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Biomedical subjects

J H Ware

Publications and source records attributed to J H Ware.

At least 37 records · Page 2Linked to original sources
PubMed1995

Localization of tissue plasminogen activator mRNA in the developing rat cerebellum and effects of inhibiting tissue plasminogen activator on granule cell migration.

Tissue plasminogen activator (tPA) mRNA was localized in the developing cerebellum and the potential role of tPA in migration of cerebellar granule cells was investigated. Proteolytic assays and Northern blots showed little variation in levels of tPA proteolytic activity or tPA mRNA expression in the developing cerebellum. The distribution of cerebellar tPA mRNA at different ages was visualized by in situ hybridization histochemistry. At postnatal day 7 (P7), most labeled cells were in the internal granule layer or developing white matter, and very few if any premigratory granule cells contained tPA mRNA. Although the molecular layer contained labeled cells at all ages, cell counts indicated that a greater percentage of cells in the molecular layer contained tPA mRNA during adulthood than during the period of granule cell migration. The most striking change in tPA mRNA expression was in Purkinje neurons, most of which began to express tPA mRNA between P7 and P14. The potential role of tPA in granule cell migration was investigated by performing migration assays in cerebellar slice explants in the presence or absence of protease inhibitors. The presence of inhibitors did not affect the distance that granule cells migrated. Data in the present study do not support a role for tPA in granule neuron migration; however, they do indicate that tPA is both spatially and temporally regulated during cerebellar development. Possible functions of tPA in the cerebellum are discussed.

Animals↗
PubMed1995

Localization of tissue plasminogen activator mRNA in adult rat brain.

The distribution of tissue plasminogen activator (tPA) messenger RNA in rat brain was studied using in situ hybridization with 35S UTP-labeled RNA probes derived from a full-length tPA cDNA. Sense strand controls produced low, even backgrounds, with small elevations in the hippocampus. Full-length antisense probes produced strong signals over cerebral ventricular ependyma (including ependyma of the subcommissural organ), meninges, blood vessels, and Purkinje cell layer of the cerebellum, as well as strong signals over scattered cells throughout the brain. Some of these scattered labeled cells were large with lightly stained nuclei, while others were small with darkly stained nuclei. The large labeled cells, which were probably neurons, constituted 6% and 8% of cells in the brain stem and neocortex, respectively, and 100% of Purkinje cells. The small cells, which were present in all areas of the brain, constituted 3-11% of cells in individual brain areas.

Animals↗
PubMed1994

Concentration of indoor particulate matter as a determinant of respiratory health in children.

The effect of passive exposure to environmental tobacco smoke in the home on respiratory symptoms and pulmonary function level was studied in a cohort of white children aged 7-11 years examined in six US cities in 1983-1988. For 2,994 children with questionnaire-based exposure data, passive exposure to an additional pack of cigarettes smoked daily in the home was associated with increased incidence of lower respiratory symptoms (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.10-1.42). For 1,237 children with two consecutive 1-week measurements in both winter and summer, a 30-micrograms/m3 increase in the annual average indoor concentration of respirable particulate matter with an aerodynamic diameter of < 2.5 microns (PM2.5)--that is, approximately the effect of one pack per day of smoking--was marginally associated with an increased cumulative incidence of lower respiratory symptoms (OR = 1.13, 95% CI 0.99-1.30). Indoor measurements of PM2.5 showed no direct association with children's pulmonary function measurements. Children whose mothers smoked during pregnancy showed a reduction of -2.6% (95% CI -5.2% to 0.1%) in volume-adjusted forced expiratory flow rates. Therefore, current indoor exposure to PM2.5 increases the cumulative incidence of lower respiratory symptoms, but is only weakly associated with decreased pulmonary function level in preadolescent children.

Air Pollution, Indoor↗
PubMed1994

Gender- and race-specific effects of asthma and wheeze on level and growth of lung function in children in six U.S. cities.

