帕瑞昔布钠对乳腺癌根治术后布托啡诺病人自控静脉镇痛时细胞免疫功能的影响

目的 评价帕瑞昔布钠对乳腺癌根治术后布托啡诺病人自控静脉镇痛(PCIA)时细胞免疫功能的影响.方法 择期行乳腺癌改良根治术女性病人60例,ASA分级Ⅰ或Ⅱ级,年龄36～ 60岁,体重48 ～ 82 kg,采用随机数字表法,将其分为2组(n=30):对照组(C组)和帕瑞昔布钠组(P组).术毕采用布托啡诺10 μg/kg行PCIA,背景输注速率2 ml/h,PCA量0.5 ml,锁定时间15 min.P组分别于术毕、术后12、24和36 h时静脉注射帕瑞昔布钠40 mg,C组给予等容量生理盐水.术后维持VAS评分≤4分;VAS评分≥5分时,静脉注射布托啡诺进行镇痛补救.分别于麻醉诱导前5 min、切皮后2h、术后6h、1、3和7d时,采集右颈内静脉血样,采用流式细胞仪检测T淋巴细胞亚群(CD3+、CD4+、CD8+)和NK细胞的水平,计算CD4+/CD8+.分别于术后2、6、12、24和48 h时,记录镇痛泵总按压次数、有效按压次数和镇痛补救药物用量.记录不良反应发生情况.结果 与C组比较,P组镇痛泵总按压次数和镇痛补救药物用量减少,镇痛泵有效按压次数增多,术后ld时CD3+、CD4+、CD4+/CD8+和NK细胞水平降低(P＜0.05),不良反应发生率差异无统计学意义(P＞0.05).结论 帕瑞昔布钠可增强术后布托啡诺PCIA的效果,减少其用量,从而改善乳腺癌根治术病人术后细胞免疫功能.     

Obesity Is Associated with Increased Prostate Growth and Attenuated Prostate Volume Reduction by Dutasteride

Background

Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors.

Objective

To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements.

Design, setting, and participants

We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy.

Intervention

Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr.

Outcome measurements and statistical analysis

Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25–29.9, and ≥30 kg/m² using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression.

Results and limitations

Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus <25 kg/m² had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p < 0.001; at 4 yr: 29.4% vs 20.1%; p = 0.001). Men on dutasteride with BMI ≥30 versus <25 kg/m² had attenuated PV reduction from baseline (at 2 yr: −14.3% vs −18.5%; p = 0.002; at 4 yr: −13.2% vs −19.3%; p = 0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08–1.93; p = 0.014; at 4 yr: OR: 1.62; 95% CI, 1.18–2.22; p = 0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed.

Conclusions

Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy.

ClinicalTrials.gov identifier

NCT00056407.     

影响1-羟基-2-氧-1,8-萘啶-3-甲酰胺类HIV整合酶链转移抑制剂抗整合酶链转移活性的主要因素

 目的 探讨影响1-羟基-2-氧-1,8-萘啶-3-甲酰胺类HIV整合酶链转移抑制剂(integrase strand transfer inhibitors, INSTIs)抗整合酶链转移(integrase strand transfer, INST)活性的主要微观结构因素。方法 采用遗传函数逼近法构建了10个1-羟基-2-氧-1,8-萘啶-3-甲酰胺类INSTIs的二维定量构效关系(2d-quantitative structure-activity relationship, 2D-QSAR)模型,从中优选出最优模型,并据此探析影响抑制剂抗INST活性的主要微观结构因素。结果 最优2D-QSAR模型的非交叉验证相关系数R²为0.8555,留一法交叉验证相关系数Q²_loo为0.7761,外部交互验证相关系数R²_ext为0.94,表明所建模型具有较好的统计学意义和稳定性。结论 1-羟基-2-氧-1,8-萘啶-3-甲酰胺类INSTIs的抗INST活性主要与描述符JX、Dipole_mag、Jurs_PNSA_1和Strain_Energy相关,可为抑制剂的进一步合理设计提供理论依据。     

Overdose Risk with Opioids for Chronic Noncancer Pain

ABSTRACT

Timely and important studies are reviewed and commentaries provided by leading palliative care clinicians. Clinical scenarios, symptoms, interventions, and treatment-related adverse events addressed in this issue are overdose risk with opioids in chronic pain; pain in the primary care setting; methadone products and risk of QT prolongation; zolendronic acid and circulating cancer cells; statins and deep venous thrombosis; and treatment for cancer-associated anorexia-cachexia syndrome.     

