This study investigated the effects of continuous therapy with oxygen on the neuropsychologic functioning of aged subjects professing problems with their memory. Nineteen men (mean age, 71 years) were evaluated on eight neuropsychologic measures during three different periods of time. Subjects were tested before any treatment, after a month of continuous therapy with oxygen, and after a period of sham treatment. The results indicated statistically significant improvement in the Wechsler Memory Quotient and, with one exception, improvement in all other measurements in favor of the treatment with oxygen. Differences between the results of this investigation and those of other studies are discussed, along with the factors possibly accounting for these differences.

Bronchodilatory and side effects of fenoterol hydrobromide (Th1165a; hydroxyphenylorciprenaline; Berotec) and isoproterenol given by inhalation were compared in a double-blind crossover study involving 20 volunteer subjects with reversible obstructive disease of the airways. Subjects inhaled medications from aerosol canisters containing fenoterol hydrobromide (0.1 mg, 0.2 mg, or 0.4 mg) or isoproterenol (0.15 mg) or an inert placebo propellant in a random sequence of five testing days. All active drugs substantially increased the forced expiratory volume in one second, the mean forced expiratory flow during the middle half of the forced vital capacity, and the specific conductance. The onset of bronchodilation after both fenoterol and isoproterenol was rapid, but the effect from fenoterol lasted much longer, up to eight hours. None of the medications cuased significant tachycardia or hypertension. After inhalation of 0.1 mg of fenoterol hydrobromide, none of the subjects reported nervousness, headache, tremor, or nausea, incontrast with results reported for isoproterenol, higher aerosol doses fo fenoterol, or oral administration of fenoterol. No additional therapeutic benefit was found in the administration of higher doses of fenoterol.

Aerosolized fenoterol in a dosage of 400 microgram was compared to isoproterenol 150 microgram in 31 asthmatic subjects during the course of a double-blind parallel 90-day study. Bronchodilator activities of the two drugs were evaluated for up to 6 hours on days 1, 45 and 90. Analysis of the data revealed that fenoterol consistently produced a significantly greater increase in FEV1, FEF25-75% and Gaw/VL. Specific airway conductance increased on each test day 25 percent or more above baseline for over three hours after use of fenoterol and for only one hour after use of isoproterenol. Fenoterol has less effect upon the cardiovascular and central nervous systems, but produced a greater incidence of shaking compared to isoproterenol. Patients used fenoterol less frequently than isoproterenol which can be attributed to the former having a greater peak effect and time course of bronchodilation. The therapeutic efficacy of fenoterol was sustained throughout this three-month study, and suggests that this relatively selective beta2 adrenergic drug will provide a well tolerated, alternative aerosol for chronic use in asthma.

We have compared bronchodilator responses to atropine and terbutaline in 39 chronic bronchitics and 16 stable asthmatics. Fasting subjects were given either 1.05 mg atropine of 5.0 mg terbutaline orally. Pulmonary function was assessed using the peak responses, namely: three 60-minute intervals for terbutaline and three 30-minute intervals for atropine. A subgroup of five reactive bronchitis patients was given a placebo with no response. Areas under the percent response-time interval curve were compared. Both patient groups responded to the same degree to atropine and terbutaline with respect to reduction of airway resistance. However, the FEV1 and V50 responses to terbutaline were markedly enhanced compared to atropine in the asthmatics while equal to the atropine response in the bronchitis patients. Thus, atropine appears to exert its effect upon both large and small airways in bronchitis, but predominantly on large airways in asthma. The results are consistent with a state of enhanced vagal tone in small airways in bronchitis compared to asthma, but other explanations are conceivable.

Forty-eight children with known asthma (ranging in age from 2 to 16 years) were studied during an acute attack. Each received either terbutaline or epinephrine subcutaneously in a random double-blind fashion. Measurement of heart rate, respiratory rate, and systemic arterial systolic and diastolic blood pressures and careful clinical assessment of obstruction of the airway were made before and at 15, 30, and 60 minutes after the administration of the drugs. Appreciable and significant clinical improvement was noted in 19 of the 24 patients in both groups and was of comparable magnitude. A small, but significant, increase in heart rate was noted in those patients requiring only one injection of terbutaline, suggesting that the drug's selectivity for the lung is relative not absolute. The present study demonstrates that terbutaline is an effective bronchodilator drug in acute childhood asthma.

The effect of administration of terbutaline on the pulmonary and cardiovascular systems was studied in ten children with status asthmaticus. Terbutaline (0.01 to 0.04 mg/kg of body weight) was given subcutaneously in multiple doses. A significant decrease in respiratory rate and in arterial blood pressure, with no significant change in cardiac rate, was seen only after the first dose of terbutaline. There was a decrease in mean arterial carbon dioxide tension and an increase in mean arterial oxygen pressure. There was gross clinical improvement following administration of terbutaline in nine of the ten patients. One patient who failed to respond to administration of terbutaline also failed to respond to intravenously administered isoproterenol. We conclude that terbutaline is effective in the treatment of status asthmaticus, with only modest effects on the cardiovascular system.

