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Biomedical subjects

P J Byard

Publications and source records attributed to P J Byard.

At least 19 recordsLinked to original sources
PubMed1997

Identifying treatments that halt progression of pulmonary disease in cystic fibrosis.

Rapid progress in cystic fibrosis research affords the possibility of halting the progress of the lung disease. We used data from 215 patients who had sputum cultures negative for Burkholderia cepacia, at least one outpatient pulmonary function test during 1990, and at least one test a year later to estimate the number of subjects and study duration required to demonstrate that a hypothetical treatment reduces the rate of decline of forced expiratory volume in 1 s (FEV1) to zero. Mean rate of decline of FEV1 (percent predicted) was about 2% predicted per year. Variability decreases with increasing time of observation. For a 1-y study, with alpha = 0.05 and beta = 0.20, over 550 patients must complete the study in each group to show that a treatment halts pulmonary decline. For a 2-y study, 86 subjects in each group are required, and for 4 y, 65. Increasing the number of data points used to determine the rate of decline of FEV1 had only small effect on sample size. Use of pulmonary function data collected at regular intervals for research purposes did not alter these conclusions. Higher initial FEV1 was associated with a greater rate of decline, and among patients with initial FEV1 > 60% predicted, younger subjects had a faster decline than did older subjects. Thus, fewer subjects will be required to detect a complete halt in progression of lung disease if the patients are young and have mild pulmonary disease.

Adolescent↗
PubMed1995

Effect of high-dose ibuprofen in patients with cystic fibrosis.

BACKGROUND: Since the inflammatory response to chronic infection contributes to lung destruction in patients with cystic fibrosis, we hypothesized that anti-inflammatory therapy might slow the progression of lung disease. METHODS: In a double-blind trial, 85 patients, 5 to 39 years of age, with mild lung disease (forced expiratory volume in one second [FEV1], > or = 60 percent of the predicted value) were randomly assigned to receive ibuprofen or placebo orally twice daily for four years. Doses were adjusted individually to achieve peak plasma concentrations of 50 to 100 micrograms per milliliter. Changes in pulmonary function, the percentage of ideal body weight, the chest-radiograph score, and the frequency of hospitalization were assessed. RESULTS: Patients randomly assigned to ibuprofen had a slower annual rate of change in FEV1 than the patients assigned to placebo (mean [+/- SE] slope, -2.17 +/- 0.57 percent vs. -3.60 +/- 0.55 percent in the placebo group; P = 0.02), and weight (as a percentage of ideal body weight) was better maintained in the former group (P = 0.02). Among the patients who took ibuprofen for four years and had at least a 70 percent rate of compliance, the annual rate of change in FEV1 was even slower (-1.48 +/- 0.69 percent vs. -3.57 +/- 0.65 percent in the placebo group, P = 0.03), and this group of patients also had a significantly slower rate of decline in forced vital capacity, the percentage of ideal body weight, and the chest-radiograph score. There was no significant difference between the ibuprofen and placebo groups in the frequency of hospitalization. One patient was withdrawn from the study because of conjunctivitis, and one because of epistaxis related to ibuprofen. CONCLUSIONS: In patients with cystic fibrosis and mild lung disease, high-dose ibuprofen, taken consistently for four years, significantly slows the progression of the lung disease without serious adverse effects.

Adolescent↗
PubMed1995

Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection.

The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.

Adolescent↗
PubMed1993

Segregation analysis of speech and language disorders.

Complex segregation analysis was performed on pedigrees ascertained through 45 probands (26 males, 19 females) with a history of preschool speech and language disorders. Hypotheses concerning mode of inheritance were tested using the POINTER segregation analysis program. Although there is strong evidence for familial transmission of this trait, we were unable to distinguish between a major gene and multifactorial transmission model using likelihood-ratio chi-square tests. Future studies with quantitative measures of speech and language disorders are needed to resolve the issue of mode of inheritance for this trait.

Adolescent↗
PubMed1990

Beta-adrenergic responses and airway reactivity in healthy adults.

