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Biomedical subjects

B C Gladen

Publications and source records attributed to B C Gladen.

At least 55 records · Page 3Linked to original sources
PubMed1988

Development after exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene transplacentally and through human milk.

OBJECTIVE: To determine whether exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE), either transplacentally or through breast feeding, affected scores on the Bayley Scales of Infant Development at 6 or 12 months of age. DESIGN: Cohort followed from birth to 1 year of age. SETTING: General community. PARTICIPANTS: Volunteer sample of 858 infants, of whom 802 had Bayley scores available at either 6 months or 12 months or both. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Bayley scales and chemical measurements were done independently. Higher transplacental exposure to PCBs was associated with lower psychomotor scores at both 6 and 12 months of age; the difference between the mean scores in the lowest and highest PCB groups was 7 points at 6 months and 8 points at 12 months. Higher transplacental exposure to DDE was associated with higher mental scores at 6 months of age (the difference between the mean scores in the lowest and highest DDE groups was 6 points), but no relationship was seen at 12 months. Exposure to either chemical through breast feeding was apparently unrelated to Bayley scores. CONCLUSIONS: Transplacental exposure to PCBs was associated with lower psychomotor scores. No deleterious effects were associated with breast feeding.

Brain↗
PubMed1987

US prevalence of occupational pleural thickening. A look at chest X-rays from the first National Health and Nutrition Examination Survey.

The prevalence of occupational pleural thickening in the United States in the mid-1970s was estimated; since asbestos often produces pleural thickening, this estimate in turn was used to estimate the prevalence of asbestos exposure. Chest x-rays obtained by the 1971-1975 National Health and Nutrition Examination Survey were reread by three readers using the International Labour Office criteria for diagnosis of pleural thickening consistent with dust exposure. All 289 x-rays showing any pleural abnormalities plus a 3-to-1 age-, sex-, and race-matched control series were reread. Using two of three readings as "positive," and extrapolating to the US population from this defined sample, the authors showed that 2.3% of males and 0.2% of females had occupational pleural thickening on x-ray, with a strong increase with age in white males. This provides a US population estimate of 1.3 million people with occupational pleural thickening and approximately 8 million people with asbestos exposure in the mid-1970s. This cohort might make a substantial contribution to cancer mortality into the next century.

Adult↗
PubMed1987

Quantitation of cellular and extracellular constituents of the pulmonary lining in rats by using bronchoalveolar lavage. Effects of silica-induced pulmonary inflammation.

The efficacy of bronchoalveolar lavage in the removal of cellular and extracellular components of the lining layer from the lungs of silica-treated and control rats was determined. Exponential functions were fitted to curves generated by plotting the quantity of lining layer constituent removed from the lungs by bronchoalveolar lavage versus the lavage number. From these exponential functions we determined the total amount of constituent available in the pulmonary extracellular lining and hence the efficacy of the lavage procedure in removing materials from the lungs. With control rats the removal of extracellular phospholipids, soluble protein, alkaline phosphatase, and beta-N-acetylglucosaminidase by bronchoalveolar lavage occurred at significantly different rates. Removal of 95% of the total available extracellular phospholipid, beta-N-acetylglucosaminidase, soluble protein, and alkaline phosphatase from the lungs required 4, 4, 8, and 11 lavages, respectively. Removal of 95% of the total available alveolar macrophages required 18 lavages. The influence of pulmonary inflammation on the efficacy of the lavage procedure was investigated by injecting silica dust intratracheally into the lungs of rats (50 mg/200- to 250-g rat) and after 3 days performing the analyses. Silica caused an inflammatory condition in the lungs resulting in the accumulation of materials in the alveoli. Highly significant increases in soluble protein (16-fold), alkaline phosphatase (9-fold), and beta-N-acetylglucosaminidase (11-fold), polymorphonuclear leukocytes, eosinophils, and lymphocytes were observed. Alveolar macrophages and extracellular phospholipid were not significantly elevated at 3 days after dosing. Silica did not alter the efficacy of the lavage procedure in removing from the lungs any of the extracellular constituents of the lung lining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects on growth, morbidity, and duration of lactation.

