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.

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.

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.

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.

In a double-blind crossover study, the effectiveness of furosemide, 40 mg twice daily, was compared with hydrochlorothiazide, 50 mg twice daily, in hypertensive patients. Both hydrochlorothiazide and furosemide significantly reduced blood pressure (BP) during three months of therapy. However, the fall in BP was consistently greater with hydrochlorothiazide than with furosemide, although the difference was significant only with respect to systolic BP. The somewhat greater antihypertensive effectiveness of hydrochlorothiazide may be related to its longer action permitting a more continuous diuretic effect and, hence, maintenance of reduced extracellular fluid volume throughout the 24-hour period.

The effectiveness of cyclobenzaprine hydrochloride, a new tricyclic skeletal muscle relaxant, was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness. The investigation was double-blind and randomized, comparing cyclobenzaprine hydrochloride (10 mg three times a day) with diazepam (5 mg three times a day) and with placebo. After two weeks of treatment, the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group. No serious adverse reactions to cyclobenzaprine were observed in the study. However, dry mouth due to cyclobenzaprine's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo.

To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation, 50 patients who suffered cardiac arrest were randomly allocated to receive manual or mechanical chest compression. Randomization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest (mean, 6.4 +/- 1.2 min). Ten patients from each group survived longer than one hour following resuscitation. Three from the mechanical group and two from the manual group were eventually able to leave the hospital. Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions. Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform.

A randomized double-blind crossover trial included 16 patients with severe congestive heart failure who received isosorbide dinitrate or placebo for eight weeks, and then the opposite treatment for eight more weeks. All patients received their usual maintenance therapy with digitalis and diuretics. Seven morbid events occurred during 85 patient-weeks of isosorbide dinitrate therapy compared with 17 during 76 patient-weeks of placebo. Severity of congestive heart failure improved in all eight patients who received isosorbide dinitrate compared with two patients who showed improvement and five whose symptoms became worse with placebo. No significant differences in physical findings, cardiac dimensions, or resting hemodynamics were observed. Maximal exercise duration increased significantly by 2.54 minutes with isosorbide dinitrate therapy, and rose insignificantly by 1.24 minutes with placebo. This preliminary trial suggests that long-term vasodilator therapy may be clinically beneficial in congestive heart failure.

Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

A prospective, randomized, double-blind study on the effect of cephaloridine prophylaxis in the surgical management of appendicitis was performed. Of the 139 patients studied, 70 received cephaloridine and 69 received placebo prophylaxis. Both groups of patients were well matched with regard to age, sex, operative findings, and bacteria isolated at operation. Postoperative wound infections were detected in 11.6% of placebo-treated patients and in 1.4% of cephaloridine-treated patients (P less than .02). Prophylactic treatment with cephaloridine of patients undergoing surgery for uncomplicated appendicitis resulted in a perceptible reduction in the rate of postoperative wound infection.

Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.

A randomized double-blind trial of 152 men with gonococcal urethritis compared the therapeutic efficacy of erythromycin estolate and erythromycin base. Twenty-one of 86 (24%) men treated with the estolate and 15 of 66 (23%) treated with the base had recurrent or persistent gonococcal infection when seen after a 9-g course of erythromycin. The serum erythromycin activity among estolate-treated patients (3.57 +/- 0.84 microgram/ml) was nearly twice that for base-treated patients (1.76 +/- 0.80 microgram/ml). Our findings do not support routine use of erythromycin for treatment of pregnant, penicillin-allergic patients.

A relative intolerance of lactose was demonstrated in 14 of 16 patients receiving nasogastric tube feedings following surgery for head or neck carcinoma. Two liquid diets differing only in the presence or absence of lactose, were administered for eight to 20 days per patient in a double-blind crossover study. Increased stool frequency, decreased stool consistency, and more frequent flatulence, borborygmi, and distention were found with the lactose diet, although classic lactose intolerance (plasma glucose rise of less than 26 mg/dl) was indicated in only two patients. Differences between amounts and times of peak rise following the glucose tolerance test and lactose tolerance test for each patient indicated the advisability of locating patients on a continuum of ability to hydrolyze lactose. The results indicate that lactose should be reduced or eliminated from tube-feeding diets to improve patient tolerance and comfort and to reduce diarrhea.

Twenty-nine patients with small cell carcinoma of the lung and without evidence of brain metastasis were randomized into two treatment groups consisting of 14 patients who received prophylactic cranial irradiation (PCI) and 15 who received none (non-PCI). All patients were treated with irradiation of the primary lesion and concomitant chemotherapy. The response rate and median survival of the two groups were not significantly different: 93% and 7.2 months in the non-PCI; 86% and 9.8 months in the PCI; P larger than or equal to .05. Brain metastasis occurred in 0/14 patients in the PCI and 4/15 in the non-PCI (P less than or equal to .05) and was the cause of major neurologic disability in each. Although PCI did not improve response rate or survival, brain metastasis with its attendant neurologic complications was effectively prevented.