Search PubMed⌕ Search

Biomedical subjects

A F Wilson

Publications and source records attributed to A F Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Statistical validity for testing associations between genetic markers and quantitative traits in family data.

In genetic analysis it is often of interest to analyze associations between traits of unknown genetic etiology and genetic markers from pedigree data. Statistical methods that assume independence of pedigree members cannot be used because they disregard the statistical dependencies of members in a pedigree. For quantitative traits, a regression model proposed by George and Elston [Genet Epidemiol 4:193-201, 1987] uses an asymptotic likelihood ratio test and incorporates a correlation structure that allows for statistical dependence among the pedigree members. The statistical validity of this test is assessed for finite samples by measuring the discrepancy between the empirical and theoretical chi-square distributions. The variance of the mean of the dependent variable is determined to be related to this discrepancy and can be used to determine whether a pedigree structure is large enough for making valid statistical inferences on the basis of the asymptotic test. A multi-generational pedigree of 200 or so individuals should in many cases be sufficient for valid results when using the asymptotic likelihood ratio test for the association between markers and continuous traits.

Family↗
PubMed1995

A graphical approach for presenting linkage results from a genomic screen.

Initially, a sib-pair linkage analysis was performed between the marker loci and six untransformed variables. Results from several variations of this initial analysis were compared using a graphical approach (P-plots) to simplify presentation. When results were compared to the generating model, most of the aspects of the generating model were recovered, although we did not find evidence of the polygenic component shared by Q2 and Q3, or evidence of linkage between MG4 and Q4 at the 0.01 level.

Chromosome Mapping↗
PubMed1995

Determination of DLCO and cardiac output from expired gas slopes with cardiogenic oscillations.

Effects of 'cardiogenic oscillations' on alveolar plateau gas concentration slope measurements, constant expiratory pulmonary capillary blood flow, and DLCO determination have not been previously described. We examined cardiogenic oscillations during constant expiratory maneuvers to assess factors influencing magnitude of oscillations as well as effect of oscillatory phase at the start and end of exhalation measurement period on alveolar gas slope. Five normal volunteers performed repeated single breath constant exhalation vital capacity maneuvers using test gas containing 2 physiologically 'inert' gases: Helium (He Mw 4) and argon (Ar Mw 40). The mixture contained 3 absorbable gases, acetylene (C2H2 Mw 26), carbon monoxide (C18O Mw 30), and oxygen. Alveolar plateau slope, magnitude of cardiogenic oscillations, relative signal to noise ratios, and effect of cardiogenic oscillation phase on measured slope were determined for each gas. Cardiogenic oscillations were present for all inert gases. Oscillations were less evident for CO. However, the effects on calculated Qc and DLCO were negligible. Cardiac oscillations of considerable magnitude are seen during single breath constant exhalation maneuvers and affect constant expiratory gas slope calculations. Cardiogenic oscillation phase does not have a significant effect on measured Qc and DLCO using constant expiratory techniques.

Adult↗
PubMed1995

Serum hormonal concentrations following transcendental meditation--potential role of gamma aminobutyric acid.

Transcendental mediation (TM) is a stylized form of physical and mental relaxation which is associated with changes in the secretion and release of several pituitary hormones. The hormonal changes induced by TM mimic the effects of the inhibitory neurotransmitter gamma aminobutyric acid (GABA). It is hypothesized that TM produces changes in pituitary hormone secretion by enhancing hypothalamic GABAergic tone, and its anxiolytic effects by promoting GABAergic tone in specific areas of the brain. This mechanism is similar to the effects of synthetic anxiolytic and tranquilizing agents such as benzodiazepines that bind to components of the GABA-A (GABAA) receptor. TM, therefore, may produce relaxation by enhancing the effects of an endogenous neurotransmitter analogous to the effects of endorphins in runners who reportedly experience a 'runner's high'.

Arginine Vasopressin↗
PubMed1995

A preliminary study of the neuropsychological heterogeneity of familial schizophrenia.

This exploratory study describes the heterogeneity of the neuropsychological deficits that characterize familial schizophrenia. Forty-six familial schizophrenics showed significantly more variability in abstraction and problem-solving and motor control than 39 non-familial schizophrenics. Cluster analyses of these two neuropsychological parameters indicate that while the non-familial schizophrenics fall into one homogeneous cluster, the familial schizophrenics fall into three relatively distinct clusters which differ significantly in their morbid risk for schizophrenic-spectrum disorder. These preliminary data suggest that frontal lobe deficits are associated with an increased familial risk for schizophrenia.

Adolescent↗
PubMed1994

A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators.