The gender-and race-specific effects of asthma/wheeze on pulmonary function level and annual growth velocity were studied in a cohort of 10,792 white and 944 black children 6 to 18 yr of age, examined annually between 1974 and 1989 in six U.S. cities. In comparison with white boys who never reported asthma or wheeze, FEV1 levels were 5.7% lower and FEF 25-75 levels were 16.9% lower for white boys with a diagnosis of asthma who reported wheeze symptoms in the past year. White girls with asthma and wheeze had FEV1 levels that were 3.4% lower and FEF25-75 levels that were 13.6% lower than white girls with never-asthma/wheeze. Asthma with wheeze was associated with a greater percent deficit in FEV1 level in boys than in girls (p < 0.01) and, particularly in preadolescence, with a significant percent increment in FVC level (1.6%) for girls but not for boys. The diagnosis of asthma with or without wheeze in the past year was associated with a greater deficit in level of lung function than the reporting of wheeze symptoms in a child without the diagnosis of asthma. The prevalence of asthma and wheeze was higher among blacks, but no race differences were found in the effects of asthma or wheeze on level of FEV1 and FEF25-75. Compared with white adolescent female ever asthmatics with no medication use, FEV1 level was 5.8% lower for those with routine medication use and 7.8% lower for those with routine and additional medication use. Although white girls with wheeze but no diagnosis of asthma had slightly slower growth of FEV1 (0.3% per year) than did white girls without asthma or wheeze, children with asthma did not have slower annual growth in percent terms. In absolute terms, growth of FEV1 was 14.7 ml/yr and FEF25-75 was 47 ml/s/yr slower for asthmatic white boys with wheeze than for those without asthma; for girls with asthma and wheeze growth of FEF25-75 was 29 ml/s/yr slower. We conclude that in absolute terms, but not in percent terms, the pulmonary function deficits associated with asthma and wheeze increase throughout childhood. In the preadolescent and adolescent years, the mechanical properties of the lungs and the inflammatory process in asthmatics may differ by gender, leading to gender differences in their pulmonary function. We also conclude that lung function may not return to normal, even when asthmatics become asymptomatic.

Adolescent↗
PubMed1994

A longitudinal study of the effects of parental smoking on pulmonary function in children 6-18 years.

The association between parental cigarette smoking and children's pulmonary function was investigated in 8,706 nonsmoking white children, followed annually by questionnaire and spirometry between 6 and 18 yr. Exposure to maternal and paternal smoking was each divided into three components: exposure in the first 5 yr of life, cumulative exposure between age 6 and the year prior to each visit; parental smoking status reported at each visit. Regression splines were used to assess the effects of parental smoking on the level and growth rate of pulmonary function adjusting for age, height, city of residence, and parental education. Models best predicting pulmonary function level included current maternal smoking and exposure to maternal smoking in the first 5 yr of life but did not include the other measures of parental smoking. After adjusting for early exposure, current maternal smoking for each pack/d was associated with a reduced level of FEV1 (-0.4%, 95% CI: -0.9, 0.1), FEV1/FVC (-0.6%, 95% CI: -0.9, -0.4), and FEF25-75% (-2.3%, 95% CI: -3.6, -1.0) in children 6 to 10 yr. These effects were slightly smaller in children 11 to 18 yr. Adjusting for current maternal smoking, those exposed to maternal smoking in the first 5 yr of life had higher FVC (+0.5%, 95% CI: -0.1, 1.2) and lower FEV1/FVC (-0.7%, 95% CI: -1.1, -0.4) and FEF25-75% (-2.8%, 95% CI: -4.4, -1.2) than those not exposed in children 6 to 10 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Acute effects of summer air pollution on respiratory symptom reporting in children.

A daily diary of respiratory symptoms was collected from the parents of 1,844 school children in six U.S. cities to study the association between ambient air pollution exposures and respiratory illness. A cohort of approximately 300 elementary school children in each of six communities were asked to keep a daily log of the study child's respiratory symptoms for one year. Daily measurements of ambient sulfur dioxide, nitrogen dioxide, ozone, inhalable particles (PM10), respirable particles (PM2.5), light scattering, and sulfate particles were made, along with integrated 24-h measures of aerosol strong acidity. The analyses were limited to the five warm season months between April and August. Significant associations were found between incidence of coughing symptoms and incidence of lower respiratory symptoms and PM10, and a marginally significant association between upper respiratory symptoms and PM10. There was no evidence that other measures of particulate pollution including aerosol acidity were preferable to PM10 in predicting incidence of respiratory symptoms. Significant associations in single pollutant models were also found between sulfur dioxide or ozone and incidence of cough, and between sulfur dioxide and incidence of lower respiratory symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

An association between air pollution and mortality in six U.S. cities.

