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排序方式: 共有6973条查询结果,搜索用时 15 毫秒
91.
Teresa Pekol J Scott Daniels Jason Labutti Ian Parsons Darrell Nix Elizabeth Baronas Frank Hsieh Liang-Shang Gan Gerald Miwa 《Drug metabolism and disposition》2005,33(6):771-777
Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore. 相似文献
92.
Klein SM Slaughter TF Vail PT Ginsberg B El-Moalem HE Alexander R D'Ercole F Greengrass RA Perumal TT Welsby I Gan TJ 《Anesthesia and analgesia》2000,91(5):1091-1095
Low molecular weight heparin (LMWH) is commonly used to prevent postoperative thromboembolism. Currently, there is no convenient test to measure the degree of anticoagulation from LMWH. This prospective study examines the relationship of thromboelastography and serum anti-Xa concentration in patients treated with enoxaparin. Twenty-four adult patients scheduled for orthopedic surgery using epidural anesthesia were enrolled. Epidural catheters were removed the morning after surgery before the commencement of subcutaneous enoxaparin 30 mg twice daily. Venous blood samples were obtained at 1) the induction of anesthesia (baseline), 2) immediately before the third dose of enoxaparin postoperatively (Day 2-trough), 3) 4 h after the third dose postoperatively (Day 2-peak), and 4) immediately before the fifth dose postoperatively (Day 3-trough). Whole blood samples were obtained for thromboelastography, activated clotting time, and anti-Xa level analyses at each of the four time intervals. At the four sample intervals, the r time (mean +/- SEM). (20 +/- 1, 25 +/- 2, 51 +/- 6, 31 +/- 3 mm) and the k time (9 +/- 0. 7, 12 +/- 1, 27 +/- 5, 14 +/- 2 mm) of the thromboelastograph were significantly correlated with the expected peak and trough levels of LMWH and serum anti-Xa levels (P: < 0.05). At the Day 3-trough, thromboelastograph r times exceeded the normal range in 6 of 25 patients (25%). Prolongation of r time and k time on postoperative Day 3 may indicate an exaggerated response to LMWH. Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. Implications: Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. The r time from the thromboelastogram correlates with serum anti-Xa concentration. 相似文献
93.
Nausea or vomiting occurs frequently after craniotomy. Because of the need for frequent postoperative neurological assessment, an effective antiemetic with minimal sedative side effects is needed. Therefore, we compared ondansetron to droperidol in a randomized, double-blinded, placebo-controlled study. A total of 60 adults requiring elective supratentorial craniotomy received standardized IV anesthesia with 4 mg of ondansetron, 0.625 mg of droperidol, or placebo at skin closure. The incidence of postoperative nausea, emesis, pain and sedation scores, and rescue antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 h. All groups were demographically similar. Differences existed for cumulative 8, 12, and 24 h incidences of nausea (24 h, P = 0.03) and emesis (24 h, P = 0.04). Within 4 h, when maximal effect could be expected from treatment, 20% of the ondansetron group, 25% of the droperidol group and 50% of the placebo group received rescue antiemetic (P = 0.12). No differences in pain (P = 0.82) or sedation (P = 0.74) scores were detected. Both ondansetron and droperidol prevent nausea; however, only droperidol reduces emesis after supratentorial craniotomy. The dose of droperidol used was not more sedating than ondansetron. Sustained reduction in nausea and emesis over 24 h indicates a preemptive benefit of prophylactic antiemetic in this surgical population. Implications: Nausea and vomiting after brain surgery are particularly troubling, because effective treatment may cause sedation, making postoperative neurological assessment difficult. Our study shows that both ondansetron and droperidol are effective in reducing nausea, and that droperidol is particularly effective in reducing vomiting. Neither drug caused more sedation than placebo. 相似文献
94.