The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators. During the baseline period, antiinflammatory agents were not permitted, and patients were treated with inhaled beta-agonists on an as-needed basis. Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were randomized to treatment groups. Subjects received either nedocromil sodium (4 mg) or placebo four times a day for 10 weeks. Statistically significant (p < 0.05) between-treatment differences (weeks 3 to 10), favoring nedocromil sodium, were determined for the asthma summary score, daytime asthma severity, asthmatic cough, morning peak flow rates, reduction of as-needed bronchodilator use, physician's assessment of asthma severity, and patient and physician opinions of treatment effectiveness. By trial end (week 10), sleep difficulty caused by asthma decreased 29% in the nedocromil sodium group and 4% in the placebo group (p = 0.006). Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma.

Adolescent↗
PubMed1994

Measuring oxygen uptake and carbon dioxide production in critically ill patients using a standard blood gas analyzer.

OBJECTIVE: The measurement of oxygen uptake and CO2 production in critically ill patients requires invasive monitoring or complex analysis equipment. This study investigates the hypothesis that oxygen uptake and CO2 production can be accurately determined by measuring oxygen and CO2 concentrations in samples from inspiratory and expiratory ventilator circuitry, using a standard blood gas analyzer. DESIGN: Prospective comparison of CO2 production and oxygen uptake measurements determined by use of a blood gas analyzer vs. a mass spectrometer. SETTING: University teaching hospital medical and surgical intensive care units (ICUs). PATIENTS: Critically ill patients (n = 46) receiving mechanical ventilation in the ICUs. INTERVENTIONS: PO2 and PCO2 were obtained with two new techniques and compared simultaneously with measurements on a mass spectrometer in critically ill, mechanically ventilated patients. Two methods were evaluated: a) arterial blood gas analyzer measurements of PO2 and PCO2 from fluid collected in traps on the inspiratory and expiratory limbs of the ventilator circuitry; b) PO2 and PCO2 measurements of inspiratory and expiratory gas samples collected in bags and injected directly into an arterial blood gas analyzer. Oxygen consumption and CO2 production were compared, using both methods of gas measurements. MEASUREMENTS AND MAIN RESULTS: Direct injection of gas samples collected in a bag from inspiratory and expiratory limbs of a breathing circuit into the arterial blood gas analyzer correlated very closely with mass spectrometer measurements for all variables (n = 32 sample measurements in 25 patients): fractional oxygen (r2 = .99, slope = 1.02, bias = 0.37%, precision = 0.54), fractional expired CO2 (r2 = .90, slope = 0.86, bias = -0.10%, precision = 0.15), oxygen uptake (r2 = .87, slope = 0.99, bias = 21.6 mL/min, precision = 38.0), and CO2 production (r2 = .98, slope = 0.95, bias = 7.90 mL/min, precision = 15.3). In contrast, although fractional oxygen and CO2 concentrations were approximated by analysis of fluid collected from inspiratory and expiratory traps, the values did not correlate well enough with mass spectrometer values to yield reasonable oxygen uptake or CO2 production results. CONCLUSION: We have demonstrated that direct Fick oxygen uptake and CO2 production can be accurately determined in mechanically ventilated patients, using direct injection of collected gas samples into standard blood gas analyzers. This simple, inexpensive technique can be performed using equipment readily available in any hospital.

Bias↗
PubMed1994

Measurement of transfer factor during constant exhalation.

BACKGROUND: Transfer factor of the lung for carbon monoxide (TLCO) was measured by a new method based on analysis of the ratio of the concentrations of carbon monoxide to an inert gas (methane) relative to lung volume during a constant exhalation. Since this new technique is based solely upon exhalation, anomalies associated with inspiration and breath holding do not affect results. Additionally, because prolonged breath holding is not required, measurements can readily be made in dyspnoeic patients. METHODS: Exhalation TLCO (TLCO,ex) was compared with the standard (Jones and Meade) 10 second breath holding TLCO (TLCO,bh) in 100 consecutive patients. Patients did not practise the exhalation manoeuvre prior to testing. RESULTS: The comparative results were very close; mean difference (bias) +/- standard deviation (precision) was 0.05 (0.84) mmol/min/kPa. The relation was equally strong in patients with severe pulmonary disease; for patients with FEV1 < 1.51 the mean difference was 0.21 (0.80) mmol/min/kPa. CONCLUSIONS: Since the results were essentially identical between the techniques, it seems that comparable pathophysiological factors affect TLCO during breath holding and constant exhalation. Constant exhalation may therefore be a useful alternative to the breath holding technique for clinical measurement of TLCO.

