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Biomedical subjects

J W Kerr

Publications and source records attributed to J W Kerr.

At least 37 records · Page 2Linked to original sources

Dose-response study of sodium cromoglycate in exercise-induced asthma.

Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate in increasing concentrations from 2 to 40 mg/ml. Saline was used as a control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after the patients had run on a treadmill for eight minutes. There was slight bronchodilation evident from the increase in baseline FEV1 after inhalation of sodium cromoglycate, the difference reaching statistical significance with the highest concentration (5.7%, p less than 0.05). After exercise the maximal percentage falls in FEV1 (means and SEM) after saline and after sodium cromoglycate at 2, 10, 20, and 40 mg/ml were 37.3 +/- 4.7, 17.3 +/- 4.1, 10 +/- 3.3, 7.6 +/- 2.4, and 12 +/- 2.9. Sodium cromoglycate inhibited the exercise-induced fall in FEV1 at all the concentrations used in the study (p less than 0.001) and its inhibitory effect increased from 2 to 20 mg/ml. The mean FEV1 returned to baseline values within 15 minutes at higher concentrations of sodium cromoglycate (20 and 40 mg/ml) and a small bronchodilator effect was noted at 30 minutes. The findings suggest that the protective effect of sodium cromoglycate in exercise asthma is dose related. At higher concentration the drug suppresses chemical mediator release from the lung mast cells and may also modify the bronchial reactivity to release mediators.

Adolescent↗

Type I allergy in mushroom soup processors.

Eight workers employed in a food manufacturing factory presented with symptoms of rhinorrhoea, dyspnoea and wheezing, originating during the preparation of dried mushroom soup. Five had positive immediate skin tests to dried mushroom extract and in four the FEV1 fell by over 30% following a bronchial challenge with mushroom dust. The features detected were those of a type I allergic response, without evidence of the extrinsic allergic alveolitis described in 'mushroom worker's lung'.

Basidiomycota↗

Effect of FPL57787 in exercise-induced asthma.

In ten patients with extrinsic asthma the effects of a new oral chromone FPL57787 and placebo were studied in a random double-blind fashion to assess the effect of FPL57787 in preventing exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to 8 min. FPL57787 gave significant protection (P less 0.01) compared to placebo from the maximum percentage fall in FEV1, FVC and MMEF after exercise. FPL57787 also produced a small but significant (P less than 0.01) percentage increase in FEV1 2 hr after the drug compared to placebo, whereas no significant increase was seen in FVC or in MMEF.

Administration, Oral↗

Effect of inhaled H1 and H2 receptor antagonist in normal and asthmatic subjects.

The effects on airflow resistance of an inhaled H1 receptor antagonist, clemastine, and an H2 receptor antagonist, cimetidine, have been investigated in normal and asthmatic subjects. No significant changes in specific conductance (sGaw) were seen in six normal subjects. In eight asthmatic subjects a significant increase in forced expiratory volume in one second (FEV1) occurred at 60 min (< 0.02), and 120 (< 0.05) after the inhalation of clemastine, whereas inhaled cimetidine had no effect on airflow resistance. Clemastine and cimetidine were tested on histamine-induced bronchoconstriction in eight normal and eight asthmatic subjects. Clemastine significantly reduced the fall in sGaw in normal subjects and the fall in FEV1 in asthmatic subjects, whereas cimetidine had no protective effect. Clemastine and ipratropium bromide were tested on methacholine-induced bronchoconstriction in eight normal subjects. Ipratropium bromide, but not clemastine, significantly reduced the fall in sGaw after methacholine. These results suggest that in normal and asthmatic subjects histamine-induced bronchoconstriction is mediated predominantly via H1 rather than H2 receptors in the airways.

Adolescent↗

Cyanide exposure in fires.

The toxic hazard from cyanide produced in fires was assessed in casualties and in firemen exposed to the fire atmosphere. The levels of cyanide and its principal metabolite, thiocyanate, were measured in blood samples from fireman, non-fetal and fatal casualties, and from controls. Although firemen did not differ significantly from controls, casualities showed significant elevation of blood-cyanide, and in a small proportion of fatalities blood-cyanide reached toxic levels.

Cyanides↗

Sodium cromoglycate and ipratropium bromide in exercise-induced asthma.

In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the baseline ratio of expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) to V50air was over 1.20 and they were called responders; the remaining five patients were called non-responders. There was a significantly lower baseline maximum mid-expiratory flow rate (MMEF) in non-responders (P less than 0.02) as compared to responders but no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Sodium cromoglycate (P less than 0.02), ipratropium bromide (P less than 0.01), and ipratropium bromide plus spdium cromoglycate (P less than 0.01) all significantly inhibited the percentage fall in FEV1 after exercise in the responders. Ipratropium bromide had no preventive action on non-responders, unlike sodium cromoglycate (P less than 0.05) and ipratropium bromide plus sodium cromoglycate (P less than 0.02). It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics, whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways.

Adolescent↗

Comparision of a glutaraldehyde-modified pollen--tyrosine adsorbate with an alum-precipitated pollen vaccine in the treatment of hay fever.