Fenoterol hydrobromide (Berotec; formerly Th 1165a) is a sympathomimetic bronchodilator drug. Twenty subjects with mild to moderate reversible bronchospasm completed a double-blind multiple crossover study of single doses of 5 mg, 7.5 mg, and 10 mg of fenoterol hydrobromide, 24 mg of ephedrine, and placebo. Spirometric and body-plethysmographic measurements were performed sequentially prior to administration of drug or placebo and each hour up to eight hours afterwards. No significant drug-response relationship was noted for pulse rate or blood pressures, and side effects (eg, shakiness, nervousness) were minimal. Administration of fenoterol resulted in bronchodilation; a peak effect was noted at two to three hours after administration, and the duration of action was up to eight hours. A statistically significant dose-response relationship was observed; therapy with 5 mg of fenoterol hydrobromide was superior to placebo and equal to ephedrine, and doses of 7.5 mg and 10 mg of fenoterol hydrobromide were significantly better than placebo or ephedrine.

The control of asthma by therapy with cromolyn sodium was studied in 28 adults with late-onset asthma associated with hypersensitivity to aspirin and nasal polyps. Four-week periods of treatment with the drug or a placebo were compared in a double-blind crossover study. A subsequent eight-week open trial in 20 patients was compared to their period of receiving placebo. There was slight but significant improvement in the forced expiratory volume in one second (FEV1; P less than 0.05) and the mean forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%; P less than 0.05) after four weeks of therapy with cromolyn sodium and in the FEV1 (P less than 0.05), the forced vital capacity (P less than 0.01), and FEF25-75% (P less than 0.01) after an additional eight weeks of therapy with cromolyn sodium. The improvement in pulmonary function was not associated with changes in the peak expiratory flow rate, the symptoms of asthma, the doses of additional medication, or the index of disability. The dosage of corticosteroids in 22 patients receiving long-term therapy with steroids was no different between the four-week periods of treatment with placebo or drug but was significantly lower (P less than 0.05) during the eight-week open trial. We conclude that administration of cromolyn sodium has a therapeutic effect in this group of asthmatic patients.

The short-term effects of smoking one to three marihuana cigarettes (900 mg of marihuana per cigarette; 2.2% delta9-tetrahydrocannabinol) on left ventricular performance were evaluated in 21 experienced users of cannabis at different times during a 94-day in-hospital study of the biologic effect of daily heavy smoking of marihuana. In six subjects, cardiac output was determined using the indocyanine-green dye-dilution technique; and in two of these individuals and 15 additional subjects, cardiac output, ejection fraction, preejection period (PEP), left ventricular ejection time (LVET), and the velocity of circumferential fiber shortening (Vcf) were determined using echocardiograms, phonocardiograms, and carotid pulse recordings. Following the smoking of one to three marihuana cigarettes, the heart rate rose 16 to 53 percent, cardiac output rose 4 to 9 percent, stroke volume did not change or fell slightly, and ejection fraction, PEP/LVET, and did not change, except for a slight increase in Vcf (15%) after three marihuana cigarettes, which could be accounted for by the associated increase in heart rate (53%). These findings suggest that in long-term heavy users of cannabis, marihuana has no significant effect on myocardial contractility independent of its effect on heart rate.

In this study, pulmonary tuberculosis was treated on an ambulatory basis, with the patients engaging in their usual activities and with a shortened period of chemotherapy. During the first year of the study, patients with pulmonary tuberculosis were randomly included in one of the following two groups: (1) group 1 received isoniazid (5 to 6 mg/kg of body weight), ethambutol (25 mg/kg), and rifampin (rifampicin, 10 mg/kg) daily for a total of six months; and (2) group 2 received the same therapy as group 1, but treatment was continued for a further six months with only isoniazid (5 mg/kg three days per week). At the beginning of the second year of the study, all subsequent patients included in the study were placed into group 1. Of the 163 patients who started the study, 136 patients (99 from group 1 and 37 from group 2) completed the treatment and converted their bacteriologic findings. There was one relapse in group 1. Adverse reactions were observed in six patients, but they did not have to interrupt treatment.

Patients with acute myocardial infarction are frequently not fed hot and cold liquids because of possible deleterious effects on heart rate, blood pressure, and cardiac rhythm. In an attempt to identify and quantify such changes, hot liquid with a temperature in excess of 70 degrees C and cold liquid at an average temperature of 7 degree C were ingested by 20 patients within 36 hours of documented myocardial infarction and by 11 control patients with severe anginal episodes or chest wall syndromes. Heart rate and rhythm were continuously monitored during ingestion of the hot and cold liquids, and blood pressure was recorded intermittently. No patient in either group had a change in cardiac rhythm or an increase in ectopy during ingestion of the hot and cold liquids. Changes in blood pressure and heart rate were also not significant during liquid ingestion by patients with infarction and control patients. The practice of avoiding ingestion of hot and cold liquids by patients with acute myocardial infarction is not supported by these observations.

