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Biomedical subjects

N C Thomson

Publications and source records attributed to N C Thomson.

At least 91 records · Page 5Linked to original sources

The effect of passive sensitisation of human bronchial smooth muscle on in vitro sensitivity to histamine.

Allergen exposure may precipitate acute bronchoconstriction and increase bronchial reactivity. We have investigated whether passive sensitisation of human airway per se or short-term exposure to mediators released by specific antigen exposure produces an alteration in in vitro smooth muscle sensitivity to histamine. Exposure to allergen produced smooth muscle contraction in sensitised tissue, but subsequent smooth muscle sensitivity to histamine was not altered. We conclude that neither passive sensitisation nor short-term exposure to mast cell mediators alters in vitro smooth muscle sensitivity to histamine.

Adult↗

The effect of indomethacin and enalapril on the cutaneous response to bradykinin.

The angiotensin converting enzyme inhibitors potentiate the wheal response to intradermal bradykinin. Both converting enzyme inhibitors and bradykinin stimulate prostaglandin synthesis and prostaglandins enhance the cutaneous response to bradykinin. We examined the possibility that the increased wheal response to intradermal bradykinin in the presence of enalapril was due to the effect of prostaglandins. Indomethacin did not inhibit the potentiation by enalapril of the wheal response to bradykinin.

Adult↗

Effect of hyperthyroidism on bronchial reactivity in non-asthmatic patients.

Thyrotoxicosis may be associated with deterioration in asthma. To determine whether bronchial reactivity to histamine is increased in hyperthyroidism 10 thyrotoxic non-asthmatic patients were assessed before and after treatment of their thyrotoxicosis. No significant change in bronchial reactivity was found after treatment.

Adult↗

Lidocaine-induced bronchoconstriction in asthmatic patients. Relation to histamine airway responsiveness and effect of preservative.

Inhaled topical lidocaine, used to produce anesthesia of the respiratory tract prior to bronchoscopy, may cause bronchoconstriction in asthmatic patients. We investigated whether the degree of histamine airway responsiveness would predict the development and extent of lidocaine-induced bronchoconstriction in 20 asthmatic patients. The provocation concentration of histamine producing a 20 percent fall in FEV1 (PC20) was measured. On a separate day, challenge with 6 ml 4 percent lidocaine (Xylocaine 4 percent topical) was performed. There was no correlation between the response to lidocaine and the histamine PC20. Five patients (25 percent) showed a fall in FEV1 of greater than 15 percent (max 42.1 percent). Three responders were rechallenged double-blind with the commercial 4 percent lidocaine preparation and with a 4 percent preservative-free lidocaine solution. There was no difference in the response to these two solutions. These results demonstrate that inhaled topical lidocaine induces bronchoconstriction in a significant proportion of patients with asthma. This response is not related to airway histamine responsiveness or to the preservative in the lidocaine preparation.

Administration, Inhalation↗

The effects of the 5 HT2 antagonist ketanserin in adult atopic asthma.

We have studied eight adult atopic asthmatic patients in a randomized double-blind, placebo-controlled, cross-over trial in order to examine the effects of the 5 HT2 antagonist ketanserin on airways function (FEV1, FVC, V50(chi), and V25(pi]. Ketanserin did not significantly change resting bronchomotor tone. Treadmill exercise caused a similar maximal percentage fall in FEV1 after both drug [16.8 (3.7)%] and placebo [19.2 (4.2)%]; ketanserin did not significantly attenuate bronchoconstriction, measured over a 20-min period after exercise. These results suggest that 5 HT2 receptors do not play a major role in the control of resting bronchomotor tone or in exercise-induced bronchoconstriction in adult atopic asthmatic patients.

Adolescent↗

Concentration-related differences in the effects of the Ca2+ agonist Bay K 8644 in human bronchus in vitro.

1. In human isolated bronchial muscle Bay K 8644 (1 nM-1 microM) increased the force of contraction. In concentrations greater than 1 microM (in sensitized tissues), and 10 microM (in control), Bay K 8644 relaxed tissues to below their pretreatment baseline tension. 2. In control tissues contracted with methacholine or LTD4, Bay K 8644 (10 microM) produced a further small contraction; Bay K 8644 (100 microM) relaxed the tissues below baseline. 3. In tissues contracted with histamine, Bay K 8644 (10-100 microM) produced only relaxation. 4. Bay K 8644 therefore has both Ca2+ agonist and Ca2+ antagonist properties, the calcium agonist activity is more pronounced in sensitized tissues.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Hydroxychloroquine in steroid dependent asthma.

