How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

BDI-1-MT治疗膀胱癌及预防其术后复发的临床观察

目的　通过临床应用膀胱腔内灌注抗人膀胱癌免疫毒素 (BDI- 1-MT) ,观察治疗膀胱癌和预防膀胱癌术后复发的效果及毒副反应。方法　对 18例术后和 5例未手术的膀胱癌病人 ,膀胱腔内灌注BDI- 1-MT 1个疗程以上 ,观察疗效、复发情况及毒副反应。结果　术后 18例随访 6～ 2 0个月未见复发 ,未手术 5例随访 6～ 2 1个月 ,其中 3例显效 ,2例有效。所有病例均无明显毒副反应。结论　膀胱腔内灌注BDI- 1-MT治疗膀胱癌和预防膀胱癌术后复发有良好效果 ,是一种值得推广的新方法。     

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.     

顺铂、氟脲嘧啶、潘生丁(DFP)联合化疗治疗晚期食管癌—附125例不同给药剂量疗效分析

采用不同剂量DFP(DDP-5-FU-PST)联合化疗,随机分4组治疗晚期食管癌125例,CR18例,PR55例,MR26例,S12例,P14例,缓解率(CR+PR)58.4％(73/125例),总有效率(CR+PR+MR)79.2％(99/125例)。不同给药剂量疗效有所差别,以DDP分次剂量30～50mg/m~2,总剂量420～450mg;5-FU分次剂量750mg/m~2。总剂量15g疗效较好,缓解率60～83.33％。中数生存时间7.8月,1年生存率16％(20/125例)。108例(86.4％)有厌食、恶心、呕吐,24例(19.2％)白细胞和血小板减少,2例在用5-FU时出现心脏毒性,无肝肾功能损害。     

白云鄂博铁稀土共生矿矿工肺内钍沉积量及其对健康影响的研究

本文报道了白云矿矿工肺内天然钍沉积量及其对健康影响的10年(1982年～1991年)研究的结果。结果。本研究采用改进了的高灵敏度负高压静电收集氧子体装置,对该矿588名接尘矿工985人次和124名非钍尘作业人员的呼出气中作氧活度的测定，前者肺内钍的平均值为0.85Bp(23.06pCi)后者肺内钍的平均值为0.15Bp(4.05pCi).接尘矿工被检者中44.4Bq(120pCi)者5人;最高的1人为5.56Bp(150pCi),经修正最高值应为11.11Bp(300pCi)。     

骨痹通天丸抗炎镇痛免疫作用研究

实验动物口服骨痹通天丸5．58g／kg．2．79g／kg，观察本品对炎症反应，局部疼痛和免疫功能的影响。结果表明，骨痹通天丸的两个剂量组对大鼠蛋清性关节肿具有不同程度的抑制作用（P＜0．01或0．05）；对二甲苯性耳廓肿仅大剂量组具有明显抑制作用（P＜0．01）；对小鼠热刺激所致的疼痛反应具有不同程度的抑制作用（P＜0．01或0．05）；对化学刺性疼痛两个剂量组均有明显抑制作用（P＜0．01）；并可抑制小鼠重要免疫器官的增长和巨噬细胞的吞噬功能（P＜0．05），对血清溶血素未显示其效应。     

Pulmonary Function in Survivors of Wilms' Tumor

The respiratory status of 47 patients surviving childhood Wilms' tumor was studied. The group that had receivedflnnk irradiation (which impinges on the lower lung) (n - 17) had a sisnijGantly lower mean percent predicted for forced expiratory volume in one second, residual volume, and total lung capaci(v when compared to those who had received no irradiation (n - 23). Those patients who had received whole-lung irradiation (n - 3) had sisnijicantly lower transfn. foctor for carbon monoxide and gas transfer per unit lung volume whm compared to the nonirradiated group (n - 23). There was no sipiftiant dimue in the prevalence of respiratory symptoms between the three groups. Patients receiving any form of radiotherapy for Wilms' tumor may have abnormulities o f pulmonary function and should have pulmonary function tests performed as part o f their long-tmn follow-up.     

水飞蓟宾-磷脂酰胆碱复合物对小鼠急性肝损伤保护作用的量效关系

目的　观察不同剂量水飞蓟宾 -磷脂酰胆碱复合物 (SPC)对四氯化碳 (CCl4)所致小鼠急性肝损伤的影响。方法　雌性小鼠随机分组给药后测定血清中谷丙转氨酶 (ALT)和谷草转氨酶 (AST)活性 ,取肝组织作病理学检查。结果　不同剂量的水飞蓟宾 -磷脂酰胆碱复合物均可明显降低CCl4所致小鼠血清中ALT和AST活性升高 ,并与剂量呈正相关。SPC组肝组织变性、坏死的程度亦明显减轻 (P <0 .0 0 1,P<0 .0 1,P<0 .0 5 )。结论　SPC对CCl4所致小鼠急性肝损伤具有明显的保护作用 ,高、中、低剂量组间降酶作用呈明显的量效关系。