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Biomedical subjects

T J Clark

Publications and source records attributed to T J Clark.

At least 55 records · Page 3Linked to original sources
PubMed1988

A comparison of mediator and catecholamine release between exercise- and hypertonic saline-induced asthma.

Serum neutrophil chemotactic activity (NCA) and plasma histamine concentrations were measured in 9 asthmatic subjects with exercise-induced asthma after inhalation challenge with ultrasonically nebulized 3.6% hypertonic saline, which was administered either in a dose-dependent manner (HSDR) or as a continuous single dose (HSC), and after cycle ergometer exercise. The mean decreases in FEV1 elicited by HSDR, HSC, and exercise were 26, 27, and 25%, respectively, and were not significantly different. There was an approximate 300% maximal increase in NCA detected after both HSC and exercise challenges. Gel filtration chromatography on columns of Ultragel ACA 34 indicated that the NCA released after HSC provocation and exercise were 600 to 700 kDa. There was an approximate 100% maximal increase in NCA after HSDR challenge, and this was significantly less (p = 0.016) than that after HSC and exercise. Exercise but not hypertonic challenge was associated with a basophilia and a significant increase in plasma histamine. There was a significant increase in plasma norepinephrine concentrations after exercise but not after HSC challenge in 7 asthmatics. Epinephrine concentrations did not change after exercise or HSC inhalation. NCA was measured in 5 subjects subjected to 2 HSC challenges that were separated by 60 min. There was an increase in NCA detected after both provocations. The increase after the second challenge was significantly greater (p = 0.27 x 10(-4)) than that observed after the initial provocation, despite a substantially reduced bronchoconstrictor response after the second challenge.

Adolescent↗
PubMed1988

Enhanced generation of leukotriene B4 by neutrophils stimulated by unopsonized zymosan and by calcium ionophore after exercise-induced asthma.

The generation of LTB4 by peripheral blood neutrophils (PMN) isolated before and for as long as 6 h after exercise-induced asthma (EIA) has been analyzed. Three and 6 h after the development of EIA, PMN isolated from 10 asthmatic subjects and stimulated in vitro by 2 x 10(8) and 4 x 10(8) zymosan particles per 2 x 10(6) PMN demonstrated a 12- and 4-fold enhancement, respectively, in the production of immunoreactive LTB4 as compared with PMN isolated before exercise. At 6 h after EIA, there was a redistribution of generated LTB4 such that 30 to 40% of LTB4 produced by zymosan-activated PMN was released extracellularly as compared with 10% before exercise. There was no significant enhancement in the generation of LTB4 by unstimulated PMN at any time point after exercise. Resolution by reverse-phase high performance liquid chromatography (HPLC) of products from [3H]arachidonic-acid-labeled and zymosan-activated PMN demonstrated that, in addition to LTB4, there was enhanced metabolism to 6-trans-LTB4, omega-oxidation metabolites of LTB4 and 5-HETE. Stimulation of PMN with 10 microM A23187 revealed a 2-, 6-, and 5-fold enhancement in the production of LTB4, 6-trans-LTB4, and 5-HETE, respectively, at 6 h after EIA, as measured by integrated ultraviolet absorbance after HPLC. There was no significant enhancement in LTB4 generation by PMN in 6 asthmatic subjects after methacholine-induced bronchospasm, and after exercise in 6 subjects who did not develop asthma. The augmentation of PMN LTB4 generation in EIA correlated with the extent of the early decrease in SGaw.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Is there a circadian variation in respiratory morbidity?

In a retrospective study of the time of presentation to an accident and emergency department patients with acute respiratory symptoms presented more commonly at night compared to a control group with abdominal pain. In a subsequent prospective study doctors from a GP deputizing service were called much more frequently at night by patients with asthma than by those with other symptoms. These findings refute the suggestion that the observed increased mortality from respiratory diseases at night results from reduced medical care as a consequence of a reluctance of patients to present during the night.

Acute Disease↗
PubMed1987

A comparison of the refractory periods induced by hypertonic airway challenge and exercise in bronchial asthma.

