Pilot evaluation of mirtazapine for the treatment of hot flashes

This prospective, single-arm, pilot clinical trial, developed to evaluate the efficacy and tolerability of mirtazapine for alleviating hot flashes, was conducted between May 2001 and January 2002. Patients' baseline characteristics were collected during the first week of the study. At the beginning of the second week, patients were started on mirtazapine at a dose of 7.5 mg at bedtime. The dose of mirtazapine was then increased to 15 mg at week 3 and to 30 mg at week 4. For week 5, patients could choose whether to take 15 mg/d or 30 mg/d. Data were obtained primarily from patient-completed questionnaires. Data from 22 evaluable women were available. For the 16 patients who completed the study, the median reductions in total daily hot flashes and weekly hot-flash scores from their baselines were 52.5% and 59.5%, respectively. Patients reported improvements in tension, trouble sleeping, abnormal sweating, distress from hot flashes, satisfaction with hot-flash control, overall quality of life, and impact of hot flashes on quality of life. Patients also reported increases in appetite and dry mouth. Although data from a double-blind, placebo-controlled clinical trial would be necessary to more definitively elucidate the efficacy and toxicity of mirtazapine in patients with hot flashes, the available data suggest that mirtazapine is a reasonable treatment to consider in patients with hot flashes, particularly in those with anxiety and sleep disturbances.     

A phase I and pharmacokinetic study of the selective, non-peptidic inhibitor of matrix metalloproteinase BAY 12-9566 in combination with etoposide and carboplatin

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix during the processes of invasion, metastasis and angiogenesis. BAY 12-9566 (BAY) is a selective, non-peptidic biphenyl inhibitor of MMPs, with nanomolar inhibitory activity against MMP-2, -3 and -9, and anti-invasive, anti-metastatic and anti-angiogenic activity in a variety of tumor models. This phase I study of oral BAY was conducted to evaluate the safety and pharmacokinetics of BAY when administered in combination with etoposide (VP-16) or in combination with VP-16 and carboplatin (CBDCA) in subjects with advanced cancer. The first cohort of patients (n=8) received a cycle of VP-16, 60 mg/m, followed 1 week later by a fixed daily oral dose of BAY, 800 mg b.i.d., to which three potential possible doses of VP-16 (low dose: 60 mg/m; mid dose: 90 mg/m; high dose: 120 mg/m) were added every 3 weeks as tolerated. The second cohort (n=5) received VP-16 (120 mg/m) and CBDCA (AUC=5) followed 1 week later by a fixed daily oral dose of BAY (800 mg) b.i.d., to which VP-16 (120 mg/m) and CBDCA (AUC=5) were added. Dose-limiting toxicity (DLT) was defined as toxicity grade 3 or above. Maximum tolerated dose was declared if two or more patients experienced DLT. A performance status of 0-2 and acceptable organ function were required for eligibility. Plasma concentrations of BAY and VP-16 were measured to investigate pharmacokinetic interactions. Eight eligible patients with a variety of tumor types (median age 64 years, range 44-76) were enrolled in the first cohort, six of who whom completed all three levels of VP-16. Progressive disease occurred in five of the eight patients; three patients continued on study with treatment. Drug level and pharmacokinetics analysis of BAY and VP-16 were also determined. The combination of BAY and VP-16 was tolerable in the first cohort, permitting enrollment of the second cohort. In the second cohort (n=5), the combination of BAY, VP-16 and CDBCA was intolerable at the doses used due to excessive hematologic toxicity in the first five patients enrolled. Pharmacokinetics and toxicity analysis was performed for this group of patients. Only Level 1 of treatment was completed for Cohort II. At this point the study was halted due to toxicity and the results of an interim analysis that failed to demonstrate sufficient clinical activity of this compound in other clinical trials. We conclude that the combination of BAY and VP-16 was well tolerated. However, the combination of BAY, VP-16 and CDBCA produces significant hematologic toxicity. Findings from this study may help to direct further studies with other inhibitors of MMPs.     

Conversion of 5-deoxypulchelloside I to caudatoside A

The iridoid caudatoside A (2) was synthesized in seven steps from the naturally occurring iridoid 5-deoxypulchelloside I (1) using a straightforward series of protection and deprotection procedures to introduce the requisite C-6 cinnamoyl ester.     

术中置管近距离放疗在骨与软组织肉瘤治疗中的应用

目的分析术中置管近距离放疗在骨与软组织肉瘤综合治疗中应用的疗效和毒性。方法163例骨与软组织肉瘤的病例，其中59例采用手术＋化疗＋外照射，另外104例采用手术＋化疗＋近距离放疗＋夕h照射的综合治疗方法。结果采用近距离放疗的一组患者有较好的疗效和较低的毒性。结论术中置管近距离放疗在骨与软组织肉瘤的综合治疗中有较好临床应用价值．．     

hTR反义PS-ODN联合顺铂对人胃癌裸鼠皮下移植瘤作用的体内研究

目的 探讨hTR反义寡脱氧核苷酸（ASODN）联合顺铂对人胃癌裸鼠皮下移植瘤的治疗作用。方法 30只裸鼠建立胃癌皮下移植瘤模型后，随机分成5组，予以不同条件处理，对照组（瘤周注射RPMI1640培养液）、ASODN组（瘤周注射反义寡脱氧核苷酸）、RODN组（瘤周注射随机寡脱氧核苷酸）、DDP组（瘤周注射化疗药物顺铂）、ASODN＋DDP组（瘤周注射反义寡脱氧核苷酸和顺铂）。治疗后定期观察肿瘤体积，计算肿瘤抑制率。采用TRAPPCR—ELISA法检测移植瘤的端粒酶活性。结果 ASODN＋DDP组、ASODN组、DDP组和RODN组的最高肿瘤抑制率分别为94.2％、84．3％，92．8％和26．9％。在端粒酶活性检测中，4个治疗组间均有统计学意义。结论 hTR反义PSODN对人胃癌裸鼠皮下移植瘤生长及端粒酶活性有一定抑制作用，且可增强DDP的上述作用。     

Reverse Gear: Cairo’s Dependence on a Disappearing Paradigm

The global increase in population projected over the next 45 years (median estimate 2.4billion) is approximately equal to the world population in 1950 (2.5 billion)[1]. Yet instead ofraising global concern, economists are focusing on relatively small reductions in populationpredicted in some rich countries, and many demographers have switched to the study ofageing. By 2004 the rate of global population growth had fallen to 1.3 percent, but theabsolute annual increase (83.1 million more births …