The responses to oral propranolol (80 mg) and placebo were compared in normal subjects during three studies on a cycle ergometer (progressive exercise and two 5-min constant work rate studies at 50 and 70% maximum). Heart rate (HR), ventilation (VE), CO2 output (VCO2) and O2 uptake (VO2) were measured in each study and metabolites in venous blood in the 70% study. Propranolol reduced HR in all studies and endurance time during progressive exercise. During constant-work-rate exercise the changes with propranolol depended on time and work rate. At 50% max, VO2, VCO2, and VE were reduced in early exercise but were similar by min 5. At 70% max, VO2 and VCO2 were again lower initially with propranolol but then rose more rapidly. By min 5 VE was greater with propranolol, coinciding with a rapidly rising venous lactate. We interpret the initial reduction in VO2 and VCO2 to reduced cardiac output and muscle perfusion with propranolol. The resulting increase in anaerobic metabolism during heavy exercise would explain the increased VE at min 5. The metabolic data are compatible with glycogen being the predominant muscle fuel.
We examined the use of partial expiratory flow-volume (PEFV) curves to obtain dose-response curves to an inhaled beta 2-adrenoceptor agonist (salbutamol) in eight normal subjects. Maximum expiratory flow at low lung volumes increased on both PEFV and full expiratory flow-volume curves, but the increase was always considerably greater on PEFV (28.4%) than on full (14.5%) curves. The percent increase in flow on the PEFV curve was not significantly influenced by the preceding volume history being 90-120 s of tidal breathing, forced expiration to residual volume, or breath holding after a full inflation. These results suggest that normal tone during tidal breathing is temporarily reduced but not abolished by a full inflation, and once basal tone has been restored it is not enhanced by a full expiration. In seven of the eight subjects a satisfactory cumulative dose-response curve to inhaled salbutamol was obtained with a plateau value of maximum flow at a dose of 110 microgram. The relatively good reproducibility of PEFV curves and the considerable bronchodilator signal obtained (29-70% increase in flow above base line in different individuals) suggest that such dose-response curves may be useful in studying normal bronchial pharmacology in vivo.
I We describe a method for assessing bronchial ,B-adrenoceptor blockade quantitatively in man. Specific airway conductance is measured after increasing doses of inhaled salbutamol and the extent to which the dose-response curve is displaced to the right after f-adrenoceptor blocking drugs is used to assess bronchial ,B-adrenoceptor blockade. 2 Salbutamol dose-response curves were plotted for six normal subjects by measuring sGaw 15 min after increasing doses of inhaled salbutamol. Salbutamol produced a 30-70% increase in sGaw. 3 Salbutamol dose response curves were obtained 2 h after oral practolol (100 mg and 200 mg) and oral propranolol (40 mg and 80 mg) on separate days and were displaced to the right. 4 The mean dose ratios for practolol 100mg and 200mg were 1.2 and 2.1 and for propranolol 40 mg and 80mg they were 21 and 61 respectively.
A case of a 64-year-old man with metastatic malignant mesothelioma is described in detail. When he presented to us he gave a history suggestive of transient ischaemic attack (TIA) 2 weeks before and 3 days after admission he developed weakness of the left upper limb. Computed tomographic scan of the brain revealed a solitary metastasis in the right cerebrum. A few days later, he developed subcutaneous metastasis in the chin. Malignant mesothelioma is considered to metastasize rarely and to spread locally. We suggest that distant metastasis in malignant mesothelioma is not uncommon and may be considered to behave like other forms of lung cancer. Treatment modalities should be studied in such patients.
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