We have compared the changes in FEV1 of 10 asthmatic patients who were subjected in random order to paired challenges with different combinations of exercise and aerosolized hypertonic 3.6% saline. The challenges were separated by 60 min when the FEV1 values had returned to within 10% of baseline values. Four patients were refractory to exercise-induced asthma (EIA) after an initial exercise task, and these patients also demonstrated a refractory period to hypertonic-saline-induced bronchoconstriction after an initial hypertonic challenge. Furthermore, hypertonic challenge produced refractoriness to EIA in the patients, and exercise rendered them refractory to hypertonic-saline-induced asthma. Six subjects were not refractory to EIA after an initial exercise task, and they were also not rendered refractory by an initial hypertonic challenge to asthma induced by hypertonic saline or by exercise. Histamine-induced bronchoconstriction in the 4 refractory subjects did not induce a refractory period to EIA, indicating that the refractory periods developing after hypertonic saline challenge and exercise were not due to the bronchoconstriction alone. Inhalation of isotonic saline in the same volumes as those used for hypertonic challenges did not induce a refractory period, indicating that the refractory period caused by the inhalation of hypertonic saline was not due to the volumes of fluid inhaled. Thus, exercise and aerosolized hypertonic saline induced refractoriness interchangeably, suggesting that airway hypertonicity and exercise produced a refractory period through a very similar, if not identical, final common pathway.

Adult↗
PubMed1987

Diurnal rhythm of asthma.

A diurnal rhythm in the occurrence and severity of asthma symptoms is almost universal with disturbed sleep due to enhanced symptoms at night paralleled by a change in lung function. The mechanisms involved are not completely understood. However, it appears to be related to an exaggerated response to a circadian rhythm in lung function observed in healthy individuals. The circadian nature of asthma must be considered in diagnosis and evaluating the adequacy of therapy. Inhaled therapy with additional suppressive and anti-inflammatory treatment as required should be effective in treating most patients with nocturnal asthma.

Asthma↗
PubMed1985

Inhaled corticosteroid therapy: a substitute for theophylline as well as prednisolone?

Topical corticosteroid treatment can be successfully achieved by inhaled therapy and can effectively provide a safe substitute for oral steroids. More than 8 million patient years of experience gained over a decade of use of inhaled steroids has shown them to be acceptable to patients and clinicians, with side effects confined to the upper airway. At daily doses of 200 to 1600 micrograms BDP or the equivalent, minor systemic activity may occasionally be demonstrated but no adverse systemic side effects have been reported. The topical anti-inflammatory treatment provided by inhaled steroids thus compares favorably with prednisolone and with other asthma therapy with respect to morbidity and mortality, suggesting that inhaled steroids combined with an inhaled beta-agonist is a safe and comprehensive treatment for chronic asthma. This parallel attack on inflammation and bronchoconstriction can be achieved with a morbidity that is much less than that of asthma and also likely to be less than that of the frequently used combination of theophylline and inhaled beta-agonist. Twice-daily regimens of inhaled steroids over a dose range of 200 to 1600 micrograms BDP or the equivalent should enable most patients with chronic asthma to receive effective therapy without recourse to potentially more toxic oral bronchodilator or steroid therapy.

Adrenal Cortex Hormones↗
PubMed1985

Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome.

Twenty patients with the Ehlers-Danlos syndrome, (10 type I, six type II, and four type IV) were studied to assess the frequency of respiratory abnormalities in this condition. Five patients (25%) had had at least one episode of haemoptysis, but none had any defect of coagulation. There was a high frequency of recurrent sinusitis, notably in those with the type I syndrome. Two patients had bullous lung disease, one of whom (type IV) had had three pneumothoraces and subsequent pleurodesis; he also had tracheomegaly (the Mounier-Kuhn abnormality). Minor skeletal abnormalities such as pectus excavatum were common, particularly in patients with type IV disease. Three patients had the straight back syndrome. There were no consistent spirometric or lung volume abnormalities, but eight patients (40%) had a raised gas transfer coefficient (Kco), possibly due to an increased intrapulmonary vascular volume. Two other patients had very low values of Kco that were unexplained.

Adolescent↗
PubMed1985

Effects of histamine on lung permeability in normal and asthmatic subjects.

