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Biomedical subjects

J W Weiss

Publications and source records attributed to J W Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1989

Distinguishable sensations of breathlessness induced in normal volunteers.

Various theories about the genesis of dyspnea have often assumed that the sensation is similar from patient to patient and is generated by a single underlying mechanism. To investigate whether breathlessness induced in normal volunteers by different stimuli represents one or more than one sensation, we studied 30 subjects in whom breathlessness was induced by each of 8 different stimuli: breath-holding, CO2 inhalation, inhalation of CO2, with ventilation voluntarily targeted below the level dictated by chemical drive, breathing with a resistive load, breathing with an elastic load, voluntary elevation of functional residual capacity, voluntary limitation of tidal volume, and exercise. For each stimulus, subjects were asked to choose description of their sensation(s) of breathlessness from a questionnaire listing 19 descriptors. The responses from this questionnaire were evaluated using cluster analysis to search for relationships among descriptors and to identify natural groupings. We found that distinct groups of descriptors emerged, i.e., subjects could distinguish different sensations of breathlessness. In addition, we found an association between certain descriptor groups and stimuli. We conclude that the term breathlessness may encompass multiple sensations, and, therefore, may not be explainable by a single physiologic mechanism.

Adult↗
PubMed1988

Low dose aminophylline selectively increases upper airway motor activity in normals.

Because certain pharmacologic agents differentially influence upper airway and diaphragm motor activity, we postulated that the adenosine antagonist theophylline might preferentially increase alae nasi activity in human subjects. Using a double-blinded, randomized, placebo controlled design, we studied the effect of low dose aminophylline (1-2 mg/kg) on alae nasi and diaphragm surface electromyographic (EMG) activity. Seven healthy volunteers served as subjects for two trials on separate days. Subjects breathed from a close circuit while end tidal PCO2 was held constant in the eucapnic range. During each trial we recorded EMG signals from the alae nasi and diaphragm before and after intravenous infusion of either aminophylline or placebo. After the administration of aminophylline, the mean alae nasi EMG signal increased 87 +/- 31 (SD)% (P less than 0.005) while the mean diaphragmatic EMG signal did not change. There was no significant change in either the alae nasi or diaphragmatic EMG signal after placebo. There was no change in minute ventilation, tidal volume, or respiratory frequency after either aminophylline or placebo. We speculate that low dose aminophylline produces a selective increase in upper airway muscle activity through stimulation of the reticular activating system.

Adult↗
PubMed1988

Alpha-methyldopa selectively reduces alae nasi activity.

1. Sedatives such as the benzodiazepines and alcohol reduce upper airway muscle activity. We hypothesized that a sedating antihypertensive, alpha-methyldopa, might have similar effects. To investigate this hypothesis we studied the effect of alpha-methyldopa on alae nasi electromyographic (EMG) activity during hypercapnia. 2. We studied ten healthy subjects and three subjects with obstructive sleep apnoea during CO2-stimulated breathing. In a preliminary study four subjects demonstrated a fall in alae nasi EMG activity 4 h after the ingestion of 500 mg of alpha-methyldopa during CO2 rebreathing. 3. In six additional normal subjects and three subjects with obstructive sleep apnoea, we studied the alae nasi EMG activity during steady-state hypercapnia with PCO2 held constant 5 torr (0.7 kPa) above baseline. On 2 separate days we studied subjects before and 2 h after they had ingested 750 mg of alpha-methyldopa or placebo. 4. In the normal subjects the mean alae nasi EMG activity fell by 34% 2 h after ingestion of alpha-methyldopa (P less than 0.05) without a change in other ventilatory parameters. 5. In the sleep apnoea group the individual mean alae nasi EMG activity fell 16-49%, with ventilation and tidal volume falling in one patient. 6. We conclude that alpha-methyldopa selectively reduces upper airway motor activity.

Adolescent↗
PubMed1987

Detection of hypercapnia by normal subjects.

1. To investigate whether changes in PaCO2 can be detected independently of the CO2-induced changes in pulmonary ventilation, we tested five normal subjects for the ability to distinguish different levels of end-tidal PCO2 (PETCO2) while holding minute ventilation constant. 2. Helped by a visual feedback system, the subjects maintained a constant ventilation targeted at a level that was higher than that dictated by the chemical drive at PETCO2 = 50 mmHg (6.7 kPa). End-tidal PCO2 was held at 40 mmHg (5.3 kPa) during the first 2 min of each test trial ('control period'); then, for 4 min ('test period'), PETCO2 was either elevated to 50 mmHg or kept at 40 mmHg. Twelve runs were performed by each subject. 3. In 24 out of the total 30 trials (80%) in which PETCO2 was raised during the test period to 50 mmHg, the subjects detected the changes. There was one false positive result (3%), when PETCO2 kept at 40 mmHg during the test period was reported as different from control. In four out of the five subjects the ability to detect the change in PETCO2 from 40 to 50 mmHg was statistically significant. 4. We conclude that increases in PETCO2 can be detected independently of changes in the absolute level of ventilation.

