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Biomedical subjects

A F Wilson

Publications and source records attributed to A F Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1987

Plasma thyroid hormones, thyroid stimulating hormone, and insulin during acute hypometabolic states in man.

Acute behavioral rest states in man are associated with marked hormonal and metabolic changes. In order to complete a hormonal profile of these states and to identify possible metabolic regulators, we measured thyroid hormones (T3 and T4), thyroid stimulating hormone (TSH), and insulin during the stylized mental practice of "transcendental mediation" (TM) and during ordinary unstylized eyes closed rest. Except for TSH, which declined acutely, hormone levels were normal and stable throughout the experiment. The stability of T3 and T4, and insulin make it unlikely that these hormones regulate the acute metabolic changes associated with these behavioral states. Decreased TSH, along with stable thyroid hormone levels, may suggest change of the set point for feedback control of TSH secretion during TM and is consistent with primarily neural modulation of TSH secretion by this behavior.

Adult↗
PubMed1987

Marked reduction of forearm carbon dioxide production during states of decreased metabolism.

We studied oxygen consumption, carbon dioxide production and acid/base changes in 62 subjects during two hypometabolic states (35 during transcendental mediation and 27 during unstylized rest). The results indicate that, during these hypometabolic states, arterial-venous CO2 content difference declines, and that during transcendental meditation, arterial-venous CO2 content difference briefly disappears. This change is due to both an increase of arterial CO2 content and a decrease of venous CO2 content. Similar, but opposite and smaller, changes occurred in arterial and venous O2 content. Respiratory quotient was low at all times and decreased during the hypometabolic states. These results are consistent with the hypothesis that, during hypometabolic states significant ketogenesis is induced, and provision of energy from the normally predominant process of beta-oxidation of fat becomes sufficient to provide energy for greatly reduced activity without entry of two carbon fragments into the tricarboxylic acid cycle; under these conditions, biochemical feedback mechanisms inhibit the tricarboxylic acid cycle. The net result of these metabolic changes could explain the major observations: absent carbon dioxide production while oxygen consumption declines but continues and the venous effluent contains more acid.

Adult↗
PubMed1986

An approach to the multivariate analysis of high-density-lipoprotein cholesterol in a large kindred: the Bogalusa Heart Study.

The genetic determination of high-density-lipoprotein cholesterol (HDL-C) levels was evaluated using segregation analysis techniques in a large multigenerational kindred with a high prevalence of coronary heart disease and myocardial infarction. Univariate segregation analysis of HDL-C levels with the effects of age and sex removed by regression provided evidence of a Mendelian mode of inheritance for a portion of the variability in HDL-C levels. Subsequent analyses included low-density-lipoprotein cholesterol (LDL-C) levels and several behavioral and anthropometric variables that affect HDL-C levels. Pedigree discriminant analysis was used to find the linear functions of the variables that maximized the likelihood given the pedigree structure and assuming monogenic segregation. The best linear function was found to be approximately equivalent to the log of the HDL-C to LDL-C ratio, with concomitant and environmental effects removed by regression. Genetic hypotheses were tested by cross-validation; linear functions derived from data on each side of the kindred were used to test hypotheses on the other side of the kindred. On one side of the kindred, all hypotheses were accepted. On the other side of the kindred, only Mendelian inheritance of the linear function was indicated. Segregation of the age- and sex-adjusted HDL-C values, and of the linear function, was evaluated using a regressive model that allows for intrafamilial correlations in addition to a monogenic effect. All analyses provide evidence for levels of HDL-C being controlled by a major locus with neither dominant nor recessive expression.

Cholesterol, HDL↗
PubMed1986

Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma.

A segregation analysis was performed on the bronchial response to a standardized methacholine inhalation challenge obtained from members of 83 families that were part of a Natural History of Asthma study population. Each bronchial response was expressed as the area under the best fitting parabolic dose-response curve. Standard methods of statistical analysis demonstrated that age, sex, and recent respiratory infection had a significant effect on the bronchial response to methacholine inhalation. Segregation analysis indicated that, although a familial component exists in the transmission of bronchial response to methacholine, the bimodal distribution of the bronchial response is not due to segregation at a single autosomal locus.

Asthma↗
PubMed1986

Time dependence of airways and lung parenchymal recoil hysteresis.