The permeability of respiratory mucosa, as measured by clearance of diethylenetriamine penta-acetate (DTPA) labelled with technetium 99m, was similar in seven normal and nine asthmatic subjects. Histamine induced bronchoconstriction was associated with a 50% increase in permeability in both groups of subjects. In normal subjects inhaled salbutamol, given as 1 mg acutely or as 200 micrograms four times daily for two weeks, had no effect on pulmonary permeability. Salbutamol, given before histamine challenge, prevented bronchoconstriction, but did not affect the increase in permeability seen in normal subjects. Low doses of histamine, sufficient to cause bronchoconstriction in the asthmatic subjects, produced little bronchoconstriction in normal subjects but caused increases in lung permeability similar to those seen in asthmatic subjects. These studies suggest that these two effects of inhaled histamine, bronchoconstriction and increased permeability, are independent.

Adult↗
PubMed1984

Inhaled therapy reduces morning dips in asthma.

14 asthmatic patients with nocturnal symptoms and morning dips in peak expiratory flow rate (PEFR) were treated with regular inhaled salbutamol for 1 or 2 weeks, followed by regular inhaled beclomethasone dipropionate, in addition to salbutamol, for a further 2 weeks. Mean PEFR rose to normal values in all but 1 patient. Morning dips in PEFR were substantially reduced in 8 patients. There was an equivalent rise in mean PEFR in the other 6 patients, but their morning dips did not improve. Inhaled salbutamol reduced the dips in the responsive patients, but addition of inhaled steroid produced further improvement. Inhaled beta agonist alone improved mean PEFR in these patients, but inhaled steroids produced most of the improvement in the other subgroup. No patient experienced side-effects. Thus mean PEFR can be improved and morning dips in PEFR reduced in a high proportion of asthmatic patients by the use of regular inhaled therapy without resorting to less-well-tolerated oral agents.

Adolescent↗
PubMed1984

Protective effect of circulating epinephrine within the physiologic range on the airway response to inhaled histamine in nonasthmatic subjects.

The specific airway conductance response of six normal subjects to increasing doses of inhaled histamine was studied on two occasions. On each occasion either epinephrine (0.025 micrograms/kg/min) or saline was infused intravenously during the histamine challenge. This dose of epinephrine, when it was administered to seated normal subjects, produces plasma levels similar to those found at the end of strenuous exercise. Epinephrine caused a significant elevation in the concentration of histamine required to cause a 35% fall in specific airway conductance (PC35), although this was in part caused by a small airway dilator effect. The mean (+/-SD) PC35 rose from 21 mg/ml (+/-6) during saline infusion to 58 mg/ml (+/-27) during epinephrine infusion, p less than 0.05. Levels of circulating epinephrine, similar to those found during exercise in normal subjects, appear to be capable of protecting against bronchoconstrictor stimuli.

Administration, Intranasal↗
PubMed1984

Effect of penbutolol and propranolol on normal airway response to salbutamol.

The specific airway conductance (sGaw) response of eight normal men to inhaled salbutamol, 200, 600, and 1800 micrograms, was measured on 3 separate days. On each occasion subjects received either placebo, long-acting propranolol (160 mg), or penbutolol (40 mg) orally in a double-blind manner after baseline lung function determination. After placebo, mean sGaw rose from a baseline of 2.07 +/- 0.15 to 2.81 +/- 0.25 kPa-1 X sec-1 after 200 micrograms salbutamol. There was little further airway dilation with higher doses of salbutamol. With long-acting propranolol, there was no significant airway dilation after 200 micrograms salbutamol but there was after 600 and 1800 micrograms inhaled salbutamol; baseline sGaw rose from 2.02 +/- 0.17 to 2.70 +/- 0.28 and 2.95 +/- 0.32 kPa-1 X sec-1. Penbutolol prevented any significant airway dilation with all doses of salbutamol. Penbutolol at the doses used appears to be a more potent blocker of beta 2-receptors than does propranolol.

Adult↗
PubMed1984

Effect of adrenergic and vagal blockade on the normal human airway response to exercise.