Healthy adults aged 18-90 years were tested for lymphocyte and granulocyte cyclic AMP responses to isoproterenol and prostaglandin E1 (PGE1), beta-adrenergic receptor density and antagonist binding properties, and for airway reactivity to methacholine. Our hypothesis was that reduced beta-adrenergic responses occur with aging and are associated with increased airway reactivity. This hypothesis was not supported by the data. Lymphocyte stimulation ratios (cyclic AMP level with stimulation/baseline cyclic AMP level) at higher concentrations of isoproterenol and PGE1 increased significantly with age. There were no significant age trends for any of the other variables. None of the beta-adrenergic responses or receptor properties correlated with airway reactivity to methacholine. beta-Adrenergic responses in lymphocytes and granulocytes from the same subject were weakly correlated at high concentrations. Prior studies which suggest that reduced beta-adrenergic responses and increased airway reactivity are concomitants of normal aging may differ from the present study in subject selection. In healthy older subjects, there appears to be no reduction in leukocyte beta-adrenergic responses or receptor properties and no change in airway reactivity.

Adolescent↗
PubMed1990

Effect of Pseudomonas cepacia colonization on survival and pulmonary function of cystic fibrosis patients.

We conducted a historical prospective study of 124 cystic fibrosis (CF) patients colonized with Pseudomonas cepacia (cases) and 124 sex and age matched non-colonized CF patients (controls). Thirty-two of the colonized patients died in the first year following P. cepacia colonization compared to 8 of the control patients, a highly significant difference (p less than 0.001). In the second year, there was no significant difference in mortality between the two groups. Cases as a group had poorer pulmonary function and chest X-ray scores than controls up to 2 years before P. cepacia first appeared in their sputum or throat cultures. Regression analysis of pulmonary function tests (percent predicted FEV1 and RV/TLC) for each subject from 3 years before to 2 years after colonization revealed significant differences between cases and controls in slope for FEV1 and in slope and intercept for RV/TLC. When compared separately according to gender, the differences between cases and controls are significant in females but not in males. These results suggest that patients with poor pulmonary function are more prone to colonization with P. cepacia, that a subgroup of these patients will be dramatically affected and die within a year, and that the organism continues to exert a less dramatic negative effect on the pulmonary function of those patients who survive the initial acute effects of colonization, particularly in female patients.

Cystic Fibrosis↗
PubMed1989

Familial aggregation of blood pressure and anthropometric variables in patrilocal households.

Fifty-three households in a small Indian fishing community were surveyed for blood pressure, pulse rate, and anthropometric measurements (height, weight, and three skinfolds). In addition to nuclear family relationships, correlations for extended family members and in-laws living within a common household were estimated by maximum likelihood. Based on likelihood ratio tests, the hypothesis that correlations among genetically unrelated pairs from the same household are zero is rejected for systolic blood pressure. Among genetically related individuals, the degree of relationship does not affect the magnitude of the blood pressure correlations. For the anthropometric measurements, family resemblance is significant only for first-degree relatives, except that the correlation for uncle-child pairs is significant for subscapular skinfold, and brother-in-law-sister-in-law pairs resemble each other for height and weight. The results suggest that common household environment is a significant determinant of blood pressure but not fatness in this population.

Blood Pressure↗
PubMed1989

Heterozygotes for cystic fibrosis: models for study of airway and autonomic reactivity.

Airway reactivity to cold air and methacholine, alpha-adrenergic and cholinergic reactivity measured as pupillary responses to phenylephrine and carbachol, respectively, and beta-adrenergic reactivity assessed by lymphocyte adenosine 3',5'-cyclic monophosphate (cAMP) response to isoproterenol were compared in 108 parents of patients with cystic fibrosis (CF) and 133 healthy adult controls. No differences were found between CF parents and controls in airway response to cold air or methacholine or in lymphocyte cAMP response to isoproterenol. Significant differences were found, however, in the response of the pupils to both phenylephrine and carbachol. Heterozygotes for CF have more reactive pupils; i.e., they require smaller doses of agonist for a 10% change in pupil size. In control subjects, the response of the pupils to phenylephrine and carbachol is highly correlated (r = 0.45, P less than 0.001), whereas in CF heterozygotes, the correlation is not significantly different from zero (r = -0.02). In controls, the pupil response to carbachol has a significant negative correlation with cold air response (r = 0.39, P less than 0.05), indicating that those whose pupils were most sensitive to carbachol had the greatest airway reactivity to cold air, but in CF heterozygotes the correlation is not significant (r = 0.10). A significant correlation exists between lymphocyte cAMP response and airway cold air response in CF heterozygotes (r = -0.32, P less than 0.05) (those whose beta-adrenergic responsiveness is low have greater airway reactivity), but not in controls. The CF parents with the most reactive airways tend to have lower beta-adrenergic responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Reproducibility of measurements of upper airway area by acoustic reflection.