A recent case report suggested that hydroxychloroquine had a steroid sparing effect in a patient with severe chronic asthma. We have studied the effect of hydroxychloroquine in a group of nine steroid dependent adult asthmatic patients using a randomised double blind crossover comparison of hydroxychloroquine and placebo. Each patient received hydroxychloroquine (400 mg/day) or placebo for 2 month periods. The effect of hydroxychloroquine or placebo on asthma control was assessed by change in steroid dosage, visual analogue symptom scores, response to beta 2 agonist and peak expiratory flow rate (PFR) measurement. The dose of prednisolone required during hydroxychloroquine treatment did not differ from that during placebo treatment or in pre-trial period. There was no significant change in symptom scores of PFR measurement. In this study an 8 week treatment with hydroxychloroquine was of no benefit to patients with chronic steroid dependent asthma.

Adult↗

Effect of house dust mite avoidance measures on adult atopic asthma.

Twenty one adult patients with asthma, with positive skin test responses to the European house dust mite, Dermatophagoides pteronyssinus, were randomly allocated to a control group or to a group applying house dust mite avoidance measures. These included an initial application of liquid nitrogen to mattresses and bedroom carpets to kill the live house dust mite population. Histamine airway responsiveness, symptom scores, peak expiratory flow rates (PEF), and house dust mite numbers were determined during the two week pretrial and eight week trial periods. Nine patients in each group completed the study. By the end of the study there was a significant reduction in live mites in the "avoidance" group but not in the control group. The avoidance group showed a significant improvement in symptom scores measured on a linear analogue scale, in the number of hours each day spent wheezing (mean reduced from 8.6 to 4.5 hours), and in PEF (l/min) both in the morning (from 364 to 388) and in the evening (from 368 to 392). These changes were not found in the control group. The provocative concentration (PC) of histamine causing a 20% fall in FEV1 (PC20FEV1) had increased significantly in the avoidance group at eight weeks (from 0.58 to 2.3 mg/ml), whereas no change was seen in the control group (from 0.93 to 1.21 mg/ml). These results show that house dust mite avoidance, combined with initial killing of the mite by liquid nitrogen, diminishes airway responsiveness and improves asthma symptom control over an eight week period in adult asthmatic patients with house dust mite allergy.

Adolescent↗

Circulating adrenaline and noradrenaline concentrations during exercise in patients with exercise induced asthma and normal subjects.

A failure of the usual increase in plasma adrenaline and noradrenaline concentrations during submaximal exercise has been suggested as a contributory cause of exercise induced asthma. Six normal subjects and six asthmatic patients underwent a standard graded maximal exercise test. Measurements of oxygen consumption, minute ventilation, exercise time, blood lactate concentration, and heart rate indicated that the two groups achieved similarly high work loads during exercise. Mean FEV1 fell by 20% in asthmatic patients after exercise. Basal plasma adrenaline concentrations (nmol/l) increased in normal subjects from 0.05 to 2.7 and in asthmatic patients from 0.12 to 1.6 at peak exercise. Noradrenaline concentrations (nmol/l) increased in normal subjects from 2.0 to 14.3 and in asthmatic patients from 1.9 to 13.7 at peak exercise. The increases in adrenaline and noradrenaline in the asthmatic patients did not differ significantly from the increases in normal subjects. Thus a reduced sympathoadrenal response to exercise seems unlikely to be an important mechanism in the pathogenesis of exercise induced asthma.

Adolescent↗

Evidence for a dual effect by beta-adrenoceptor antagonists on post-exercise airway calibre.

The effect of selectivity of beta-adrenoceptor antagonists on resting and post-exercise airway calibre in normal subjects was studied. Eight normal subjects were given atenolol 50 mg, propranolol 80 mg and placebo orally, in random order, double-blind. Specific airways conductance and flow-volume curves (partial and complete) were recorded before, 2 hours after drug administration and after exercise. Neither beta-adrenoceptor antagonist had a measurable effect on lung function tests at rest. The post-exercise increase in flow rates measured from partial flow volume curves was inhibited by propranolol but not by the beta-1-selective adrenoceptor antagonist atenolol, whereas both drugs caused a decrease in specific airways conductance after exercise. Beta-adrenoceptor antagonists may have a dual effect on airway calibre. Firstly, a direct effect on the beta-2 receptors in airway smooth muscle may occur. Secondly, beta-adrenoceptor blockade may, in the large airways, inhibit vagal pre-junctional beta-1 receptors which normally inhibit acetylcholine release at the nerve ending, thereby permitting vagally-induced airway narrowing.