Ten normal, non-asthmatic subjects performed an 18 min graduated exercise test on a static exercise bicycle on 3 separate days. They received either no medication, or propranolol 80 mg orally 2 h before, or ipratropium bromide 0.216 mg by inhalation 30 min before, the start of exercise. With no medication, transpulmonary index (TPI), a measure of airway resistance, fell linearly during exercise from a resting value of 0.269 +/- 0.024 to 0.170 +/- 0.014 kPa X 1(-1) X s by the end of exercise. This returned to baseline between 2 and 4 min after stopping exercise. Propranolol elevated baseline TPI slightly from 0.270 +/- 0.024 to 0.294 +/- 0.024 before exercise and during exercise this fell linearly to 0.185 +/- 0.016 kPa X 1(-1) X s. The fall in TPI during exercise after propranolol was not significantly different from the fall seen with no medication. Six minutes after exercise stopped TPI rose to 0.336 +/- 0.035 kPa X 1(-1) X s after propranolol. All values for TPI from 4 min to 16 min after exercise were significantly higher after propranolol than the corresponding values found after no medication (P less than 0.05). Ipratropium bromide decreased baseline TPI from 0.264 +/- 0.024 to 0.163 +/- 0.013 kPa X 1(-1) X s (P less than 0.001) and this did not change significantly further either during or after exercise. Normal subjects show considerable airway dilatation during exercise and this appears to result from inhibition of resting vagal tone. The sympathetic system does not appear to mediate the airway dilatation during exercise, but it may be important in protecting against post-exercise bronchoconstriction.

Adult↗
PubMed1984

Adrenaline secretion during exercise.

By studying six normal subjects during graduated treadmill exercise, we have confirmed that there is very little rise in venous plasma adrenaline levels during mild or moderate exercise. During a second study, adrenaline was infused intravenously in six resting subjects at a rate of 0.025 micrograms min-1 kg-1. This elevated the basal plasma adrenaline level from 0.28 +/- 0.04 nmol/l to 0.92 +/- 0.16, 1.16 +/- 0.20 and 1.28 +/- 0.19 nmol/l at 3, 5 and 7 min after the start of the infusion. The same adrenaline infusion was repeated in the same subjects 7 min after they started moderate exercise at a constant rate on a static exercise bicycle. Just before the start of the infusion, 7 min after the onset of exercise, plasma adrenaline had risen to 0.36 +/- 0.07 nmol/l. This rose to 1.86 +/- 0.30, 1.98 +/- 0.26 and 2.19 +/- 0.29 nmol/l at 3, 5 and 7 min after the start of this second infusion. Five minutes after the end of the infusion, while the subjects were still exercising, the mean level was 0.56 +/- 0.04 nmol/l. The venous plasma level of adrenaline is the result of a balance between the secretion of adrenaline by the adrenal medulla and the clearance of adrenaline from plasma. Our results suggest that the lack of any significant rise in plasma adrenaline during moderate exercise does not result from an accelerated clearance of adrenaline by exercising tissue. The clearance rate of adrenaline from plasma is reduced during exercise. There is no significant increase in secretion by the adrenal medulla in response to the stimulus of mild or moderate exercise.

Adult↗
PubMed1984

Acute airway changes induced by coughing.

The effects of voluntary coughs on specific conductance measurements were studied in normal, atopic and asthmatic subjects before and after bronchoconstriction with histamine. The responses were variable, the most frequent change being temporary bronchodilation in the 30 seconds after a voluntary cough in the presence of histamine-induced bronchoconstriction. The effects of the two components of coughing, namely a full inhalation and a cough without a preceding deep inhalation, were studied in a similar manner. After challenge with histamine had reduced specific conductance by approximately 50%, full inhalations produced a temporary increase in conductance. Modified coughs without deep inhalation after histamine most often resulted in a temporary small decrease in conductance. One atopic subject showed marked, prolonged airway narrowing after a single full inhalation before histamine. We conclude that the major effects on airway smooth muscle produced by coughs result from the deep inhalation. In challenge studies coughs may affect subsequent airways resistance measurements. Such brief changes are not clinically important but may affect the results of inhalation challenge studies. Occasionally individuals show more prolonged bronchoconstriction after such manoeuvres.

Airway Resistance↗