Adult↗
PubMed1994

Investigation of computer lung model-predicted DLCO during single-breath maneuvers.

A computer model based on the theoretical gas absorption equations of Martonen and Wilson (J. Math. Biol. 14: 203-220, 1982) was developed to predict changes in single-breath diffusing capacity of the lung for carbon monoxide (DLCO) with alterations in anatomic dead space, alveolar volume, and inspiratory time. The computer model predictions were compared with results obtained from normal subjects performing DLCO maneuvers under correspondingly altered conditions to assess the validity of the Martonen-Wilson equations. In normal subjects, a theoretical "ideal" single-breath DLCO was derived from measured DLCO and adjusted to instantaneous inspiratory and expiratory times with this three-phase computer model. Clinical single-breath DLCO measurements with increased external dead space and inspiratory and expiratory times in normal subjects correlated well with our mathematical model predictions (all r > 0.80, P < 0.001) but did not correlate closely with the predicted effects of alveolar volume on DLCO. This study demonstrates that uniform gas absorption equations of Martonen and Wilson closely predict changes in observed DLCO with systematic variation of inspiratory and expiratory time in normal subjects at full lung volume and appear to be a reasonable estimation of normal physiological events during single-breath carbon monoxide absorption.

Adult↗
PubMed1994

Acidosis stimulates beta-endorphin release during exercise.

Elevated blood levels of beta-endorphin have been associated with high-intensity exertion, but the stimulus for beta-endorphin release is unknown. Some studies of exercise have associated beta-endorphin release with increased exertion levels, but other evidence suggests that acidosis may stimulate the release of beta-endorphin. This study examines acidosis as a possible stimulus for beta-endorphin release by examining the effects of arterial blood gases, whole blood lactate, and respiratory changes on beta-endorphin levels and by examining the effects of buffering during exercise on these levels. Initially, seven healthy adult males were evaluated during incremental exercise. During incremental exertion, indicators of acidosis correlated with endorphin levels: pH (r = -0.94), PCO2 (r = -0.85), HCO3- (r = -0.88), base excess (r = -0.94), and lactate (r = 0.89). A multivariate model showed that beta-endorphin levels were predicted best by the change in base excess. A time course analysis showed that beta-endorphin responses peaked postexercise and paralleled blood acid levels. Subsequently, subjects were compared after alkali loading and placebo during constant-intensity exercise at 85% of maximal exertion to determine whether acidosis is necessary for endorphin release. Treatment with a buffer, which effectively maintained pH above 7.40, significantly suppressed endorphin release (F = 3.07; P < 0.0001). The results of this study indicate that acidosis rather than any other physiological change associated with high-intensity exertion is the primary stimulus for beta-endorphin release.

Acidosis↗
PubMed1994

Thoracoscopic laser ablation of pulmonary bullae. Radiographic selection and treatment response.

The purpose of this study was to develop objective preoperative selection methods for predicting outcome in patients undergoing thoracoscopic laser ablation of emphysematous pulmonary bullae. Initial radiographic presentation was correlated with physiologic function both before and after the operation in 24 patients entered into a prospective clinical protocol for evaluation of carbon dioxide laser treatment of emphysematous pulmonary bullae. Nineteen surviving patients underwent follow-up evaluation 1 to 3 months after the operation. Pulmonary function test results showed improvements in spirometry (forced vital capacity increased 0.82 +/- 0.125 L, forced expiratory volume in 1 second increased 0.36 +/- 0.07 L, and maximum voluntary ventilation increased 11.69 +/- 2.6 L/m; p < 0.002); airway resistance decreased by 0.9 +/- 0.35 cm of water/L per second, and specific conductance increased 0.019 +/- 0.006 L/cm H2O per second (p < 0.02). Lung volumes improved (residual volume decreased 1.25 +/- 0.23 L, p < 0.001) without significant change in resting gas exchange. Quantitative radiographic grading of extent of preoperative pulmonary bullae correlated well with response to laser treatment in patients with preoperative and postoperative studies. Patients with large bullae accompanied by crowding of adjacent lung structures, upper lobe predominance, and minimal underlying emphysema had greatest improvement in pulmonary function results with laser bullae ablation (p < 0.05). However, some patients with multiple smaller bullae and diffuse emphysema also demonstrated objective improvement after operation. Quantitative radiographic analysis of the extent of bullous disease and the degree of associated emphysema can be used to determine short-term postoperative pulmonary response and may be useful in selecting future thoracoscopic laser bullae ablation candidates. Additional follow-up will be necessary to further improve selection criteria and help define the long-term role of thoracoscopic laser treatment of bullous emphysema.

