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Biomedical subjects

S D Anderson

Publications and source records attributed to S D Anderson.

At least 19 recordsLinked to original sources
PubMed1992

The airway microvasculature and exercise induced asthma.

It has been proposed that exercise induced asthma is a result of "rapid expansion of the blood volume of peribronchial plexi" (McFadden ER, Lancet 1990;335:880-3). This hypothesis proposes that the development of exercise induced asthma depends on the thermal gradient in the airways at the end of hyperpnoea. The events that result in exercise induced asthma are vasoconstriction and airway cooling followed by reactive hyperaemia. We agree that the airway microcirculation has the potential for contributing to the pathophysiology of exercise induced asthma. We do, however, question whether reactive hyperaemia, in response to airway cooling, is the mechanism whereby hyperpnoea provokes airways obstruction in asthmatic patients. Further, we question whether vasoconstriction accompanies dry air breathing and whether an abnormal temperature gradient and rapid rewarming of the airways are prerequisites for exercise induced asthma. From published experiments we conclude that dry air breathing is associated with vasodilation and increase in airway blood flow rather than vasoconstriction and a decrease in blood flow to the airways. We propose that the stimulus for the increase in airway blood flow is an increase in osmolarity of the airway submucosa. This osmotic change is caused by the movement of water to the airway lumen in response to evaporative water loss during hyperpnoea. The increase in airway blood flow may occur directly or indirectly by the osmotic release of mediators. Exercise induced asthma is most likely to be due to the contraction of bronchial smooth muscle caused by the same mediators. Whether it is enhanced or inhibited by alterations in airway blood flow is not yet established in man.

Airway Resistance↗
PubMed1992

Nedocromil sodium inhibits the airway response to hyperosmolar challenge in patients with asthma.

We studied 16 asthmatic subjects sensitive to changes in airway osmolarity to determine whether nedocromil sodium has any effect on airway narrowing caused by hypertonic saline challenges. Nedocromil sodium (10 mg) or its vehicle was inhaled 10 min before a challenge with ultrasonically nebulized 4.5% NaCl. FEV1 was measured before challenge and 1 min after each challenge period of 0.5, 1, 2, 4, 8, 8 and 8 min. The challenge was stopped when there was a 20% fall in FEV1 from baseline or after the final challenge period. We measured airway sensitivity, that is, the provoking dose of 4.5% NaCl required to induce a 20% reduction in FEV1 (PD20FEV1) and calculated the fold difference in PD20FEV1 after the intervention. After inhaling nedocromil sodium there was a 3.95-fold improvement in PD20 (p < 0.001) when compared with the vehicle day. After pretreatment with nedocromil sodium two of the 16 subjects were completely protected against 4.5% NaCl challenge, and six developed a plateau in their response. We conclude that nedocromil sodium is effective in reducing airway narrowing in response to 4.5% NaCl challenge in asthmatic subjects, and it appears to be unique in its ability to produce a plateau in response to acute administration of a drug before a bronchial challenge.

Administration, Inhalation↗
PubMed1992

Inhaled steroids modify bronchial responses to hyperosmolar saline.

We investigated the effects of inhaled beclomethasone dipropionate (BDP) on airway sensitivity (provocative dose producing a 20% fall in forced expiratory volume in one second (FEV1) from baseline (PD20)) and reactivity (slope of the dose-response curve) to inhaled aerosols of hyperosmolar (4.5%) saline, and histamine or methacholine. This was an open study on 13 patients referred to the laboratory by their respiratory physician for investigation of their asthma. These challenges were performed on separate days before (initial visit) and 8.8 +/- 0.8 (SD) weeks (range 5.6-12.4 weeks) after (visit 1) a treatment period with BDP (dose range 600-1,500 micrograms.day-1). At visit 1 there was a significant reduction in sensitivity to 4.5% NaCl and histamine/methacholine and in reactivity. The PD20 increased 5.6 fold for 4.5% NaCl and 4.1 fold for histamine/methacholine. All patients remained responsive to histamine/methacholine and a fall in FEV1 > 20% to 4.5% saline was documented in 10 of the 13 patients. We conclude that treatment with BDP reduces sensitivity and reactivity to both osmotic and pharmacological challenge.

Administration, Inhalation↗
PubMed1991

Anxiety and depression in tinnitus sufferers.

