We carried out a randomized study of 49 consecutive patients with unresectable primary lung cancer to determine whether clarithromycin (CAM), a 14-membered ring macrolide, can improve outcome. A total of 49 patients (42 patients with non-small-cell lung cancer and 7 patients with small-cell lung cancer) had received prior chemotherapy, radiotherapy or both during their hospital stay. They were randomly allocated into two study groups on the first visit after discharge: 25 patients (22 patients with non-small-cell lung cancer, 3 patients with small-cell lung cancer) were assigned to receive CAM (400 mg/day, orally), and 24 patiens (20 patients with non-small-cell lung cancer, 4 patients with small-cell lung cancer) did not receive CAM. CAM treatment after randomization was open and the treatment was to be continued as long as the patients could tolerate CAM. There was no significant difference in the median survival time for small-cell lung cancer between the CAM group and the non-CAM group. However, CAM treatment significantly increased the median survival time for non-small-cell lung cancer patients, the median survival for the CAM group was 535 days and that for the non-CAM group was 277 days. Analyses of prognostic factors showed that only treatment with CAM was predictive of longer survival for non-small-cell lung cancer, and other tested covariates had no effects on the prognosis. There were no remarkable side effects observed in the CAM group throughout treatment. We conclude that long-term treatment using CAM is beneficial for unresectable non-small-cell lung cancer patiens and that it can increase the median survival of patients with advanced disease.

Wistar Hannover rats, which have recently been introduced into Japan, are expected to be used in reproductive and developmental toxicity studies, yet the accumulation of background data is insufficient. This paper describes our historical data on the reproductive ability of this strain of rat. Three lots of sexually matured females (40 each) were received from CLEA JAPAN, Inc. with males of the same strain (30 or 36 each) and mated. A total of 47 dams were killed on gestation day 20 to examine their fetuses. The remaining 71 pregnant females were allowed to deliver spontaneously and observed for common reproductive parameters. The mating and fertility indices of females were both 99.2%. Overall mean numbers of implants and live fetuses at cesarean sectioning were 12.5 and 11.5, respectively. Fetal resorptions and deaths occurred at an incidence of 8.6%. Morphological examinations of fetuses revealed low incidences of spontaneous malformations (each one case of double aortic arch and absent cervical vertebral arch) and a variety of common variations. The followings are overall means of major reproductive parameters obtained from females with live birth: no. of implants, 12.5; no. of pups delivered, 11.8; viability index of pups at birth, 99.8%; and days of age at sexual maturation (vaginal opening and preputial separation), 30.3 and 42.8, respectively. Our present observations confirmed a minimal deviation among 3 lots of animals in terms of reproductive abilities. These results suggest that this strain of rat can be used in reproductive and developmental toxicity studies, although the sensitivity to toxicants remains to be elucidated.

No abstract

No abstract

-A two-generation reproductive toxicity study was conducted with 2,4-dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting effects. Wistar-Hannover rats, 24/sex/ group, were given diet containing 2,4-DCP at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of the test substance on parental animals and their offspring over 2 successive generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and food consumption of females were lowered significantly during the treatment period. Effects on body weights and food consumption were more serious in the 8000 ppm group, both males and females being significantly affected. Reproductive effects of the test substance were also observed in the 2000 and 8000 ppm groups dose-dependently. Observations included significantly increased uterine weights of F1 and/or F2 female weanlings and reduced numbers of implantation sites and live births of F1 parental females. These results suggest that 2,4-DCP has weak reproductive toxicity, possibly based on endocrine activity. However, the basic mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.