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Biomedical subjects

P W Stewart

Publications and source records attributed to P W Stewart.

At least 19 recordsLinked to original sources

Plasma HIV burden in Malawian children co-infected with rotavirus.

Fifty-eight HIV-infected children with acute rotavirus diarrhea were tested for plasma HIV RNA. There was no difference between acute and convalescent mean viral loads, and little change in CD4 cell counts. Compared with the 16 children who died within 4 weeks, 31 survivors had slightly lower viral loads at presentation and significantly higher CD4 cell counts. Low CD4 cell counts, but not HIV-1-RNA concentrations, were predictive of Death. Local, enteric rotavirus infection did not appear to affect blood HIV viral load or CD4 cell counts in this small group of children.

Acute Disease↗

Longitudinal sero-reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS.

The relationship between viral infection with Kaposi sarcoma-associated herpesvirus (KSHV) and the onset of Kaposi sarcoma (KS) in AIDS patients is incompletely understood. This study investigates the use of three serological assays to predict the development of KS in HIV-positive patients. Serially collected serum samples from 36 patients with KS and matched controls in the Swiss HIV Cohort Study (SHCS) were analyzed in a case control study. Three serologic assays to detect antibodies against KSHV (nuclear and membrane antigen immunofluorescence assay, N-IFA, M-IFA and ORF 65.2 ELISA) were used to determine the predictive value of KSHV-seropositivity. Serial samples from the cases were also analyzed to determine longitudinal patterns of seroreactivity and identify cases of seroconversion. Assay sensitivity for detection of KSHV antibodies was highest for M-IFA (83%), followed by N-IFA (74%) and 65.2 ELISA (52%). At the time of initial serum sampling (median 4.7 years before KS), only the N-IFA distinguished case and control sera (61% vs. 32%) and no assay was clearly predictive of subsequent onset of clinical KS. Moreover, an unexpectedly high rate of reversions to seronegativity were observed by N-IFA (27/33) as well as by 65.2 ELISA (11/26) in the longitudinal analysis. Analysis of the ORF65.2 ELISA index indicated that these reversions before the clinical onset of KS were associated with antibody levels that frequently hovered around the level of detectability. A marked increase in ORF 65.2 antibody titer occurred in a third of the patients at the time of KS diagnosis. Only two seroconversions were documented. KSHV infection within the SHCS is likely to have preceded HIV infection. KSHV infection alone is not highly predictive of KS development in this cohort of HIV-infected homosexual men as compared with matched controls. Three KSHV serologic assays, though sensitive at the time of clinical KS are inconsistently positive before the development of AIDS-related KS.

AIDS-Related Opportunistic Infections↗

Linear equality constraints in the general linear mixed model.

Scientists may wish to analyze correlated outcome data with constraints among the responses. For example, piecewise linear regression in a longitudinal data analysis can require use of a general linear mixed model combined with linear parameter constraints. Although well developed for standard univariate models, there are no general results that allow a data analyst to specify a mixed model equation in conjunction with a set of constraints on the parameters. We resolve the difficulty by precisely describing conditions that allow specifying linear parameter constraints that insure the validity of estimates and tests in a general linear mixed model. The recommended approach requires only straightforward and noniterative calculations to implement. We illustrate the convenience and advantages of the methods with a comparison of cognitive developmental patterns in a study of individuals from infancy to early adulthood for children from low-income families.

Adolescent↗

Variation of lipids and lipoproteins in premenopausal women compared with men and postmenopausal women. DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) Investigators.