To evaluate the extent and nature of the variability of measurements of upper airway area by acoustic reflection (AAAR), we made repeated measures of pharyngeal AAAR in 10 normal adult volunteers. We selected mean pharyngeal area as a better index of upper airway size than peak pharyngeal area or pharyngeal volume. Within-run variability of this measure was 8 +/- 4% (SD) (coeff of variation). This variability could not be explained by changes in lung volume or differences in phase of respiration. Five subjects had tracheal and pharyngeal area measured by using both the custom-made wax mouthpiece (W) and a commercial rubber pulmonary function mouthpiece (R). Reproducibility of pharyngeal AAAR was within 10% (coeff of variation) using R, but measurements of pharyngeal AAAR varied with the different types of mouthpiece, as W/R ranged from 0.72 to 1.70. In contrast, measurements of midtracheal area were similar for both mouthpiece types [mean W/R = 0.97 +/- 14 (SD)]. The acoustic reflection technique yields a reproducible index of pharyngeal size that does not vary with phase of respiration or modest changes in lung volume. Either W or R may be used to make clinical measurements, but the type of mouthpiece should be consistent and specified.

Acoustics↗
PubMed1988

Relationship between lung volume and tracheal area as assessed by acoustic reflection.

To determine whether airway size correlates with measures of lung or body size, we used the acoustic reflection technique to calculate tracheal cross-sectional area in 103 healthy young adults. Men have significantly larger tracheas than women [2.48 +/- 0.08 vs. 1.91 +/- 0.05 (SE) cm2, P less than 0.001]. Within each sex, there is no correlation between tracheal size and body size or maximal expiratory flows. There is a significant positive correlation between tracheal area and vital capacity in males only (r = 0.36, P less than 0.01). These results support the concept of dysanapsis, relatively independent growth of the airways and lung parenchyma, as well as sex-related differences in airway size and growth. Inherent airway size may be a factor in the development and/or progression of lung disease.

Acoustic Impedance Tests↗
PubMed1988

Relationships among airway reactivity, pupillary alpha-adrenergic and cholinergic responsiveness, and age.

Healthy adult volunteers (n = 122), who denied personal history of lung disease or family history of cystic fibrosis or asthma, took no interfering medications, and had forced expiratory volume in 1 s greater than or equal to 80% predicted, underwent methacholine challenge and pupillary reactivity testing. Pupil diameter measured in dark and light test conditions declined with age (Pearson's r = -0.54 and -0.36). Pupillary alpha-adrenergic responsiveness (expressed as the concentration of phenylephrine required to dilate the pupil 1 mm) was significantly correlated with age. Older subjects required lower concentrations for dilation and therefore were more sensitive to phenylephrine. Pupillary cholinergic responsiveness (the concentration of carbachol required for 1-mm constriction) was not significantly correlated with age. Therefore the significantly smaller baseline pupil size in the elderly cannot be explained by failure of alpha-adrenergic receptor responses or by increased pupillary cholinergic responsiveness. We found no significant correlation of methacholine bronchial reactivity with age. In addition, there was no relation between airway reactivity and pupillary alpha-adrenergic or cholinergic responsiveness in this sample of healthy adults. These findings, taken with others in the literature, suggest that the contribution of alpha-adrenergic and cholinergic responsiveness to nonspecific airway reactivity in healthy persons is small, if it exists at all, and that there is no significant change in airway reactivity with age in healthy adults.

Adolescent↗
PubMed1988

Pulmonary function in obligate heterozygotes for cystic fibrosis.