Nineteen patients with hay fever symptoms received nine weekly injections of pyridine-extracted alum-precipitated grass pollen vaccine (Alavac P). The results were compared with agroup of twenty patients who received a three injection series of a glutaraldehyde-modified pollen-tyrosine vaccine (Pollinex). In both groups 65% had a subjective improvement in their symptoms and no significant difference in symptom scores was obtained throughout the pollen season. In the Pollinex group a lower incidence of systemic side effects was recorded.

Adolescent↗

The effect of thymoxamine and cromolyn sodium on postexercise bronchoconstriction in asthma.

Of the 22 patients with extrinsic bronchial asthma, 13 patients developed post-exercise bronchoconstriction after treadmill exercise, whereas in 9 patients treadmill exercise had no effect on the ventilatory capacity. No statistical difference in the resting lung volumes and CO transfer factor was found between the two groups. A significant inhibition of postexercise bronchoconstriction was observed in 12 of 13 patients following thymoxamine or cromolyn sodium inhalation. Inhibition of postexercise bronchoconstriction by alpha blockade with thymoxamine suggests that increased alpha adrenergic activity in the presence of diminished beta receptor responsiveness to catecholamines, norepinephrine released during exercise could have a marked alpha agonistic effect giving rise to bronchoconstriction. It has been suggested that cromolyn sodium has a cyclic phosphodiesterase inhibiting action. This might increase levels of AMP and restore the beta receptor responsiveness to catecholamines.

Airway Obstruction↗

A 12-month double-blind assessment of betamethasone valerate aerosol in the management of asthma.

A double-blind trial of the topically active corticosteroid, betamethasone valerate in aerosol form, in the control of chronic asthma is reported. The results show that this is an extremely effective therapeutic agent in non-steroid dependent but nonetheless moderately severe asthmatics. Patients were well controlled on 800 mug of betamethasone valerate daily and control was maintained over a 12-month period. This form of treatment has few undersirable side effects but there is probably an increased incidence of oropharyngeal and laryngeal candidiasis. In particular, adrenocortical suppression was not noted.

Adolescent↗

Response of lymphocyte guanyl cyclase to propranolol, noradrenaline, thymoxamine, and acetylcholine in extrinsic bronchial asthma.

The lymphocyte guanyl cyclase response to alpha-agonists was studied in 10 normal people and 12 patients with bronchial asthma. In the normal subjects alpha-adrenergic stimulation with noradrenaline plus propranolol and cholinergic stimulation with acetylcholine evoked significant increases in cyclic guanosine monophosphate formation. In addition the alpha-receptor blocking drug thymoxamine produced a significant stimulation of this enzyme system, and the effects of thymoxamine and acetylcholine were additive. This suggests that receptors for cholinergic and alpha-adrenergic agents are independent. In contrast, lymphocyte guanyl cyclase activity did not show a significant response to these agents in patients with acute asthma. In asthmatic patients in remission the responses were partially restored. The significance of these results for control of bronchomotor tone and the relation of guanyl cyclase activity to cyclic adenosine monophosphate in normal subjects and patients with asthma is discussed.

Acetylcholine↗

Effect of alpha receptor blocking drug, thymoxamine, on allergen induced bronchoconstriction in extrinsic asthma.

In ten patients with extrinsic bronchial asthma, allergen provoked bronchospasm was significantly inhibited by the alpha receptor blocking drug thymoxamine given intravenously. In two of these patients thymoxamine by inhalation also effectively inhibited allergen induced bronchoconstriction. It is suggested that thymoxamine may be acting either by increasing intracellular levels of cyclic AMP and thus inhibiting mediator release following allergen challenge or by modifying the airways response to these mediators by altering the bronchomotor tone. The variable responses recorded after allergen challenge in presence of alpha blockade with thymoxamine suggests that the dominant effect is on the bronchomotor tone rather than the mediator release.

Administration, Intranasal↗

Response of leucocyte adenyl cyclase to isoprenaline and effect of alpha-blocking drugs in extrinsic bronchial asthma.

The finding by several workers that biochemical responses to catecholamines are diminished in asthmatic patients during periods of active asthma as compared to normal subjects has led to the recognition of the beta-adrenergic blockade phenomenon, a common accompaniment of extrinsic bronchial asthma. Using an intact cell method to measure leucocyte adenyl cyclase activity, we have been able to show that there is a noticeably reduced responsiveness of this enzyme system (which is now identified with beta-receptor function) to isoprenaline in the leucocytes of patients suffering from acute bronchial asthma, but that asthmatic patients in remission could not be distinguished from normal persons in this respect. Evidently the defective beta-receptor function may be associated with overactivity of the alpha-receptors in acute bronchial asthma, since the responsiveness to isoprenaline stimulation could be restored towards normal by concomitant treatment of the leucocytes of these patients with alpha-receptor blocking drugs such as phentolamine or thymoxamine. Ouabain, though somewhat less potent, also enhanced responsiveness to isoprenaline stimulation. The relation of these results to the clinical observation of adrenaline resistance in active asthma suggests that alpha-receptor blocking drugs may be of value in restoring the sensitivity of beta-receptors to sympathomimetic amines.

Acute Disease↗