Numerous studies have reported cyclic fluctuations in lipids and lipoproteins as a function of the phase of the menstrual cycle. However, the reported patterns are quite variable and have led to an unclear picture of the influence of the menstrual cycle on the variability of lipids, and hence of the role of the menstrual cycle phase in the interpretation of serum lipids for premenopausal women. As part of the DELTA Study (Dietary Effects on Lipoproteins and Thrombogenic Activity), we evaluated the cyclic variation of circulating lipids and lipoproteins in 39 premenopausal women and compared intraindividual variances in these women, 18 postmenopausal women, and 46 men under conditions of tight dietary control. Cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, apolipoproteins A-1 (apo A-1) and B-100 (apo B-100), and lipoprotein (a) [Lp(a)] all demonstrated cycling in the premenopausal women. However, the observed cycling accounts for only a small fraction of the total biologic variability of lipids in premenopausal women. The magnitude of total intraindividual variability based on coefficient of variation (CV) for these lipids in premenopausal women (CV, 4% to 8.1%) was similar to that found for men (CV, 4.3% to 9.1%) and for postmenopausal women (CV, 3.7% to 6.7%). These results suggest that protocols for screening and monitoring of serum lipids in premenopausal women need not differ from those used for men or postmenopausal women.

Adult↗

Ozone-induced respiratory symptoms: exposure-response models and association with lung function.

Ozone-induced respiratory symptoms are known to be functions of concentration, minute ventilation, and duration of exposure. The purposes of this study were to identify an exposure-response model for symptoms, to determine whether response was related to age, and to assess the relationships between symptom and lung function responses to ozone. Four hundred and eighty-five healthy male volunteers (ages 18-35 yrs) were exposed to one of six ozone concentrations at one of three activity levels for 2 h. Symptoms and forced expiratory volume in one second (FEV1) were assessed at the end of 1 and 2 h. The exposure and response data were fitted by a nonlinear exposure-response model previously found to describe FEV1 response. The proportion of individuals experiencing moderate or severe cough, shortness of breath, and pain on deep inspiration were accurately described as functions of concentration, minute ventilation, and time. Response was inversely related to age for shortness of breath (p=0.0001), pain on deep inspiration (p=0.0002), and cough (p=0.0013). Controlling for exposure differences, symptom responses were significantly but weakly (correlation coefficient 0.30-0.41) related to the FEV1 response. In conclusion, the exposure-response model did accurately predict symptoms, response was inversely related to age.

Adolescent↗

Turner syndrome: a pattern of early growth failure.

The purpose of this study was to determine the pattern of early growth in girls with Turner syndrome. Analysis was performed on a total of 464 longitudinal measurements of height, obtained from birth to 8 years of age from 37 girls with Turner syndrome who did not have significant cardiac disease or autosomal abnormalities. All data were obtained prior to the initiation of any hormonal therapy. Mean height SDS fell from -0.5 at birth to -1.5 at age 1 year and -1.8 at age 1.5 years. Growth curves fitted using the first two components of the infancy-childhood-puberty model of growth revealed that growth failure was due to (a) mild growth retardation in utero, (b) slow growth during infancy, (c) delayed onset of the childhood component of growth and (d) slow growth during childhood. Physicians should consider the diagnosis of Turner syndrome in any girl with an unexplained failure to thrive or with short stature, even during the first 2 years of life.

Body Height↗

Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients.

Recent studies suggest that inflammation plays a role in the pathogenesis of lung disease in cystic fibrosis (CF). The goal of the present study was to quantitatively compare bronchoalveolar lavage fluid (BALF) inflammation and its relation to bacterial infection, between children with CF and children with other chronic respiratory problems. Differential cell counts, immunoreactive interleukin 8 (IL-8), and quantitative bacterial cultures were done in BALF from 54 CF (median age 1.8 yr) and 55 control patients (median age 1.0 yr) who underwent bronchoscopy for clinical indications. Among infected CF patients, those with Pseudomonas aeruginosa did not have more inflammation than those without P. aeruginosa. The ratio of neutrophils or of IL-8 to bacteria in BALF was significantly greater for CF patients compared with control subjects, regardless of pathogen. Calculation of linear regression for either neutrophils or IL-8, as a function of bacterial quantity, yielded positive slopes for both CF and control patients, but with significant elevations for CF. We conclude that the inflammatory response to bacterial infection is increased or prolonged in CF compared with control patients, and that this increase is not necessarily due to pathogens specific for CF (e.g., P. aeruginosa). These data may provide further rationale for anti-inflammatory therapy early in CF.

Bronchoalveolar Lavage Fluid↗

Subacute Pb exposure during development and unbaited tunnel maze performance in mice.

