Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats.

(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct.     

某部队医院1999～2001年心血管药物应用分析

目的：了解某部队医院心血管类药物应用现状和发展趋势。方法：以限定日剂量法和消耗金额排序法对1999-2001年该院心血管类药物水泵品种和金额进行归类统计，分析该类药物用药情况。结果：该类药物费用上升较快；钙拮抗药，防治心绞痛药物和降压药等应用最多；临床应用以国产和合资生产品种为主。结论：该类药物费用增加很快，应注意合理用药。     

原发性卵巢平滑肌肉瘤临床分析(附3例报告及国内20例综合分析)

目的 探讨原发性卵巢平滑肌肉瘤的临床特点、诊断、治疗方法，以及可能预后相关因素。方法 对3例原发性卵巢平滑肌肉瘤综合国内近10年报道20例进行分析。结果 原发性卵巢平滑肌肉瘤可发生于任何年龄，主要为绝经后妇女。临床表现不典型，诊断主要依靠病理，同时结合免疫组化Desmin( )，Vimentin( )诊断。结论 原发性卵巢平滑肌肉瘤恶性度高，预后差，并且可能与分化程度及其微血管相关。治疗以手术为主，辅以合适的放疗和化疗综合治疗。     

瘤内注射重组人p53腺病毒治疗晚期肺癌临床试验观察

目的 观察重组人p53腺病毒注射液(rAd-p53)在晚期肺癌治疗中的疗效和毒副反应。方法 12例IIIb-IV期肺癌及3例肺转移癌,CT定位经皮肺穿刺瘤内注射rAd-p53,1 次/周×4/疗程;通过临床观察、CT及病理对照及短期随访进行评价。结果 治疗后2 月观察肿瘤缩小5例(33.3%),无变化7例(46.7%),增大3例(20%);治疗后病理观察:癌组织坏死,癌细胞稀少(6/11,54.5%);除自限性发热外,无明显毒副反应。结论rAd-p53瘤内注射治疗肺癌,无明显毒副作用,能较好地抑制局部肿瘤的发展,尤其对失去手术机会,不能耐受放化疗的患者,是一种可行的有前景的方法。     

Comparison between isotropic and nonisotropic dosimetry systems during intraperitoneal photodynamic therapy

BACKGROUND AND OBJECTIVE: On-line monitoring of light fluence during intraperitoneal photodynamic therapy (IP PDT) is crucial for safe light delivery. A flat photodiode-based dosimetry system is compared with an isotropic detector-based system in patients undergoing IP PDT. STUDY DESIGN/MATERIALS AND METHODS: Flat photodiodes and spherical detectors were placed side by side in the abdomen, for simultaneous light dosimetry in 19 patients. Tissue phantom experiments were performed to provide a preliminary estimate of the tissue optical properties of the peritoneum. RESULTS: The conversion factor between systems for 630-nm light was found to be 1.7 +/- 0.12. The mu(eff) of the tissues in the abdomen is estimated to vary between 0.5 cm(-1) to 1.4 cm(-1) assuming a mu(s)' = 7 cm(-1). CONCLUSIONS: The measured conversion factor should allow for comparison of light fluences with future clinical protocols that use an isotropic-based detector system. Differences in the optical properties of the underlying tissues may contribute to the variability in light measurements.     

凉血清营颗粒对Ⅰ型变态反应的影响

目的:研究凉血清营颗粒对Ⅰ型变态反应的影响.方法:用天花粉蛋白所致小鼠速发型超敏反应及大鼠同种异体被动超敏反应(PCA)观察对Ⅰ型变态反应的影响;用化合物48/80所致小鼠过敏性休克死亡及大鼠颅骨肥大细胞模型观察对肥大细胞脱颗粒的影响;用组织胺所致小鼠皮肤毛细血管通透性亢进试验观察对组织胺的直接对抗作用.结果:凉血清营颗粒能一定程度拮抗天花粉蛋白所致小鼠过敏性休克及大鼠PCA,并能明显抑制化合物48/80及天花粉蛋白所致腹腔或骨膜肥大细胞脱颗粒,还能明显对抗组织胺所致毛细血管通透性亢进.结论:凉血清营颗粒具有显著的抗Ⅰ型变态反应作用,此作用可能是其能抑制IgE生成、肥大细胞脱颗粒及直接拮抗组织胺作用的综合效果.     

防滑钢针及Y形酒精滴管在下肢骨牵引病人中的应用

为探讨自制防滑钢针及Y形酒精滴管在下肢骨牵引病人中的应用效果.选择需行下肢骨牵引的病人100例,随机分成实验组和对照组各50例.实验组采用自制防滑钢针及Y形酒精滴管;对照组采用传统钢针及酒精点滴.观察2组病人钢针滑动、压疮、针道感染情况.结果实验组钢针牵引滑动率显著低于对照组(P＜0.01).针道感染率明显低于对照组(P＜0.01).表明应用自制防滑钢针及Y形酒精滴管效果确切,经济实用,使用方便,可有效避免并发症的发生.     

Treatment of 116 cases of facial pigmented spots by auricular needle-embedding method

以耳穴子宫、神门、内分泌、肺为主穴,根据辨证选取配穴,埋针治疗面部色素斑患者116例,全部治愈.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的：研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应，并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较。方法：经病理确诊的晚期大肠癌83例分为以下两组：治疗组行奥沙利铂(oxalipatin)130mg／m^2静脉滴注，第1天给药：氟尿嘧啶(5-FU)425mg／m^2静脉滴注，第1-5天给药；亚叶酸钙(CF)100mg／m^2静脉滴注，第1～5天给药；每3周重复。对照组行氟尿嘧啶(5-FU)42h5mg／m^2静脉滴注,第1～5天给药；亚叶酸钙(CF)100mg／m^2。静脉滴注，第1-5天给药；每3周重复。每例患者至少完成两个周期。结果：治疗组有效率为46．5％，常见的毒性反应为神经毒性；对照组有效率为17．5％，与治疗组差别有统计学意义，未见神经毒性，其他毒性与治疗组无统计学差异。结论：奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好，毒副反应较轻，疗效高于氟尿嘧啶加亚叶酸钙方案。     

Ⅲb期宫颈癌的放射治疗并化疗疗效观察

目的:观察放射治疗并同期化疗Ⅲb期宫颈癌的疗效及不良反应.方法:对59例Ⅲb期宫颈癌患者随机分为放射治疗 化疗组(放、化组)和单纯放射治疗组(单放组).两组放疗方案相同,化疗与放疗同时进行.结果:近期有效率放、化组为100%,单放组为92.3%,两组无明显差异(P＞0.05);5年生存率放、化组为69.7%,单放组为42.3%,两组有显著差异(P＜0.05);恶心、呕吐消化道反应和白细胞降低率放、化组较单放组明显高(P＜0.01 P＜0.05),放射性直肠炎、膀胱炎两组无差异(P＞0.05);远处转移率单放组明显高(P＜0.05).结论:放射治疗同时化疗可提高局部控制率及5年生存率,减少远处转移率.不良反应经对症治疗后,症状减轻或消失.