Biomedical subjects

R Wood-Baker

Publications and source records attributed to R Wood-Baker.

25 records · Page 2Linked to original sources

PubMed1993

The comparative actions and adverse effect profile of single doses of H1-receptor antihistamines in the airways and skin of subjects with asthma.

BACKGROUND: The development of potent H1-receptor antagonists that are free of adverse effects has renewed interest in their use in the treatment of asthma. METHODS: We performed a study of the action of chlorpheniramine, terfenadine, brompheniramine, cetirizine, cyproheptadine, clemastine, and astemizole compared with placebo on histamine-induced skin wheals and bronchoconstriction in a single group of patients with asthma. Another group underwent methacholine bronchoprovocation. RESULTS: Antihistamine pretreatment increased mean baseline measurements of forced expiratory volume in 1 second (FEV1) between 2.58% and 9.28% compared with placebo, which was significant for all drugs except brompheniramine and clemastine. Compared with placebo, all antihistamines provided significant protection against histamine-induced bronchoconstriction when measured as the provocation concentration required to cause a 20% fall in FEV1; terfenadine and cetirizine provided significantly greater protection than other antihistamines. Protection against histamine-induced skin wheals, measured as the slope of the log concentration-response curve, was only significant for the new drugs, terfenadine and cetirizine. There was a good correlation between the protective effect of the drugs in the skin and airways (r = 0.85; p < 0.01). No significant difference in methacholine provocation concentration required to cause a 20% fall in FEV1 values between treatments was found. CONCLUSIONS: The new H1-receptor antagonists terfenadine and cetirizine provided significantly better protection than the older antihistamines against the action of histamine in the skin and airways. None of the antihistamines showed evidence of anticholinergic activity in the asthmatic airways at the doses studied.

Adult↗

PubMed1993

Plasma and urinary histamine in allergen-induced early and late phase asthmatic responses.

The local release of histamine is considered to be largely responsible for the early asthmatic response to inhaled allergen, although its contribution to the late response is less well-established. To investigate this we have measured the changes in forced expiratory volume in one second (FEV1), plasma histamine and urinary N tau-methylhistamine, in 10 asthmatics following inhaled allergen. To estimate the significance of any changes, we also measured plasma histamine concentrations following inhalation of histamine by nine normal subjects. Following allergen inhalation, the FEV1 fell a mean maximum 38% (SD 13%) from baseline at 15 min, associated with an increase in plasma histamine from a mean (SD) 0.22 (0.08) to 0.64 (0.47) ng.ml-1 at 10 min. During the late asthmatic response, plasma histamine concentrations did not depart significantly from baseline concentrations. There were no significant changes in urinary N tau-methylhistamine excretion. Inhalation of histamine by normal subjects at concentrations up to 4 mg.ml-1 showed no significant change in plasma concentrations, but at 16 mg.ml-1 there was an increase from a mean (SD) baseline 0.25 (0.10) ng.ml-1 to a mean maximum 0.83 (0.53) ng.ml-1 at 1 min. The early asthmatic response to inhaled allergen in asthmatics is accompanied by a significant increase in plasma histamine, approximately equivalent to an inhaled concentration of 16 mg.ml-1, whereas no significant changes in histamine were found during the late asthmatic response.

Adult↗

PubMed1993

The time course of action of three differing doses of noberastine, a novel H1-receptor antagonist, on histamine-induced skin wheals and the relationship to plasma drug concentrations in normal human volunteers.

1. The time course and magnitude of effect of the novel H1-receptor antagonist noberastine, structurally modified from astemizole to achieve a more rapid onset while retaining a good duration of action, has been investigated using histamine-induced skin wheals in healthy volunteers. 2. The pharmacokinetics and pharmacodynamics of three doses (10, 20 and 30 mg) have been studied in a double-blind, placebo controlled, randomised cross-over trial involving 12 healthy male volunteers. 3. All doses of noberastine caused inhibition of histamine-induced skin wheals, which were significantly different from placebo (P < 0.0001) when assessed as the area under the percent inhibition of the response vs time curves. 4. Following single dose administration of 10, 20 and 30 mg noberastine significant inhibition of histamine-induced skin wheals occurred and this effect persisted beyond 24 h. 5. At the higher (20 and 30 mg) doses studied significant inhibition of the histamine-induced skin wheal occurred by 1 h of dosing, whereas this did not occur until 2 h following the 10 mg dose. 6. An increase in plasma concentrations of noberastine was seen after administration of all doses, with mean (s.d.) concentrations of 4.14 (3.70), 8.38 (7.81) and 12.66 (11.82) ng ml-1 1 h following administration of 10, 20, and 30 mg respectively. 7. Visual analogue scale measurements of drowsiness identified no sedative effects above those of placebo at any of the dose levels. 8. We conclude that noberastine is an effective H1-receptor antagonist in the human as assessed by its effect on histamine-induced skin wheals.

