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.

Forced expiratory spirograms were obtained before and for six hours after 25 subjects ingested ephedrine and placebo in a double-blind crossover study. Significant changes in the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1.0) were noted on days when ephedrine was administrated, while the mean forced expiratory flow during the middle half of the FVC (FEF25-75%) failed to indicate significant bronchodilation. When FVC increases after therapy with a bronchodilator drug, one is no longer measuring flow during the same volume segment and driving pressure (static transpulmonary pressure [Pst]) as before administration of the bronchodilator drug. Volume-adjusting the FEF25-75% after therapy to the same volume and Pst over which flow is being measured in the tracings before bronchodilator therapy yielded highly significant increases in flow after administration of the bronchodilator drug.

Two grams of methylprednisolone was administratered to ten patients with acute myocardial infarction at an average of 13 hours from the onset of symptoms; pain in the chest was not relieved in six of the ten patients. In one hour, no significant improvement was noted in the function of the ischemic segments (examined using a multiaxis echocardiographic method) or in the S-T segments of the 12-lead electrocardiogram. Left ventricular filling pressure soon increased by an average of 4 mm Hg (P less than 0.005), without ventricular dilatation or a Frank-Starling response, suggesting a decrease (ischemic?) in myocardial compliance. Cardiac output by Swan-Ganz thermodilution later increased by 21 percent (P less than 0.01) when a decrease in peripheral vasoconstriction was evident. In contrast, small-dose beta-adrenergic blockade using 0.2 mg of pindolol intravenously after administration of methylprednisolone immediately relieved pain in the chest in all six patients. Elevation of the S-T segments was reduced by 34 percent (P less than 0.05) within 15 minutes, and the contractile function of the ischemic segments improved markedly, by 3 mm or to 34 percent of normal, from the 4 percent of normal before administration of pindolol (P less than 0.005). Hemodynamic function did not deteriorate in the eight patients with uncomplicated infarction or moderate left ventricular failure. Therapy with pindolol thus reduced clinical, electrocardiographic, and myocardial mechanical signs of acute ischemia safely, while administration of methylprednisolone had no short-term protective effect.

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.

The effects of inhaling 0.4 mg of fenoterol hydrobromide (Berotec), 0.2 mg of albuterol (salbutamol), or placebo were compared in a double-blind three-way crossover study in a group of 12 asthmatic patients. After inhalation of fenoterol, the maximum increase in the forced expiratory volume in the first second (FEV1) was 0.76 L (48 percent) and in the peak expiratory flow (PEF) was 100 L/min (47 percent). The corresponding figures after inhalation of albuterol were 0.68 L (46 percent) and 98 L/min (48 percent), respectively. In comparison with administration of placebo, the FEV1 was significantly increased until six hours after inhalation of either drug. From three to six hours after inhalation, the effect of administration of fenoterol (as measured by FEV1 or PEF) significantly exceeded that of albuterol. Administration of either drug resulted in approximately equal bronchodilation (as measured by the increase in FEV1 or PEF), the effect of inhalation of fenoterol being of longer duration.

A CO2 rebreathing method for the measurement of cardiac output was evaluated by comparison with the direct Fick O2 method in 26 studies performed in 18 patients who were critically ill. The method requires measurement of CO2 output by collection of expired gas, of arterial PCO2, and of mixed venous PCO2 by rebreathing. Twenty-five comparisons were within +/- 20% of the direct Fick measurements, at cardiac outputs varying between 1.4 and 6.4 L/min. Knowledge of the cardiac output increased the quality of the interpretation of arterial blood PO2 measurements in the assessment of pulmonary gas exchange disturbances.

We studied the frequency of cardiac arrhythmias during routine tests of pulmonary function by using continuous electrocardiographic recording and a computerized method to quantitate arrhythmias. A total of 150 patients with chronic obstruction of airways were studied before, during, and after routine tests of pulmonary function performed before and after intermittent positive-pressure breathing (IPPB) with a bronchodilator aerosol. The only significant (P less than 0.01) change was an increased frequency of atrial premature beats during tests of pulmonary function. Spirometric studies, maximal voluntary ventilation, and IPPB with a bronchodilator aerosol were equally likely to induce atrial premature beats. Routine tests of pulmonary function represent an additional causal factor in producing arrhythmias in patients with obstruction of airways, although no clinical consequences were evident in the course of the study.

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.