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Biomedical subjects

R Neutra

Publications and source records attributed to R Neutra.

15 recordsLinked to original sources

Clusters galore: insights about environmental clusters from probability theory.

The posterior probability of a causal explanation given that an environmental cancer cluster is statistically significant depends on the prior probability of an environmentally caused cluster, the sensitivity of the statistical test and its specificity. The prior probability is low, because it is rare to have enough carcinogen in the general environment to cause a relative risk of cancer high enough to achieve statistical significance in a small geographic area. The sensitivity and specificity are not great. The likelihood that a census tract escapes statistically significant elevations in all 80 types of cancer can be calculated. Many of the thousands of census tracts will, by chance alone, have at least one type of cancer whose elevation is statistically significant. Actual observation from a large cancer registry confirms this probabilistic prediction. Applying the principles of Bayes' Theorem would suggest that most statistically significant environmental cancer clusters are not due to environmental carcinogens. One would have to investigate hundreds of environmental cancer clusters to find one with a true environmental cause.

Bayes Theorem

Optimization of protein-production by the baculovirus expression vector system in shake flasks.

Shake flasks were successfully employed for the cultivation of Spodoptera frugiperda (Sf-9) insect cells and for the production of beta-galactosidase, a recombinant model protein, utilizing the baculovirus expression vector system. The culture doubling time and maximal cell density were 20 h and 5 x 10(6) cells/ml respectively. The optimal liquid volumes for flasks rotating at 100 rpm were 25-40% of the flask total volume. Enzyme production (about 600 mg/l) was best at a multiplicity of infection of between 1 and 20 and at a cell density at time of infection of 0.7 x 10(6) cells/ml. At a rotation speed of 100 rpm, Pluronic F-68 had no effect on growth and enzyme production.

Animals

Symptom prevalence and odor-worry interaction near hazardous waste sites.

Retrospective symptom prevalence data, collected from over 2000 adult respondents living near three different hazardous waste sites, were analyzed with respect to both self-reported "environmental worry" and frequency of perceiving environmental (particularly petrochemical) odors. Significant positive relationships were observed between the prevalence of several symptoms (headache, nausea, eye and throat irritation) and both frequency of odor perception and degree of worry. Headaches, for example, showed a prevalence odds ratio of 5.0 comparing respondents who reported noticing environmental odors frequently versus those noticing no such odors and 10.8 comparing those who described themselves as "very worried" versus "not worried" about environmental conditions in their neighborhood. Elimination of respondents who ascribed their environmental worry to illness in themselves or in family members did not materially affect the strength of the observed associations. In addition to their independent effects, odor perception and environmental worry exhibited positive interaction as determinants of symptom prevalence, as evidenced by a prevalence odds ratio of 38.1 comparing headaches among the high worry/frequent-odor group and the no-worry/no-odor group. In comparison neighborhoods with no nearby waste sites, environmental worry has been found to be associated with symptom occurrence as well. Potential explanations for these observations are presented, including the possibility that odors serve as a sensory cue for the manifestation of stress-related illness (or heightened awareness of underlying symptoms) among individuals concerned about the quality of their neighborhood environment.

Adult

Hypotheses to explain the higher symptom rates observed around hazardous waste sites.

Five studies were carried out around hazardous waste sites in California in which the main route of exposure was to low-level parts per billion concentrations of either gaseous emissions or airborne dust particles. Although there was no evidence suggesting excesses in cancer or birth defects, the total number and the prevalence of many of subjective symptoms were higher in areas near the site than in control neighborhoods. We discuss a number of causal processes that could explain these results. We conclude that a classical toxicological response and mass psychogenic illness are not valid explanations. Recall bias may explain part of the pattern. We present data from situations where stress alone from environmental anxiety has produced a similar magnitude of excess symptoms in populations. The fact that excess symptoms in waste site neighbors is found primarily in those who complain of odors or who are worried about environmental chemicals suggests the possibility that autonomic, stress-mediated mechanisms or behavioral sensitization are active in the genesis of these symptoms. A variety of confounders were controlled for. The hypothesis that chemically "acquired immune deficiency" can cause subtle symptomatology as a prodrome to subsequent serious disease has been raised in testimony at several toxic tort trials about waste sites. Although this hypothesis seems unlikely, particularly at sites such as the ones we studied with low airborne exposures, if true it would have profound regulatory implications.

Anxiety

Pregnancy outcomes in women potentially exposed to solvent-contaminated drinking water in San Jose, California.

During 1980-1981, solvents leaked from an underground storage tank of a semiconductor firm in southern Santa Clara County, California, contaminating local drinking water. The contaminated well was closed in December 1981. An epidemiologic study conducted in 1983 confirmed statistically significant excesses of adverse pregnancy outcomes in an exposed community compared with an unexposed community, but could not establish a causal connection between the leak and the adverse outcomes. This study expanded the first study; adverse pregnancy outcomes occurring in 1980-1985 were studied in two communities exposed to the contaminated drinking water and in two demographically comparable but unexposed communities. The period 1980-1981 was the time period in which the well was considered to have been contaminated and 1982-1985 was considered the postcontamination time period. Both exposed and unexposed communities were considered unexposed during the latter period (1982-1985). Out of 10,055 households surveyed, interviews were conducted with 1,105 women who reported one or more eligible pregnancies. Miscarriages and birth defects were validated by medical record review or physician reports. Although the authors again observed statistically significant excesses of spontaneous abortions and birth defects in the originally studied exposed area in 1980-1981, they observed deficits of these outcomes in the second exposed study area. Adjustment for potential confounders did not alter these findings. Analyses of pregnancy outcomes during 1981 in relation to exposure estimates based on hydrogeologic modeling of water and contaminant distribution within the exposed areas also indicated that the leak was not likely to have caused the observed excesses of adverse pregnancy outcomes in the originally studied area.

