A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.     

Financial strain, received support, anticipated support, and depressive symptoms in the People's Republic of China.

The purpose of this study is to examine the interface between financial strain, informal received economic support, informal anticipated financial support, and psychological distress in later life. Data provided by a large probability sample of older adults in the People's Republic of China reveal that the relationship between financial difficulty and psychological distress is stronger for older adults who receive more economic assistance. However, the results involving anticipated support are in the opposite direction. More specifically, the association between financial problems and psychological distress is lower for older adults who believe that others stand ready to help in the future should the need arise. A detailed theoretical rationale is developed to explain these results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

固态继电器为电动汽车电池监测提供便利

电动汽车常被喻作“归来的孩子”，因为这项技术在多年前进入市场后便一直沉寂，直至最近才再次活跃起来。其实，电动汽车早于1835年首次于美国出现，到1899年，纽约市接近90％的出租车都是由电力驱动。然而，当电力启动器和内燃机变得完善时，电动汽车的使用就迅速衰退。随着如今对环境保护的关注，由燃烧碳氢化合物造成的污染，加之汽油成本高升的影响，再次     

BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer

BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.     

Titanium and bioactive glass-ceramic coated titanium as materials for keratoprosthesis

The current problem with keratoprosthesis is the ingrowth of corneal or conjunctival epithelium into the anterior chamber. This may lead to infections and extrusion of the prosthesis as well as to the development of retroprosthetic membrane and secondary glaucoma. Glass-ceramic coated and uncoated titanium has been tested as material for the keratoprosthesis to prevent epithelial ingrowth. Twenty-two Supra-Descemet's membrane keratoprostheses were inserted in the eyes of 22 rabbits for 1, 2, 4, 8, or 12 months. The prosthesis had an optic part made of polymethylmetacrylate (PMMA). The support for the optic part and the flange of the prosthesis were made of titanium. Eleven of the prostheses were coated with glass-ceramic. The histological sections of the enucleated eyes were prepared through the central part of the cornea and the prosthesis using a cutting-grinding method. The histological analysis was made on both halves of the implants separately giving two analysis areas in each eye. All 11 titanium prostheses were retained for the time period planned. Two glass-ceramic coated prostheses were lost at 2 and 4 weeks, respectively. This was caused by difficulties at surgery due to a thick coating. These eyes were excluded from the histological analysis. No significant ingrowth of epithelium was seen in 15/18 (83%) and in 16/22 (73%) of the analysed areas of the glass-ceramic coated and titanium prostheses, respectively. Titanium appears to be a suitable material for the keratoprosthesis. The ingrowth of the epithelium may be hindered further by coating the titanium with bioactive glass-ceramic.     

Cardiovascular effects of conventional sulfonylureas and glimepiride

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activated KATP channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly all animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.