Although research has linked chronic, low-level Pb exposure to behavioral and cognitive changes in humans and animals, far less is known about the effects of transient, subchronic Pb exposure during early postnatal development. The need to understand such effects is underscored by the possibility that subchronic Pb exposure may not produce chronically elevated blood-Pb levels, but may produce long-term behavioral changes. To test this hypothesis, we investigated the effect of low-level Pb exposure on unbaited tunnel maze performance in Binghamton Heterogeneous Stock mice. Mice were either nontreated or given subchronic sodium acetate, 5, 10, or 25 mg/kg Pb acetate intragastrically on postnatal (PN) days 6, 9, 12, 15, and 18. No further Pb exposures were given after postnatal day 18. Blood-Pb measurements were taken from selected mice on PN 18, 19, 23, 28, and 38. On PN 38-42, all mice were individually tested in an unbaited tunnel maze under nondeprived conditions. Locomotor activity, exploration, and experience-dependent changes in cul-de-sac entries were recorded. Although Pb did not affect bodyweight and blood-Pb levels were below 10 microg/dl at the time of behavioral testing, a history of low-level preweaning Pb exposure caused a dose-dependent increase in cul-de-sac entries. This behavioral change was dissociable from changes in bodyweight, degree of exploration or an a priori bias to enter cul-de-sacs. The current results support the hypothesis that brief, subchronic Pb exposure during development produces behavioral changes that last well beyond the exposure period, even when blood Pb declines to within "acceptable" levels (l0 microg/dl).

Analysis of Variance↗

Stress, social support, and substantiated maltreatment in the second and third years of life.

OBJECTIVE: The purpose of this research was to determine whether risk factors for a maltreatment report in the first year of life, especially the interaction of life event stress and social support, persist into the second and third years of life. METHOD: Predominantly low income mothers who had been interviewed shortly after the birth of infants in a longitudinal cohort were re-interviewed around the infants' first birthdays, and reports to North Carolina's Central Registry of Child Abuse and Neglect were tracked for substantiated maltreatment reports. RESULTS: Variables significantly associated with a substantiated maltreatment report in the second or third year of life (p < .01) were first year maltreatment reports and participation in Medicaid. Three interactions between a stressful life event indicator variable and a social support indicator variable were significant predictors of substantiated second or third year reports (p < .05). CONCLUSIONS: Even in the presence of significant risk factors from the first year of life, life event stress can increase the risk of a substantiated maltreatment report in the second or third years of life, but social support may moderate the effect of life events.

Adolescent↗

ApoE genotype does not predict lipid response to changes in dietary saturated fatty acids in a heterogeneous normolipidemic population. The DELTA Research Group. Dietary Effects on Lipoproteins and Thrombogenic Activity.

Recent studies have suggested that variations in apoE genotypes may influence the magnitude of plasma lipid changes in response to dietary interventions. We examined the ability of apoE genotype to predict plasma lipid response to reductions in percent of calories from total fat (TF) and saturated fat (SF) in a normolipidemic study population (n = 103) heterogeneous with respect to age, gender, race, and menopausal status. Three diets, an average American diet (34.3% TF, 15.0% SF), an AHA Step 1 diet (28.6% TF, 9.0% SF), and a low saturated fat (Low-Sat) diet (25.3% TF, 6.1% SF) were each fed for a period of 8 weeks in a three-way crossover design. Cholesterol was kept constant at 275 mg/d; monounsaturated and polyunsaturated fat were kept constant at approximately 13% and 6.5% of calories, respectively. Fasting lipid levels were measured during each of the final 4 weeks of each diet period. Participants were grouped by apoE genotype: E2 (E2/2, E2/3, E2/4); E3 (E3/3); E4 (E3/4, E4/4). Relative to the average American diet, both the Step 1 and Low-Sat diets significantly reduced total cholesterol, LDL cholesterol, and HDL cholesterol in all three apoE genotype groups. No evidence of a significant diet by genotype interaction, however, could be identified for any of the measured lipid and lipoprotein end points. Additional analysis of the data within individual population subgroup (men and women, blacks and whites) likewise provided no evidence of a significant diet by genotype interaction. Thus, in a heterogeneous, normolipidemic study population, apoE genotype does not predict the magnitude of lipid response to reductions in dietary saturated fat.