Adult↗

PubMed1992

Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist.

The sulfidopeptide leukotrienes C4, D4, and E4 are released from mast cells in response to allergen challenge and may be involved in the bronchoconstrictor response to inhaled allergen in asthma. Since mast cell activation may also be implicated in exercise-induced bronchoconstriction, we assessed the inhibitory effects of a potent orally active leukotriene D4 receptor antagonist, ICI 204219 (20 mg), on the bronchoconstrictor response to exercise in eight male asthmatic patients in a placebo-controlled, randomized crossover study. Exercise challenge respiring dry air was performed on a treadmill at constant speed and gradient 2 h after drug administration, and bronchoconstriction was assessed as change in FEV1 over 30 min postexercise. No significant effect on airway caliber, measured as FEV1, was noted 2 h after ICI 204219. The mean maximum percentage fall in FEV1 following exercise was 36.0% following placebo, and reduced to 21.6% after ICI 204219 (p less than 0.01). Analysis of the time course of bronchoconstriction showed that inhibition was most marked over the latter part of the period assessed. These data indicate that the release of sulfidopeptide leukotrienes makes a major contribution to exercise-induced bronchoconstriction.

Adult↗

PubMed1991

Reassessment of asthma management in an accident and emergency department.

To determine if shortcomings in asthma management in the Accident and Emergency (A & E) department identified in a previous (1983) study (Reed et al. Thorax 1985; 40: 897-902) had been corrected, we retrospectively reviewed the case records of patients attending with asthma between December 1987 and November 1988. There was an increase in the number of patients attending with asthma; 0.73 per 1000 in 1988 versus 0.57 per 1000 in 1983. Sixty-seven percent of patients were self-referred and 80% presented between 1600 h and 0800 h. There was inadequate recording of the asthma history and examination findings. Peak expiratory flow (PEF) was recorded in 86% before treatment (compared to 11% in 1983) and 70% after treatment. In addition, a prospective study of 40 patients responding to a questionnaire 2 weeks after discharge, revealed persistent symptoms of unstable asthma in 50%. Although there has been a marked improvement in the use of PEF measurements since the 1983 study, the standards of management of asthma patients may still be inadequate as evidence by the presence of unstable asthma symptoms in many of those discharged. A standardized management protocol which provides guidelines for treatment based on PEF has been introduced to the A & E department.

Adult↗

PubMed1990

Dose-response relationship of the H1-histamine antagonist, ebastine, against histamine and methacholine-induced bronchoconstriction in patients with asthma.

In a double blind, randomised, placebo controlled trial in a group of extrinsic asthmatics, we have evaluated the potency and selectivity of ebastine, a new piperidine-type H1-receptor antagonist, against histamine and methacholine-induced bronchoconstriction. The median histamine PC20FEV1 value following placebo was 3.15 mg/ml (0.24-58.84). When compared with placebo, ebastine produced significant protection at 10 mg (median PC20 = 31.36 mg/ml, p = 0.008) and 30 mg (median PC20 = 42.14 mg/ml, p = 0.001) but there appeared to be no significant dose effect. Ebastine also produced a small shift in the methacholine concentration-response curves to the right. We conclude that ebastine is an effective antagonist of histamine-induced bronchoconstriction in the asthmatic airway with evidence of minor blockade of methacholine-induced bronchoconstriction.

Adult↗

PubMedDate not supplied

Outcome of a smoking cessation programme run in a routine hospital setting.

BACKGROUND: Although tobacco smoking remains the largest preventable cause of mortality in Australia, resources to assist with cessation remain scarce. Research studies have demonstrated improved cessation rates with interventions such as counselling and pharmacotherapy, but there is little information on success in routine clinical practice. AIMS: To determine the outcome of a smoking cessation programme run in a routine hospital outpatient setting. METHODS: A prospective audit of patients referred to an outpatient smoking cessation programme by hospital specialists or general practitioners. The programme consisted of fortnightly counselling sessions, with nicotine replacement therapy when clinically indicated. Self-reported abstinence rates were determined by contacting patients by letter or telephone at 3 and 12 months. Abstinence was confirmed, whenever possible, by measuring the expired carbon monoxide (CO) concentration. RESULTS: Over 12 months, 226 new patients were seen through the programme. There was a correlation between the number of cigarettes smoked and the baseline Fagerstrom score (r = 0.49, P < 0.001). Approximately 40% of subjects could not be contacted for follow up. At 3 months the self-reported abstinence rate was 31%, falling to 19% by 12 months. Measurement of expired CO concentrations proved that self-reported abstinence was reliable. CONCLUSIONS: The abstinence rates achieved by our programme compared well with those previously reported in the literature, demonstrating the effectiveness of a smoking cessation programme run in routine clinical practice. There was an increasing relapse rate during the period of follow up.

Adult↗