Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study

Patients on cyclosporin A (CsA) often develop hyperuricaemiaand gout. In transplant patients the use of uricosuric drugsfor treating hyperuricaemia may be preferable to allopurinolbecause of the known interaction of the latter with azathioprine.We therefore prospectively studied the uricosuric efficacy of100 mg benzbromarone (Bbr;Desuric®) daily in 25 CsA-treatedrenal transplant patients with stable graft function and hyperuricaemia(>359 µmol/l for females, >491 µmol/l formales). Benzbromarone decreased plasma uric acid from 579±18µmol/l to 313±24 µmol/l (mean±SEM;P<0.001) and thereby normalized plasma uric acid in 21 of25 patients. The remaining four patients had creatininc clearancesbetween 21 and 25 ml/min, the lowest of the entire study group.Mean fractional clearance of uric acid increased from 5.4±0.4%to 17.2±1.0% (P<0.001). The relative decrease of plasmauric acid closely correlated with baseline creatinine clearance(r=0.67; P<0.001). CsA trough values were not influenced.None of the patients experienced any significant side-effects.As an unexpected find-ing, urinary uric acid excretion increasedfrom 2082 ± 175 µmol7sol;24 h to 3233 ±232µmol/24 h after 4 weeks' treatment with benzbromarone. In conclusion, benzbromarone normalized plasma uric acid inall CsA-treated renal transplant recipients with a creatinineclearance >25 ml/min. Due to its excellent efficacy and lackof significant side-effects, benzbromarone appears to be preferableto allopurinol in CsA-treated renal transplant recipients witha creati nine clearance over 25 ml/min.     

环丙沙星治疗急性细菌性痢疾29例临床疗效观察

食源性急性菌例２９例中２８例大便培养为弗氏２ａ志贺氏菌。经２天吡哌酸加ＴＭＰ短程快速治疗，２９例无一例治愈。依据药敏试验改用环丙沙星治疗，其中１１例感染严重者先予静脉点滴，每１２小时２００ｍｇ，１￣２天，症状好转即改口服，每１２小时２５０ｍｇ。另１８例口服，疗程均为４天。用药后，平均退热时间１．３２天，大便次数恢复正常时间平均２．１０天，大便常规正常时间平均２．８６天，２８例大便培养阳性者，平均阴     

曲肘式机构的优化设计

以功效系数为目标函数,相应地确定了设计变量和约束函数,对塑料注塑机合模机构的参数进行优化计算,提高了机构的综合性能。     

复配杀虫母液灭蚊效果评价

目的 :评价复配杀虫母液灭蚊虫效果。方法 :设试验区和对照区 ,试验区用有效成分含量 2 0 %的复配杀虫母液按 5 m l/ m3超低容量喷雾 ;对照区用 2 0 % DDVP同浓度超低容量喷雾。结果 :复配杀虫母液超低容量喷雾 2 h后 ,蚊密度下降率为 93.3% ,RPI为 2 6 .7;4h后下降率为 98.3% ,RPI为 12 .4。结论 :复配杀虫母液用超低容量喷雾能迅速杀灭成蚊 ,是特殊情况下短时间内降低室内成蚊密度较为理想的杀虫药剂。     

Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

Rhesus monkeys (n=5) were prepared with chronic IV catheters and trained to lever press under a PR schedule of drug injection. The schedule consisted of five components, each made up of four trials (i.e., 20 trials total). Each trial within a component had the same response requirement. The response requirement in the first component was 120/trial and doubled in successive components to a maximum of 1920 in the fifth. A trial ended with an injection or the expiration of a 12-min limited hold (LH). The inter-trial interval (ITI) was 15 or 30 min. Following an injection or expiration of the LH, all stimulus lights were extinguished and responding had no consequence for the remainder of the trial. A session ended when either all 20 injections were self-administered or the response requirement was not met within the LH for two consecutive trials. The number of injections/session and responses/session increased with dose for cocaine (0.012–0.1 mg/kg per injection) and procaine (0.12–2.0 mg/kg per injection) at both ITI values. At the 15-min ITI, responding decreased again at higher doses in some monkeys with cocaine and in all monkeys with procaine. At maximum, cocaine maintained significantly more injections and responses/session when the ITI was 30 min than when it was 15 min. In contrast, the increase in ITI did not increase the maximum maintained by procaine. Cocaine was approximately 10-fold more potent than procaine and maintained at maximum significantly more injections and responses than procaine when the ITI was 30 min but not when the ITI was 15 min. These results are consistent with previous studies demonstrating that cocaine is a more efficacious positive reinforcer than procaine. Moreover, they extend recent findings suggesting that number of injections/session provides a measure of PR performance that is amenable to statistical analysis and may, therefore, be useful in establishing reliable differences among drugs in terms of relative reinforcing efficacy. Reliable quantification of between-drug differences in reinforcing efficacy can enhance not only estimates of relative abuse liability but also pharmacological analysis of central mechanisms mediating reinforcing effects.     

Mammographic screening: case-control studies.

BACKGROUND: The case-control design can be used to evaluate the benefit of cancer screening programmes. MATERIALS AND METHODS: This paper outlines the main methodological features of the case-control design in this context, and indicates some potential biases. It also reviews the existing case-control literature on mammographic screening. RESULTS: Case-control studies consistently indicate a reduction of approximately 50% in breast cancer mortality associated with mammography. This result indicates greater benefit than shown in randomised trials; however, one should recognise that trials indicate effectiveness whereas case-control studies indicate efficacy. The two types of evidence are broadly compatible when one allows for screening non-compliance and contamination in the randomised trials. CONCLUSIONS: The case-control evidence supports and is consistent with the findings of randomised trials of mammography. Effectiveness estimates from trials indicate the benefit of screening to the population as a whole, and are pertinent to the public policy debate as to the value of offering screening. In contrast, case-control studies indicate benefit to actual screening participants. As such, case-control estimates of efficacy are appropriate for individual decision-making by women about their use of mammography when it is potentially available to them.     

Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.     

精神分裂症患者氯氮平使用现况调查

目的:了解精神分裂症患者氯氮平的使用现状。方法:按一定的抽样比例,抽取10个省市46家专科医院或综合医院精神科,于2002年4月22日至24日,采用自制问卷对4779例门诊和住院精神分裂症患者进行氯氮平使用情况调查。结果:39.0%(1863/4779)的患者使用氯氮平治疗,平均剂量为(216±133)mg/d;其中41.2%的患者为联合用药,合并使用抗胆碱能药物者为19.2%。与未使用氯氮平的患者比较,使用氯氮平的患者病程较长、家庭收入较低;男性及住院患者更多使用氯氮平,氯氮平治疗者疗效指数低于非氯氮平治疗者。患者的性别、就诊部门、家庭收入和是否首次住院以及抑郁和攻击症状为是否使用氯氮平治疗的影响因素。结论:精神分裂症患者氯氮平使用率为39.0%,其中41.2%为联合用药。是否使用氯氮平治疗与患者的经济状况和临床特征等因素有关。