Hysteresis of airways and lung parenchymal recoil was examined in normal subjects by measuring specific conductance (sGaw) and lung elastic recoil (Pst,L) before and 5, 10, 15, and 30 s after deep inspiration (DI). Routine lung function tests were normal before and after inhaled metaproterenol. sGaw increased significantly for 10 s after DI. Also, sGaw(DI) was greater than sGaw in 11 of 12, 8 of 12, 7 of 12, and 6 of 12 subjects at 5, 10, 15, and 30 s, respectively, after DI. The response of sGaw to DI and metaproterenol correlated significantly with each other (r = 0.82, P less than 0.001). However, after metaproterenol, sGaw(DI) did not exceed sGaw. Pst,L decreased significantly for 15 s after DI, with the lowest measured Pst,L(DI) values occurring 5 s after DI (P less than 0.01-0.001). Both sGaw(DI) and Pst,L(DI) values returned to base line (preinspiration) in a time-dependent exponential manner, with time constants of 9.2 +/- 4.9 and 11.3 +/- 6.1 s, respectively; these time constants were not significantly different from each other. We conclude that airways hysteresis is the predominant finding in normal subjects (even without prior pharmacological bronchoconstriction) before but not after metaproterenol; Pst,L decreases after DI and, in normal individuals, returns to base line in a time-dependent manner; and the time-dependent behavior of airways and lung parenchymal hysteresis have opposite (and unequal) effects on airway caliber.

Adult↗
PubMed1986

Comparison of once-a-day and twice-a-day theophylline in asthma.

Sustained-release theophylline compounds given once (Uniphyl) or twice (Theodur) daily were compared in adult asthmatics. Following a single dose of oral medication, large and peripheral airways bronchodilation occurred; response to theophylline correlated significantly with the log plasma theophylline concentration. Cardiac output and stroke volume, measured noninvasively using the acetylene technique, also increased significantly. During maintenance therapy, both preparations caused similar improvements in pulmonary function and symptoms; however, side effects were less with once-daily therapy.

Asthma↗
PubMed1986

Supine change in arterial oxygenation in patients with chronic obstructive pulmonary disease.

In normal subjects, recumbent PaO2 differs from upright PaO2 as a function of the relationship between FRC and closing volume. However, in patients with lung disease, the factors controlling PaO2 change. Furthermore, the distribution of airway closure does not strictly reflect gravitational gradients in pleural pressure. Hence, we evaluated the effects of recumbency on PaO2 in patients with advanced COPD. We conducted pulmonary function tests and measured PaO2, AaPO2, change from upright to supine FRC, VE, cardiac output (QT), and mixed venous oxygen saturation (SvO2). Eight patients with COPD in whom PaO2 decreased in the supine position (Group I) were compared with 8 patients with COPD in whom PaO2 improved in the recumbent position (Group II); the only anthropometric difference between the groups was greater body weight in Group II (p less than 0.05). Pulmonary function was comparable in the 2 groups. In both groups, FRC decreased with recumbency, but supine FRC and delta FRC did not differ between groups nor correlate significantly with PaO2, AaPO2, or venous admixture (QVA/QT). Supine SVO2 increased in both groups, but supine QT increased significantly only in Group I. In Group II, recumbent QVA/QT did not change significantly, whereas recumbent QVA/QT increased (p less than 0.02) in Group I. The cause for increased QVA/QT in Group I was reduced VE plus increased QT while supine; in contrast, by maintaining a higher supine VE and by not increasing QT significantly, an increase in QVA/QT was prevented in Group II subjects, an increase that would otherwise have overwhelmed the benefits of increased recumbent SVO2 on PaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1985

Comparison of clinical effects and pharmacokinetics of once-daily Uniphyl and twice-daily Theo-Dur in asthmatic patients.

A pharmacokinetic study using theophylline syrup in adult asthmatic patients demonstrated a mean apparent volume of distribution of 0.38 liters/kg, mean elimination rate constant of 0.10 hours-1, and variable rates of clearance of theophylline (total body clearance of 0.38 to 0.96 ml/kg per minute). Subsequently, the asthmatic patients were compared using a cross-over design after maintenance Uniphyl (once daily at 8 a.m. or at 8 p.m.) and Theo-Dur (twice daily at 8 a.m. and 8 p.m.). Total daily maintenance theophylline dosage, calculated from the pharmacokinetic data, was identical in all three cross-over phases. At the end of each phase, plasma theophylline levels were measured every two hours and spirometric determinations were made every four hours (excluding 4 a.m.) for 24 hours. The following results were observed: highest peak and mean plasma theophylline concentration and area under the concentration-time curves with evening Uniphyl (p less than 0.05); prolonged time-to-peak theophylline concentration after nocturnal compared with daytime dosing; diurnal variation in pulmonary function and plasma theophylline concentrations; no significant differences between the three maintenance treatments in asthmatic symptoms or spirometric results.