Aged↗
PubMed1993

Measurement of cardiac output by automated single-breath technique, and comparison with thermodilution and Fick methods in patients with cardiac disease.

Accurate noninvasive methods are needed for determination of cardiac output. Current methods are generally complex or may be unreliable. A previously described method, based on absorption of acetylene gas during a constant exhalation that enables calculation of cardiac output by estimating pulmonary capillary circulation, is incorporated in a new, automated commercial product (SensorMedics 2200). In this study, cardiac output by single-breath acetylene blood flow measured with this device was compared with the standard thermodilution and direct Fick methods in 20 patients undergoing cardiac or pulmonary artery catheterization. Patients inhaled test gas mixture to total lung capacity and exhaled at a constant rate through an adjustable resistor. Lung volumes and noninvasive acetylene blood flow value were calculated automatically. Correlation between the automated single-breath technique and both thermodilution and Fick cardiac output determinations was very high (correlation coefficients were 0.90 and 0.92, respectively), regression slopes were close to identity (0.98 and 0.90), and bias (-0.39 and -0.79 liter/min) and precision (0.94 and 1.02) were good; when shunt correction was applied, bias was reduced to 0.06 and 0.35 liter/min, respectively. Rapid, accurate, noninvasive measurement of cardiac output was easily obtained using the automated device. This technique may have a wide applicability for noninvasive evaluation of patients with cardiac disease and for monitoring effects of therapeutic interventions.

Absorption↗
PubMed1993

Methods and applications of genetic analysis in the study of cardiovascular disease: a summary of contributions to GAW8.

The analyses of data provided for the cardiovascular disease section of Genetic Analysis Workshop 8 are briefly summarized. Methods using twin, segregation, and linkage analyses are used to determine, characterize, and localize genetic components involved in the etiology of cardiovascular disease and to explore the interaction of these components with known environmental risk factors.

Cardiovascular Diseases↗
PubMed1993

Statistical validity of the Haseman-Elston sib-pair test in small samples.

Simulation experiments were used to determine the empiric type I error rate of the Haseman-Elston sib-pair test for linkage between a quantitative trait and a marker locus in samples with 60 or fewer sib pairs. The effect of different levels of marker-locus heterozygosity on statistical validity was also considered. The test was performed on the trait and each of five unlinked markers, and evaluated using two different degrees of freedom for the t-distribution. The number of degrees of freedom in the first evaluation was based on the number of sib pairs in each sibship, sigma s(i)(s(i) - 1)/2 - 2. In the second evaluation, the number of degrees freedom was based on the number of sibs minus 1 in each sibship, sigma (s(i) - 1) - 2. Empirically determined type I error rates using sigma s(i)(s(i) - 1)/2 - 2 degrees of freedom were slightly liberal. For sigma (s(i) - 1) - 2 degrees of freedom, the estimated empiric p-values were nearly identical to their respective nominal p-values. Decreasing levels of heterozygosity did not increase the empiric type I error rate when the sample size was small.

Computer Simulation↗
PubMed1993

Linkage analysis in a large pedigree ascertained due to essential familial hypercholesterolemia.

Sib-pair linkage analysis was used to screen a large pedigree, ascertained through four members with hypercholesterolemia, for evidence of linkage between 12 quantitative traits and 15 genetic marker loci. Traits were analyzed on the untransformed, natural log and square root-transformed scales. After adjusting for multiple tests, there is a suggestion of linkage between height and the Kidd blood group on chromosome 18 and between VLDL cholesterol, and possibly triglyceride, and KM on chromosome 2.

Body Height↗
PubMed1993

Melatonin and gonadotropin secretion after acute exercise in physically active males.

Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone, testosterone (T) and melatonin were measured in seven physically active male volunteers after exercise on a treadmill using the Bruce protocol. Measurements were made on blood samples obtained before exercise, within 30 s after exercise, at 15 min after exercise, and subsequently at 30-min intervals after exercise for a total duration of 180 min. Serum LH concentration fell from a peak post-exercise level of 15.7 (4.7) IU.l-1 [mean (SD)] to a nadir of 10.3 (2.4) IU.l-1 (P < 0.004). Nadir values in individual volunteers were seen between 60 and 150 min after exercise. This fall in serum LH was paralleled by a similar fall in the concentration of serum T. Serum melatonin concentrations did not change significantly after exercise. It is concluded that melatonin, despite is reported anti-gonadotropic properties, does not play a role in the depression of serum LH after acute strenuous exercise in physically active males.

Adult↗
PubMed1993

A device for overcoming discoordination with metered-dose inhalers.

BACKGROUND: Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS: We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS: Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION: Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination.

Adolescent↗