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Biomedical subjects

F K Ennever

Publications and source records attributed to F K Ennever.

At least 19 recordsLinked to original sources
PubMed1998

Cryptosporidium in tap water: comparison of predicted risks with observed levels of disease.

Waterborne transmission of Cryptosporidium parvum is well-established as a source in outbreaks of cryptosporidiosis; however, the role of tap water in endemic disease is unclear. The authors applied a risk assessment approach incorporating uncertainty analysis to examine the potential role of tap water in the transmission of endemic C. parvum infection. The model had two components: exposure-infection, to relate low-dose exposure to infection; and infection-outcome, to include the probabilities of clinical outcomes leading to case detection and reporting. The population was divided into four subgroups: adults and children with and without acquired immunodeficiency syndrome (AIDS). Because of the high degree of uncertainty associated with available measures, a plausible baseline concentration of oocysts, 1 per 1,000 liters, was assumed for input to the model. In the non-AIDS subgroups, the predicted median annual risk of infection was approximately 1 in 1,000 (non-AIDS adults: 0.0009 infection/person/year, 95% confidence interval (CI) 0.0003-0.0028), while in the AIDS subgroups the predicted risk was 2 in 1,000 (AIDS adults: 0.0019 infection/person/year, 95% CI 0.0003-0.0130). When the risks were applied to the 1995 New York City population, more than 6,000 infections were estimated, with 99% occurring in the non-AIDS categories. Estimates of the overall probabilities that an infection would result in a reported case predicted that three reported illnesses would occur out of every 10,000 infections in non-AIDS adults (95% CI 5 x 10[-5] to 2 x 10[-3]), with a 10-fold higher probability in the non-AIDS pediatric subgroup. In contrast, the majority of infections occurring in the AIDS subgroup were predicted to result in reported cases (AIDS adults: probability = 0.61, 95% CI 0.39-0.80). When the model was applied to the New York City population, the calculated number of tap-water-related cases per year in the non-AIDS subgroups was six (95% CI 1-29), and in the AIDS subgroups it was 34 (95% CI 6-240).

Acquired Immunodeficiency Syndrome↗
PubMed1995

Parent preferences and prenatal testing for neural tube defects.

Previous analyses of prenatal screening for neural tube defects have generally found benefits to exceed costs. The usual screening battery follows an elevated maternal serum alpha-fetoprotein level with high-resolution ultrasound and/or amniocentesis. Current thinking focuses on weighing the risk of a false-negative (an abnormality missed) against the risk of an amniocentesis-induced fetal loss. This thinking neglects the risk of a false-positive (an unaffected fetus labeled abnormal) and individual parents' preferences concerning a false-negative vs a fetal loss. With these risks included, we find that high-resolution ultrasound is appropriate for all women with elevated serum alpha-fetoprotein. Women with moderately elevated serum alpha-fetoprotein who have negative ultrasound scans need no further testing, nor do women with highly elevated serum alpha-fetoprotein and positive ultrasound scans. Further testing using amniocentesis to confirm the ultrasound result is appropriate for women with moderately elevated serum alpha-fetoprotein and positive ultrasound scans, and for women with highly elevated serum alpha-fetoprotein and negative ultrasound scans. The actual cutoffs defining normal, moderately elevated, and highly elevated serum alpha-fetoprotein depend on several parameters, particularly the underlying prevalence of neural tube defects and the parents' preferences.

Cost-Benefit Analysis↗
PubMed1995

Blood lead levels in North Carolina painters.

1. Blood lead levels were examined in 127 housepainters in North Carolina between April and September, 1993. Each participant filled out a questionnaire and gave a blood sample. The questionnaire covered the individual's work history, concentrating on paint-removal activities and personal protection, and also covered potential nonoccupational sources of lead exposure. Blood samples were analysed for lead content using atomic absorption spectroscopy. 2. The geometric mean blood lead level was 0.33 mumol L-1 (6.8 micrograms dL-1). No blood lead samples were found to exceed the occupational standard of 1.93 mumol L-1 (40 micrograms dL-1). The three highest samples had levels between 0.97 and 1.45 mumol L-1 (20 and 30 micrograms dL-1); this represented 2.4% of the study sample. 3. No statistical association was found between blood lead levels in these painters and their painting activities, including using dust masks for personal protection. 4. Current painting practices in this group of North Carolina painters do not appear to elevate blood lead levels above the occupational standard.

Adolescent↗
PubMed1992

Response of the ke test to NCI/NTP-screened chemicals. III. Complementary value of ke in screening for carcinogens.

The value of using a physico-chemical carcinogen-screening test, the ke test, in conjunction with the Salmonella typhimurium/microsome assay (the Ames test) and/or structural alerts of reactivity (the S/A test), is analyzed on the basis of the response of the three tests to 171 chemicals of known rodent carcinogenicity. The Ames test is widely used to screen chemicals for potential carcinogenicity; however, its relatively low sensitivity (proportion of true positives among carcinogens tested) has prompted a search for complementary tests that increase sensitivity without an unacceptable decrease in specificity (proportion of true negatives among non-carcinogens tested). The S/A test is a structural analysis based on recognition of chemicals groups likely to react with DNA. The S/A test does not complement the Ames test well, because of the high similarity of responses (dependence) between these two tests. The ke test measures the affinity of a test chemical for electrons, and has a sensitivity and specificity comparable to the Ames test. The ke test is shown in this work to complement both the Ames test and the S/A test. Addition of the ke test to either the Ames test or the S/A test results in a substantial decrease in false negatives and an approximately equal increase in false positives, which is a trade-off that would be desirable in all but the least risk averse situations. The S/A and ke battery has a sensitivity of > 0.9, and could be applied to untested chemicals without any biological testing. In view of these observations, it is proposed that the ke test be considered in developing future strategies to optimize the screening of potential carcinogens in the most cost-effective manner.

