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31.
Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer. 总被引:1,自引:0,他引:1
Cynthia X Ma Suresh Nair Sachdev Thomas Sumithra J Mandrekar Daniel A Nikcevich Kendrith M Rowland Tom R Fitch Harold E Windschitl Shauna L Hillman Steven E Schild James R Jett Coleman Obasaju Alex A Adjei 《Journal of clinical oncology》2005,23(25):5929-5937
PURPOSE: A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-na?ve patients with non-small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8. RESULTS: One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms. CONCLUSION: Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated. 相似文献
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33.
Reduction by the gut microflora of animals and man 总被引:2,自引:0,他引:2
I R Rowland 《Biochemical pharmacology》1986,35(1):27-32
34.
The dopamine (DA2) agonist, quinpirole hydrochloride (LY 171555), has been reported to inhibit central presynaptic release of norepinephrine, an effect similar to that of clonidine, an alpha 2-adrenoceptor agonist. Since clonidine exerts an antidipsogenic effect on all types of laboratory-induced drinking, the objective of these experiments was to determine whether administration of quinpirole hydrochloride produced a similar effect. The drinking responses of rats to administration of angiotensin II (200 micrograms/kg, SC), isoproterenol (25 micrograms/kg, SC), and hypertonic saline (1 M NaCl, 1% of body weight, IP) were blocked by administration of quinpirole hydrochloride (7.5 mg/kg, IP). When administered alone, quinpirole had no effect on water intake. Thus, the antidipsogenic effect of quinpirole hydrochloride resembles that of clonidine and suggests that release of norepinephrine occurs centrally at some point along the final common pathway for drinking in rats. 相似文献
35.
During a 20-month period, fractures of the clivus occurring after craniocerebral trauma were diagnosed with computed tomography (CT) in 11 patients. Five patients had longitudinally oriented fractures; these were fatal in four patients due to either vertebral-basilar artery occlusion, brain stem trauma, or both. Six other patients had transversely oriented fractures that extended through the carotid canal and petrous temporal bone. While less frequently contributing directly to mortality, transverse fractures were also associated with cerebrospinal fluid leaks (two patients) and a cavernous sinus-carotid fistula (one patient). They were not as frequently associated with Horner syndrome or cranial nerve deficits as suggested in the current literature. This retrospective evaluation reveals two distinct injury patterns that demonstrate a difference in related morbidity and mortality. 相似文献
36.
Eccentric ballooning of the distal esophagus was observed radiographically in 11 of 23 patients (48%) who underwent Heller myotomy for achalasia. While, to the authors' knowledge, ballooning at the site of myotomy incision has not been described previously in the radiologic literature, it should be recognized as a normal and frequent postoperative finding. Radiologists should be aware of this finding so that it is not mistaken for postoperative abnormalities following esophagomyotomy or an epiphrenic diverticulum. 相似文献
37.
38.
Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis 总被引:20,自引:0,他引:20
To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis. 相似文献
39.
40.
John S. Fallick M.D. David R. Farley M.D. Michael B. Farnell M.D. Duane M. Ilstrup M.S. Charles M. Rowland M.S. 《Journal of gastrointestinal surgery》1999,3(2):156-161
The utility of placing biliary, pancreatic, or enteric "venting"tubes (externally draining devices traversing the bowel or
bile duct that have their distal tip located intraluminally near the biliary or pancreatic anastomosis) when performing a
pancreaticoduodenectomy has received little attention to date. We hypothesize that these venting tubes do not decrease the
morbidity or mortality associated with pancreatico-duodenectomy and may actually be a source of additional morbidity. To characterize
our use of and the effect of these drains, we retrospectively analyzed 136 pancreaticoduodenectomies (127 partial, 9 total)
performed over a 24-month period. Venting drain use, drain type and size, drain location, duration of intubation, hospital
course, and postoperative complications were noted. Venting tubes were used in 80 patients (59%). The use of these drains
had no significant relationship to postoperative length of stay, the development of major complications, overall morbidity,
or mortality (P >0.05). Such drains also did not significantly shorten the length of hospital stay (P >0.05) or improve outcome when available to augment local control following luminal leak (n = 6) or regional abscess (n =
7). These drains were removed at a median interval of 29 days postoperatively (range 6 to 77 days). Seven patients had complications
that were directly related to the venting drain; four of these patients had a documented infra-abdominal luminal leak from
the site of drain removal, whereas the other three were hospitalized for presumed leakage secondary to immediate, severe abdominal
pain following removal of the drain. These seven patients were elderly (mean age 70 years) and often harbored pancreatic ductal
carcinoma (n = 6). Intraluminal drains afford no distinct advantage in terms of shortening the postoperative length of stay,
decreasing operative morbidity and mortality, or improving local control with regional sepsis in pancreaticoduodenectomies.
Furthermore, they may add an additional source of morbidity and we no longer employ them routinely. 相似文献