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.

Orally administered clindamycin and penicillin were compared for effectiveness in preventing streptococcal infections in 202 randomly assigned patients with previous rheumatic fever (RF). Among 143 patients aged 21 years or younger observed for 537 patient-years, the number of streptococcal infections (and number per patient-year) was 23 (0.084) in the penicillin group and 12 (0.045) in the clindamycin group. Excluding uncooperative patients, the rate of streptococcal infection remained less, though not statistically significant, in the clindamycin group than in the penicillin group. Two RF recurrences occurred in the penicillin group, and no recurrence occurred in the clindamycin group. Clindamycin was well tolerated except for possible mild gastrointestinal symptoms in six patients. Clindamycin can be substituted for penicillin for RF prophylaxis when there is allergy to penicillin or concern about the development of penicillin-resistant mouth organisms.

A prospective, double-blind evaluation of the efficacy and safety of prophylactic cephalosporins was done in 57 patients undergoing noncardiac thoracic surgery. Twenty-eight received cephalosporin therapy, and 29 received placebo. Overall, the incidence of postoperative infections was the same; infections developed in five (17.8%) of the 28 patients in the cephalosporin group and in five (17.2%) of the 29 patients in the placebo group. Of the five deaths attributable to infection, three occurred in patients receiving placebo and two in patients receiving cephalosporin therapy. No differences were noted in WBC counts, fever, duration of hospitalization, hypersensitivity reactions, or abnormal liver functions. However, drug fever, phlebitis, and abnormal renal function occurred more often in the patients receiving cephalosporin therapy.

We tested the effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian (h1n1) influenza. The trial lasted seven weeks and was double-blind and placebo controlled. The dosage used was 200 mg daily. Efficacy in prevention of serologically confirmed clinical influenza was 70.7%. Efficacy in prevention of infection, symptomatic or asymptomatic, was 39.4%. Side effects seen were all mild, began within two days of the start of the trial, and terminated rapidly on cessation of prophylaxis. The withdrawal rate attributable to use of amantadine was 6.2%. Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects. It is concluded that amantadine is safe and effective in prophylaxis of H1N1 strains, as has been shown previously for other subtypes of A influenza.

A prospective, randomized, double-blind study was carried out to determine whether vitamin C prophylaxis, 2.0 g/day, vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period. Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group. There was no difference between the two groups in the incidence or duration of colds. The vitamin C group rated their colds as being less severe, but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost. This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold.

We compared low-dose, continuous insulin infusion with a conventional high-dose intravenous bolus method of insulin administration in 18 episodes of diabetic ketoacidosis. The average rate of reduction in serum glucose concentration was 9.5 +/- 3.8%/hr in the continuous infusion group and 10.7 +/- 4.7%/hr in the bolus group. Arterial blood pH was corrected to 7.35 by 9.9 +/- 2.6/hours in the continuous infusion group and by 10.4 +/- 3.2/hours in the bolus group. The above means are not significantly different between groups. By the time pH was corrected to 7.35, patients in the continuous infusion group had received 121 +/- 44 units of insulin, whereas those in the bolus group had received 326 +/- 152 units. The continuous low-dose insulin infusion method is as safe and efficacious as the conventional high-dose intravenous bolus method.

The bronchodilator effect of carbuterol hydrochloride, a new adrenergic agonist, was compared with that of ephedrine sulfate in 12 patients with bronchial asthma. A 2-mg dosage of carbuterol hydrochloride, three times daily, was used in comparison with a 25-mg dosage of ephedrine sulfate, three times daily. The drugs were orally administered for ten-day periods in a double-blind, randomized manner. After carbuterol therapy, the mean increases in forced expiratory volume in one second and midmaximal expiratory flow rate were significantly greater in a four-hour period than those noticed with ephedrine. A decrease in bronchodilator response to both drugs was noticed on the tenth day. No side effects were noticed with carbuterol at the aforementioned dosage. The results of our study indicate that carbuterol is a safer and more effective bronchodilator than ephedrine.