We followed 858 children from birth to one year of age to determine whether the presence of polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in breast milk affected their growth or health. Neither chemical showed an adverse effect on weight or frequency of physician visits for various illnesses, although differences were seen between breast-fed and bottle-fed children, with bottle-fed children being heavier and having more frequent gastroenteritis and otitis media. Children of mothers with higher levels of DDE were breast-fed for markedly shorter times, but adjustments for possible confounders and biases did not change the findings. In absence of any apparent effect on the health of the children, we speculate that DDE may be interfering with the mother's ability to lactate, possibly because of its estrogenic properties.

Body Weight↗
PubMed1987

Progression of type II cell hypertrophy and hyperplasia during silica-induced pulmonary inflammation.

Type II cell hyperplasia and hypertrophy were quantitated in the lungs of rats exposed to silica by using intratracheal injection. Hypertrophic type II cells were separated from normal type II cells by means of centrifugal elutriation of cells dispersed from the lungs by using protease. Type II cell hypertrophy was also quantitated, in situ, by measuring cell profile areas in lung sections. As a means of distinguishing between the hyperplastic and hypertrophic responses of type II cells we followed the progression of these two responses as a function of time and of dose. Seven, 14, and 28 days after a single intratracheal injection of silica (10 mg/rat), hypertrophic type II cells accounted for 33, 35, and 57% of the total type II cells recovered from the lungs. In contrast, hypertrophic type II cells accounted for less than 15% of the type II cells from control lungs. The appearance of hypertrophic type II cells was dose-related when examined 2 weeks after dosing; however, after only 1 week, the response of the type II cell appeared independent of dose. The hypertrophic response of type II cells could not be separated from the hyperplastic response according to either dose or time responses. These data support the hypothesis that in the lungs of silica-treated rats, the hypertrophic type II cell may be the proliferative type II cell. In addition, the hypertrophic type II cell appears to underlie the marked increases in surfactant levels seen in silica-treated lungs.

Alkaline Phosphatase↗
PubMed1986

Effects of silica on the composition of the pulmonary extracellular lining.

The effects of intratracheally injected silica on lung weights and on alveolar macrophages, polymorphonuclear leukocytes, phospholipid, protein, N-acetyl-beta-glucosaminidase, and alkaline phosphatase of the extracellular lining of rat lungs were studied as functions of dose and time. All of these parameters increased with time up to 12 days after a single injection of silica (200 mg/kg) and showed a dose dependence in their responses. Extracellular soluble protein increased 19.8-fold from 1.9 to 37.6 mg/pair of lungs. The composition of the extracellular soluble protein was very similar to that found in normal lungs as determined with two-dimensional-polyacrylamide gel electrophoresis. Although most of the soluble proteins in lavage effluents were similar to those found in serum, several serum proteins were absent, indicating that the selectivity of the lungs for certain serum proteins was maintained after treatment with silica. Increases in extracellular soluble proteins could not be accounted for by damage to the blood/air barrier. Extracellular phospholipid increased 12.1-fold from 1.74 to 21.1 mg/pair of lungs. The phosphatidylcholine content of this phospholipid resembled that of normal pulmonary surfactant but was different from that in free cells lavaged from the lungs of control and silica-treated rats. Increases in extracellular phospholipid were probably due to silica effects on the surfactant system and not to destruction of or release by free cells in the alveoli. N-Acetyl-beta-glucosaminidase and alkaline phosphatase increased approximately 33- and 6-fold, respectively, in response to silica. The number of alveolar macrophages and polymorphonuclear leukocytes increased 1.5- and 75-fold, respectively. Calculation of partial correlations revealed statistically significant relationships among extracellular phospholipids, soluble proteins, and the two hydrolytic enzymes, suggesting that these components were being released into the lung lining from a common source or by a common mechanism.

Acetylglucosaminidase↗
PubMed1986

Neonatal effects of transplacental exposure to PCBs and DDE.

Neonatal effects of transplacental exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) were examined in a study of 912 infants. Birth weight, head circumference, and neonatal jaundice showed no relationship to PCBs or DDE. We also administered the Brazelton Neonatal Behavioral Assessment Scales, which are psychologic and neurologic tests designed for use in newborn infants. The results of these tests showed that higher PCB levels were associated with hypotonicity and hyporeflexia and that higher DDE levels were associated with hyporeflexia.

Birth Weight↗
PubMed1986

Association of amino levulinate dehydratase levels and ferrochelatase inhibition in childhood lead exposure.