Adult↗

Prediction of ozone-induced FEV1 changes. Effects of concentration, duration, and ventilation.

The purpose of this analysis of previously published data was to identify a model that accurately predicts the mean ozone-induced FEV1 response of humans as a function of concentration (C), minute ventilation (VE), duration of exposure (T), and age. Healthy young adults (n = 485) were exposed for 2 h to one of six ozone concentrations while exercising at one of three levels. Candidate models were fitted to portions of the data and evaluated on the basis of their ability to predict the mean response of independent samples. A sigmoid-shaped model that is consistent with previous observations of ozone exposure-response (E-R) characteristics was identified and found to accurately predict the mean response with independent data. This model in a more general form may allow the prediction of responses under conditions of changing C and VE. We did not find that response was more sensitive to changes in C than in VE, nor did we find convincing evidence of an effect of body size upon response. We did find that response to ozone decreases with age. In summary, we have identified a biologically plausible, predictive model that quantifies the relationship between the ozone-induced change in FEV1, and C, VE, T, and age.

Adolescent↗

DMSA chelation during co-exposure to lead: increased locomotor activity in lead-exposed mice but not controls.

We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA) on indices of "hyperactive" behavior in lead-exposed and control Binghamton Heterogeneous Stock (Het) mice. As expected, 6 weeks of ingestion of 0.5% lead acetate in drinking water reduced immobility in a forced water swim relative to controls. DMSA did not attenuate this behavioral change. In fact, DMSA interacted with lead exposure to increase locomotor activity in the forced water swim. DMSA also apparently excacerbated lead's tendency to reduce immobility. While any generalizations to human populations should be cautioned, these results and others suggest the need for further research.

Animals↗

Risk of child abuse or neglect in a cohort of low-income children.

The purposes of this research were to identify risk factors for reported child abuse or neglect and to examine the roles of stress and social support in the etiology of child maltreatment. Mothers of newborn infants with biomedical and sociodemographic risk factors were recruited from community and regional hospitals and local health departments in 42 counties of North and South Carolina selected for geographic distribution and for large numbers of such newborns. For every four such mothers, the next mother to deliver an otherwise normal newborn was sought. Mothers were interviewed shortly after giving birth, and state Central Registries of Child Abuse and Neglect were reviewed when each infant was 1 year of age. Eight hundred forty-two of 1,111 recruited mothers were successfully interviewed in their homes between March 1986 and June 1987. Seven hundred forty-nine North Carolina births who resided in the state more than 6 months were eligible for inclusion in the analysis. Logistic regression with backward elimination procedures was used in the analysis. Maternal education (p < .01), number of other dependent children in the home (p < .01), receipt of Medicaid (p < .01), maternal depression (p < .05), and whether the maternal subject lived with her own mother at age 14 years (p < .05) were the best predictors of a maltreatment report. Further examination revealed an interaction effect between stressful life events, as measured by life event scores, and social well-being (p < .01). For children born at risk for social and/or medical problems, extreme low income (participation in public income support programs), low maternal education, maternal depression, the presence of any other young children in the home, and a mother's separation at age 14 years from her own mother significantly predict child maltreatment reports in the first year of life. In addition, stressful life events, even if perceived positively, may increase or decrease the risk of maltreatment reports, depending upon the presence of social support.

Adolescent↗

Cross generation lead ingestion: behavioral and physiological effects in mice.

We examined some developmental and behavioral sequelae of exposing Binghamton Heterogeneous Stock (HET) mice to a 0.5% aqueous lead acetate solution (as the only available fluid source) for either none, one, two, or three generations. Lead exposure, regardless of generation, resulted in decreased body weight and a delay in age of first eye opening relative to controls, but did not delay home nest return latencies. Drinking the lead solution, across two and three successive generations, resulted in a marked and apparently cumulative decrease in pup viability, as well as an increase in dam fatality rates. However, no such cumulative or residual effects were observed on the behavioral activity of those mice who managed to survive. Perhaps a selection effect for lead-tolerant mice occurred in the present study; such an effect could account for the apparent lack of cumulative and residual behavioral effects.