BACKGROUND: Recent studies have reported associations between particulate air pollution and daily mortality rates. Population-based, cross-sectional studies of metropolitan areas in the United States have also found associations between particulate air pollution and annual mortality rates, but these studies have been criticized, in part because they did not directly control for cigarette smoking and other health risks. METHODS: In this prospective cohort study, we estimated the effects of air pollution on mortality, while controlling for individual risk factors. Survival analysis, including Cox proportional-hazards regression modeling, was conducted with data from a 14-to-16-year mortality follow-up of 8111 adults in six U.S. cities. RESULTS: Mortality rates were most strongly associated with cigarette smoking. After adjusting for smoking and other risk factors, we observed statistically significant and robust associations between air pollution and mortality. The adjusted mortality-rate ratio for the most polluted of the cities as compared with the least polluted was 1.26 (95 percent confidence interval, 1.08 to 1.47). Air pollution was positively associated with death from lung cancer and cardiopulmonary disease but not with death from other causes considered together. Mortality was most strongly associated with air pollution with fine particulates, including sulfates. CONCLUSIONS: Although the effects of other, unmeasured risk factors cannot be excluded with certainty, these results suggest that fine-particulate air pollution, or a more complex pollution mixture associated with fine particulate matter, contributes to excess mortality in certain U.S. cities.

Adult↗
PubMed1993

A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery.

BACKGROUND: Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion. METHODS: We compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep hypothermia and support consisting predominantly of low-flow cardiopulmonary bypass in a randomized, single-center trial. The criteria for eligibility included a diagnosis of transposition of the great arteries with an intact ventricular septum or a ventricular septal defect and a planned arterial-switch operation before the age of three months. RESULTS: Of 171 patients with D-transposition of the great arteries, 129 (66 of whom were assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum, and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had a ventricular septal defect. After adjustment for diagnosis, assignment to circulatory arrest as compared with low-flow bypass was associated with a higher risk of clinical seizures (odds ratio, 11.4; 95 percent confidence interval, 1.4 to 93.0), a tendency to a higher risk of ictal activity on continuous electroencephalographic (EEG) monitoring during the first 48 hours after surgery (odds ratio, 2.5; 95 percent confidence interval, 1.0 to 6.4), a longer recovery time to the first reappearance of EEG activity (only in the group with an intact ventricular septum, P < 0.001), and greater release of the brain isoenzyme of creatine kinase in the first 6 hours after surgery (P = 0.046). Analyses comparing durations of circulatory arrest produced results similar to those of analyses comparing treatments. CONCLUSIONS: In heart surgery in infants, a strategy consisting predominantly of circulatory arrest is associated with greater central nervous system perturbation in the early postoperative period than a strategy consisting predominantly of low-flow cardiopulmonary bypass. Assessment of the effect of these findings on later outcomes awaits follow-up of this cohort.

Brain Ischemia↗
PubMed1993

Respiratory and irritant health effects of ambient volatile organic compounds. The Kanawha County Health Study.

Kanawha County, West Virginia, is one of the largest chemical manufacturing centers in the United States. In 1988, a survey of respiratory and irritant symptoms was administered to all third grade to fifth grade children attending 74 elementary schools in Kanawha County, and concentrations of 15 volatile organic compounds were measured at each school. Exposures were characterized by school location, by the sum of the concentrations of five petroleum-related compounds, and by the sum of the concentrations of 10 compounds more specific to industrial processes. Children enrolled in schools within the valley had higher rates of doctor-diagnosed asthma (odds ratio (OR) = 1.27, 95% confidence interval (CI) 1.09-1.48) and a higher score on a composite indicator of five chronic lower respiratory symptoms (OR = 1.13, 95% CI 1.02-1.26) than children who were enrolled in schools outside of the valley. The incidence of chronic respiratory symptoms was also positively associated with the concentrations of volatile organic compounds. The estimated change in the odds ratio for chronic lower respiratory symptoms associated with a 2-micrograms/m3 change in process-related compounds was 1.08 (95% CI 1.02-1.14). No consistent pattern was found between acute irritant symptoms in the 2 weeks preceding questionnaire administration and either proximity to industry or exposure to volatile organic compounds. The authors conclude that exposure to volatile organic compounds, including emissions from chemical manufacturing plants, is associated with increased rates of chronic respiratory symptoms characteristic of reactive airways.

Air Pollutants↗
PubMed1993

Race and gender differences in respiratory illness prevalence and their relationship to environmental exposures in children 7 to 14 years of age.

