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Biomedical subjects

N M Lefcoe

Publications and source records attributed to N M Lefcoe.

At least 37 records · Page 2Linked to original sources
PubMed1982

Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide.

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 micrograms/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p less than 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (delta PEFR, p = 0.12). Having the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (1) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug's long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.

Adrenal Cortex Hormones↗
PubMed1982

The addition of an aerosol anticholinergic to an oral beta agonist plus theophylline in asthma and bronchitis. A double-blind single dose study.

In two groups of patients, 15 with asthma and 15 with chronic bronchitis, the bronchodilator effects of ipratropium bromide, of fenoterol plus theophylline, and of the combination of the three drugs, were compared using a double-blind, single-dose, placebo-controlled format. Ipratropium bromide caused rapid bronchodilatation which was not significantly different in asthmatic patients and patients with bronchitis (delta FEV1 = .29 L in one hour in asthmatic patients, .18 L in patients with bronchitis). In contrast, fenoterol plus theophylline induced a considerably greater effect in asthmatic patients (delta FEV1 = .41 L in one hour) than in those with bronchitis (delta FEV1 = .07 in one hour). The use of the three drugs in combination compared with ipratropium bromide alone, or fenoterol plus theophylline alone, resulted in a significant additional bronchodilatation in asthmatic patients. In the patients with bronchitis, the triple combination was clearly superior to fenoterol plus theophylline. A similar trend was present in comparing the triple combination to ipratropium bromide, but the difference did not reach statistical significance. There was no evidence of synergism when ipratropium bromide was combined with fenoterol plus theophylline in that the total bronchodilator effect was approximately additive. Asthmatic patients and the physician were able to distinguish the triple combination from placebo. No such ability was demonstrated with respect to those with bronchitis. All three drugs were well tolerated. Side effects were mostly mild, and none was related to the use of ipratropium.

Administration, Oral↗
PubMed1981

A clinical trial of combined cromolyn/beclomethasone treatment for chronic asthma.

Some patients with chronic asthma treated with beclomethasone aerosol (BA) derive significant symptom benefit, yet have persisting adrenal suppression due in part to their BA therapy. The daily dose of BA required is higher in patients with atopy. We therefore assessed the usefulness of ancillary treatment with cromolyn sodium (CS), a drug known to inhibit atopic asthma, to try to improve the balance of risk vs benefit in such patients. Thirty asthmatics, well controlled on high-dose BA (mean, 1,040 micrograms +/- 97 SE) but with morning cortisol levels averaging approximately 10 micrograms/dl, were allocated randomly to placebo or CS inhalant, used in addition to their regular BA and other asthma medications. After 4 wk, their BA dose was halved. Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows, and by spirograms and morning serum cortisol tests every 4 wk. Mean cortisol levels rose 27% after BA dose reduction (p less than 0.05) but asthma worsened. Risk-benefit assessments 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75%. The distributions of good, fair, and poor risk-benefit responses were the same in both CS and placebo-treated groups (p = 0.20). In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients, CS might prove useful, but in these adult chronic asthmatics with this particular therapeutic problem, there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen.

Aerosols↗
PubMed1981

Change in smoking status among school-aged youth: impact of a smoking-awareness curriculum, attitudes, knowledge and environmental factors.

The present study examined the relationships between exposure to a smoking awareness curriculum, attitudes toward and knowledge about smoking, sociodemographic and smoking exposure characteristics, and change in smoking status over three years. During this period, 4.5 per cent of the students decreased their involvement with cigarettes, 56.6 per cent reported no change, and 38.9 per cent reported an increase. Exposure to the curriculum did not bear a significant relationship to change in smoking; however, changes in peer smoking, knowledge, and parental smoking were significant predictors.

Attitude to Health↗
PubMed1981

Utility of behavioral self-help manuals in a minimal-contact smoking cessation program.

The effectiveness of two commercially available smoking cessation manuals was evaluated under minimal therapist contact conditions. Forty cigarette smokers who volunteered to participate in a self-help quit smoking program were randomly assigned to one of three conditions: 18 to Pomerleau and Pomerleau's 1977 manual, 13 to Danaher and Lichtenstein's 1978 manual, and nine to a waiting-list control. Six-month follow-ups indicate that the former manual offers a useful treatment approach, while no firm conclusions can be made regarding the latter manual. Utility of self-help manuals in multilevel treatment programs is discussed.

Adolescent↗
PubMed1980

Studies of the action of nicotine in guinea-pig tracheal smooth muscle: interaction with beta-adrenoceptor antagonists.

Nicotine produced cholinergic excitatory and adrenergic and non-adrenergic inhibitory responses in isolated guinea-pig trachea. Responses were blocked by hexamethonium (10 micro M), lidocaine (85 micro M) or tetrodotoxin (0.01 micro M) demonstrating that nicotinic receptors in nervous tissue were being activated. In the presence of atropine (0.1 micro M), inhibitory responses to nicotine were partially blocked by specific, experimentally determined, beta-blocking concentrations of pindolol or sotalol or by pretreatment with 6-hydroxydopamine or reserpine but were completely blocked by the less specific beta-blocking drugs 1- and dl-propranolol. Parallel experiments on guinea pig ileum revealed a marked attenuation by dl-propranolol of the atropine sensitive, cholinergic excitatory response to applied nicotine. The non-beta-adrenoceptor blocking agent d-propranolol, produced qualitatively similar attenuation of all excitatory and inhibitory responses to nicotine on both preparations. The remarkable susceptibility of nicotine-induced, neurally mediated responses to low, beta-blocking concentrations of dl-propranolol and to low concentrations of both of its racemates suggests that the non-specific actions of these compounds may have much more significance than is customarily believed. Such studies on the interaction between nicotine and some beta-adrenoceptor blocking drugs are consistent with the hypothesis that non-beta-blocking so-called 'non-specific membrane depressant actions' of dl-propranolol may in concentrations previously considered 'sub-local anaesthetic', significantly depress physiological transmission induced by activation of nicotinic receptors.