Animals↗

Correlates of recurrent wheezing in school-age children. The Physicians of Raleigh Pediatric Associates.

Correlates of recurrent wheezing were examined in a case-control study involving 343 children ranging from 7 to 12 yr of age and recruited from a general pediatric practice. Positive skin tests for allergy were observed in 35% of a random sample of children without recurrent wheezing, and in 77% and 90% of children who had experienced from two to four episodes and five or more episodes, respectively, of recent wheezing. By logistic regression analysis, sensitization to dust mite (odds ratio [OR]: 5.2; 95% CI: 3.0 to 9.0), cat (OR: 15.5; 95% CI: 3.4 to 70.8), and Alternaria (OR: 6.8; 95% CI: 2.1 to 21.5) antigens was consistently associated with recurrent wheezing. Sensitization to pollen antigen(s), observed in 60% of allergic children, was not associated with wheezing. A family history of asthma was a significant predictor of recurrent wheezing (OR: 3.2; 95% CI: 1.7 to 5.9) after adjusting for its association with positive skin tests. Environmental tobacco smoke (ETS) exposure was associated with an increased risk of recurrent wheezing in nonallergic children and in allergic females, but not in allergic males. ETS exposure was not associated with positive skin tests for allergy. A history of wheezing with respiratory illness before 2 yr of age was associated with a modest risk of recurrent wheezing between 7 and 12 yr of age (OR: 2.3; 95% CI: 1.2 to 4.6), a risk that did not differ by allergic status or gender. Theoretically, the prevalence of recurrent wheezing in this population could be reduced approximately 65% by controlling exposure to indoor allergens and ETS.

Allergens↗

Proportion of moderately exercising individuals responding to low-level, multi-hour ozone exposure.

The purpose of this study was to describe the proportion of moderately exercising individuals experiencing significant respiratory responses to low-level, multi-hour ozone exposure as a function of ozone concentration and exposure duration. Sixty-eight healthy, nonsmoking adults, ages 18 to 34 yr, underwent two or more 6.6-h exposures to 0.0, 0.08, 0.10, or 0.12 ppm ozone. Five hours of exercise was performed during exposure, and lung function was measured before exposure and following each hour of exposure. For each combination of concentration and duration, each individual was determined to either have or not have experienced a 10% or greater decrement in FEV1. A logistic function was used to model the proportion of individuals experiencing such a decrement as a function of concentration and exposure duration. Bootstrap 90% confidence intervals (CIs) were calculated around the predictions. The model was found to give predictions that were in good agreement with observed data. The lowest level of exposure (C x T) for which the 90% CI excluded zero was approximately 0.2 ppm-h. For exposure to 0.12 ppm ozone for 6.6 h, 47% (90% CI = 30 to 65%) of exposed individuals were predicted to experience a 10% decrement in FEV1. A greater proportion of younger adults than of older adults were found to experience a given effect for a given exposure.

Adolescent↗

Urban black women's perceptions of breast cancer and mammography.

The purpose of this study was to examine differences in perceptions of breast cancer and mammography between black women who wanted a mammogram and those who did not. The subjects were 186 low socioeconomic black women who attended an inner city community health clinic (83% response rate). There were no significant differences on the demographic and background variables between women who did (N = 139) and did not (N = 47) want a mammogram. The knowledge level of both groups regarding breast cancer was poor. Those who desired a mammogram perceived themselves as more susceptible to breast cancer, and considered breast cancer more severe than those who did not want a mammogram. Neither group identified many barriers to obtaining a mammogram. The majority (at least 88 percent of those who wanted a mammogram and at least 55 percent of those who did not) agreed with each of the five benefit items. Eighty-five percent of both groups agreed they would receive a mammogram if their physician told them to do so. The two Health Belief Model components which accounted for the largest percentage of the variance between women who wanted a mammogram and those who did not were perceived benefits (13 percent) and perceived susceptibility (3 percent).

Adult↗