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Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. 总被引:11,自引:0,他引:11
Fairooz F Kabbinavar Joseph Schulz Michael McCleod Taral Patel John T Hamm J Randolph Hecht Robert Mass Brent Perrou Betty Nelson William F Novotny 《Journal of clinical oncology》2005,23(16):3697-3705
PURPOSE: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan. PATIENTS AND METHODS: Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed. RESULTS: Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation. CONCLUSION: Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival. 相似文献
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Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness 总被引:1,自引:0,他引:1
J P Paskert M J Yaremchuk M A Randolph A J Weiland 《Journal of reconstructive microsurgery》1987,3(3):253-263
Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host. 相似文献
4.
To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation. 相似文献
5.
Cloacal exstrophy, centered on the maldevelopment of the primitive streak mesoderm and cloacal membrane, results in bladder and intestinal exstrophy, omphalocele, gender confusion, and hindgut deformity. The surgical management and outcome of 10 of 14 survivors (1965 to 1988) are described. Genotypic males (6) were assigned male (2) or female (4) phenotype. Genotypic females (4) were unchanged. All had omphalocele closure in the newborn period. Two had loop stomas. Eight had end stomas (ileostomy [6], ileocolostomy [2]). Toddler and adolescent reconstruction differed in each. Early in the study, abdominoperineal pull-through failed in four patients, necessitating permanent stoma. Four patients had a stoma from the outset. Augmentation using colon remnant improved water loss and nutrition in two infants. Exstrophy turn-in for urinary reservoir was considered in all, but was impossible in three who required urinary diversion. Six patients had exstrophy turn-in and now void by clean intermittent catheterization (4), continent vesicostomy (1), and incontinent (1). Hindgut augmentation improved urinary capacity in two. Two genotypic-phenotypic males had penile lengthening. Four genotypic male-phenotypic females had early orchiectomy with subsequent clitoroplasty or vaginoplasty. Four genotypic-phenotypic females had clitoroplasty or vaginoplasty. Cloacal exstrophy is compatible with a useful life and sound psychologic development, but requires staged reconstruction with long-term support and follow-up. 相似文献
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J. Randolph Swartz Ira M. Lesser Kyle B. Boone Bruce L. Miller Ismael Mena 《International journal of geriatric psychiatry》1995,10(6):437-446
Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both 133Xenon (133Xe) (47 subjects, 47–82 years old) and 99Tc-hexamethylpropyleneamine oxime (99Tc-HMPAO) (27 subjects, 47–80 years old). The 133Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The 99Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study. 相似文献
10.
Perceptions of Parenting and Depression-Proneness in the Offspring: Dysfunctional Attitudes as a Mediating Mechanism 总被引:2,自引:0,他引:2
This research attempted to clarifythe mechanismthrough which dysfunctional parenting leads todepression in the offspring. Consistent with theorizingbyBeck (1967), we tested a three-stage causal pathway wherein dysfunctional parenting should giverise to dysfunctional attitudes in the offspring which,in turn, should give rise to depression-proneness in theoffspring. Another objective of this study was to further delineate the types of parentingbehaviors that give rise to dysfunctional attitudes inthe offspring. To this end, a large sample of collegestudents (N = 246) completed measures assessing four parenting dimensions (i.e., low care,overprotection, perfectionistic expectations, andcriticalness) as well as measures assessingdysfunctional attitudes, general depression-proneness,and current depression. Support for the depressogenic effects of allfour parenting dimensions was obtained in that eachparenting dimension correlated significantly withdysfunctional attitudes and depression tendencies in the offspring. Moreover, path analyses supportedBeck's three-stage causal model with perfectionistic andcritical parenting playing a particularly prominentrole. Last, after controlling for current depression, the partial correlations among the variables inthe three-stage model remained significant, suggestingthat the present findings were not simply the result ofa mood congruency effect. These findings illuminate additional parenting behaviors that can havedepressogenic effects and indicate that these parentingbehaviors exert their effects, at least in part, by wayof instilling dysfunctional attitudes in the offspring. 相似文献