This paper focuses upon the relationship between tinnitus and personality. One hundred and twelve members of a tinnitus self-help group completed psychological and tinnitus questionnaires. In line with prior studies we found that tinnitus was associated with elevated anxiety trait and depression. Unlike previous work, use of a validated subjective tinnitus scale allowed us to directly test the strength of association. Although both anxiety trait and depressive tendency were significantly correlated with overall tinnitus severity, the coefficients were of low magnitude. Advancing age was related to a reduction in depressive tendency; and being male was associated with lower anxiety and depression scores. While hypothesizing a bi-directional causality between personality and the impact of tinnitus, we acknowledge that only longitudinal research can unequivocally test this.

Adaptation, Psychological↗
PubMed1991

Local airway heat and water vapour losses.

A previously developed time-dependent mathematical model of the heat and water vapour transport in the human respiratory tract for mouth breathing (Daviskas et al., J. Appl. Physiol. 69:362-372, 1990) was applied to calculate the local quantities of heat and water transfer. The results of the heat and water losses agreed with experimental data. The contribution of each airway to the conditioning of inspired air was found to depend on the inspired air conditions and the pattern of breathing as expected. The greater proportion of the total heat and water loss was calculated to occur within the upper airways. However, below the pharynx, the rate of water loss during hyperpnea was calculated at a much faster rate than in the resting state. The rate at which water is returned to the airways may not be adequate to keep the periciliary fluid isotonic. These findings support the proposal that the intrathoracic airways could become significantly dehydrated during hyperpnea. The use of calculated local heat and water transfer rates may help to predict the site of stimuli to exercise-induced asthma.

Asthma↗
PubMed1991

Tinnitus severity measured by a subjective scale, audiometry and clinical judgement.

Tinnitus is discussed, with particular reference to the problem of assessing severity. The authors argue that tinnitus severity can only usefully be determined by measuring the impact of tinnitus on an individual, and therefore propose a scale to estimate severity in these terms. Data presented on 112 members of a tinnitus self-help group, demonstrated the reliability of a Subjective Tinnitus Severity Scale (S.T.S.S.), with a coefficient alpha of 0.84. This indicates a high degree of internal consistency, i.e.: statistically this scale is measuring aspects of a single dimension. The validity was established in a separate sample of 30 clinic attenders, where mean S.T.S.S. scores were found to correlate highly with two independent clinical ratings of severity (r2 = 0.76, p less than 0.001, and r2 = 0.73, p less than 0.001). Additionally, in these patients S.T.S.S. scores were significantly associated with several audiometric variables, although the correlations were of low magnitude.

Audiometry↗
PubMed1991

Osmotic challenges in the assessment of bronchial hyperresponsiveness.

It is now well recognized that a change in osmolarity of the periciliary fluid is a potent stimulus to airway narrowing and may be a common cause for provoking an attack of asthma. This has led to the use of nonisotonic aerosols to document bronchial hyperresponsiveness in patients with clinical asthma. These aerosols are generated by ultrasonic nebulizers, and the most commonly used are water, hyperosmolar sodium or potassium chloride, and dextrose. An increase in specific airway resistance of 100% or a reduction in FEV1 of 20% is considered as an abnormal response to these aerosols. There are a number of factors that affect the airway response to these aerosols, and these include the osmolarity of the solution and its ionic content and pH. In addition responses may be affected by a previous challenge or medication. It is not known precisely how these aerosols act to induce airway narrowing, but it is not by a direct action on smooth muscle. It is thought that a change in osmolarity of the airways causes the release of inflammatory mediators, which then act to narrow the airways. For this reason challenge by nonisotonic aerosols is different from challenge by histamine and methacholine and may be preferable for the diagnosis of asthma and assessment of its treatment.

Adrenergic beta-Agonists↗
PubMed1991

Characteristics of bronchial hyperresponsiveness in chronic obstructive pulmonary disease and in asthma.

By studying the characteristics of BHR in subjects clearly defined as having asthma or COPD, it is apparent that there are both similarities and differences. These responses can be broadly explained in terms of present knowledge of the pathologic features and the mechanisms causing the abnormalities in the two diseases, and they highlight the important differences between the diseases. It seems likely that tests of BHR with histamine and methacholine cannot be used to distinguish asthma from COPD in subjects with a mild decrease in FEV1 and symptoms that do not clearly suggest asthma or COPD. However, a dose-response curve to methacholine is helpful. If there is a plateau, and the PD20 FEV1 is more than 4.0 mumol, it is unlikely to be asthma. If there is no plateau, a test with propranolol or SO2 may be useful to discriminate the two diseases. The similarities in the responses-especially those to histamine-explain why there is frequently difficulty in deciding the nature of the disease present in an individual subject. Is it important to distinguish the two diseases? In the introduction it was suggested that it is important for understanding these diseases, for prognosis, for treatment, and ultimately for prevention. It remains difficult to determine prognosis from any single test of bronchial responsiveness, and response to prophylaxis (stopping smoking, allergen avoidance) plus drug treatment over several years is probably needed to predict outcome in an individual patient. Finally, despite the valid hypothesis proposed by Orie and coworkers (2), it seems unlikely that studying the characteristics of BHR will shed light on the "host" factors present in both diseases that remain poorly understood.