Adult↗
PubMed1985

Hormonal control in a state of decreased activation: potentiation of arginine vasopressin secretion.

Behaviorally induced stress is associated with increased arginine vasopressin (AVP) secretion. In this report we describe a phasic conditioned response of AVP secretion yielding 2.6-7.1 times normal plasma concentration of this hormone in association with a physiological state of decreased activation, that associated with the mental technique of "transcendental meditation" (TM) in long-term practitioners (6-8 years of regular elicitation). Such a very large phasic response of AVP was previously unknown in the normal physiology of AVP. This elevation was not accompanied by elevation of plasma osmolality. Unstylized ordinary eyes closed rest in a separate group of subjects studied in the same manner was associated with normal plasma AVP concentration. Galvanic skin resistance (GSR) increased during both TM and rest with significantly larger increase associated with TM. Other measures of activation, including muscle metabolism, and the Spielberger Anxiety Inventory indicated marked relaxation in association with TM. In previous research it has been shown that blood pressure does not change acutely during this behavior. These observations indicate that neither stress nor operation of other usual homeostatic control mechanisms are responsible for elevated for AVP in the meditators. It is speculated that the apparently unique mechanism of TM-induced AVP secretion may be more specifically related to the behavioral effects of meditation.

Adult↗
PubMed1985

Modulation of red cell metabolism by states of decreased activation: comparison between states.

Marked decline of red cell metabolism has been described during the acute state of decreased activation associated with the stylized mental technique of transcendental meditation (TM) in long-term meditators (5-10 years regular elicitation, TM instructors). It is not known whether unstylized rest is accompanied by a similar effect and it is not known what effector(s) may contribute to red cell metabolic changes in these states. In the present study ordinary, unstylized rest was found to be accompanied by small increase of red cell glycolytic rate. Apparently, either repeated elicitation of TM behavior or some special feature of this practice become associated with new mechanisms of metabolic control than those previously in operation. Although the data of this study do not permit isolation of the precise psychological determinants of this effect, the range of possible physiological effectors can be delimited. Blood pH, PCO2, PO2, and phosphate can be eliminated as significant for red cell metabolic control during both TM and rest, and based upon related studies, several known hormones such as insulin, T3, T4, arginine vasopressin, oxytocin, prolactin and growth hormone can also be eliminated as responsible effector(s).

Acid-Base Equilibrium↗
PubMed1985

Role of Alternaria and Penicillium spores in the pathogenesis of asthma.

The ability to harvest spore-rich isolates of molds permitted quantitative studies of their role in the pathogenesis of asthma. Alternaria and Penicillium were selected as examples of ubiquitous molds that readily induce IgE antibodies and are of contrasting sizes. Extracts from those spores were prepared for skin tests and aerosol bronchial challenges. Intact spores were used in the same subjects in bronchial challenges delivered by a Spinhaler. Seven patients with a history of mild asthma received a total of 16 bronchial challenges with the mold to which they had been sensitized. Provocative doses in spore equivalents for a 35% drop in SGaw, 20% drop in FEV1, or 25% drop in PEFR were sought for each challenge. Density dependence-flow rates were also determined. Environmental spore survey data were obtained and compared with the challenge doses for these spores. It was found that immediate-type asthma was readily provoked by both whole spores and by their extracts, in some subjects fewer intact than extracted spores were required, delayed-type asthma occurred only after whole spore challenges, SGaw was the most sensitive and equally specific of the pulmonary function tests, and provocative doses of spore equivalents were within natural exposure ranges. The study confirmed that Alternaria and Penicillium spores in relatively natural states and numbers were potent immunopathogens for asthma.

Adolescent↗
PubMed1984

Major gene model for the inheritance of catechol-O-methyltransferase activity in five large families.