Race and gender differences in respiratory illness prevalence rates were assessed in a cohort of 8,322 white children and 1,056 black children 7 to 14 yr of age from four U.S. cities. Boys had higher rates of wheeze, asthma, cough, phlegm, and bronchitis than girls. Black children had higher rates of persistent wheeze, shortness of breath with wheeze, asthma, chronic cough, and chronic phlegm than white children. We examined whether the racial disparity in respiratory illness prevalence could be accounted for by environmental exposures and socioeconomic factors. The proportion of families without a parent who had graduated from high school was higher for blacks than for whites, as was the proportion of single-parent households. Black children took up smoking less frequently; their mothers smoked fewer cigarettes. Personal and maternal smoking predicted higher rates of persistent wheeze, chronic cough, chronic phlegm, and chest illness. The relative odds for persistent wheeze were 1.34 (1.07, 1.69) for smoking children compared with nonsmoking children. The relative odds for persistent wheeze were 1.35 (1.13, 1.60) for children whose mother smoked > 30 cigarettes per day versus children with no maternal smoke exposure. Other predictors of respiratory illnesses included parental respiratory illness, parental education, only-child status, single-parent household, air conditioner use, and body mass index. Nevertheless, adjustment for socioeconomic factors, environmental exposures, and body habitus did not significantly reduce the excess respiratory illness prevalence observed among black children. The adjusted relative odds were 1.47 (1.25, 1.74) for persistent wheeze and 1.57 (1.17, 2.10) for asthma for black children versus white children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pulmonary function growth velocity in children 6 to 18 years of age.

Pulmonary function growth rate varies with a child's stage of growth. Since attained pulmonary function reflects the cumulative effects of growth, insults, and repair, rate of growth may be a more sensitive indicator of a child's current pulmonary health status. The sample for analyses included 2,478 white boys and 2,785 white girls followed annually by questionnaire and spirometry. Empirically derived annual growth velocities, peak velocity (Vpk), and age at which peak velocity occurred (Agepk) were determined for height, FVC, FEV1, and FEF25-75 for each child. Mean velocity curves for height, FVC, FEV1, and FEF25-75, stratified by sex and Agepk of height (an indicator for early, middle, or late maturity) were produced as a function of age. The differences between Agepk of FVC, FEV1, and FEF25-75 and Agepk of height (i.e., the lag period) were compared by sex and by the indicator of maturity. Linear regression analyses were performed to investigate associations between Vpk and Agepk of height, as well as between the lag period and Agepk of height. As is generally observed in height growth, there were considerable variations in the age of onset and magnitudes of the adolescent growth spurts of the pulmonary function parameters both between sexes and among children of the same sex. The duration of adolescent growth spurt appeared to be similar for all children, regardless of early, middle, or late maturity. Thus, those who matured earlier had shorter total growth periods than those who matured later. On the other hand, early maturers had greater growth velocities during preadolescence and greater adolescent Vpk than later maturers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Menstrual function after tubal sterilization.

More than 10 million women in the United States have undergone tubal sterilization. There has been concern that this procedure may increase the risk of later menstrual dysfunction. The Collaborative Review of Sterilization (CREST) is a large, multicenter, prospective study of tubal sterilization in the United States. This report describes CREST participants who were interviewed immediately before sterilization and again in annual poststerilization interviews for up to 5 years between 1978 and 1988. The authors analyzed reported changes in six menstrual cycle characteristics for 5,070 women undergoing interval sterilizations. Longitudinal, multivariate regression was used to adjust for baseline menstrual function and other potential confounders. Five years after sterilization, 35% of the CREST participants reported high levels of menstrual pain, 49% reported heavy or very heavy menstrual flow, and 10% reported spotting between periods. In contrast to the fifth year, the first year of follow-up was similar to presterilization menstrual function; in the first year, 27% of participants reported high menstrual pain, 41% reported heavy menstrual flow, and 7% reported spotting. These findings may be affected by aging of the cohort and other study limitations, but they suggest that if tubal sterilization leads to changes in menstrual function, such changes may take some time to develop.

Adolescent↗
PubMed1992

Effects of cigarette smoking on rate of loss of pulmonary function in adults: a longitudinal assessment.