Asthma↗
PubMed1991

Duration of protection by inhaled salmeterol in exercise-induced asthma.

Beta-adrenoceptor agonists such as albuterol are very effective in preventing exercise-induced asthma (EIA) when they are given as an aerosol immediately before exercise. However, their duration of protection against EIA is usually less than 2 h. This may be due partly to their rapid clearance from the airways. Salmeterol is a highly lipophylic compound that is thought to bind to an exoreceptor near the beta-receptor. The objective of this study was to compare the protective effect of salmeterol with albuterol against EIA. Exercise was performed 0.5, 2.5, 4.5, and 6.5 hours after administration of the active drugs. Subjects attended the laboratory on four days within six weeks and cycled for 8 min breathing dry compressed air. We studied 17 asthmatic subjects (aged 19 to 49 years) with moderate to severe EIA. Salmeterol (50 micrograms) or albuterol (200 micrograms) was given from a metered dose inhaler via a spacer (Volumatic). On the control day, the mean work load +/- 1 SD was 174 +/- 47 W, ventilation (VE) was 77.9 percent +/- 11.2 percent of the target ventilation (60 percent maximum voluntary ventilation [MVV]), and heart rate was 170 +/- 14 beats per minute. This intensity was maintained for all tests. FEV1 was measured before and after exercise and was expressed as percent predicted and as percentage of the preexercise value (percentage of fall). Thirty minutes after treatment, both drugs were effective in inhibiting EIA--percentage of fall in FEV1, 17 +/- 12 after salmeterol; percentage of fall in FEV1, 15 +/- 15 after albuterol. At 2.5, 4.5, and 6.5 hours, the reduction in FEV1 was significantly less (p less than 0.01) after salmeterol compared with albuterol. At 6.5 hours, the percentage of fall in FEV1 was 20 +/- 10 after salmeterol and 36 +/- 12 after albuterol. Salmeterol also had a more prolonged action as a bronchodilator and values for FEV1 were significantly higher compared with those on albuterol at 4.5 and 6.5 hours. At 6.5 hours, the FEV1 percent predicted was 96 +/- 10 after salmeterol and 84 +/- 12 after albuterol (p less than 0.01). We conclude that the extent of protection against EIA and the bronchodilation induced by both drugs was similar, but that salmeterol has a longer duration of action compared with albuterol. The reason for its superior duration of action may be due to a slower clearance of the drug from the airways.

Administration, Inhalation↗
PubMed1991

Inhaled clemastine, an H1 antihistamine inhibits airway narrowing caused by aerosols of non-isotonic saline.

Asthmatic subjects were challenged with aerosols of hyper- and hypotonic saline 15 min (Group A) and 90 min (Group B) after inhaling clemastine. Measurements were made of forced expiratory volume in one second (FEV1) before and after medication and after challenge. When the FEV1 values (% predicted) were compared on the active and placebo days they were higher 15 min after clemastine (p less than 0.05) for both challenges and higher 90 min after clemastine inhalation (p less than 0.05) for the hypertonic challenge. The % fall in FEV1 was compared after the same concentration of saline aerosol had been given on both active and placebo days. In Group A the % fall in FEV1 on the clemastine day was reduced after challenge with hypertonic (p less than 0.02) and hypotonic (p less than 0.03) aerosol. In Group B there was a reduction in the % fall in FEV1 on the clemastine day only after hypertonic challenge (p less than 0.04). The protective effect afforded by clemastine was unrelated to change in baseline lung function. We conclude that histamine is an important mediator of the airway response to non-isotonic aerosols and suggest that the aerosol route of administration may be useful for delivering antihistamines.

Administration, Inhalation↗
PubMed1990

Terfenadine modifies airway narrowing induced by the inhalation of nonisotonic aerosols in subjects with asthma.

