From June 1973 to August 1977, three hundred thirty-seven patients with small cell carcinoma of the lung were included in randomized therapeutic trials. By February 1979, fifty-one patients (15%) had survived for 18 months, including 29 (9%) in clinical complete remission. Of the latter patients, readmitted for restaging, including bone marrow examination, peritoneoscopy, and bronchomediastinoscopy, residual tumor was found in four. Treatment was discontinued in the remaining patients; six subsequently had relapses, while three patients died, free of disease, of other causes. Sixteen patients are still alive and free of disease more than 19 to 50 months after the primary diagnosis; seven were treated with combination chemotherapy alone, including four who initially had distant metastatic disease. The remaining nine patients had regional disease and were treated with both chemotherapy and radiotherapy, including prophylactic brain irradiation in four patients. Long-term survival can be achieved in a small number of patients in all stages of small cell carcinoma with intensive combination chemotherapy.

A self-care book that guides patients in seeking home care or physician care for 63 medical problems was assessed in three randomly selected groups of families to determine the book's effect on the number of visits to physicians. The first group was given the book and an optional seminar on its use; the second group was identical to the first but each family was promised $50 if their visits to physicians dropped by one third; the third group was a control group (total, 699 families). The book had no significant effect on the number of physician's visits during six- and 12-month study periods even though one half of the families read most or all of the book, and more than one third used it for a specific medical problem. Large-scale distribution of this self-care book therefore did not result in significantly less dependence on physicians for treatment of acute medical problems.

The comparative effectiveness of three comprehensive therapeutic programs was studied in 118 patients with mild to moderate acne vulgaris. A topical program of tretinoin, benzoyl peroxide, and water avoidance was found to be as effective as the more commonly employed program of systemic tetracycline therapy with topically applied tretinoin and better than a program using systemic tetracycline therapy with abradant cleansers. At 16 weeks of therapy for all groups, the degree of skin dryness correlated with lack of improvement. Skin dryness is established as an aggravating factor in both the pathogenesis and treatment of acne. The topical program was nonirritating, well accepted by patients, and less expensive than the other two regimens.

In a double-blind, placebo-controlled study, 51 patients with recurrent herpes simplex labialis were treated with topical ether or placebo within 24 hours of onset of a lesion. There was no noteworthy difference between groups given ether and placebo in progression of lesions, healing time, duration or intensity of pain, and duration or quantity of virus excretion. The ether also failed to reduce appreciably lesion virus titer, even when lesions were cultured immediately after topical application. Despite these results, 75% of the patients receiving ether and 77% of those receiving placebo reported effective reduction of the severity and duration of lesions. The marked placebo effect in the treatment of recurrent herpes infection helps to emphasize the need for objective measurements and placebo-controlled studies.

The Aspirin Myocardial Infarction Study (AMIS) was a National Heart, Lung and Blood Institute-sponsored, multicenter, randomized, double-blind, and placebo-controlled trial designed to test whether the regular administration of aspirin to men and women who had experienced at least one documented myocardial infarction (MI) would result in a significant reduction in total mortality over a three-year period. Cause-specific mortality, nonfatal events, and side effects were also evaluated. Over a 13-month period, 4,524 persons between the ages of 30 and 69 years were randomized to either 1 g of aspirin per day (2,267 persons) or placebo (2,257 persons). High levels of patient compliance to study protocol were indicated by various measures. Total mortality during the entire follow-up period was 10.8% in the aspirin group and 9.7% in the placebo group. Three-year total mortality was 9.6% in the aspirin group and 8.8% in the placebo group. The percentage of definite nonfatal MI was 8.1% in the placebo group and 6.3% in the aspirin group. Coronary incidence (coronary heart disease mortality or definite nonfatal MI) was 14.1% in the aspirin group and 14.8% in the placebo group. Symptoms suggestive of peptic ulcer, gastritis, or erosion of gastric mucosa occurred in 23.7% of the aspirin group and 14.9% in the placebo group. Based on AMIS results, aspirin is not recommended for routine use in patients who have survived an MI.

The efficacy of a daily dosage regimen of subsalicylate bismuth in preventing or reducing the severity of diarrhea among young healthy adults was evaluated in a double-blind, randomized, placebo-controlled trial. Diarrhea developed in 14 (23%) of 62 students receiving subsalicylate bismuth compared with 40 (61%) of 66 students taking a placebo. The protective effect of subsalicylate bismuth was apparent within a day or two of the study onset and became more obvious as the number of days at risk increased. The students treated with subsalicylate bismuth experienced fewer intestinal complaints and were less likely to pass soft or watery stools of any number. Once diarrhea occurred, enteropathogens were less commonly identified in stools of students receiving subsalicylate bismuth (33%) compared with placebo (71%). Subsalicylate bismuth was well tolerated by students during the 21-day trial.