Carcinogenicity Tests↗
PubMed1990

Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells.

The structural basis of the induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Cvt) in Chinese hamster ovary cells was investigated by the CASE (Computer Automated Structure Evaluation) method, an artificial-intelligence-based system. Using the relevant National Toxicology Program data bases CASE identified a set of structural determinants responsible for the induction of SCE and another one for Cvt. A comparison between the structural determinants associated with SCE and Cvt revealed an overlap of only 22.6%, while the overlap between SCE and the determinants of mutagenicity in Salmonella is 54.5%. This indicates a) that the structural bases of the two phenomena differ and b) that it is likely that SCE, but not Cvt, involves a significant electrophilic/DNA-damaging component.

Animals↗
PubMed1990

An association between mutagenicity and carcinogenic potency.

A comparison between mutagenic and non-mutagenic rodent carcinogens studied by the U.S. National Toxicology Program revealed that as a group, rat carcinogens mutagenic in Salmonella typhimurium are more potent than their non-mutagenic counterparts.

Animals↗
PubMed1990

Relationship between carcinogenicity in rodents and the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells.

Two independent analyses were carried out to compare the induction of sister chromatid exchanges and of chromosomal aberrations as predictors of carcinogenicity. Using both a classical and a Bayesian approach, as well as by analysis of the structural fragments generated by CASE, an artificial intelligence system, it is included that individually neither of these tests is a satisfactory predictor of carcinogenicity. However, because the analysis revealed that each of the cytogenetic assays responds to a different set of structural features associated with carcinogenicity, it can be concluded that the assays can be included in a battery of tests to improve predictivity.

Animals↗
PubMed1990

Predicted reduction in lung cancer risk following cessation of smoking and radon exposure.

Recently there has been considerable public and regulatory concern that radon, produced by the decay of naturally occurring uranium, can accumulate in homes, offices, and schools at levels that may substantially increase the risk of lung cancer. The major cause of lung cancer is smoking, and radon appears to interact multiplicatively with smoking in causing lung cancer. Thus, the most effective way to reduce the increased risk of lung cancer resulting from radon exposure is to cease smoking. In this paper, a model for the risks associated with radon exposure that was developed by a committee of the National Academy of Sciences is used to calculate the benefits, in terms of reduction in lifetime risk of lung cancer, of ceasing to smoke, ceasing radon exposure, or ceasing both. Ceasing to smoke is considerably more beneficial than ceasing radon exposure, and thus policymakers addressing the health effects of radon should place priority on encouraging individuals to stop smoking.

Adult↗
PubMed1990

Value-of-information analysis of testing strategies: estimating the effect of uncertainty about the proportion of chemicals that are true human carcinogens.

Choosing a cost-effective strategy for classifying chemicals as human carcinogens and non-carcinogens depends upon the costs of false positives (carcinogens erroneously treated as non-carcinogenic) and false negatives (non-carcinogens erroneously treated as carcinogenic); upon the accuracy (sensitivity and specificity) of the classification strategy; and upon the underlying proportion of carcinogens in the population of chemicals to be classified. If these values are known, value-of-information analyses can indicate the most cost-effective among three strategies: classify as carcinogenic without testing, classify as non-carcinogenic without testing, or choose the most cost-effective test and classify on the basis of the test result. When some or all of the values are uncertain, the analysis becomes more complex, but still helps to guide decisions among the three classification strategies.

Animals↗
PubMed1989

Application of the carcinogenicity prediction and battery selection method to recent National Toxicology Program short-term test data.

Identification of potentially cancer-causing chemicals is a priority in our society. Short-term assays for mutation or chromosomal damage, which are rapid, inexpensive, and reproducible, have found widespread use; however, concern has arisen recently because such assays do not coincide completely with the standard rodent bioassay for carcinogenesis. Lack of perfect correlation is not surprising, given the complex, multicausal nature of the carcinogenic process. We have developed methodologies for interpreting short-term tests to predict carcinogenicity, which allow consideration of the influence of the proportion of carcinogens expected in the tested chemicals, the complexities of the rodent carcinogenesis bioassay, and factors affecting the worth of information. These methodologies are applied to a set of data on genotoxicity and carcinogenicity of 73 chemicals (NTP-73) recently published by the National Toxicology Program; they illustrate that with this approach, batteries of short-term tests can indeed be predictive of rodent carcinogenicity or noncarcinogenicity and that batteries are more predictive than the Salmonella assay alone. The analysis is validated using an additional group of chemicals with results in the same short-term tests as NTP-73.

Animals↗
PubMed1989

Genotoxic carcinogenic risk of a new non-tobacco-burning cigarette.

The recent development of a non-tobacco-burning cigarette has led to much controversy. In the present study, we analyzed the DNA-modifying ('genotoxic') potential of the emissions of this 'new' cigarette. Based upon the reported results of short-term tests (mutagenicity, clastogenicity, DNA damage), the 'new' cigarette has a greatly decreased potential for genotoxic carcinogenicity when compared to the 'regular' cigarette. The analysis does not address the possibility of cancer induction by a non-genotoxic or promotional mechanism, nor the cardiovascular and addictive risks of cigarette smoking.

Animals↗