A single-blind clinical trial compared step 2 combination therapy consisting of 50 or 100 mg of hydroflumethiazide plus either 0.125 to 0.250 mg of reserpine, 500 to 2,000 mg of methyldopa, or 80 to 320 mg of propranolol hydrochloride, in 59 patients whose elevated blood pressure (BP) failed to respond adequately to the thiazide alone. After nine weeks of treatment, diastolic BP was reduced below 90 mm Hg in all 20 patients treated with the reserpine-hydroflumethiazide combination, in 13 of the 19 patients treated with methyldopa and hydroflumethiazide, and in 16 of the 20 patients treated with propranolol and hydroflumethiazide. Changes in laboratory values were not substantial; adverse reactions occurred only in the methyldopa group. Although the three treatment regimens were similar with respect to safety and efficacy, the reserpine-hydroflumethiazide combination offers the advantages of more convenient dosage at lower cost.

Randomized trials comparing surgical treatments of breast cancer show that radical mastectomy offers no greater benefit than simple mastectomy followed by radiotherapy. Furthermore, in terms of survival, radical mastectomy seems to be no better than wide excision followed by radiotherapy when the disease is clinically diagnosed as stage 1. The incidence of diagnosed breast cancer showed an 18% increase between 1935 and 1965 and a 50% increase between 1965 and 1975. However, breast cancer mortality has remained unchanged for at least the past 40 years. Analysis of survival curves of women with breast cancer suggests that two or more populations exist, with about 40% suffering fatal outcome unaffected by treatment. The remaining 60% exhibit a relative mortality only modestly different from that of women of similar ages without evidence of disease. Increasing detection of an entity that is histologically defined as malignant but biologically relatively benign could account for the observed increase in incidence.

Randomized clinical trials in 300 patients undergoing major abdominal surgery or hip replacement arthroplasty were performed to investigate the efficacy of dihydroergotamine mesylate, heparin calcium, or a combination of dihydroergotamine with heparin in preventing postoperative deep-vein thrombosis (DVT). The diagnosis of DVT was established by an uptake test using fibrinogen labeled with iodine 125; in patients undergoing hip replacement, phlebography was also employed to confirm or refute the presence of isotopic thrombi. The data indicate that the combination of dihydroergotamine and heparin is more effective than heparin or dihydroergotamine alone in preventing DVT.

Preliminary to a stimulant comparison study, 31 children with minimal brain dysfunction randomly received either placebo or a megavitamin combination. During a two-week trial, only two children responded so well that stiumlants were not considered necessary; both were in the placebo group. Change scores from pretest to posttest on four blind ratings by teachers and parents did not show a significant difference between the placebo and vitamin groups.

In a single-blind comparative study of the cases of 30 moderately hypertensive patients, clonidine hydrochloride and prazosin hydrochloride had similar effectiveness in lowering blood pressure. Neither agent had significant effects on the renin-aldosterone axis. Addition of polythiazide to prazosin and chlorthalidone to clonidine notably increased the antihypertensive effect of both drugs. Serum cholesterol levels were observed to decrease when prazosin and clonidine were given and to rise when the diuretics were added to the regimen. The patients treated with clonidine were troubled by side effects, particularly drowsiness and dry mouth. Prazosin was better tolerated, with side effects tending to diminish with time. The "first-dose" effect was seen in two patients given prazosin, but it did not limit treatment. Both diuretics induced notable hypokalemia.

Eighty-nine men with gonococcal urethritis were randomly treated with trimethoprim-sulfamethoxazole, four tablets (trimethoprin, 320 mg, and sulfamethoxazole, 1,600 mg) twice daily for two days, or ampicillin, 3.5 g, plus probenecid, 1 g, in a single dose. Forty-one (95.3%) of 43 patients who received trimethoprin-sulfamethosazole and 41 (97.6%) of 42 given ampicillin were cured. Neither drug caused major side effects. All isolates of Neisseria gonorrhoeae were susceptible in vitro to trimethoprim-sulfame-thoxazole, and all but one were inhibited by ampicillin. The ampicillin-resistant strain (minimum inhibitory concentration, 4 micrograms/ml) produced penicillinase and was reovered from a patient who responded to treatment with trimethoprim-sulfamethoxazole. There was no significant correlation between the minimum inhibitory concentrations of trimethoprim-sulfamethoxazole and ampicillin. It is concluded that trimethoprim-sulfamethoxazole is as efficacious and safe as ampicillin in the therapy of gonococcal urethritis.