Data are reported for four race-sex and three age subgroups of the Hypertension Detection and Follow-up Program (HDFP). Throughout the HDFP trial, for black men, black women, white men, and white women and for persons aged 30 to 49, 50 to 59, and 60 to 69 years at entry, control of blood pressure was consistently better for Stepped Care (SC) than Referred Care (RC) participants. This difference in degree of control was least for white women; it was less for whites than for blacks of the same sex. For white men, black men, and black women and for age subgroups 50 to 59 and 60 to 69 years, five-year all-cause death rates were substantially lower--by 15% to 28%--for the SC subgroups compared to the RC subgroups.

The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with "mild" hypertension.

A multicentric trial compared the effect of chlorpheniramine maleate with a placebo on the signs and symptoms of the common cold. Two hundred seventy-one patients were domiciled for 48 hours and evaluated during this period and for four days afterwards. Evaluations by both patients and physicians showed that chlorpheniramine maleate was superior to placebo in lessening the degree of symptoms of the common cold. Statistically significant differences were found both on the first day and as late as the seventh day. Significant differences and trends were shown in such measures as total objective score, physicians' evaluation of symptoms. The overall incidence of side effects other than drowsiness did not differ between the treatment groups.

A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile.

Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF.

A double-blind clinical trial was undertaken to evaluate the efficacy of orally given cromolyn sodium vs that of pacebo in the management of food allergy. Fourteen children, aged 2 to 15 years, with milk allergy and concomitant allergies to one or more foods were given cromolyn or placebo. Eleven had positive intradermal skin reactions or coproantibodies to offending antigens. Treatment was begun while the children were receiving elimination diets; they were challenged with specific antigen only after 48 hours of drug administration. Crossover took place if the initial agent was ineffective. Cromolyn afforded protection in 11 of 13 trials, whereas placebo was effective in only three of nine trials. By chi 2 analysis, the drug's effect was statistically significant.

The effectiveness of epinephrine was compared to that of a combination of epinephrine and aminophylline in the initial treatment of acute asthma. Forty-four patients with 51 episodes of acute asthma were evaluated. Peak flow spirometry served as an objective measure of airway resistance, and theophylline levels were determined at fixed intervals throughout the study. Epinephrine and aminophylline were not found to be superior to epinephrine alone. There was no correlation between mean serum theophylline levels and the magnitude of improvement. Rapidity of emergency department discharge and frequency of admission was independent of treatment method. The failure of epinephrine-aminophylline to effect more rapid or profound improvement in pulmonary function might suggest that epinephrine alone, or an equivalent sympathomimetic is a rational choice in the initial treatment of acute asthma.

Cefazolin sodium, 500 mg intramuscularly twice daily, was compared with penicillin G procaine, 600,000 units intramuscularly twice daily, in the treatment of 82 patients with pneumococcal pneumonia. Patients were randomly assigned except when there was a history of penicillin allergy. The patients received treatment for five days or until they were afebrile for 48 hours. No patients experienced side effects or allergic reactions. All patients recovered satisfactorily without relapses. Cefazolin in the previously described dosage is as effective as penicillin in the treatment of pneumococcal pneumonia.

Ticarcillin disodium and gentamicin sulfate serum levels were measured one and five hours after intravenous administration. Patients receiving ticarcillin plus gentamicin had a significantly lower mean gentamicin level one and five hours after antibiotic administration than patients receiving cephalothin sodium plus gentamicin. The serum ticarcillin levels were significantly lower five hours after administration in patients receiving ticarcillin plus gentamicin than in those receiving ticarcillin plus cephalothin. Low antibiotic serum levels in patients with serious infections treated with these antibiotic combinations are of potential clinical significance; therefore, to ensure an optimal antimicrobial therapy, it is advisable to determine the drug serum concentrations (especially aminoglycoside) even in patients with normal renal function when treating with combinations of antimicrobials.

Twenty-eight patients completed a double-blind study of the antihypertensive effects of ticrynafen compared with those of hydrochlorothiazide. The results of blood pressure reduction were comparable in the two groups. After six months, 12 patients were crossed over to ticrynafen therapy from hydrochlorothiazide. They maintained their blood pressure reduction. The most striking difference between the two groups was in the uric acid response. The uric acid level in the patients receiving hydrochlorothiazide therapy rose from a baseline of 5.9 to 7.5 mg/dL (normal range, 3.0 to 8.0 mg/dL). The uric acid level of those patients receiving ticrynafen therapy decreased from a baseline of 6.4 mg/dL to a low of 3.3 mg/dL. In view of ticrynafen's appreciable antihypertensive and uric-acid-lowering effects, it appears to be a useful new antihypertensive drug.

Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.

A prospective experimental design evaluated the ability of a series of educational and motivational interventions to enhance self-treatment by adult asthmatics and to reduce use of emergency department services for asthma attacks. After treatment for an asthma attack, subjects were randomly assigned to the following sequential interventions: (1) reinforcement by interpersonal similarity at the time of the emergency visit, (2) recepit of positive written appeals, and (3) follow-up telephone reinforcement. The asthmatic nurse educator was generally more effective in achieving short-term reduction of emergency department visits. Although the usefulness of the positive written appeal increased when employed by the asthmatic nurse, there were no substantive independent effects of the written message on emergency department use.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.