Airway reactivity is associated with rapid decline in pulmonary function with age or packyears of smoking in otherwise normal subjects. Because heterozygotes for cystic fibrosis (CFHZ) have a higher prevalence of airway reactivity than do controls, we tested the hypothesis that CFHZ have a more rapid decline in pulmonary function with age or packyears of smoking than do controls. We performed spirometry on 280 parents of children with CF and 280 age-matched control parents of children with heart disease. The ALA-DLD-78 questionnaire was also administered to these volunteers. Although the CF parents report wheezing apart from a cold more frequently than control parents, they show no greater decline of pulmonary function (FEV1, FEF25-75%, or FEV1/ht3) with age or packyears of smoking than do controls. The complaint of wheezing apart from a cold contributes significantly to the variance of FEV1 and FEF25-75% even when the effects of height, age, packyears of smoking, sex, and CF heterozygosity are controlled. The hypothesis that obligate heterozygotes for CF have increased age- or smoking-related decline in airflow is not supported by these data. Instead, the results suggest that any pulmonary function abnormalities associated with CF heterozygosity are small and not clinically significant and that CF heterozygosity per se is not a major risk factor for development and progression of obstructive airways disease.

Adult↗
PubMed1987

Family resemblance for anthropometric and blood pressure measurements in Black Caribs and Creoles from St. Vincent Island.

This paper examines family resemblance for five anthropometric measurements (height, weight, triceps skinfold, upper arm circumference relaxed [UACR] and flexed [UACF] and for systolic and diastolic blood pressure in a group of adult Caribbean islanders of primarily African ancestry. Six hypotheses about family resemblance are tested by using path analysis and likelihood ratios. Significant intergenerational transmission is found only for height and UACR. For weight, UACF, and diastolic blood pressure, non-transmissible sibling resemblance is the primary component of family resemblance, although significant marital resemblance exists for diastolic blood pressure. Triceps skinfold and systolic blood pressure show no evidence of any family resemblance. Although results for highly heritable traits such as height are comparable to reports from other populations, measurements with a large contribution from common family environment or residual environmental effects, such as triceps skinfold or blood pressure, have much lower family resemblance in this population than in other populations. We hypothesize that this difference is due to the fact that adult children and their parents do not share a common household in this culture and to the presence of major nonfamilial environmental factors contributing to obesity and hypertension in this population.

Adult↗
PubMed1987

Recreational use of psychoactive drugs by patients with cystic fibrosis.

We assessed unprescribed psychoactive drug use in 173 adults with cystic fibrosis. Twenty (11%) regularly smoked tobacco. Cigarette smoking ranged from 1 to 30 years (2 to 60 pack-years). Alcohol was used by 60%, and marijuana by 20% of the patients. Pulmonary symptoms were often increased the day after alcohol ingestion. Alcohol occasionally caused nausea, vomiting, and headache if the patient was taking some cephalosporin derivatives (such as cefsulodine) or chloramphenicol. Marijuana often aggravated chronic pulmonary symptoms, although some patients reported transient relief during use. Comparison with a retrospectively selected control group did not show faster short-term pulmonary deterioration in the tobacco smokers. Physicians who deal with cystic fibrosis and other chronic illnesses should be cognizant of interactions of unprescribed and prescribed drugs. Recreational use of unprescribed psychoactive drugs should be considered if unexpected symptoms occur in older patients.

Adolescent↗
PubMed1985

Family resemblance for components of craniofacial size and shape.

Path analysis is used to analyze family resemblance for eight principal components extracted from 30 anthropometric measurements of the craniofacial complex. Based on likelihood ratio tests, the null hypothesis of no assortative mating is rejected for the nasal height component. The null hypothesis of no common sibling environmental effect is rejected for the cranial size, craniofacial breadth, and nasal height components. Finally, the hypothesis that transmission from both mother and father is equal to 1/2, consistent with simple autosomal polygenic inheritance, is rejected for components corresponding to craniofacial breadth and upper facial height, thus implicating some effect of familial environment. Transmissibility is higher for components related to cranial size and facial height than for those related to facial breadth or ear dimensions.

Adolescent↗
PubMed1984

A family study of anthropometric traits in a Punjabi community: I. Introduction and familial correlations.

Data on 40 anthropometric measurements from 144 nuclear families in Chandigarh, India, are presented. Most families contain a pair of monozygotic or dizygotic twins, one or more singleton siblings, and their parents. Familial correlations for age-sex standardized, normalized measurements are estimated by maximum likelihood for marital, parent-child, sibling, and twin pairs. Heterogeneity tests for sex-specific subtype correlations male-male, male-female, female-female) indicate that the sex of the relative plays no significant role in the magnitude of the familial correlations except for maternal effects and differences among male and female twin pairs for a few of the variables. Marital correlations are high for body measurements, but not for head or face variables. Twin correlations seem to indicate a higher level of heritability than correlations from other family members.

Adolescent↗