A semi-quantitative direct contact assay using fluorescein diacetate and L929 mouse fibroblasts in monolayer culture

Summary A semi-quantitative procedure is described for measuring cell viability after short-term exposure to a test substance using a monolayer culture. Test substances are placed in direct contact with cell monolayers for various time intervals. The substances are removed and the monolayers are incubated in the presence of fluorescein diacetate. Monolayers are viewed under a fluorescent microscope and the percentage of fluorescing (viable) cells is estimated. The method is suitable for examining cytotoxic effects at short times of exposure and for discriminating between test substances that give similar, low toxicity endpoints in standard 24-h assays.     

Cisplatin-associated anaemia in patients with solid tumours

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatincontaining regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.     

脂蛋白（a）对肾小球系膜细胞的作用

目的探讨脂蛋白（ａ）［Ｌｐ（ａ）］对肾小球系膜细胞（ＧＭＣ）的作用。方法将体外培养的系膜细胞，加脂蛋白（ａ）刺激后，测定细胞生长率和细胞上清中血小板活化因子（ＰＡＦ）、肿瘤坏死因子（ＴＮＦ）、乳酸脱氢酶（ＬＤＨ）及纤维连结蛋白（ＦＮ）水平，并以未经刺激者作对照。结果经脂蛋白（ａ）刺激４８小时，在终浓度５～２０ｍｇ／Ｌ时细胞生长率轻度增加，而在５０～４００ｍｇ／Ｌ时细胞生长率明显下降。刺激１８小时，细胞上清中ＰＡＦ的水平明显高于对照，且与脂蛋白（ａ）浓度呈明显正相关（ｒ＝０．９３７，Ｐ＜０．０１）；Ｌ９２９细胞的杀伤率有所增加，但未达５０％；ＬＤＨ的水平在脂蛋白（ａ）１００ｍｇ／Ｌ以下时有所增加；刺激１８、４８、７２小时后的细胞上清纤维连结蛋白均为阴性。结论脂蛋白（ａ）对系膜细胞体外增殖有低浓度轻度促进、高浓度抑制的双向作用，对细胞ＰＡＦ的产生具有浓度依赖的促进作用，并能增加细胞上清中ＬＤＨ及ＴＮＦ水平，因而可通过多种途径介导肾小球损伤。     

补肾中药对雄激素致不孕大鼠卵巢核仁组成区蛋白的影响

观察补肾中药对雄激素致不孕大鼠卵巢核仁组成区蛋白的影响。用ＳＤ雌性大鼠幼仔，出生９ｄ龄注射丙酸睾丸酮，制成雄激素致不孕大鼠（ＡＳＲ）模型。８０ｄ龄灌服补肾中药水溶液两周。１００ｄ龄心脏灌注处死。以核仁组成区蛋白嗜银染色（ＡｇＮＯＲ）和增殖细胞核杭原（ＰｃＮＡ）为指标，观察卵巢颗粒细胞、间质腺细胞的形态学变化。结果：补肾中药能够使ＡＳＲ卵巢颗粒细胞增殖、卵泡发育。治疗组的ＡｇＮＯＲ和ＰｃＮＡ计数明显高于模型组，而与对照组之间无显著差异。结论：补肾中药的这种作用可能是通过调节了下丘脑－垂体－卵巢性腺功能的结果，从而促使卵巢颗粒细胞发育、卵泡成熟。     

Respiratory health status in swine producers using respiratory protective devices

A cross-sectional survey on respiratory health in swine producers showed that 30% of 301 examined men usually used a dust mask when working inside a barn. They did not differ significantly from dust mask nonusers in respect to respiratory symptoms and lung function. This analysis was undertaken to determine whether the respiratory health of dust mask users was associated with reasons why they had started individual respiratory protection. The subjects were recontacted in order to identify those who started using a mask to deliberately prevent symptoms (42 men) and those who started protection because of pre-existing respiratory symptoms (44 men). Not unexpectedly, betweengroup comparisons of respiratory symptoms and lung function suggest that swine producers who wear dust masks for preventive purposes have better respiratory health than those who wear dust masks because of symptoms or those who do not use individual respiratory protection. The individual reasons for starting dust mask usage should be examined among potential determinants of the outcomes of prospective studies which can then provide more valid assessment of the effect of individual respiratory protection. © 1993 Wiley-Liss, Inc.     

白炭黑粉尘对肺脏的作用

大鼠气管注入(剂量50mg)或自然吸入白炭黑粉尘,引起肺组织以细胞性结节为主的病理改变。注入组的肺重、肺胶原蛋白及类脂的含量均显著地高于正常对照组,但比石英对照组低得多。说明白炭黑粉尘对肺脏的作用表现为非特异性反应性改变。应重视它的远期作用,做好白炭黑生产和使用部门的劳动保护工作。     

激素敏感型肾病单个核细胞培养上清液对大鼠肾小球多阴离子及超微结构的影响

用刀豆蛋白Ａ刺激激素敏感型肾病单个核细胞，并将其培养上清液灌注于大鼠肾内。结合电镜观察，用图像分析仪及体视学方法分别对其肾组织胶体铁染色切片和电镜照片上的足突和滤过裂隙的平均宽度进行测定。结果表明：该病极期上清液灌注的鼠肾小球多阴离子明显减少，足突肿胀、融合，滤过裂隙变窄；而该病缓解组和正常对照组则为阴性。说明该病单个核细胞培养上清液可引起鼠肾小球微小病变型肾病综合征的病变，并揭示该变化可能是由其上清液中一种异常的Ｔ淋巴细胞因子所致。     

Phase II trial of piroxantrone in metastatic breast cancer

Summary Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m² intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m². We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

Phase I/II trial of dipyridamole, 5-fluorouracil,leukovorin, and mitoxantrone in metastatic breast cancer

Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m² by mouth every 6 h (700 mg/m²/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m² was given intravenously immediately prior to 5-FU 375 mg/ m² intravenously on days 1–5. Mitoxantrone 6 mg/m² was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m² days 1–2, 5-FU 375 mg/m² days 1–2, mitoxantrone 6 mg/m² on day 2, and dipyridamole 175 mg/m² every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.