目的:探讨准分子激光上皮瓣下角膜磨镶术(laserepithelialkeratomileusis,LASEK)手术并发症的类型、产生原因及处理方法。方法:应用LASEK治疗等效球镜为-7.25~14.50D的高度近视眼53例(106眼),对术中和术后产生的并发症进行相关原因分析。结果:LASEK术中并发症主要有上皮瓣剥离困难、破碎、游离、皱褶、局限性缺损等,术后并发症主要有角膜上皮下雾状混浊(Haze)、最佳矫正视力下降、屈光度回退、眩光、上皮瓣溶解等。结论:严格掌握LASEK的手术适应证,熟练掌握手术技巧和正确处理角膜上皮瓣的各种并发症是保证LASEK成功的关键。 相似文献
95.
Suresight手持验光仪在儿童屈光检查的应用 总被引:27,自引:3,他引:27
目的探讨Suresight手持自动验光仪应用于儿童验光的准确性及其特点,为儿童屈光普查和流行病学调查寻找简便可行的验光方法.方法对89例患者(178眼),分别用Suresight手持验光仪进行自然状况下和使用阿托品后验光及散瞳检影验光.结果儿童屈光不正种类以远视性屈光不正为主(82.0%).Suresight手持验光仪与散瞳检影验光相比较,球镜度数:使用阿托品后手持验光仪与散瞳检影法检出的结果呈高度正相关(r=0.890);自然状况下手持验光仪与散瞳检影法检出的结果亦有相关性(r=0.591.).柱镜度数:使用阿托品散瞳后手持验光仪与检影法检出的结果呈高度正相关(r=0.950),自然状况下手持验光仪与散瞳检影法检出的结果亦呈高度正相关(r=0.910).手持验光仪比检影验光法散光的检出率高,但主要是≤0.75D的低度散光.柱镜轴向:手持验光仪在睫状肌麻痹状态下与视网膜检影法测定结果比较,轴向差值≤10°者占81.3%,自然状况下与视网膜检影法比较,轴向差值≤10°者占82.7%.结论Suresight手持验光仪对屈光普查和流行病学调查有较好的使用价值. 相似文献
96.
97.
当转型后手中的权力即将随着医院剥离、重组而付之东流,能否做到泰山崩于前而不为所动?当新东家的到来将让你在所有同僚面前扬眉吐气,是否还能义正词严地拒绝他们的光荣策反?当进和退都意味着遭遇深渊,如何选择两种死亡中的任何一项必然?医院转型、重组、剥离对谁来说都不是一件轻松的事。在利益和权力的角逐中,有沧海横流的英雄本色,更有勾心斗角的人心真实…… 相似文献
98.
浅析我国台湾地区药害救济法及制度借鉴 总被引:6,自引:1,他引:6
目的 借鉴我国台湾地区的药害救济制度,探索我国大陆的药害救济制度.方法 详细解析我国台湾地区的药害救济法的立法背景、目的以及药害救济法的具体内容.结果与结论 这种制度对于我国大陆医药制度的改革和发展具有一定的借鉴和参照的价值. 相似文献
99.
目的评价体外循环降温期不同的氧分压对二尖瓣置换患者术后的影响。方法75例二尖瓣置换术患者,按体外循环降温末期动脉血氧分压数,分成低氧组、常氧组和高氧组,记录体外循环结束后第1、8、16小时多巴胺用量。术后麻醉清醒时间和呼吸机辅助时间,同时记录患者的年龄、体重、体外循环时间、升主动脉阻断时间和左室射血分数。结果体外循环术后第1小时内,常氧组多巴胺用量明显小于低氧组和高氧组(P〈O.05),术后第8小时,常氧组多巴胺用量明显小于低氧组(P〈O.05)。术后麻醉清醒时间和呼吸机辅助时问各组问无显著性差异。结论二尖瓣置换术体外循环降温期,常氧分压氧合有利于术后早期患者心功能恢复。 相似文献
100.
Kapoor L Gan MD Bandyhopadhyay A Das MB Chatterjee S 《The Annals of thoracic surgery》2000,69(1):291-292
We describe an alternative step in the transatrial approach to the repair of ventricular septal defects. We temporarily detach the chorda of the obscuring tricuspid valve from its attachment to the septum to expose the ventricular septal defect. 相似文献