能障碍(ED)的影响,探讨它们之间的关系。方法:依据美国国立卫生研究院慢性前列腺炎症状指数评分表(NIH-CPSI)、中国早泄患者性功能评分表(C ISFPE)、国际勃起功能问卷评分表(IIEF-5);采用和患者面对面交谈、询问,并分别记录623例慢性前列腺炎患者的NIH-CPSI评分、C ISFPE评分、IIEF-5评分。结果:623例18~57岁的慢性前列腺炎患者中,PE发生率为39.0%,其中轻度占26.2%、中度占12.0%、重度占0.8%;ED发生率为16.9%,其中轻度占14.9%、中度占1.0%、重度占1.0%。慢性前列腺炎患者PE的发生率以年轻者为多,18~29岁组为42.9%(103/240)、30~39岁为37.0%(95/257)、40~57岁组为35.7%(45/126);ED发生率以年龄高者为多,18~29岁组为13.8%(33/240)、30~39岁为11.3%(29/257)、40~57岁组为34.1%(43/126)。统计学分析发现,NIH-CPSI评分与早泄评分以及与IIEF-5评分均无明显相关性。结论:慢性前列腺炎的症状轻重与PE和ED的轻重程度无明显的相关性。     

阿扑吗啡与勃起功能障碍

ED是男科的常见病之一,其一线治疗方法是口服药物。阿扑吗啡(APO)作为中枢多巴胺受体激动剂,其舌下含片几乎对不同程度的ED患者都有效,且起效快、耐受性好、安全性高,特别是对于接受硝酸盐治疗而禁用西地那非的患者。现对其药代动力学、作用机制及疗效、安全性进行综述。     

Developing Organ Offer and Acceptance Measures: When 'Good' Organs Are Turned Down

Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs.     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.     

Perugia urodynamic method of analysis (PUMA): a new advanced method of urodynamic analysis applied clinically and compared with other advanced methods.

AIMS: The aim of this study is to compare PUMA curves with different pathologic conditions causing bladder dysfunction in 158 men and 83 women. METHODS: PUMA results in terms of bladder outlet obstruction and detrusor contractility were compared in 92 men with benign prostatic hypertrophy (BPH) and p(ves) congruent with p(det) (i.e., p(abd) congruent with 0) with the results of the urodynamics operator's opinion, the provisional International Continence Society method, Abrams and Griffith's diagram, urethral resistence factor (URA), Sch?fer's diagram, and Watt factor. PUMA curves correlated reliably with different pathologic conditions such as obstructive BPH, orthotopic bladder, cystocele, the neurological bladder, and bladder diverticulum. Statistical analysis indicated excellent agreement between PUMA and URA; agreement with other methods was good in cases of obstruction and nonobstruction. In doubtful cases, as diagnosed by standard methods, PUMA agreed only with the Abrams and Griffith's diagram. PUMA and Wmax were in good agreement on detrusor con traction force. Agreement between PUMA and Sch?fer's diagram was excellent for patients with detrusor hypercontractility and good for patients with detrusor hypocontractility and normocontractility. PUMA is the only method applicable to women. It is easy to perform. When integrated with other diagnostic tests, it provides realistic data for diagnosis, medical or surgical therapy, and outcome.     

内镜下鼻胆管引流治疗急性梗阻性化脓性胆管炎(附25例报告)

目的探讨急性梗阻性化脓性胆管炎伴多器官衰竭的治疗方法。方法对25例急性梗阻性化脓性胆管炎伴多器官衰竭的患者采取以内镜下鼻胆管引流术、经鼻胆管冲洗及灌注抗生素为主的非手术综合治疗,观察患者治疗前后的血清总胆红素水平、B超下胆总管内径变化,并对患者临床资料进行回顾性分析。结果本组25例患者除2例需转外科急诊手术治疗外,其余23例内镜下胰胆管造影、内镜下鼻胆管引流术成功,胆汁引流通畅,多器官衰竭得以纠正,急性梗阻性化脓性胆管炎伴多器官衰竭治愈率为92.0%。结论对急性梗阻性化脓性胆管炎伴多器官衰竭患者采取内镜下鼻胆管引流术、静脉应用和经鼻胆管冲洗及灌注抗生素为主的综合治疗是有效、安全的。     

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.