A change in osmolarity of the respiratory tract is a potent stimulus for provoking an attack of asthma. The mechanism for this is thought to be the release of histamine and other mediators from airway mast cells. We studied the effect of a potent and selective H1 receptor antagonist on the airway response to nonisotonic aerosols (NIA) in 12 asthmatic subjects 19 to 57 yr of age. Terfenadine (T) (180 mg) or its placebo (P) was given 150 min before challenge with NIA. The FEV1 was measured before and after the inhalation of aerosols of isotonic (0.9%), hypertonic (1.8, 3.6, 4.5, and 5.4%), and hypotonic NaCl (0.6, 0.3, and 0%) aerosols. Each concentration of aerosol was inhaled for 3 min, and each day the concentration was increased or decreased until a 20% fall in FEV1 was recorded. Terfenadine caused a significant reduction in airway narrowing as assessed by (1) the percent fall in FEV1 (hypertonic mean +/- 1 SD P, 26.1 +/- 9.5 versus T, 15.6 +/- 14, p = 0.025; hypotonic P, 29.8 +/- 13.1 versus T, 16.6 +/- 13.1, p less than 0.02); (2) the lowest FEV1 percent predicted (%FEV1) (hypertonic P, 61 +/- 13 versus T, 76 +/- 16, p less than 0.005; hypotonic P, 56 +/- 10 versus T, 78 +/- 14, p less than 0.001) documented at the dose common to both placebo and terfenadine test days; (3) the difference in %FEV1 before and after challenge (hypertonic, p less than 0.034; hypotonic, p less than 0.035).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

The evoked cochlear mechanical response in laboratory primates. A preliminary report.

The evoked cochlear mechanical response has been recorded in two species of laboratory primates, Macaca irus and Erythrocebus patas. The responses are very similar to those obtained in humans although the response to each click is of shorter duration. The response is vulnerable to the ototoxicity of furosemide and etacrynic acid and to noise exposure. At and near threshold an active generator of mechanical energy within the cochlea is proposed. The significance of such a generator and a possible source are discussed.

Animals↗
PubMed1979

Limitation of work performance in normal adult males in the presence of beta-adrenergic blockade.

The effect on work performance of a single oral dose of the cardio-selective beta-adrenoreceptor blocking agent, metoprolol, was compared with an equipotent dose of the non-selective agent, propranolol, in the same subjects. A number of biochemical and physiological variables including heart rate, oxygen consumption, ventilation, lactate, free fatty acid and glucose levels were measured. Following exercise in the presence of both active drugs, subjects complained of excessive leg fatique. For the group there was a significant reduction in the total work performed and the maximum heart rate achieved on both drugs. There was a significant correlation between plasma levels of metoprolol, reduction in total work performed and reduction in maximum heart rate. By contrast, after propranolol, there was a wide variation in work performed at a time when the reduction in maximum heart rate was similar for all subjects. This suggests for propranolol that a reduction in heart rate alone is an inappropriate guide to the impairment of work performance. There was a fail in the circulating level of free fatty acids at the end of exercise in the presence of both drugs and it is possible that this biochemical variable contributed to the decrease in work performance.

Adult↗
PubMed1978

Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias.

The present experiments were undertaken to assess the role of neurons in the nucleus raphe magnus (NRM) in mediating opiate and stimulation-produced analgesias. A cannode for both electric stimulation and local opiate microinjection was placed in the midbrain preiaqueductal gray region of decerebrate or chloralose-urethane anesthetized cats. Microelectrodes recorded the responses of medullary NRM neurons. Raphe-spinal neurons were identified by antidromic activation from the cerevical spinal cord. Fifteen of 20 raphe-spinal cells tested were excited by electrical stimulation of the midbrain. Of 49 NRM neurons tested, 26 were excited by either systemic or midbrain injection of opiate agonist. Twelve of 33 NRM cells tested by midbrain microinjection were excited. In 10 the effect was reversed by naloxone. Seventeen raphe-spinal neurons were tested; 5 showed naloxone-reversible excitation to either midbrain or intravenous injection of opiates. NRM neurons respond to auditory and somatic stimuli; at least half respond maximally to somatic stimuli of noxious intensity. These findings are consistent with the hypothesis that the raphe-spinal projection mediates opiate and electrical stimulation-produced effects from midbrain sites. The properties of raphe-spinal neurons suggest that they are part of a negative feedback system which monitors and limits the output of spinal dorsal horn pain-transmission neurons.

Action Potentials↗