Carbon Dioxide↗
PubMed1987

Cold facial stimulation reduces breathlessness induced in normal subjects.

Patients with breathlessness commonly describe subjective relief when seated near an open window or in front of a fan. Previous studies suggest that a flow of air or application of cold solutions to the face, nasal mucosa, or pharynx may alter ventilation. We hypothesized that a flow of cold air directed against the cheek would reduce the sensation of breathlessness associated with loaded breathing. Sixteen subjects breathed on a device with an inspiratory resistive load (63 cm H2O/L/s) while PCO2 was maintained at 55 torr for 5 min. All studies were performed 4 times with each subject, twice with cold air directed against the cheek (4 degrees to 10 degrees C, 4 km/h) and twice with no flow on the subject. Subjects were asked to rate their breathlessness using a modified Borg scale. Cold air directed on the face reduced breathlessness induced by an inspiratory resistive load and hypercapnia (6.2 +/- 1.7 Borg scale units with no flow, 5.1 +/- 1.7 with cold air; p less than 0.002) without causing a significant reduction in ventilation. This effect was not observed when cold air was directed to the leg and does not appear to be associated with a reduction in the ventilatory response to hypercapnia or with initiation of the diving reflex. We conclude that cold air directed against the cheek significantly reduces dyspnea associated with the combination of hypercapnia and an inspiratory resistive load.

Adult↗
PubMed1987

Airway effects of monosodium glutamate in subjects with chronic stable asthma.

We studied the effect of oral monosodium glutamate (MSG) on airways function in 12 subjects with a history of chronic stable asthma in a double-blind, randomized, crossover protocol. Subjects ingested either 25 mg/kg of MSG or sodium chloride (equimolar to MSG) following a 6-hour fast. Spirometry [forced expiratory volume in 1 second (FEV1) and forced vital capacity] was performed before administration of the test substances and for a minimum of 4 hours thereafter. At no time during the observation period was the mean change in FEV1 more negative following MGS than following placebo. MSG is unlikely to be a contributing factor in bouts of bronchospasm in subjects with asthma, and routine avoidance of MSG by individuals with asthma need not be advised.

Adult↗
PubMed1986

Mechanisms of pulsus paradoxus during resistive respiratory loading and asthma.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.

Adult↗
PubMed1986

The effects of passive CO2 removal on breathing pattern in humans.

To determine the effects of nonventilatory CO2 transfer on breathing pattern, we monitored breathing in 7 patients with renal failure undergoing hemodialysis. A respiratory inductance plethysmograph was used to record ventilation before and during dialysis. The duration of inspiration (TI), the duration of each breath (TTot) and the duty cycle (TI/TTot) did not differ for the pre-dialysis and the dialysis periods. In contrast, for each patient the mean tidal volume (VT) fell significantly during dialysis (p less than 0.05), accounting for the reduction in minute ventilation (p less than 0.005). The mean inspiratory flow rate (VT/TI) also fell (p less than 0.01), demonstrating that nonventilatory CO2 loss via the dialysis bath is associated with reduced respiratory drive.

Adult↗
PubMed1984

Airways responsiveness in a population sample of adults and children.

Nonspecific bronchial responsiveness was assessed with eucapneic hyperpnea to subfreezing air in a population-based sample of 134 adults and 213 children in East Boston, Massachusetts. Increased responsiveness was considered to be present if the decrease in forced expiratory volume in one second with cold air divided by the initial vital capacity was greater than 9%. Men and women had similar bronchial responsiveness, but children and young adults (24 yr of age and younger) were significantly more likely to be responders than were older subjects (p less than 0.001). Children with a doctor's diagnosis of asthma at any time in the past were twice as likely (42.9%) to be responders as were nonasthmatic children (19%) (p = 0.004). Ninety-two percent (11/12) of currently active asthmatics were responders. However, a large percentage of asymptomatic children had increased levels of bronchial responsiveness (18.9%). This cross-sectional study demonstrates the feasibility of measurement of nonspecific bronchial responsiveness in epidemiologic studies, and its relationship to age and wheeze symptoms in children.

Adult↗
PubMed1983

Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy.

Five normal human subjects inhaled aerosols generated from solutions of leukotriene D (LTD) to determine the bronchoconstrictor potency and the time course of airway obstruction produced by this constituent of slow-reacting substance of anaphylaxis. The dose-effect and time-effect curves were compared with curves similarly generated for the well-characterized airway constrictor histamine. Leukotriene D was, on average, 5,900 times more potent than histamine on a molar basis in producing an identical decrement in maximal expiratory flow rate at 30% of control vital capacity above residual volume. In addition, although LTD had a rapid onset of effect, similar to that of histamine, the airway obstruction produced by LTD was longer lasting, thereby reflecting more closely the response of asthmatic allergic individuals to antigen inhalation. The response of these subjects to inhalation of LTD was not altered by ingestion of aspirin, suggesting that the airway obstruction was not mediated by cyclooxygenase products of arachidonic acid.

