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Biomedical subjects

A F Wilson

Publications and source records attributed to A F Wilson.

At least 19 recordsLinked to original sources
PubMed1996

Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass.

BACKGROUND: Homozygous carries of the D allele of the angiotensin-converting-enzyme (ACE) gene have been reported to be at increased risk for various cardiovascular disorders, including left ventricular hypertrophy. We investigated the potential role of the ACE gene in influencing left ventricular mass. METHODS: Quantitative echocardiographic data and DNA samples were available for 2439 subjects from the Framingham Heart Study. ACE genotypes were determined by an assay based on the polymerase chain reaction. (The D allele of the ACE gene contains a deletion, whereas the I [insertion] allele does not.) Left ventricular mass and the prevalence of left ventricular hypertrophy, adjusted for clinical covariates, were analyzed according to genotype. Genetic linkage between the ACE locus and left ventricular mass was evaluated by quantitative analysis of pairs of siblings. RESULTS: The ACE genotype was associated neither with left ventricular mass nor with the prevalence of left ventricular hypertrophy. Mean (+/-SE) left ventricular mass (adjusted for sex) among subjects carrying the DD, DI, and II genotypes was 165+/-1.6, 165+/-1.3, and 166+/-2.0 g, respectively (P=0.90). The prevalence of left ventricular hypertrophy among the three genotype groups was 15.6 percent, 13.6 percent, and 15.6 percent, respectively (P=0.36), and the adjusted relative risk of left ventricular hypertrophy associated with the DD genotype was 1.10 (95 percent confidence interval, 0.86 to 1.19). Linkage analysis in 759 pairs of siblings using both the ACE D/I marker and a microsatellite polymorphism at the neighboring locus for the human growth hormone gene failed to support any role of ACE in influencing left ventricular mass. CONCLUSIONS: The ACE genotype showed no association with echocardiographically determined left ventricular mass, nor did it confer an increased risk of left ventricular hypertrophy. We found no appreciable role of the ACE gene in influencing left ventricular mass.

Adult↗
PubMed1996

Animal model for thoracoscopic laser ablation of emphysematous pulmonary bullae.

BACKGROUND AND OBJECTIVE: Thoracoscopic laser techniques have been described for treatment of pulmonary bullae. Clinical application of this procedure has proliferated despite limited data regarding efficacy or optimal techniques. The objective of this study was to develop an animal model for investigating laser treatment of bullous lung disease. STUDY DESIGN/MATERIALS AND METHODS: Sixty-two New Zealand White rabbits (3-5 kg) were injected intravenously with 0.35 cc sterile-filtered Sephadex G-100 beads (1 g/100 cc suspension). Three hours later, rabbits were anesthetized, intubated, and 10 cc 0.7% heat-treated or 1% untreated carrageenan solution was instilled endotracheally into a catheter wedged in a mainstem bronchus. RESULTS: Bullae formed over 4-6 weeks in 33% of the animals treated with 0.7% heat-treated carrageenan, and 90% of animals receiving 1% untreated carrageenan (P < 0.005) as demonstrated by serial thoracoscopy. Thoracoscopy was performed at 6-8 weeks using 5 mm trocars under general anesthesia and mechanical ventilatory support. Animals developed pulmonary bullae ranging in size from 0.5 to 2 cm. Bullae were ablated under thoracoscopic visualization using a CO2 laser with a 4 mm OD rigid probe and short focal length in a defocused mode, or an Nd:YAG laser with a 0.4 mm diameter flexible fiberoptic probe. Animals recovered quickly following thoracoscopy. CONCLUSION: We have successfully developed an animal model for thoracoscopic laser ablation of emphysematous pulmonary bullae. This animal model should be useful in investigating treatment of bullous lung disease in humans.

Animals↗
PubMed1996

Comparison of continuous versus pulsed CO2 and Nd:YAG laser-induced pulmonary parenchymal lung injury in a rabbit model.