Adult↗

Tea-dust induced asthma.

A 55-yr old female worker in a tea-packing production line developed asthma to tea-dust. She had no previous history of chest disease, and skin prick testing to a solution of tea-dust and to a variety of common allergens were all negative. Diagnosis was established by serial peak expiratory flow rate readings. Bronchial provocation challenge with tea-dust demonstrated a late asthmatic reaction.

Asthma↗

In vivo and in vitro human airway responsiveness to leukotriene D4 in patients without asthma.

We have examined the in vivo airway responsiveness to leukotriene (LT) D4 in 11 patients without asthma who were to undergo thoracotomy and compared this responsiveness with in vitro sensitivity and in vitro contractility of bronchial smooth muscle to LTD4. In vivo responses were measured by the provocation concentration producing a 10% fall in FEV1, a 30% fall in partial flow rate at 30% of total lung capacity from a partial forced expiratory maneuver, and a 35% fall in specific airway conductance. In vitro sensitivity was measured as the concentration of LTD4 producing a 50% of maximum contraction and maximum-induced tension. The smooth muscle content of the bronchial strip was estimated microscopically, and the absolute quantity of muscle strip was compared with the maximum tension generated by that bronchial smooth muscle sample. In vivo results varied over 2 log units, and in vitro sensitivity, over 1 log unit. The absolute amount of smooth muscle present in bronchial strips correlated with maximal LTD4-induced tension. There was no relationship between in vivo responsiveness and in vitro sensitivity nor between in vivo responsiveness and maximum tension generated, even when this was corrected for the proportion of smooth muscle present in each bronchial strip. These results suggest that in vivo airway responsiveness to LTD4 is not determined by airway smooth muscle sensitivity or its ability to generate tension alone. Other factors must be influencing the response of the airway to LTD4. Nevertheless, the finding of a positive correlation between the absolute amount of smooth muscle present in bronchial strips and maximal LTD4-induced tension suggests that hypertrophy and/or hyperplasia of airway smooth muscle may contribute to in vivo airway hyperresponsiveness.

Aged↗

Agonist-induced contractile responses of human bronchial muscle in vitro: effects of Ca2+ removal, La3+ and PY108068.

The effects of reducing the extracellular Ca2+ concentration ([Ca2+]0), the effects of La3+ and the dihydropyridine Ca2+ entry blocker PY108068 on contractile responses in human isolated bronchial strips have been compared. Reducing [Ca2+]0 or the presence of La3+ (1 mM) caused a reduction in basal tone, whereas PY108068 (1 microM) had no effect on unstimulated preparations. Response to KCl and A23187 were, in general, more markedly depressed by reducing the entry of extracellular Ca2+, with La3+ or PY108068 than were those to histamine, methacholine and LTD4. The effects of reducing [Ca2+]0, La3+ and PY108068 on responses to the receptor-mediated agents suggest that intracellular Ca2+ may be mobilized upon receptor activation, whereas responses to KCl and A23187 appear to be dependent upon the influx of extracellular Ca2+. More than one source of activator Ca2+ can therefore be involved in the development of contractions in human airway smooth muscle. These findings are in accord with those observed for in vitro airways preparations from experimental animals.

Bronchi↗

A new adaptable computerized system for the measurement of specific airways conductance.

We have developed an automated system for the measurement of specific airways conductance (SGaw) which differs in several aspects from other reported automated systems. In seven subjects this system was used to measure baseline SGaw and the provocation concentration (PC) of histamine producing a 35% fall in SGaw. The results produced were compared with those obtained by manual analysis using both one limb and two limbs of the inspiratory part of the flow/box pressure curve. Using the automated system, baseline SGaw and PC35SGaw results were similar to those obtained by the two limbs method of manual analysis, but the analysis time was considerably reduced. A single measurement of SGaw was obtained within 2-3 seconds. Both the automated and two limbs manual methods of analysis were more reproducible than the one limb method of manual analysis.

Adult↗