Adrenergic beta-Antagonists↗
PubMed1980

Incorporation of rapid smoking in a community service smoking withdrawal program.

Posttreatment abstinence rates of 50% had been found in a smoking withdrawal program which included group hypnosis and group counseling. A session of rapid smoking was added to the procedures with the intention of further increasing abstinence rates. Only 13% of the smokers exposed to the combined program quit smoking as compared to 38% of the smokers who participated in the same program but with session of group hypnosis excluded. Possible expanations of the obtained results include motivational reduction, procedural deviations, and medical screening. Suitability of rapid smoking for community service programs is discussed.

Adult↗
PubMed1978

Minimum dose requirements of steroid-dependent asthmatic patients for aerosol beclomethasone and oral prednisone.

In 34 steroid-dependent asthma patients who improved markedly during 2 mo of treatment when progressively larger doses of beclomethasone aerosol were added to their oral prednisone regimen, we subsequently reduced both steroids to ascertain the minimum dose of each needed to prevent recurrence of significant asthmatic disability. After 80 wk of follow-up, 15 patients had successfully terminated oral prednisone; 19 were better controlled with a combination of aerosol plus oral steroid than with either drug alone; all patients previously unable to convert to alternate-day prednisone did so successfully during the combined therapy. The minimum effective maintenance dosage varied greatly among these patients-the median values being 2.5 mg prednisone and 1,200 microgram beclomethasone per day. The latter ranged from 200 to 1,8000 microgram. Only 4 patients were satisfactorily controlled without prednisone on 400 microgram beclomethasone per day or less. Seven needed extra intranasal beclomethasone to help control the nasal polyps which worsened after prednisone withdrawal. Suppression of plasma cortisol levels, apparently attributable to the beclomethasone, persisted in most patients, but on the average this was no worse than before commencing this treatment and valuable clinical improvement accrued. There were no other important complications of the regimen. In most of these patients with severe chronic asthma, optimum control of the disease required combined aerosol-oral therapy and maintenance doses of beclomethasone higher than those usually recommended. In some patients, effective control of chronic asthma by beclomethasone treatment may require acceptance of some persisting suppression of adrenal function as a considered risk.

Administration, Oral↗
PubMed1977

A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma.

In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.

Adult↗
PubMed1977

The effects of ephedrine on the physiological and psychological responses to submaximal and maximal exercise in man.

The purpose of this study was to determine whether a single full therapeutic dose (24 mg) of ephedrine taken orally has any effect upon physical performance and fitness. Twenty-one healthy males, aged 19-30 years, were tested on three occasions within three weeks using a double-blind modified crossover design. The effects of ephedrine were determined by comparing the differences between drug and control conditions using paired t-tests. The test battery included measures of muscle strength, endurance and power, lung function, reaction time, hand-eye coordination, anaerobic capacity and speed, cardio-respiratory endurance, and responses to maximal and submaximal effort, including maximum oxygen intake, ratings of perceived exertion and speed of recovery from effort. Despite a slight stimulating effect on blood pressure and on exercise and recovery heart rates, 24 mg of ephedrine had no effect on any of the measures of physical work capacity. Ephedrine had no effect on lung function of healthy young men, but may have assisted the learning of certain simple psychomotor tasks.

Double-Blind Method↗
PubMed1975

Particulates in domestic premises. II. Ambient levels and indoor-outdoor relationships.

Three indoor environments, two residential and on institutional, were monitored for particulate and gaseous air pollutants over a one-year period. Inside air particulate levels decreased at night and under conditions of no household activity. Different homes showed different time lags in correlating inside vs outside particle counts. Indoor particle count reduction correlated to rate of air flow through the precipitator. The standard, portable household vacuum cleaner produced about a 100% increase in counts of particles measuring 1.0 mum and larger, as compared to a 50% increase produced by the central vacuum system. Particulates that were smaller than 1.0 mum were not substantially affected by smoking. The indoor gaseous pollutants showed very low maximum levels.

Activities of Daily Living↗
PubMed1975

The effect of cocaine on the responses of the differently innervated laryngeal and bronchial ends of the guinea pig trachea in vitro to clinically used bronchodilators.

Fluorescent histochemical studies indicate that guinea pig tracheal smooth muscle has sparse adrenergic innervation with the greatest nerve density being located at the laryngeal end. In the present study, log dose-response lines were obtained for dl-isoprenaline (ISO), l-adrenaline (ADR) l-noradrenaline (NOR), salbutamol (SALB), and orciprenaline on isolated tracheal chains prepared from both the laryngeal (L) and bronchial (B) ends of the trachea. Responses were obtained in the absence and presence of the Uptake1 blocker, cocaine (0.67 and 6.7 muM) which markedly potentiated responses to NOR and ADR but failed to significantly alter responses to ISO and SALB on L preparations. The degree of potentiation obtained on B preparations was significantly less for NOR and ADR and was not significant for the other agents. In addition, experiments were carried out on tracheal chains which developed their normal tone in the absence of carbachol, and also on preparations obtained from 6-hydroxydopamine treated animals. The present findings, based on selective potentiation of NOR and ADR, support evidence that the degree of adrenergic innervation to the guinea pig trachea is greater at the laryngeal end, and the results obtained with cocaine strengthen the argument that it has a pre-synaptic site of action.

Albuterol↗