Multiple cardiac contractile protein abnormalities in myopathic Syrian hamsters (BIO 53 : 58)

Hearts of genetically myopathic male hamsters (BIO 53 : 58) were studied at 1 month, 2 months, 3 months, 4 to 5 months and 7 months of age. The time course of alterations in the cardiac myofibrillar ATPase activity, the relationship of myofibrillar ATPase activity to free [Ca2+], myosin ATPase activity and the distribution of heavy chain myosin isoenzymes were evaluated. Mg2+-Ca2+ ATPase activity of cardiac myofibrils in myopathics was increased in 4 month and 7 month-old hamsters. Elevated Mg2+ ATPase activity was found as early as in 2-month-old hamster. However, there was no loss in the regulation of the myopathic myofibrillar assembly as measured by the PCa response (10(-7) M to 10(-4) M Ca2+). Scans of SDS electrophoresis slab gels of cardiac myofibrillar proteins from control (C) and myopathic animals (M) did not show any differences at any age group (1, 4 and 7 months). There was a significant decrease in myosin Ca2+ ATPase activity and actin activated Mg2+-ATPase activity at 4 to 5 months and 7 months of age in the myopathic hearts. At all ages in normal and myopathic animals cardiac myosin consisted of three isoenzymes, V1, V2 and V3. At all ages in controls and at 1 to 3 months in myopathics, V1 predominated and the isoenzyme distribution was V1 greater than V2 greater than V3. However, in myopathics at 4 to 5 months, the distribution was V1 = V3 greater than V2 and at 7 months was V3 greater than V2 greater than V1. Our experiments suggest alterations in different components of the contractile protein system that occur at different stages of myopathy.     

Protective effect of 3-aminobenzamide,an inhibitor of poly (ADP-ribose) synthetase,against streptozotocin-induced diabetes

Summary The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142±14U·islet^–1·h^–1; streptozotocin (0.5mg/ml) 31±8; 3-aminobenzamide (l.0 mg/ml) 96±11; streptozotocin plus 3-aminobenzamide 122±19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.     

西地那非联合十一酸睾酮治疗糖尿病性勃起功能障碍的安全性有效性多中心研究*

目的观察西地那非联合十一酸睾酮治疗糖尿病患者阴茎勃起障碍的疗效和安全性.方法2009年1月至2011年12月多中心收集广州市番禺区中心医院、上海交通大学医学院附属仁济医院、上海市中医医院泌尿男科门诊糖尿病性勃起功能障碍患者共100例,患者签署知情同意书后,根据国际勃起功能指数表(IIEF-5)进行自我评分.随机分为两组:A组:50例,控制血糖常规治疗的基础上服用西地那非(50mg prn)加十一酸睾酮(80mg/Bid);B组:50例,在控制血糖常规治疗的同时给予西地那非治疗,两组均治疗12周.观察两组患者治疗前后的疗效,并记录患者服药后的不良事件以评价其安全性.结果共计82例完成本次研究,其中A组42例、B组40例.两组患者IIEF-5评分在治疗后均显著增加,而A组较B组增加更显著,差异具统计学意义(P<0.05).治疗后每周性交频率均显著增加,A组较B组增加更明显,差异具统计学意义(P<0.05).其中A组显效率高达59.5%,有效率为88.1%,明显高于B组(显效率30.00%,有效率55.00%),P<0.05.A组37例患者性交时阴茎能满意勃起,而B组只有22例患者性交时阴茎能满意勃起;两组均未出现任何不良反应.结论西地那非联合十一酸睾酮治疗糖尿病性勃起功能障碍较单用西地那非可显著改善患者的勃起能力,且安全性好.     

帕瑞昔布钠超前镇痛的有效性评价:meta分析

目的 采用meta分析方法评价帕瑞昔布钠用于超前镇痛的有效性.方法 检索PubMed、Embase、Cochrane数据库和CNKI数据库,不限定发表时间和语言.收集帕瑞昔布钠应用于超前镇痛的随机安慰剂对照研究.采用改良Jadad法评价文献质量.以术后1、6、12和24h时视觉模拟评分(VAS评分)、术后24 h内吗啡用量、术后恶心呕吐发生情况为评价指标.采用RevMan 5.0.2软件进行meta分析.结果 纳入14项研究,Jadad评分均≥4分,包括1086例患者.分为安慰剂组和术前静脉注射帕瑞昔布钠40 mg组.Meta分析结果显示:与安慰剂组比较,术前静脉注射帕瑞昔布钠40mg组术后1、6、12和24 h时VAS评分降低,术后24 h内吗啡用量减少,术后恶心呕吐发生率降低(P＜0.05).结论 术前静脉注射帕瑞昔布钠40 mg可产生显著的超前镇痛效果,有助于降低术后镇痛的不良反应.     

Central nervous system control of the lower urinary tract: new pharmacological approaches to stress urinary incontinence in women

PURPOSE: Despite the prevalence of stress urinary incontinence in women there are no approved drugs for the disease. MATERIALS AND METHODS: Designing medical therapies requires a comprehensive understanding of how the internal and external sphincters are neurologically controlled. In this review recent advances in mapping storage and micturition reflexes, and the association of serotonergic and noradrenergic systems with these reflexes are discussed. RESULTS: Urine storage and micturition are controlled by a series of hard wired reflexes that are under the modulatory influence of serotonin and norepinephrine. Augmentation of the serotonergic and noradrenergic systems with duloxetine increases bladder capacity and urethral rhabdosphincter activity. The increase in sphincter activity is mediated by alpha1 adrenergic receptors and 5-hydroxytryptamine receptors. CONCLUSIONS: Increasing rhabdosphincter activity with duloxetine may offer a therapeutic benefit in women with stress urinary incontinence.