Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2001
ReviewBeyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention.
Although tamoxifen appears to markedly reduce breast cancer risk in women with a prior diagnosis of atypical hyperplasia or in situ carcinoma, it is not clear what other groups of women receive substantial benefit. Major breast chemoprevention priorities are to (1) develop new agents that (a) have fewer side effects, (b) are effective in ER--as well as tamoxifen-resistant precancerous tissue, and (c) are compatible with hormone therapy; and (2) develop efficient clinical strategies including prognostic and predictive morphologic and molecular biomarkers. Breast tissue may be repeatedly sampled for evidence of intraepithelial neoplasia by fine needle aspiration, ductal lavage, or needle biopsy to select candidates at highest short-term risk as well as to monitor response in small proof of principle studies prior to a large cancer incidence trial. ⋯ Retinoids, rexinoids, and deltanoids may be efficacious in ER+ tissue resistant to tamoxifen. Agents which should theoretically have activity in ER- or ER+ precancerous tissue include polyamine synthesis inhibitors, tyrosine kinase inhibitors, combined demethylating agents and histone deacetylase inhibitors, as well as metalloprotease and angiogenesis inhibitors. Sample Phase I and Phase II clinical trial designs are reviewed using modulation of molecular markers and breast intraepithelial neoplasia as the major endpoints.
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West Nile virus, first isolated in 1937, is among the earliest arthropod-borne viruses discovered by humans. Its broad geographical distribution, not uncommon infection of humans, transmission by mosquitoes, and association with wild birds as enzootic hosts were well documented by the mid-1960s. However, West Nile virus was not considered to be a significant human pathogen because most infections appeared to result in asymptomatic or only mild febrile disease. ⋯ In addition the epidemic in the northeastern United States was unusual in the association of West Nile virus infection with fatal disease of birds, suggesting a change in the virulence of the virus toward this host. Understanding the risk factors that contributed to these three urban epidemics is important for minimizing the potential for future occurrences. This review will attempt to compare observations on the biology of West Nile virus made over about 60 years prior to the recent epidemics to observations made in association with these urban epidemics.
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Ann. N. Y. Acad. Sci. · Dec 2001
Historical ArticleSpecific features of the spread of tuberculosis in Russia at the end of the 20th century.
This study shows the dynamics of the epidemiological process over the last decade and presents the causes of the deterioration in TB control. Explanations are given for the TB mortality rate increase, the trustworthiness of the data, and the factors influencing its formation. The present-day TB epidemiological situation in Russia is characterized by an increase in exogenous infection. ⋯ In the 1990s this trend has changed. TB infection spreads according to trends that are quite similar to those at the beginning of 20th century. The official TB morbidity rate does not reflect the true level of incidence because of undetected TB cases (approx. 10%).
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Ann. N. Y. Acad. Sci. · Dec 2001
Review Multicenter StudyEarly lung cancer action project: annual screening using single-slice helical CT.
The advent of helical CT imaging held promise for the early diagnosis, and thereby, for enhanced curability of lung cancer--a highly fatal disease. In 1993, the Early Lung Cancer Action Project (ELCAP) was initiated and experimentally screened a cohort of 1,000 high-risk persons. ⋯ CT-based screening (compared to traditional radiology) was clearly shown to enhance the detection of lung cancer at earlier and more curable stages. A discussion follows of the meaning of the results and possible future screening protocols.
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Ann. N. Y. Acad. Sci. · Dec 2001
ReviewProduct liability forecasting for asbestos-related personal injury claims: a multidisciplinary approach.
This paper focuses on three aspects of forecasting models for asbestos-related disease/injuries relating to the Manville asbestos case: (1) The structure of forecasting models for asbestos-related personal injuries. (2) The epidemiologic evidence supporting the selected model structure and the constraints on the modeling assumptions imposed by that evidence. (3) The range of uncertainty associated with projections based on these forecasting models and issues relating to decision making under uncertainty.