Adult↗
PubMed1983

Relationship between bronchial responsiveness to hyperventilation with cold and methacholine in asthma.

Twenty-seven subjects with asthma and normal baseline lung function were challenged with aerosols of methacholine (M) and by isocapnic hyperventilation with cold air (HV). Stimulus-effect relationships were determined for each provocational technique on separate days and were expressed as the dose required to produce a 20% fall in forced expired volume in 1 sec (FEV1) obtained by linear interpolation from log stimulus vs. response curves (PD20). Each stimulus was applied with a sufficient intensity to produce a 20% or greater fall in FEV1 in each subject. The PD20 for M correlated significantly with the PD20 for HV (p less than 0.001) when the latter was expressed in liters per minute. The correlation between cumulative M PD20 and HV PD20 expressed as a percent of maximal voluntary ventilation was significant but less strong. We conclude that the airway response to HV reflects nonspecific bronchial hyperresponsiveness and that the dose of HV is best determined as the absolute level of ventilation.

Adolescent↗
PubMed1983

Effect of intermittent mandatory ventilation on respiratory drive and timing.

Seven patients receiving chronic ventilatory support were studied to better define the effects of intermittent mandatory ventilation (IMV) on the control and timing of spontaneous breathing between mandatory breaths. Each of these patients could sustain adequate spontaneous ventilation, as reflected by stable end-tidal carbon dioxide concentration (FETCO2), and arterial oxygen saturation (SO2) during periods of unassisted ventilation of sufficient duration to allow study. Inspiratory time (TI), respiratory cycle duration (Ttot), tidal volume (VT), and tracheal occlusion pressure (P0.1) were measured as IMV rate was progressively reduced. Respiratory timing was unaltered by decreasing IMV frequency; however, VT increased progressively. The P0.1 and mean inspiratory flow rate (VT/TI) also increased with each decrease in IMV rate, whereas FETCO2 and arterial SO2 remained constant. Thus, in these stable but ventilator-dependent patients, IMV did not alter respiratory timing or chemical stimuli, but it did alter respiratory drive as measured by VT/TI and P0.1.

Adult↗
PubMed1982

Bronchoconstrictor effects of leukotriene C in humans.

Maximum expiratory flow rate at 30 percent of vital capacity above residual volume served as an index of airway obstruction in comparing the effects of leukotriene C and histamine administered by aerosol to five normal persons. Leukotriene C was 600 to 9500 times more potent than histamine on a molar basis in producing an equivalent decrement in the residual volume. The leukotriene C response was slow in onset and prolonged, reminiscent of the effects of aerosol allergen challenge in asthmatic allergic subjects.

Adult↗
PubMed1982

Bronchodilatation, lung recoil, and density dependence of maximal expiratory flow.

Using normal human subjects we have measured maximal expiratory flow rates with air (Vmaxair) and after a washin of 80% He-20% O2 (VmaxHeO2) and static elastic recoil pressures of the lung [Pst(L)] both before and after administration of a beta-agonist, terbutaline. The effects of inhaled drug were compared with those of the subcutaneously administered agent, each given in doses to produce maximal bronchodilatation as assessed by increases in Vmaxair in the mid-vital capacity. Although there was a significant yet modest decrease in Pst(L) only after injection of the agent, density dependence (DD), assessed as the ratio of VmaxHeO2 to Vmaxair, increased significantly and comparably after either route of administration. A modest decrease in Pst(L), therefore, did not affect the changes in DD.

Adolescent↗
PubMed1982

Effects of inhaled sympathomimetics on obstructive response to respiratory heat loss.

To investigate the influence of inhaled sympathomimetics on the obstructive response to airway cooling, we had six asymptomatic atopic asthmatics perform eucapnic hyperventilation with frigid air at various levels of ventilation after pretreatment with aerosols of metaproterenol or placebo in a random blind fashion. In control experiments, eucapnic hyperventilation produced a progressive decrease in 1-s forced expiratory volume in a stimulus-response fashion as the level of ventilation rose in successive challenges. Metaproterenol did not produce an all-or-none blockade, but rather a parallel shift in the stimulus-response curve so that its protective effects could be overcome by increasing the stimulus. There was no effect on respiratory heat loss. These results explain, in a quantitative fashion, why a treatment schedule that permits a person with asthma to perform a given exercise task without difficulty becomes ineffective as the thermal burden or severity of the task increases.

Adult↗