Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Optimal control of a revenue management system with dynamic pricing facing linear demand

This paper considers a dynamic pricing problem over a finite horizon where demand for a product is a time‐varying linear function of price. It is assumed that at the start of the horizon there is a fixed amount of the product available. The decision problem is to determine the optimal price at each time period in order to maximize the total revenue generated from the sale of the product. In order to obtain structural results we formulate the decision problem as an optimal control problem and solve it using Pontryagin's principle. For those problems which are not easily solvable when formulated as an optimal control problem, we present a simple convergent algorithm based on Pontryagin's principle that involves solving a sequence of very small quadratic programming (QP) problems. We also consider the case where the initial inventory of the product is a decision variable. We then analyse the two‐product version of the problem where the linear demand functions are defined in the sense of Bertrand and we again solve the problem using Pontryagin's principle. A special case of the optimal control problem is solved by transforming it into a linear complementarity problem. For the two‐product problem we again present a simple algorithm that involves solving a sequence of small QP problems and also consider the case where the initial inventory levels are decision variables. Copyright © 2006 John Wiley & Sons, Ltd.     

Intrathecal Ziconotide in the Treatment of Chronic Nonmalignant Pain: A Randomized,Double‐Blind,Placebo‐Controlled Clinical Trial

Objective. The safety and efficacy of intrathecal (IT) ziconotide was studied in a randomized, double‐blind, placebo‐controlled trial. Materials and Methods. Patients (169 ziconotide, 86 placebo) with severe chronic nonmalignant pain unresponsive to conventional therapy and a visual analog scale of pain intensity (VASPI score) ≥ 50 mm were treated over a 6‐day period in an inpatient hospital setting. Initial starting dose was 0.4 µg/hour and was titrated to analgesia or intolerance (maximum dose 7.0 µg/hour). The starting and maximum doses were reduced to 0.1 µg/hour and 2.4 µg/hour, respectively, due to adverse events (AEs). Results. The mean percent reduction in VASPI score from baseline was 31.2% and 6.0% for ziconotide‐ and placebo‐treated patients, respectively (p ≤ 0.001). During the initial titration phase, a significantly greater percentage of patients in the ziconotide group compared to the placebo group reported AEs, including abnormal gait, amblyopia, dizziness, nausea, nystagmus, pain, urinary retention, and vomiting. Conclusion. Ziconotide provided significant analgesia in patients for whom conventional therapy failed. However, there was a considerable incidence of ziconotide‐associated AEs due to the rapid titration and high doses administered.     

慢性心衰患者电话干预的随机试验：DIAL试验

目的:明确集中的电话干预能否降低慢性心衰门诊患者死亡或因心衰加重而住院的发生率。设计:多中心、随机对照试验。地点:阿根廷的51个中心(包括公立、私立的医院及流动设施)。参与者:1518例患有稳定的慢性心衰且已接受最佳药物治疗方案治疗的门诊患者,由心脏科主治医师分层后随机分为电话干预组和常规治疗组。干预:在常规治疗的基础上,由一个中心通过护士频繁的电话随访对患者进行教育、辅导和监督。主要观察指标:全因死亡或由于心衰加重而住院。结果:99.5%的患者完成了全部随访。常规治疗组758例患者中由于心衰加重而住院或死亡的比例(235…     

衰老对大鼠阴茎组织NO-cGMP通路及端粒酶活性的影响研究

目的探讨衰老对大鼠阴茎组织结构、NO(nitric oxide)-cGMP(cvclic Guanosine Monophosphate)通路及端粒酶活性的影响作用。方法本课题以不同月龄大鼠阴茎组织及培养的平滑肌细胞为研究对象,检测不同月龄大鼠阴茎组织中NO量、NOS(Nitric Oxide Synthase)活性、cGMP量、端粒酶活性及海绵体结构的变化,并比较大鼠、人阴茎组织及大鼠原代海绵体平滑肌细胞的端粒酶活性。结果(1)大鼠阴茎组织中NO量、NOS活性均先升高后降低,各月龄组间有显著差异。阴茎组织cGMP含量逐渐降低,各月龄组间差别显著；(2)随龄增加,平滑肌纤维逐渐减少,胶原纤维增多,粗大成团,窦状隙变少、变窄：(3)大鼠阴茎组织端粒酶活性以2月龄活性最高,随龄增加逐渐下降。人阴茎组织中无端粒酶活性。结论(1)衰老对大鼠阴茎组织结构、NO．cGMP通路及端粒酶活性有显著影响,提示衰老与ED关系密切；(2)大鼠阴茎组织有端粒酶活性,可作为研究细胞衰老与ED关系有关端粒酶的模型。     

Identifying Risk Drinking in Expectant Fathers

Abstract: Background: Identification of risk drinking in expectant fathers may be helpful as an important part of efforts to minimize maternal alcohol use, and as an opportunity to inform them about a problematic practice during a critical developmental stage for the couple. The purpose of this study was to evaluate the T‐ACE screening questionnaire, which asks about t olerance to alcohol, being a nnoyed by other's comments about drinking, attempts to c ut down, and having a drink first thing in the morning (“ e ye‐opener”), in the male partners of pregnant women who themselves were T‐ACE positive. Methods: Two hundred fifty‐four male partners were asked to complete the T‐ACE embedded in a health survey, the Alcohol Use Disorders Identification Test (AUDIT), and other questions about their alcohol use in the past 30 days when their pregnant partners had a median gestation of 11.5 weeks (T₁). After delivery, male partners again completed the T‐ACE and quantity‐frequency questions (T₂). The predictive ability of the T‐ACE and AUDIT was compared, using risk drinking (>4 drinks/day or >14 drinks/week) as the criterion standard. Results: A substantial minority of male partners had risk drinking, 31 percent at T₁ and 25 percent at T₂. Although the AUDIT was better than the T‐ACE as an independent predictor of risk drinking, the latter was most accurate when the tolerance threshold exceeded 2 drinks, the same established for pregnant women. The sensitivity (T₁ = 84.6%, T₂ = 82.8%) and specificity (T₁ = 43.8%, T₂ = 51.1%) of the T‐ACE at this threshold compared favorably with those of the AUDIT at the standard cut point of 8. Conclusions: The T‐ACE may be a practical way for clinicians to identify risk drinking in both pregnant women and expectant fathers. (BIRTH 33:2 June 2006)     

儿科背式输液架的研制与应用

输液架是医院不可缺少的工具之一，国内医疗单位使用的输液架多种多样，但仅适用于病房使用，而适合儿科患儿移动的背式输液架甚少。针对以上缺陷，我们自行设计了一种可调式背式移动输液架，已应用于500例儿科患儿，效果较好。现介绍如下。     

Cumulative probability of pregnancy following IVF with ICSI and fresh or frozen embryo transfer.

The authors studied the cumulative probability of pregnancy for up to 4 consecutive embryo transfer (ET) cycles with ICSI performed for male factor. Transfers could be either fresh or frozen. The clinical pregnancy rate (PR) for the first 4 cycles were similar [44% (61/366); 31% (44/138); 45% (14/31); 44% (4/9)]. Delivery rates were also similar. There was a lower PR on the second retrieval vs. the first retrieval (47% vs. 29%), but this may be related to most of the second retrievals occurring in the second transfer cycle (67%, 31/55); this may be explained by women who were poor responders and required another retrieval without a frozen ET. The majority of transfers in cycle 1 were fresh, whereas cycles 2-4 used primarily frozen-thawed embryos. These data should be helpful for patients requiring IVF with ICSI in deciding to continue with more IVF cycles or consider other