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Biomedical subjects

G E Marlin

Publications and source records attributed to G E Marlin.

At least 19 recordsLinked to original sources

Pharmacokinetics and tolerability of a single oral 600-mg dose of doxycycline.

The pharmacokinetics of a single orally administered 600-mg dose of doxycycline (six 100-mg film-coated tablets) was studied in 18 healthy subjects. Plasma doxycycline levels remained above 1.35 mumol/L for 48 hours and compared favourably with the mean inhibitory concentrations of doxycycline against the common infecting organisms in chronic bronchitis. In a separate tolerability study in 37 healthy subjects, there was no significant difference between doxycycline and placebo in the incidence of adverse effects.

Adult

The influence of food on the bioavailability of new formulations of erythromycin stearate and base.

1. The effect of food on the bioavailability of two new formulations of erythromycin, 1) erythromycin stearate, 500 mg (Erythrocin, 250 mg capsule-shaped tablets) and 2) erythromycin base, 500 mg (Eryc, 250 mg capsules containing enteric-coated pellets) was studied in 16 healthy subjects. 2. The study was a balanced, randomized Latin square design and was conducted on 4 days. The four treatments were erythromycin stearate immediately before (EB) and after EA) breakfast and erythromycin base immediately before (eB) and after (eA) breakfast. 3. The mean +/- s.d. maximal plasma erythromycin concentrations were 2.09 +/- 1.06, 0.37 +/- 0.40, 1.8+ +/- 1.15 and 1.91 +/- 1.57 micrograms/ml and the mean +/- s.d. times at which these occurred were 1.3 +/- 0.7, 2.3 +/- 0.9, 4.4 +/- 1.9 and 4.3 +/- 1.1 h for EB, EA, eB and eA respectively. 4. The mean +/- s.d. areas under the curves (0 to 8 h) were 4.99 +/- 2.41, 1.04 +/- 1.57, 4.93 +/- 2.98 and 4.98 +/- 3.14 for EB, EA, eB and eA respectively. 5. The bioavailability of erythromycin stearate was significantly reduced by the prior administration of food, whereas the absorption of the base was not inhibited by food.

Adult

Combined cholinergic antagonist and beta 2-adrenoceptor agonist bronchodilator therapy by inhalation.

The bronchodilator effects of 40 microgram ipratropium bromide (I) and 400 microgram fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double-blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side-effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma.

Adult

Tracheobronchopathia osteochondroplastica.

The clinical, pathological and physiological features of two patients suffering from tracheobronchopathia osteochondroplastica (TO) are described. Unequivocal evidence of extrapulmonary airways obstruction was not able to be obtained by lung function testing, despite extensive central airway involvement in both patients. TO is a rare condition of which there is only one other clinical report from this country. As the bronchoscopic appearance may closely resemble that of endobronchial neoplasms, TO should be remembered in the differential diagnosis of patients with haemoptysis.

Aged

Relationship between bronchial and arterial diameters in normal human lungs.

In order to find an objective method for measuring narrowing of small airways, eight lungs from four people without lung disease were inflated and fixed at 25 cm of water pressure. Eight to nine blocks were taken at random from each of six parasaggital slices from each lung, sectioned, and stained. The size of the bronchioles (airways without cartilage) in relation to their accompanying arteries was determined. The internal bronchiolar diameter was compared with three different arterial diameters (the internal, external medial, and external adventitial). The ratio of the internal bronchiolar diameter to the external adventitial arterial diameter was constant between lungs (0.62 +/- 0.02) and independent of the method of inflation or the position within the lungs. This ratio may provide a useful index of bronchiolar narrowing in disease.

Adolescent

Correlation between the function and structure of the lung in smokers.

To study the relationship between morphologic changes and alteration of lung function, the excised lobes of 21 smokers and one nonsmoker who required lobectomy for small peripheral tumors were inflated and fixed in formalin, and measurements of bronchiolar narrowing and degree of emphysema were made. All patients had comprehensive pulmonary function tests (including diffusing characteristics, the single-breath N2 test, measurements of elastic recoil, and flow-volume measurements with air and helium) performed before lobectomy. Eight of the lobes excised from the smokers had emphysema of grade 15 or more, the greatest being grade 50. Lobes from 11 patients had evidence of airway narrowing. There were 6 lobes with both emphysema and airway narrowing. Pulmonary function was abnormal in some aspect in all lobes except that from the nonsmoker. Whereas the tests of diffusing capacity, particularly the fractional uptake of CO, correlated with the degree of emphysema, the tests of elastic recoil were not predictive of this early degree of emphysema. The degree of small-airway narrowing correlated with maximal mid-expiratory flow rate and the single-breath N2 test. The maximal flow/static recoil pressure curves were the most sensitive indicators of airway abnormality in the patients with emphysema.

Aged

Plasma and saliva concentrations for a new formulation of erythromycin stearate.

Erythromycin saliva and plasma concentrations were determined in 10 subjects after the first and fourth doses of a new formulation of erythromycin stearate ('Erythrocin'), 500 mg 8-hourly, taken immediately before food. Consistent absorption occurred and the steady state plasma levels compared favourably with the minimal inhibitory concentrations of erythromycin for common respiratory pathogens. There was a significant positive correlation between steady state saliva and plasma levels.

Administration, Oral

Arrest of alveolar multiplication in kyphoscoliosis.

A detailed morphometric study of the lungs of an adult patient with severe kyphoscoliosis of childhood onset is reported. The number of alveoli was less than the normal adult range and corresponded to the predicted values for a 12-month-old infant. This may have been a result of both premature cessation of alveolar multiplication as well as alveolar atrophy. The alveolar size was larger than normal suggesting that after cessation of alveolar multiplication further lung growth occurred by an excessive increase in alveolar size.