Abnormalities, Drug-Induced

How do cancer risks predicted from animal bioassays compare with the epidemiologic evidence? The case of ethylene dibromide.

Cancer risks for ethylene dibromide (EDB) were estimated by fitting several linear non-threshold additive models to data from a gavage bioassay. Risks predicted by these models were compared to the observed cancer mortality among a cohort of workers occupationally exposed to the same chemical. Models that accounted for the shortened latency period in the gavaged rats predicted upper bound risks that were within a factor of 3 of the observed cancer deaths. Data from an animal inhalation study of EDB also were compatible with the epidemiologic data. These findings contradict those of Ramsey et al. (1978), who reported that extrapolation from animal data produced highly exaggerated risk estimates for EDB-exposed workers. This paper explores the reasons for these discrepant findings.

Animals

Secular rates and correlates for gastroschisis in California (1968-1977).

This study reports on an epidemiological investigation of gastroschisis using birth certificate data from California for the period of 1968-1977. Gastroschisis has been reported to be on the increase in a number of countries. The distribution of the 166 California gastroschisis cases reported during this time period indicated a clear upward secular trend (P less than .001) with the rate per 1,000 increasing from .006 in 1968 to .089 by 1977. This secular trend was observed in every maternal age group and for gravidity level 1. Gastroschisis also occurred more frequently among younger mothers (P less than .001) and low gravidity mothers (P less than .001). Omphalocele, another eventration defect, was also examined but did not display an upward secular trend.

Abdominal Muscles

A pitfall in sampling medical visits.

Samples of outpatient visits often must be used to identify users of a health facility with a given chronic condition. Such samples can lead to biases, however, because patients with more frequent visits are overrepresented. These biases can be avoided by a weighting procedure in which each sampled visit is weighted inversely to the number of clinic visits made by that patient during the sample period. This procedure proved critical in estimating the number and characteristics of hypertensive patients seen in the medical clinic of a teaching hospital. The unweighted estimate of the number of hypertensives was 7,373 patients, more than three times the weighted estimate of 2,250. Similarly,, the number of visits per year by these patients would be overestimated by almost 50 per cent without weighting. The estimated proportion of hypertensives still under treatment after 18 months was 68 per cent without weighting, compared to 51 per cent with weighting. Thus biases from failure to weight may be substantial. Analogous biases and solutions apply to other sampling problems in health services research.

Humans

Fetal death in eclampsia: I. Its relation to low gestational age, retarded fetal growth and low birthweight.

Of 173 eclamptics admitted to the only public maternity hospital in Cali, Colombia 44 had stillbirths making a rate of 25-4 per cent. Fetuses delivered before 32 weeks had nearly four times the stillbirth rate of those delivered at term. Those weighing less than 1600 g. had stillbirth rates about six times higher than those weighing above 2500 g. An attempt was made to divide the risk conveyed by low birthweight into two components; that which was due to low gestational age, and that which was due to an abnormally low rate of growth during the gestational time available. Deviation of birthweight below that expected for age (retarded fetal growth, RFG) was used as a measure of the latter component. RFG became more common as gestation progressed and was associated with fetal death only in the latter part of gestation and with marginal statistical significance. After 35 weeks, fetuses at or below two standard deviations from Gruenwald's mean weight for gestational age (Gruenwald, 1966) had a fetal death rate five times higher than those at the mean. The risk of fetal (intrauterine) death conveyed by low gestational age has not been definitively explained. Alternative pathophysiological mechanisms are discussed.

Birth Weight

Fetal death in eclampsia: II. The effect of non-therapeutic factors.

The ability of 15 variables to predict fetal death is examined among 173 eclamptic women admitted to the only public maternity hospital in Cali, Colombia, between 1st Janurary 1964 and 31st December 1970. In addition to low gestational age and retarded fetal growth, high systolic pressure and the unmarried status carried excess risk. Primiparae appeared to be of lower risk because their eclampsia tended to occur late in gestation and was characterized by less retarded fetal growth. Older women and women with a history of abortion appeared to be of higher risk because they tended to have higher systolic pressures. A discriminant function risk formula is presented which generated groups with a nine-fold difference in fetal death rates. This formula could be used to standardize for relevant non-therapeutic factors which meant vary between patient groups who had received different therapeutic regimens.

Abortion, Spontaneous

Hydrogeologic assessment of exposure to solvent-contaminated drinking water: pregnancy outcomes in relation to exposure.

We recently concluded that exposure to solvent-contaminated drinking water was an unlikely explanation for observed excesses of adverse pregnancy outcomes during 1980-1981 in the Los Paseos neighborhood of Santa Clara County, California, because these excesses were not observed in an adjacent exposed area. The validity of this conclusion depends on the assumption that the two areas had comparable exposure. Using quantitative methods to model movement of the solvent leak plume and water flow within the distribution system, we estimated that women with adverse outcomes were no more likely to have received contaminated water than women with normal live births. These results strengthen the conclusion that exposures to water from the contaminated well were not responsible for the excess of adverse outcomes observed in the Los Paseos area.

Abnormalities, Drug-Induced