Ipratropium bromide (also known as Sch 1000) is a new atropine-like bronchodilator drug whose mechanism of action is via an anticholinergic pathway and may decrease cyclic guanosine monophosphate. Although of established efficacy in asthma, there are no studies of the use of ipratropium in patients with chronic bronchitis. The single metered aerosol doses of 10 mug, 20 mug, 40 mug and 80 mug of ipratropium bromide, 75 mug and 150 mug of isoproterenol, and placebo were studied in 20 adult patients, half with asthma and half with chronic bronchitis. To qualify, all patients demonstrated at least 20% improvement in the forced expiratory volume in one second while in the drug-free state when tested with isoproterenol. All subjects were tested for six hours with each agent in a double-blind crossover design. The dose-response aspects of the study indicate that in bronchial asthma the optimal range of dosage is 40 mug to 80 mug of ipratropium bromide. These doses are superior to isoproterenol in duration of action. In chronic bronchitis, all doses of ipratropium showed prolonged efficacy, but 80 mug was superior. Isoproterenol lacked this sustained efficacy. No significant alteration in pulse or blood pressure was observed. Ipratropium appears to be an important addition to the bronchodilator agents used in isoproterenol-responsive obstructive pulmonary disease.

The effect of disodium cromoglycate and Sch 1000 on exercise-induced asthma was studied in nine patients. The exercise stimulus consisted of either treadmill running or jogging; spirometric measurements were made before and at intervals after exercise. In six patients, disodium cromoglycate and Sch 1000 were both effective in preventing exercise-induced asthma. In two patients, Sch 1000 was effective, while disodium cromoglycate gave no protection. In the remaining patient, disodium cromoglycate was more effective than Sch 1000. The findings of this study suggest that the mechanism of exercise-induced asthma may be multifactorial, and the relative importance of each factor may vary in different patients.

Terbutaline, a new bronchodilator drug reported to have selective affinity for beta 2-adrenergic receptors, was compared with epinephrine in the treatment of 49 adult subjects with acute bronchial asthma. Under double-blind conditions, 24 subjects received 1.0 mg of terbutaline sulfate, and 25 subjects received 0.5 mg of epinephrine hydrochloride subcutaneously. Spirometric measurements, heart rate, and blood pressure, as well as subjective responses, were recorded prior to, and then at 5, 15, 30, 60, and 120 minutes after administration of the drug. The results indicate that terbutaline is an effective bronchodilator drug in subjects with acute asthma; however, the heart rate rose significantly after administration of terbutaline, with a maximal increase of 25 percent above control. Review of the literature reveals that tachycardia is a consistent finding when subcutaneous doses of terbutaline in excess of 0.25 mg are administered. Stimulation of beta 1-adrenergic receptors in the heart appears to be the most important factor involved in this response. A lesser cardioaccelerator effect was observed after administering epinephrine in a dose producing an equivalent degree of bronchodilatation.

A 5-percent solution of the sympathomimetic bronchodilator, metaproterenol sulfate (Alupent) was evaluated by comparison with an 0.5-percent solution of isoproterenol in a double-blind crossover study before and after 60 days of inhalation of metaproterenol administered at least four times daily via a hand-bulb nebulizer. Data from tests of pulmonary function obtained in 27 asthmatic patients indicated that metaproterenol sulfate in this dose form surpassed isoproterenol in the duration of effect after seven weeks of continuous administration. Side effects did not necessitate the interruption of metaproterenol therapy. No evidence of the development of tolerance to the drug was shown by any of the patients at the end of the study.

The clinical results and changes in sputum found in both a short-term inpatient trial and a subsequent long-term outpatient investigation (three-month double-blind controlled study) of 82 patients with chronic bronchitis treated with a new mucolytic agent, S-carboxymethylcysteine (Mucodyne), are reported. Fluidification of sputum with reduction in certain measurements of the viscosity of morning sputum aliquots, associated with improvement in the ability to cough up bronchial secretions, significant increase in sputum volume output, and improvement in ventilation (as estimated by the forced expiratory volume in one second), were observed in both trials as dose-related responses, with an increase in the ease of expectoration and a reduction in cough frequency and dyspnea. Therapy with S-carboxymethylcysteine was well tolerated, and there were no serious adverse effects, either immediate or delayed. We suggest that the effect of the drug in fluidifying sputum may be due to a mucoregulatory mechanism which reverses the sputum macromolecular disturbances seen in chronic bronchitis.

A simplified method for estimation of one-minute oxygen uptake (VO2-1) during treadmill grade walking at vertical power requirements of 250, 750, and 1,000 kg-meters/min was devised, where power=weight (kg) X grade (fractional) X walking speed. All subjects were men. There were 29 controls, 34 subjects with coronary arterial disease (of whom 18 had had myocardial infarction), nine subjects with diffuse pulmonary disease, and four subjects with ischemic vascular disease. Abnormally reduced values for VO2-1 were related to these diseases and, more specifically, to a history of myocardial infarction and (in pulmonary subjects) to reduced single-breath diffusing capacity. Lowest values of VO2-1 for a group were found in ischemic vascular disease. Reduced response of VO2-1 may therefore be caused by central defects of oxygen transport.