Female

Salbutamol by pressure-packed aerosol and by intermittent positive pressure ventilation in chronic obstructive bronchitis.

The forced expiratory volume in one second (FEV1) response to salbutamol administered by pressure-packed aerosol 200 microgram, and intermittent positive pressure ventilation (IPPV), 5 and 10 mg, was determined in 60 patients with chronic bronchitis with airway obstruction. The bronchodilator response to salbutamol by IPPV was greater than by pressure-packed aerosol only in patients with severe airways obstruction and little additional benefit was gained with the 10 mg dose.

Aerosols

Assessment of combined oral theophylline and inhaled beta-adrenoceptor agonist bronchodilator therapy.

1. The bronchodilator effects of 500 microgram rimiterol by pressurized aerosol, 375 mg oral theophylline and both drugs in combination were compared in a randomized, placebo-controlled, double-blind trial in eight patients with chronic, partially reversible airways obstruction. 2. The four treatments were (i) oral theophylline, placebo aerosol (TP); (ii) oral placebo, rimiterol aerosol (PR); (iii) oral theophylline, rimiterol aerosol (TR) and; (iv) oral placebo, placebo aerosol (PP). The aerosol was administered 2 h after the oral treatment. 3. Significant bronchodilatation (% FEV1 change from control) compared to PP occurred with TP from 60 to 480 min and with TR from 60 to 300 min, whereas with PR only for 45 min (P less than 0.05). 4. The mean, peak % FEV1 increases from control were 51.8% at 125 min, 31.7% at 125 min, 26.1% at 210 min and 0.9% at 30 min for TR, PR, TP and PP respectively. 5. At 125 min (5 min after aerosol inhalation) the mean % FEV1 change from control with TR (51.8%) Was significantly greater than with PR (31.7%), TP (22.2%) (P less than 0.05) and PP (-2.4%) (P less than 0.01). 6. The mean, peak plasma theophylline levels were 10.19 microgram/ml at 120 min and 9.98 microgram/ml at 180 min with TR and TP respectively. Theophylline half-life ranged between 4.3 and 12.5 h (mean +/- s.e. mean, 8.0 +/- 0.8 h). 7. Additive bronchodilatation was produced when rimiterol was administered with theophylline at a time when therapeutic plasma theophylline levels were achieved.

Administration, Oral

Characterization of beta-adrenoceptor subtype mediating the metabolic actions of salbutamol.

1. The following four intravenous treatments were administered in a balanced, randomized, Latin square design to four healthy volunteers: (1) saline injection (10 min); salbutamol infusion (0.15 microgram kg-1 min-1 for 60 min) (sS), (2) propranolol injection (0.3 mg kg-1 for 10 min); salbutamol infusion (pS), (3) practolol injection (2 mg kg-1 for 10 min); salbutamol infusion (PS) and (4) saline injection; saline infusion (ss). 2. Heart rate was recorded and venous blood taken for estimation of insulin, glucose and potassium before and after each injection (0 and 12-15 min) and at various times during the infusion (30,45,60 and 75 min). 3. The mean, peak % heart rate changes from baseline, control were +65.8%, +23.0%, -10.9% and -12.1%, the mean, peak % glucose changes, +61.0%, +7.1%, +3.6% and +6.9%, and the mean, peak % insulin changes, +298%, +28%, -28% and -43% during the infusions for sS, PS, ss and pS respectively. 4. The mean serum potassium levels before the injections and at the completion of the infusions were 3.98 and 3.08 4.03 and 3.63, 4.07 and 4.15, and 4.03 and 4.13 meq/l for sS, PS, ss and pS respectively. 5. Propanolol completely abolished the cardiac and metabolic responses of salbutamol. 6. Practolol produced only partial cardiac beta-adrenoceptor blockade, but completely inhibited the metabolic actions of salbutamol.

Adult

An investigation of "absolute plasma level effect relationships" and "absolute cardioselectivity" with respect to beta-adrenoceptor blockade.

In a group of 6 healthy (but physically unfit) volunteers an investigation was made of whether there was a true plasma level effect relationship and absolute "cardioselectivity" with respect to beta-adrenoceptor blockade due to practolol. To this end three treatments were given orally, namely placebo, practolol 100 mg and practolol 400 mg. Cardiac beta-adrenoceptor blockade was assessed by measuring the inhibition of exercise heart rate and pulmonary beta-adrenoceptor blockade was assessed by measuring the reduction in exercise peak flow rate, up to 24 h after each dose. Plasma practolol levels were determined spectrophotometrically. From the results obtained there was no reason to doubt the existence of a valid relationship between cardiac beta-adrenoceptor blocking activity and the plasma concentration of practolol. It was also concluded that even in non-asthmatics, practolol does not possess absolute "cardioselectivity" since significant reductions in peak flow rate were discernible during vigorous exercise, particularly when the large dose had been given.

Adult

Comparison of terbutaline and salbutamol aerosols.

The bronchodilator effects of terbutaline, 500 microng, and salbutamol, 200 microng, by pressurised aerosol were compared in 16 patients (eight asthma, eight chronic bronchitis with asthma). Salbutamol produced greater bronchodilatation than terbutaline for the initial hour after inhalation. Thereafter, there was no difference in action and an effective bronchodilator response was maintained by each drug for at least four hours. beta2-adrenoceptor stimulating drugs by inhalation are widely used in the treatment of asthma. The purpose of this study was to compare the bronchodilator efficacies of two of these drugs, terbutaline and salbutamol by pressurised aerosol, in patients with partially reversible airways obstruction.

Adult