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Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1‘-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1‘-NHhexyl lead compound were prepared and evaluated against L. major in macrophage culture to further develop structure−activity relationships (SAR). Toxicity toward mammalian cells was measured in a human leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe2 substitution pattern on the acridine greatly increased toxicity to L. major without altering mammalian toxicity, increasing IVTIs over that of the lead compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial drug mepacrine also resulted in potent antileishmanial activity and high IVTIs. Earlier suggestions of the utility of 2‘-OR groups in lowering mammalian cytotoxicity were not borne out in this wider study. A series of very lipophilic 1‘-NRR (symmetric dialkylamino)-substituted analogues showed relatively high antileishmanial potency, but no clear trend was apparent across the series, and none were superior to the 1‘-NH(CH2)5Me subclass. Subsets of the most active 1‘-N(R)(CH2)5Me- and 1‘-N(alkyl)2-substituted compounds against L. major were also evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, but no consistent SAR could be discerned in these physiologically diverse test systems. The present study has confirmed earlier conclusions that lipophilic electron-donating groups at the 1‘-position of 9-anilinoacridines provide high activity against L. major, but the SAR patterns observed do not carry over to the other parasites studied.

Mortality among 306 Roman Catholic sisters (nuns) from Mankato, Minnesota, was assessed during the period 1936-1988; daily use of nursing services by survivors was determined in 1986; and the ability of survivors to eat, dress, and perform other self-care activities was evaluated in 1987. The median age at death was 89.4 years for sisters with educational attainment of a bachelor's degree or higher, 82.2 years for sisters with some high school or college education, and 82.0 years for sisters with only a grade school education. Odds ratios were calculated for "survival and independence" (i.e., sisters survived to 1986 (ages 75-94 years) and did not use daily nursing services at that time). These odds ratios were 2.67 (95% confidence interval (CI) 1.16-6.16) for sisters with a bachelor's degree or higher, 1.00 for the reference group with some high school or college, and 0.94 (95% CI 0.32-2.73) for sisters with only grade school. Sisters with a bachelor's degree or higher were also more likely than others to survive to old age while maintaining their ability to perform self-care activities. These findings suggest that college graduates lived longer and maintained their ability to care for themselves longer than other persons.

Findings described in this report are for 6,763 white male Seventh-day Adventists who completed a dietary questionnaire in 1960. Between 1960 and 1980 mortality data were collected on cohort members. Overweight men had a significantly higher risk of fatal prostate cancer than men near their desirable weight. The predicted relative risk of fatal prostate cancer was 2.5 for overweight men. Suggestive positive associations were also seen between fatal prostate cancer and the consumption of milk, cheese, eggs, and meat. There was an orderly dose-response between each of the four animal products and risk. The predicted relative risk of fatal prostate cancer was 3.6 for those who heavily consumed all four animal products. The results of this study and others suggest that animal product consumption and obesity may be risk factors for fatal prostate cancer.

This report examines the association between mortality from all causes during a 21-year period and frequency of consumption of 28 specific foods among 27,530 adult California members of the Seventh-Day Adventist Church. Food consumption was measured at the beginning of the study (1960) by a self-administered questionnaire. Deaths were identified by computer-assisted matching of study subjects to the file of death certificates for all deaths that occurred in California during 1960-1980. All-cause mortality showed a significant negative association with green salad consumption and a significant positive association with consumption of eggs and meat. For green salad and eggs, the association was stronger for women; for meat, the association was stronger for men. All the observed associations were adjusted for age, sex, smoking history, history of major chronic disease, and age at initial exposure to the Adventist Church.