BACKGROUND AND OBJECTIVE: Laser techniques have recently been described for treatment of patients with emphysema and bullous lung disease. Laser exposure of the pulmonary parenchyma during these procedures is complicated by laser-induced lung injury with substantial associated morbidity. Animal investigations are needed to develop methods that reduce lung injury. We hypothesized that the depth of injury could be reduced by pulsing laser exposures, with the goal of limiting thermal effects to more superficial tissue levels. In this study, we compared acute and chronic histologic injury resulting from pulsed- versus continuous-mode CO2 and Nd:YAG laser pulmonary parenchymal exposures in rabbits. STUDY DESIGN/MATERIALS AND METHODS: A total of 40 New Zealand White (NZW) rabbits underwent thoracotomy followed by exposure with CO2 laser (n = 10 continuous vs. n = 10 pulsed at 250 Hz with duty cycle 0.15 ms) or ND:YAG laser (n = 10 continuous vs. n = 10 pulsed at 10 Hz with duty cycle 0.10 sec) to the visceral pleural surface using 1 minute of laser exposure (5 watts, defocused to 70 W/cm2 power density) to the exposed lung surface. Rabbits were sacrificed at 4 and 21 days post-injury, and lungs were examined histologically. RESULTS: CO2 and Nd:YAG laser treatment resulted in substantial pulmonary parenchymal injury. While CO2 laser-induced damage was distinct from Nd:YAG histologically, pulsed-mode laser exposures did not reduce lung injury for either laser. Acute edema occurred to depths of 1180 +/- 338 microns for continuous-mode CO2 laser exposures compared to 1,340 +/- 430 microns in pulsed mode (p = .77). For Nd:YAG laser exposure, acute edema depth was 750 +/- 748 microns continuous versus 1120 +/- 367 microns pulsed mode (p = .65). Chronic lung fibrosis depth was 450 +/- 164 microns for CO2 continuous mode compared to 575 +/- 170 microns in pulsed mode (p = .61). Lung fibrosis depth for Nd:YAG was 550 +/- 96 microns, continuous versus 484 +/- 180 microns pulsed mode (p = .76). CONCLUSION: The similarity in injury between pulsed- and continuous-mode exposures suggests that thermal relaxation times are long relative to the selected pulse frequencies in intact living rabbit lungs. Alternatively, brief high-energy pulsations may increase focal temperatures with a tendency to increase injury depth relative to the penetration of the laser light. Thus, pulsed laser modes in these settings appear to be ineffective in reducing laser-induced lung injury in clinical settings.

Animals↗
PubMed1996

Almost simultaneous measurement of cardiovascular and gas exchange variables during maximal exercise.

We measured gas exchange variables such as oxygen uptake, carbon dioxide output, and lung diffusing capacity using noninvasive techniques almost simultaneous with assessment of cardiovascular variables such as pulmonary blood flow at several levels of treadmill exercise up to and including maximal capacity. We utilized a single breath exhalation technique for measurement of diffusing capacity and cardiac output and breath by breath methodology for evaluating oxygen uptake. The equipment required for these measurements--rapid gas analyzers, oximeters, on-line computation, and pneumatic valves--are well within the capabilities of many exercise laboratories and are not difficult to use with subjects even at the heaviest levels of exercise. The results agreed well with values reported in the literature. From these entirely noninvasive measures, we calculated mixed venous oxygen saturation and maximal tissue oxygen diffusing capacity.

Adult↗
PubMed1996

Heritability of salt sensitivity in black Americans.

Salt sensitivity is defined as a change in blood pressure in response to changes in salt and water homeostasis. Found in 73% of hypertensive and 36% of normotensive blacks, it is generally considered a hallmark of hypertension in blacks. The higher prevalence of salt sensitivity in blacks compared with whites suggests a genetic influence on this trait, but there is little direct evidence of heritability. We determined the extent to which salt sensitivity is correlated in black families and estimated the heritability of this phenotype. Black families were recruited through a hypertensive proband. Both hypertensive and normotensive adults were phenotyped with respect to salt sensitivity with an intravenous sodium-loading, furosemide volume-depletion protocol. Salt sensitivity was defined as the difference between sodium-loaded and volume-depleted blood pressure. We enrolled 20 families, comprising 30 parent-offspring pairs and 115 adult sibling pairs. Age-adjusted familial correlations ranged from .33 to .44, .19 to .37, and .12 to .21 for mean arterial and systolic and diastolic pressure responses to the salt sensitivity maneuver, respectively. Corresponding heritability estimates were 0.26 to 0.84, 0.26 to 0.74, and 0.004 to 0.24, respectively. These data strongly suggest a heritable component of salt sensitivity.

Adult↗
PubMed1996

CO2 and Nd:YAG laser-induced pulmonary parenchymal lung injury in a rabbit model.

Laser exposure of the pulmonary parenchyma during treatment of emphysema and other clinical indications causes acute lung injury. Animal investigations are needed to understand and control laser-induced lung injury. We hypothesized that lung injury is deeper from Nd:YAG laser exposures than CO2 exposures because of deeper penetration of Nd:YAG wavelength light. We compared the temporal evolution of histologic injury in rabbits resulting from continuous mode shallow CO2 and Nd:YAG laser pulmonary parenchymal exposures applied in rabbits. Forty-six New Zealand white (NZW) rabbits underwent treatment with CO2 laser (n=18), Nd:YAG laser (n=18), or sham thoracotomy control (n=10) to the visceral pleural surface using 1 min of exposure (5 watts, defocused to 70 W/cm2 power density for both lasers). Animals were killed at 0, 4, 7, 21, and 49 d after exposure. Lung injury, similar to that seen clinically in humans, developed in all laser-treated animals. Injury progressed from ischemia and vascular congestion, to edema and necrosis, followed by pleural and parenchymal fibrosis. The acute injury was qualitatively distinct and slightly deeper in CO2 than Nd:YAG-treated animals (p<0.02) despite the shallower depth of penetration of the CO2 laser. These findings may imply that higher absorption coefficient for CO2 laser energy results in greater focal temperatures and injury in the areas of direct exposure, and suggest that Nd:YAG laser exposure at these settings may cause shallower injury than CO2 lasers in humans undergoing clinical treatment.

Absorption↗
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↗