The basis for the clinical variation in response to lead exposure in children is not well understood. We studied selected children from a large lead screening program in whom elevation of red cell protoporphyrin concentration (a measure of inhibition of the enzyme ferrochelatase) was markedly above or below average for a given blood lead level. We then measured the activity of the enzyme amino levulinate dehydratase in 306 of these children, and found that ALA-d activity was lower in children with higher protoporphyrin elevation, independent of the effects of lead. This observation, coupled with reports in the literature of families with ALA-d deficiencies and elevated red cell protoporphyrin values, makes likely a genetic basis for some of the variation in susceptibility to lead. The mechanism by which the two effects are associated remains unknown.

Adolescent↗
PubMed1986

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects of maternal factors and previous lactation.

The authors measured polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in maternal serum, cord blood, placenta, and serial samples of breast milk from 868 women. Almost all samples of breast milk showed detectable levels of both chemicals. Overall, values for DDE in this study are within the range of those found previously, whereas those for PCBs are somewhat higher. Possible causes of variation in levels were investigated. For DDE, older women, Black women, cigarette smokers, and women who consumed sport fish during pregnancy had higher levels; only age and race showed large effects. For PCBs, older women, women who regularly drink alcohol, and primiparae had higher levels. In addition, both chemicals showed modest variation across occupational groupings. Casual exposure to a PCB spill did not result in chemical levels different from background. In general, women have higher levels in their first lactation and in the earlier samples of a given lactation, and levels decline both with time spent breast-feeding and with number of children nursed. These striking declines are presumably a measure of exposure to the child.

Adolescent↗
PubMed1986

The beta-geometric distribution applied to comparative fecundability studies.

A convenient measure of fecundability is time (number of menstrual cycles) required to achieve pregnancy. Couples attempting pregnancy are heterogeneous in their per-cycle probability of success. If success probabilities vary among couples according to a beta distribution, then cycles to pregnancy will have a beta-geometric distribution. Under this model, the inverse of the cycle-specific conception rate is a linear function of time. Data on cycles to pregnancy can be used to estimate the beta parameters by maximum likelihood in a straightforward manner with a package such as GLIM. The likelihood ratio test can thus be employed in studies of exposures that may impair fecundability. Covariates are incorporated in a natural way. The model is illustrated by applying it to data on cycles to pregnancy in smokers and nonsmokers, with adjustment for covariates. For a cross-sectional study, when length-biased sampling is taken into account, the pre-interview attempt time is shown to follow a beta-geometric distribution, so that the same methods of analysis can be applied even though all of the available data are right-censored. For a cohort followed prospectively, there will be some couples enrolled whose fecundability is effectively 0, and for such applications, the beta could be considered to be contaminated by a distribution degenerate at 0. The mixing parameter (proportion sterile) can be estimated by application of the expectation-maximization (EM) algorithm. This, too, can be carried out using GLIM.

Biometry↗
PubMed1985

Study of human lactation for effects of environmental contaminants: the North Carolina Breast Milk and Formula Project and some other ideas.

The presence of environmental contaminant chemicals in human milk, their demonstrated toxicity, and the lack of data in human beings led to the North Carolina Breast Milk and Formula project, a three-center prospective birth cohort study of 856 children. In this study, we measure polychlorinated biphenyls (PCBs) and DDE in milk and other fluids, follow the course of lactation, and note growth, morbidity and development in the children. Lactation is hormonally complicated and has parts that are plausibly interfered with by contaminant chemicals, and certain kinds of morbidity that occur in breastfed children might also represent the result of chemical contamination of milk. Preliminary data analysis confirms the widespread presence of chemicals in milk; women with higher DDE levels do not breast-feed as long, but this is not true for women with higher PCBs. Besides this study, several case-control or survey-type studies, such as studies of failure to thrive, certain rashes, or short-term breast-feeding would be helpful. Laboratory studies of enzyme induction are now feasible in children and might be a very sensitive if not totally specific endpoint for study of PCBs in milk.

Breast Feeding↗
PubMed1985

Potential reproductive and postnatal morbidity from exposure to polychlorinated biphenyls: epidemiologic considerations.

There is both laboratory and epidemiologic evidence that PCBs are toxic to several phases of reproduction. Workplace exposure is an important but small part of the exposure to these compounds, since most of the population has detectable levels in blood or fat. Studies in the general population on PCBs and reproduction have not been done. Some studies in workers are under way, and in epidemic PCB poisonings, small babies with a distinct clinical syndrome are seen. We review some of the laboratory and epidemiologic data and the methods available for study of reproduction in humans; study of any highly exposed group should be done and studies of spontaneous abortion, birth weight and certain congenital anomalies should look for an effect of PCBs.

