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41.
Richard L Schilsky Jeremey Levin William H West Alfred Wong Bruce Colwell Michael P Thirlwell Rafat H Ansari William N Bell Robin L White Barbara B Yates Paul V McGuirt Richard Pazdur 《Journal of clinical oncology》2002,20(6):1519-1526
PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m(2)/1.15 mg/m(2) twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m(2)/20 mg/m(2) once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P =.01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P =.354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS. 相似文献
42.
Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation 总被引:8,自引:0,他引:8
A. C. Jones E. A Miles J. O. Warner B. M. Colwell T. N. Bryant J. A. Warner 《Pediatric allergy and immunology》1996,7(3):109-116
Blood samples were obtained from fetuses and premature babies (n=51) (15-34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PB MC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur. birch tree pollen, β-lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3 H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p < 0.0001), cat fur (p=0.042), birch pollen (p=0.022) and β-lactoglobulin (p=0, 006). The point in gestation when cells from some individuals began responding to the allergens with a ratio of 2. 0 was at approximately 22 weeks. PBMC proliferative response ratios were higher from samples from babies > 22 weeks gestation compared to < 22 weeks for the mitogen and all allergens, except mellitin. There was also a greater proportion of positive responders from samples > 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher prolifera tive response in infant cells stimulated with birch pollen (p=0.005) and higher proportion of positive responders (p=0.01) in the group of babies whose mothers had been exposed to hirch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth. 相似文献
43.
M. F. Lopes-Virella G. Sherer H. Wohltmann D. Sens J. A. Colwell 《Metabolism: clinical and experimental》1985,34(12):1079-1085
Low density lipoproteins (LDL) isolated from poorly controlled diabetic patients are known to be taken up and degraded by fibroblasts at a lower rate than LDL isolated from normal subjects. This aberrant metabolic behavior has been attributed to a diabetic-related abnormality in LDL composition yet to be characterized. The studies reported in this article show that the decrease in uptake and intracellular degradation of LDL from diabetic patients is further enhanced when the cells are exposed to lipoprotein deficient serum (LPDS) isolated from the same poorly controlled diabetic patients. Comparative studies of the composition of LPDS obtained from normal donors and poorly controlled diabetic patients showed an increase in saturated and total unesterified fatty acids (UFA), lecithin, apolipoprotein A1, and immunoreactive insulin in the LPDS from diabetic patients. We postulate that exposure of cells to LPDS obtained from poorly controlled diabetic patients may induce changes in the composition of the fibroblast membrane and alter its fluidity, leading to further decrease in the uptake and degradation of LDL. During poor diabetic control, cell membrane changes, and modification of LDL composition are likely to act either additively or synergistically to induce an abnormal LDL-cell interaction. This abnormal interaction may be a relevant factor to explain the greater incidence of arteriosclerosis in diabetes mellitus. 相似文献
44.
45.
Platelet function and diabetes mellitus. 总被引:2,自引:0,他引:2
46.
The renal uptake and excretion of insulin in the dog 总被引:1,自引:0,他引:1
47.
Fatal vascular outcomes following major orthopedic surgery 总被引:1,自引:0,他引:1
Dahl OE Caprini JA Colwell CW Frostick SP Haas S Hull RD Laporte S Stein PD 《Thrombosis and haemostasis》2005,93(5):860-866
Major orthopedic surgery is known to be associated with potentially serious arterial and venous vascular complications, although uncertainty exists about current event rates. Using electronic databases and investigator contact, we identified randomized and cohort studies reporting overall mortality and fatal vascular events. Where possible, studies reporting high autopsy rates (>60%) were examined. Pooled incidences were calculated from eligible studies. For Autopsy studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis could not be calculated, while with prophylaxis they were 0.44% (95% confidence interval 0.02 to 0.87%) and 0.43% (0.01 to 0.85%). For patients undergoing hip fracture surgery, the corresponding rates without prophylaxis were 15.9% (14.5 to 17.3%) and 1.9% (1.4 to 2.4%). With prophylaxis, mortality and fatal pulmonary embolismrates were 8.5% (7.3 to 9.7%) and 1.0% (0.6 to 1.5%). Among Cohort studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis were 0.93% (0.57 to 1.29%) and 0.36% (0.14 to 0.59%). For patients receiving prophylaxis (7 to 14 days), mortality and fatal pulmonary embolism were 0.57% (0.51 to 0.62%) and 0.18% (0.14 to 0.21%). Patients undergoing hip fracture surgery receiving prophylaxis hadmortality and fatal pulmonary embolismrates of 3.2% (2.8 to 3.6%) and 0.30% (0 to 0.61%). Vascular events contributed towards approximately 50% of all deaths with similar proportions due to ischemic heart disease, cardiac failure and pulmonary embolism. In conclusion, although prophylaxis results in a reduction in overall mortality and fatal pulmonary embolism, vascular events continue to be a common cause of mortality. 相似文献
48.
49.
Oxidized zirconium femoral components reduce polyethylene wear in a knee wear simulator 总被引:2,自引:0,他引:2
Ezzet KA Hermida JC Colwell CW D'Lima DD 《Clinical orthopaedics and related research》2004,(428):120-124
Polyethylene wear remains a major problem that can jeopardize the long-term durability of prostheses used in total knee arthroplasty. Oxidized zirconium is a material that combines the strength of a metal with the wear properties of a ceramic. This study evaluated the wear rates of polyethylene inserts against oxidized zirconium femoral components. Three oxidized zirconium femoral components and three Co-Cr femoral components of identical geometry used in total knee arthroplasty were articulated against standard tibial components with modular tibial inserts made of noncross-linked ultra-high molecular weight polyethylene. Gravimetric and volumetric polyethylene wear rates were calculated after 5 million gait cycles on an AMTI knee wear simulator. Oxidized zirconium reduced polyethylene wear by 42% compared with Co-Cr alloy. This study shows that oxidized zirconium can reduce polyethylene wear substantially when used for fixed-bearing total knee arthroplasty. 相似文献
50.
Hall VL Hardwick M Reden L Pulido P Colwell C 《Orthopaedic nursing / National Association of Orthopaedic Nurses》2004,23(3):163-71; quiz 172-3
During the past 30 years, the unicompartmental knee arthroplasty has undergone growing pains with various implant designs, refining indications, and improving surgical techniques and instrumentation. Today, studies show survivorship results comparable to the tricompartmental total knee arthroplasty and a renewed interest has emerged. Even though the unicompartmental knee arthroplasty is recommended for only a select 10-15% who have osteoarthritis of the knee, it has many advantages over the total knee arthroplasty. Although the nursing care and rehabilitation are similar to the total knee arthroplasty, including wound care, prophylactic antibiotics, and venous thromboembolism prophylaxis, the patient frequently has less pain, increased range of motion, shorter hospitalization, and fewer complications, resulting in a quicker rehabilitation. 相似文献