Five large families including 1,189 individuals were each ascertained through one proband with essential hypertension. Four of the probands were white and one was black. Erythrocyte catechol-o-methyltransferase (COMT) activity was measured in 551 family members. Standard statistical methods were used to investigate sex, age, and family differences in COMT activity. Maximum-likelihood methods were used to fit mixtures of normal distributions to COMT activity. COMT activity is distinctly bimodal. Pedigree segregation analyses were performed on the untransformed COMT values, their square roots, and natural logarithms in each family. In no family and under none of the three transformations was it possible to reject the hypothesis of Mendelian transmission of a major gene with two alleles in Hardy-Weinberg equilibrium. In most cases a genetic hypothesis with complete dominance or recessiveness, or a hypothesis of equal transmission probabilities was rejected. While the different transformations had a large effect on the skewness and kurtosis of the overall distribution of the data, they had little effect on the outcome of these segregation analyses. Therefore, this study strongly supports the concept that variation in COMT activity is due in large part to the effects of a major gene.

Adult↗
PubMed1984

Linkage relationships between a major gene for catechol-o-methyltransferase activity and 25 polymorphic marker systems.

Segregation analysis has provided evidence suggesting the existence of a major gene for catechol-o-methyltransferase (COMT) activity in man. Five large families (4 Caucasian, 1 black), with a total of 1,189 individuals, were ascertained as part of a genetic study of blood pressure. Erythrocyte COMT activity and status at 25 polymorphic genetic marker loci were determined on more than 518 individuals in these pedigrees. Genetic linkage analysis of COMT with each of the 25 marker loci was performed in two ways: 1) using parameter estimates from segregation analysis of untransformed COMT activity, and 2) using parameter estimates from segregation analysis of the power transformation of the COMT activity that maximized the likelihood of the genetic hypothesis in each family. Tight and close linkage were excluded at 21 and 15 loci, respectively. A lod score of 1.27 at theta = 0.1 was found between the loci for COMT activity and phosphogluconate dehydrogenase (PGD). Transformation of the data had little effect on the outcome of the linkage analysis.

Catechol O-Methyltransferase↗
PubMed1984

Bromocriptine in the management of end of dose deterioration in Parkinson's disease.

Thirty-three patients with advanced Parkinson's disease complicated by end of dose deterioration were treated with bromocriptine. The drug was slowly increased so that by treatment week 24 the mean daily dose of bromocriptine was 22mg and levodopa had been decreased by an average of 15 percent. The majority of improvement in daily fluctuations and Parkinsonian disability score was documented by 8 weeks, at which time the mean daily bromocriptine dose was only 12mg. End of dose deterioration was reduced in 78 percent of the patients (mean 43% improvement). Total Parkinsonian disability score was decreased by 33 percent. Adverse effects were minimal; the most common was mild transient early treatment nausea which occurred in 15 percent of the patients. The slow introduction of small doses of bromocriptine, combined with minimal levodopa reduction, can give Parkinsonian patients significant improvement in end of dose deterioration.

Adult↗
PubMed1984

Non-invasive measurement of cardiac output by a single breath constant expiratory technique.

A new single breath test has been developed that measures pulmonary blood flow (Qc) and pulmonary tissue volume by using the fact that Qc is proportional to the relationship between the absorption rate of acetylene (C2H2) from the alveolar gas and the rate of change of lung volume during constant expiratory flow. To make these measurements a bag in bottle system with a rolling seal spirometer, a mass spectrometer, and a minicomputer with analogue to digital conversion have been used. Qc was compared with cardiac output measured by the thermodilution technique in 20 patients with cardiac disease; some also had mild chronic obstructive pulmonary disease. The mean (SD) resting Qc for the group was 5.27 (1.22) l/min and the cardiac output measured by thermodilution was 5.30 (1.31) l/min. The mean difference between the two estimations of cardiac output was 0.03 l and the standard deviation of this difference was 0.76 l. The Qc technique was not successful in patients with an FEV1/FVC less than 60%, but seemed to be accurate in those with higher FEV1/FVC values. Correction of Qc for the effect of venous admixture in 14 patients resulted in an average 19% overestimation of cardiac output (6.01 (2.52) l/min v 5.05 (1.64) l/min). It is concluded that cardiac output can be accurately measured in patients with cardiac or mild pulmonary disease. No correction for venous admixture due to ventilation-perfusion mismatch was necessary in these patients, presumably because the large breath used by the technique overcomes most mild ventilation-perfusion maldistribution. These findings, in addition to the non-invasive nature of the technique, suggest potential value for the measurement of cardiac output in various clinical conditions.

Adult↗