Abnormalities, Drug-Induced↗
PubMed1984

Estimating disease rates from a diagnostic test.

Incidence and remission rates are often estimated from studies that employ a diagnostic test to indicate the presence of disease. The apparent rates that result from a simple study design with one test given at two time points will be substantially different from the true rates, even if the error rates of the test are low. Estimation of the true rates requires extra assumptions or extended designs with more tests or more time points. The authors illustrate their points with the use of two examples, the second of which compares the estimates obtained to actual data from a study of onchocerciasis (river blindness) in Guatemala.

Adolescent↗
PubMed1983

Chromatographic evidence of polychlorinated biphenyl exposure from a spill.

Women who were part of a study in which polychlorinated biphenyls (PCBs) were measured in breast milk were exposed accidentally to a PCB spill. While the overall level of PCBs found in their milk was not different from background levels, the chromatograms showed unusual peaks that indicate the presence of heavily chlorinated PCBs of the kind that were spilled.

Aroclors↗
PubMed1982

Spontaneous abortion: the role of heterogeneous risk and selective fertility.

The study of spontaneous abortion risk is complicated by the fact that a woman's successive pregnancies are not independent events. Non-independence may distort any analysis of spontaneous abortion risk that includes successive pregnancies. In order for an analysis of spontaneous abortion to take non-independence into account, a model must be developed. Previous attempts to describe non-independence have focused on the closely-related issue of whether the risk of abortion increases with successive pregnancies (i.e., with gravidity). Authors using various analytic strategies have reached conflicting conclusions about the gravidity effect. We review these attempts in detail, and in so doing, develop a synthesized viewpoint. We conclude that three factors powerfully affect the occurrence of spontaneous abortion: (1) a heterogeneous risk of abortion (constant for each woman but differing among women); (2) selective fertility (a tendency to control fertility on the basis of previous pregnancy outcomes); and (3) increased risk with maternal age. We demonstrate with a simulation model that these three factors alone can produce a spurious gravidity effect of a size similar to the effect found in actual data. Furthermore, we propose that these three factors offer a framework for a generalized analytic approach to spontaneous abortion, one that takes into account the non-independence of successive pregnancies.

Abortion, Spontaneous↗
PubMed1981

Concurrent exposure to lead, cadmium, and arsenic. Effects on toxicity and tissue metal concentrations in the rat.

Male rats were exposed to dietary Pb (200 ppm), Cd (50 ppm), or As (50 ppm) as arsenate either alone or in combination for 10 weeks using a 2 x 2 x 2 factorial design. Cd and As reduced weight gain even when differences in food intake were taken into account, and administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased RBCs were observed after administration of Pb, Cd, or As, and more cells were observed when two or three metals were concomitantly administered. Despite increased numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination. Analysis of blood chemistries showed normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, but not by Cd or As. SGOT activity was reduced by As alone. Serum alkaline phosphatase was reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, but Cd or As alone or in combination had no effect. Liver weight/body weight ratios were reduced in animals fed Cd. Kidney histology showed predominantly Pb effects, i.e., intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies and mitochondrial swelling. Concurrent administration of Cd reduced total mean bone and kidney Pb levels by 50% and 60%, respectively, and this was associated with a decrease in kidney intranuclear inclusions. Cd exposure also reduced renal, femur, and liver concentrations of Fe by 33%, 43%, and 63%, respectively, decreased femur Zn by 27%, but increased renal Zn by 20%. Administration of As produced mild swelling of tubule cell mitochondria, increased mean total renal Cu to 200% of control, and increased liver Fe by 44%. Dietary Pb produced increased urinary excretion of ALA and coproporphyrin. Dietary exposure to As caused increased urinary excretion of uroporphyrin and to a lesser extent coproporphyrin, whereas dietary Cd caused no significant changes in urinary levels of any of the porphyrins measured. Pb plus As produced an additive effect on coproporphyrin excretion but not that of ALA or uroporphyrin. These studies indicate that interactions between common toxic elements do occur and are characterized by alterations in both tissue trace metal levels and toxicity.

Animals↗