Publications

The past decade of research has brought us closer to an understanding of the mechanisms whereby alcohol promotes fibrosis in liver. The perivenular and perisinusoidal fibrosis that characterizes alcoholic cirrhosis suggests that it is a unique entity, distinct from other types of fibrotic liver disease. On a cellular level, though, the target population and the regulatory events that control fibrogenesis may be typical of all types of fibrotic liver disease. The putative pathways to alcoholic fibrosis are exemplified in Figure 1. Fibrosis can be either the direct result of a stimulus from ethanol or one of its metabolites to a target cell population, presumably the lipocytes, or it can begin indirectly in response to hepatic inflammation. The indirect pathway to hepatic fibrosis is likely to be initiated by cytokines, elaborated by inflammatory cells. In addition, invasion of the liver by inflammatory cells may disrupt the normal hepatic extracellular matrix, which may in itself act as a stimulus for fibrogenesis by altering critical cell-matrix interactions. If alteration of the normal hepatic matrix is sufficient to promote fibrogenesis, it may act as a fixed stimulus that perpetuates fibrogenesis in the absence of ongoing inflammation. This may explain the progression of alcoholic fibrosis in some patients in the apparent absence of alcoholic hepatitis. It has been gratifying to observe a consensus emerge among experimental observations regarding the process of alcoholic fibrosis. In particular, the discovery of transitional cells in fibrotic liver tissue, and their relationship to lipocytes, correlates well with studies documenting activation of lipocytes in culture to a fibrogenic phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired immunodeficiency syndrome (AIDS) surveillance data for both the United States and San Francisco indicate that Kaposi's sarcoma is more common in homosexual and bisexual men with AIDS than in other adults with AIDS, and that the proportion of newly diagnosed AIDS cases presenting with Kaposi's sarcoma has been significantly declining over time. The changing epidemiology of Kaposi's sarcoma was analyzed in a well-characterized cohort of homosexual and bisexual men; laboratory and interview data from a sample of these men were evaluated for determinants of and cofactors associated with Kaposi's sarcoma. Among 1,341 men with AIDS, the proportion presenting with Kaposi's sarcoma declined from 79% in 1981 to 25% in 1989. Compared with other men with AIDS, men with Kaposi's sarcoma had a shorter interval from human immunodeficiency virus (HIV) seroconversion to AIDS diagnosis (median, 77 vs. 86 months). Men with and without Kaposi's sarcoma did not significantly differ with respect to number of sexual partners, history of certain sexually transmitted or enteric diseases, use of certain recreational drugs (including nitrite inhalants), or participation in certain specific sexual practices. The decline in Kaposi's sarcoma may at least partly be due to a shorter latency period from infection to disease. Although cofactors for the development of Kaposi's sarcoma may exist, many previously hypothesized agents were not supported by this analysis.

In a study of occupational illness reported to a regional poison control center and to gauge the center's outreach and services, we did follow-up interviews of 301 case contacts over a 6-month period. We ascertained referral routes, reasons for contacting the poison control center, and awareness of the center's function. For 122 cases a nonphysician was the initial poison control center contact. Of the nonphysician contacts, 41 had already consulted a health care provider and been referred to the poison control center for assistance. Of the 70 persons with exposure, only 21 had been aware before their exposures that poison control center services might include occupational chemical illness consultation. Physicians and nonphysicians expressed similar reasons for contacting the poison control center, with 118 of 301 identifying the need for an exposure hazard risk assessment. These data suggest that although those contacting a poison control center because of occupational illness include a variety of cases, they have many similar service needs.

To evaluate trends in the length of survival for patients with acquired immunodeficiency syndrome, we calculated survival following diagnosis of acquired immunodeficiency syndrome for 4323 cases reported in San Francisco, Calif, between July 1981 and December 31, 1987. Patients were followed up prospectively through December 31, 1988. The median survival for all patients was 12.5 months, with a 5-year survival rate of 3.4%. Significantly improved survival was observed for patients diagnosed with Pneumocystis carinii pneumonia in 1986 and 1987. Survival for patients diagnosed with Kaposi's sarcoma declined significantly between 1981 and 1987. Survival was unchanged among patients diagnosed with other opportunistic infections or malignancies. Proportional hazards analyses indicated that initial diagnosis, age, and year of diagnosis were significant predictors of survival. For a subset of patients (n = 644), therapy with zidovudine was an additional significant predictor of survival. This study suggests that survival following diagnosis of acquired immunodeficiency syndrome has improved in recent years, primarily among patients with carinii pneumonia. Therapy with zidovudine may be partially responsible for these recent improvements.