The effects of smoking and inhalation of carbon monoxide on the systolic time intervals and blood pressure were examined in ten healthy smokers with a mean age of 24.3 years. Each subject smoked a low-nicotine cigarette with a ventilated filter (0.1 mg nicotine, 1.1 vol percent CO), and a high-nicotine plain cigarette (2.6 mg nicotine, 4.5 vol percent CO), as well as a cigar in random sequence and in a standardized way. Cigar smoke was not inhaled. The product heart rate x blood pressure was increased and the left ventricular ejection time index (LVETc) prolonged following smoking the high-nicotine cigarette, whereas changes after smoking the low-nicotine cigarette and the cigar were not as pronounced. These changes are presumably caused by nicotine-induced catecholamine release. Inhalation of CO did not affect cardiac performance acutely as shown by unchanged systolic time intervals. When a high-nicotine cigarette was smoked after the subject received a beta blocker, a significant prolongation of the pre-ejection period index (PEPc) occurred as a result of the increased afterload. Thus, the effects of catecholamines on parameters of myocardial contractility (PEPc, PEP/LVET) were presumably offset by the increased afterload. We conclude that the acute hemodynamic changes of smoking in healthy subjects depend upon the amount of nicotine absorbed.

The effect of therapy with lidoflazine on maximal exercise in the upright position was evaluated in 21 patients with angina pectoris. The study consisted of the following three consecutive periods: (1) a three-month period of receving placebo; (2) six months of therapy with lidoflazine; and (3) a six-month period in which patients were randomized to either therapy with lidoflazine or placebo. Functional status was monitored by multistage tests of exercise capacity and the amount of nitroglycerin consumed. From period 1 to period 2, the mean maxial exercise time increased from 4.4 to 6.5 minutes (48 percent; P less than 0.001), and the external workload increased by 68 percent (P less than 0.001). the mean heart rate at two minutes of exercise decreased from 114 to 101 beats per minute (P less than 0.001) but was unchanged at symptom-tolerated maximal exercise. During period 3, the patients receiving therapy with liodflazine maintained their improved exercise tolerance, and the reduction in mean heart rate at two minutes of exercise persisted. Patients receiving placebo during period 3 had a decrease in exercise tolerance, and the mean heart rate at two minutes of exercise increased to control values. Lidoflazine in effective as an antianginal medication, in part due to suppression of the heart rate during exercise.

One hundred sixty-seven patients with extensive well-differentiated and 120 patients with extensive poorly differentiated squamous cell carcinoma of the lung received chemotherapy as part of a randomized study by the Veterans Administration Lung Group. Chemotherapy was administration at random using one of the following four regimens: (1) cyclophosphamide alone; (2) cyclophosphamide plus 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU); (3) doxorubicin (adriamycin) plus cyclophosphamide; and (4) doxorubicin plus CCNU. With data on survival as the criteria for evaluation, it has been shown that combined chemotherapy using doxorubicin plus cyclophosphamide achieves greater median survival for patients with squamous cell cancer of the lung than single-drug chemotherapy using cyclophosphamide, under the conditions of this study; however, prolongation of life is still minimal, and better treatment is required. About 20 percent of the patients receiving any of the four regimens developed serious toxic effects from therapy with the drugs.

The use of steroids to decrease the size of the infarct and the mortality in patients with acute myocardial infarction has long been the subject of controversy. In the present study, two large doses of methylprednisolone were administered intravenously to 14 patients with relatively uncomplicated myocardial infarction within 17 hours after the onset of symptoms, whereas a comparable group of 15 patients with myocardial infarction served as controls. The size of the infarct was assessed utilizing serial measurements of serum levels of creatine phosphokinase and its myocardial isoenzyme, the MB form of creatine phosphokinase. There was no significant difference between the two groups of patients with regard to peak cumulative levels of total creatine phosphokinase and the MB form of creatine phosphokinase. Similarly, there was no difference between the two groups in mortality or in the incidence of malignant ventricular arrhythmias, atrioventricular block, congestive heart failure, or extensions of the infarct. We conclude that high intravenous doses of steroids given early in the course of myocardial infarction have neither deleterious nor beneficial effects.

The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.

Based on a study indicating a significant rate of reactivation of tuberculosis in Veterans Administration patients with inactive disease, a cooperative study was initiated to determine the prophylactic effect of isoniazid on the rate of reactivation. A randomized double-blind study was designed, utilizing three regimens, two with isoniazid and one with placebo only. Two consecutive years of taking pills in one of the three regimens was followed by five years of observation. A total of 7,036 patients with inactive disease, some of whom had received prior chemotherapy, were entered into the study. Only 63 reactivations of tuberculosis were found, for a total rate of reactivation of 9/1,000 (less than 1%) over the seven-year period. Although no significant differences in the rate of reactivation were found among any of the regimens, there was a significant reduction in the rate of reactivation among those who had not received any prior chemotherapy and received isoniazid (INH) in this study, compared with those who received placebo only.

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.

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.

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.

In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.

Twenty-five steroid-dependent severely asthmatic patients, ranging in age from 20 to 67 years, were hospitalized. Baseline laboratory and pulmonary function testing was followed by reduction of prednisone therapy to 5 mg daily and by entry into a randomized double-blind study of placebo vs active aerosol triamcinolone acetonide (300mug four times daily). In this four-week trial, aerosol triamcinolone acetonide further reversed airway obstruction and proved to be an effective substitute for large oral doses of steroids in steroid-dependent patients with severe asthma. No significant improvement occurred in the maximum midexpiratory flow or the maximum velocity of air flow after 50 percent or 75 percent of the vital capacity had been expelled. There was no significant difference in the frequency of untoward effects between the groups taking aerosol triamcinolone acetonide and its vehicle. No patient demonstrated any definite return of adrenal function.

Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.