Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian,fallopian tube or primary peritoneal cancer

Objective

We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC).

Methods

Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m² IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS).

Results

Thirty-four patients received a median of 7 treatment cycles (range, 2–26). Median follow-up was 25.7 months (range, 3.0–47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38–71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25–59), 18 stable disease (53%; 35–70) and 2 progressive disease (6%; 1–20). Median PFS was 7.9 months (95% CI, 4.6–10.9), with a median OS of 25.7 months (95% CI, 15.4–29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of > 6 months prior to enrollment. Grade 3–4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3–4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment.

Conclusions

Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.     

Adolescent binge drinking and risky health behaviours: Findings from northern Russia

Background

Some evidence suggests that in recent years the prevalence of heavy drinking has increased among Russian adolescents. However, as yet, little is known about either heavy alcohol consumption or its relationship with other adolescent health risk behaviours in Russia. The aim of this study therefore was to investigate the association between binge drinking and health risk behaviours among adolescents in Russia.

Methods

Data were drawn from the Social and Health Assessment (SAHA), a survey carried out in Arkhangelsk, Russia in 2003. Information was obtained from a representative sample of 2868 adolescents aged 13–17 regarding the prevalence and frequency of binge drinking (five or more drinks in a row in a couple of hours) and different forms of substance use, risky sexual behaviour and violent behaviour. Logistic regression analysis was used to examine the association between binge drinking and adolescent involvement in various health risk behaviours.

Results

Adolescent binge drinking was associated with the occurrence of every type of health risk behaviour – with the sole exception of non-condom use during last sex. In addition, there was a strong association between the number of days on which binge drinking occurred and the prevalence of many health risk behaviours.

Conclusions

Binge drinking is associated with a variety of health risk behaviours among adolescents in Russia. Public health interventions such as reducing the affordability and accessibility of alcohol are now needed to reduce binge drinking and its harmful effects on adolescent well-being.     

Effects of the NMDA-antagonist,MK-801, on stress-induced alterations of dopamine dependent behavior

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day × 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.     

Preparation of bovine serum albumin loaded poly (D,L-lactic-co-glycolic acid) microspheres by a modified phase separation technique

BSA-loaded mcirospheres were prepared by a modified phase separation method, in which petroleum ether (PE) containing a certain amount of Span 80 rather than poly (dimethylsiloxane) (PDMS) was adopted as coacervating agent. Process parameters such as Span 80 concentration, the volume and addition rate of coacervating agent, polymer concentration, agitation rate during the phase separation process and PE type were evaluated to optimize the protein encapsulation. It was found microspheres with high yield (>80.0%) and entrapment efficiency (>90%) could be obtained using PE containing 5.0% Span 80 as the coacervating agent. Microspheres with small particle size (<10?µm) could be produced successfully with appropriate process parameters. In vitro release study suggested that burst release was significantly influenced by Span 80 concentration, polymer concentration and PE type and the burst release could be reduced to <20% with optimized formulation. A biphasic release behavior in vitro test was observed for the microspheres prepared by this method. GC analysis demonstrated that residual solvent of DCM and petroleum ether was decreased dramatically in comparison with PDMS used as a conventional coacervating agent.     

探讨认知护理干预对美沙酮维持治疗者偷吸行为的影响

目的：探讨认知护理干预对美沙酮维持治疗者偷吸行为的影响。方法：把门诊在治的美沙酮维持治疗者75人作为研究对象,根据随机原则分干预组37人与对照组38人。对干预组建立健康护理档案、进行认知护理干预;对照组进行单纯美沙酮药物治疗。记录所有研究对象的每月尿吗啡检测结果。结果：干预组尿检总阴性次数大于对照组（P〈0．01）,持续阴性率高于对照组;干预组在第9个月、12个月尿检阴性数大干对照组（P〈0．05）;组内比较,干预组第9、12个月与第1个月比较统计存在显著差异（P〈0．01）,对照组无差异性。结论：认知护理干预能减少美沙酮维持治疗者偷吸行为。     

认知行为治疗拒绝上学的研究

目的：探讨认知行为治疗（CBT）及联合氟西汀治疗拒绝上学的疗效。方法：选择2009年10月至2012年10月符合拒绝上学诊断标准的患者95例,年龄8～18岁。将95例患者随机分为CBT组（n=47）、CBT＋氟西汀组（n=48）,疗程12周,治疗前后采用焦虑自评量表（SAS）、抑郁自评量表（SDS）评价,记录每组的返校率。结果：CBT组治疗前后SAS和SDS比较差异有统计学意义（P〈0.01）,返校率74.5%;CBT＋氟西汀组治疗前后SAS和SDS评分比较差异有统计学意义（P〈0.01）,返校率83.3%。两组间返校率比较差异无统计学意义（P〉0.05）。结论：CBT和CBT联合氟西汀均可以有效治疗拒绝上学,氟西汀不能提高CBT治疗拒绝上学的疗效。     

用差示扫描量热法及激光拉曼光谱研究足叶乙甙对二棕榈酰磷脂酰胆碱脂质体膜流动性影响

本文用DSC和激光拉曼光谱研究抗癌药物足叶乙甙(4-去甲基表鬼臼毒素-β-D-乙叉吡喃葡萄糖甙,简称VP 16-213)与二棕榈酰磷脂酰胆碱(DPPC)脂质体的作用。VP 16-213分子掺入DPPC脂质体双层中,不但使相转变温度向高温移动,而且吸热峰的半高宽度随VP 16-213浓度增加而变宽。其Raman光谱在频率2850 cm~(-1)处的C-H键对称伸缩振动亦随着药物浓度增加而减弱。这些结果表明VP 16-213分子是定域在脂双层中DPPC分子链的C_1～C_9亚甲基区域,使脂质体的有序性提高而流动性降低。     

三七种子贮藏习性研究

目的研究三七种子的贮藏习性,为三七种子的保存提供科学依据。方法用TTC法测定不同水分和不同温度贮藏三七种子生活力。结果三七种子对干燥脱水的忍耐能力类似顽拗型种子,其最低安全含水量为17%。结论三七种子为顽拗型种子,对低温极为敏感,不适宜采用低温贮存。     

蛇胆川贝液和蛇胆汁中牛磺胆酸的SPE-HPLC法测定

目的 :建立蛇胆川贝液和蛇胆汁中牛磺胆酸含量的测定方法。方法 :含磷酸二氢钾的样品与甲醇的混合溶液流过Sep PakC18固相萃取微柱。固相萃取微柱吸附溶液中强保留物质以保护分析柱 ,牛磺胆酸被固相萃取微柱饱和吸附后的流出液作反相高效液相色谱法测定用的供试液。色谱条件 :SupelcosilLC 8色谱柱 (15 0mm× 4 .6nm ,5 μm)为分析柱 ,甲醇 0 .4 %磷酸二氢钾溶液 (5 6∶4 4 ,V/V)为流动相 ,检测波长 2 0 3nm ,进样体积为 5 0 μL。 结果 :在 0 .0 2 5 3～0 .2 5 3mg·mL-1浓度范围内 ,牛磺胆酸钠进样浓度与峰面积响应值呈良好的线性关系 ,r =0 .9999;平均回收率为10 1.3% ,RSD为 0 .4 0 % (n =6 )。结论 :本法简便实用 ,分析结果准确可靠 ,可作为中成药蛇胆川贝液和蛇胆汁的质量控制方法     

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.