Data from a random sample of 8,191 men and women selected in six U.S. cities and examined on three occasions over a 6-yr follow-up period were analyzed by longitudinal methods to describe the effects of smoking history and current smoking behavior on rate of loss of pulmonary function during adult life. Former smokers had age- and height-adjusted rates of decline (34.3 ml/yr for men and 29.6 ml/yr for women) comparable with those of never smokers (37.8 ml/yr for men and 29.0 ml/yr for women) but much smaller than those of continuing smokers (52.9 ml/yr for men and 38.0 ml/yr for women). The accelerated rate of loss of FEV1 among smokers depended linearly on the number of cigarettes smoked per day during the interval between examinations. The estimated increase in rate of loss associated with smoking was 12.6 ml/yr per pack/day for men and 7.2 ml/yr per pack/day for women. These longitudinal estimates of the effects of smoking were approximately 50% larger than estimates obtained from cross-sectional analysis of the initial pulmonary function examination. Men who started smoking had accelerated rates of loss (55.9 ml/yr) as did women (43.1 ml/yr). Smokers who stopped smoking between examinations had reduced declines (41.2 ml/yr for men and 28.7 ml/yr for women) compared with continuing smokers. The age-specific rates of loss suggest that the benefits of cessation may be greatest among the youngest smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Longitudinal studies with continuous responses.

The analysis of serial measurements obtained in longitudinal studies plays an increasingly prominent role in applied research. The last few years have seen the development of many new techniques for carrying out analyses, including computer software. These methods can be used in a variety of standard problems, including repeated measures and cross-over designs, as well as growth curve analyses. We review these new methods, their application, and available computer packages. Data from a longitudinal study of lung function is used to illustrate the methods.

Adolescent↗
PubMed1991

Association of indoor nitrogen dioxide with respiratory symptoms and pulmonary function in children.

The effect of indoor nitrogen dioxide on the cumulative incidence of respiratory symptoms and pulmonary function level was studied in a cohort of 1,567 white children aged 7-11 years examined in six US cities from 1983 through 1988. Week-long measurements of nitrogen dioxide were obtained at three indoor locations over 2 consecutive weeks in both the winter and the summer months. The household annual average nitrogen dioxide concentration was modeled as a continuous variable and as four ordered categories. Multiple logistic regression analysis of symptom reports from a questionnaire administered after indoor monitoring showed that a 15-ppb increase in the household annual nitrogen dioxide mean was associated with an increased cumulative incidence of lower respiratory symptoms (odds ratio (OR) = 1.4, 95% confidence interval (95% Cl) 1.1-1.7). The response variable indicated the report of one or more of the following symptoms: attacks of shortness of breath with wheeze, chronic wheeze, chronic cough, chronic phlegm, or bronchitis. Girls showed a stronger association (OR = 1.7, 95% Cl 1.3-2.2) than did boys (OR = 1.2, 95% Cl 0.9-1.5). An analysis of pulmonary function measurements showed no consistent effect of nitrogen dioxide. These results are consistent with earlier reports based on categorical indicators of household nitrogen dioxide sources and provide a more specific association with nitrogen dioxide as measured in children's homes.

Air Pollutants↗
PubMed1991

Sensitive subgroups and normal variation in pulmonary function response to air pollution episodes.

The Clean Air Act requires that sensitive subgroups of exposed populations be protected from adverse health effects of air pollution exposure. Hence, data suggesting the existence of sensitive subgroups can have an important impact on regulatory decisions. Some investigators have interpreted differences among individuals in observed pulmonary function response to air pollution episodes as evidence that individuals differ in their sensitivity. An alternative explanation is that the differences are due entirely to normal variation in repeated pulmonary function measurements. This paper investigates this question by reanalyzing data from three studies of children exposed to air pollution episodes to determine whether the observed variability in pulmonary function response indicates differences in sensitivity or natural interoccasion variability. One study investigated exposures to total suspended particulates (TSP), the other two investigated exposure to ozone. In all studies, each child's response to air pollution exposures was summarized by regressing that child's set of pulmonary function measurements on the air pollution concentrations on the day or days before measurement. The within-child and between-child variances of these slopes were used to test the hypothesis of variable sensitivity. Regression slopes did not vary significantly among children exposed to episodes of high TSP concentration, but there was evidence of heterogeneity in both studies of ozone exposures. The finding of heterogeneous response to ozone exposure is consistent with the epidemiologic and chamber studies of ozone exposures, but the lack of evidence for heterogeneous response to TSP exposures implies that observed variation in response can be explained by sampling variability rather than the presence of sensitive subgroup.

Air Pollution↗