A long-term comparative field trial of three live, attenuated rubella vaccines (HPV-77 DE-5, HPV-77 DK-12, and Cendehill) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Rubella hemagglutination-inhibition (HI) tests on prevaccination serum specimens from 7,931 children in the two study areas indicated an overall susceptibility to rubella of nearly 70%. The rates of seroconversion of 5,153 seronegative subjects to HPV-77 DE-5, HPV-77 DK-12, and Cendehill vaccine were 97.5%, 99.9%, and 99.8%, respectively. Over the subsequent four-year follow-up period, during which time natural exposure to rubella was minimal, the percent decline of geometric mean titers did not vary substantially among the three vaccine groups and measured about twofold for all three. A total of only 28 vaccines (0.7%) who seroconverted to one of the vaccines in 1969 lost all measurable antibody by 1974. Measurable antibody persisted in more than 98% of all vaccinees over the four-year period. Reinfection, thought possibly to be an important factor in maintaining titers, did not occur frequently in the study population and could not be related to outbreaks of disease.

The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospective controlled study of 820 patients. The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine (125I) was reduced from 16.0% in the control group to 4.2% in treated patients. More important, the incidence of popliteal or femoral vein thrombosis was reduced from 2.9% to 1.0%. Prophylaxis resulted in a slight increase in bleeding-minor wound hematoma, mean volume of blood transfused, and a post-operative hematocrit fall in treated patients. However, increased bleeding was clinically minor, and prophylaxis was well tolerated.

In this double-blind, randomized study, 200 normal subjects received a three-day course of one of five treatment regimens: lincomycin hydrochloride monohydrate injection (sterile solution, 300 mg/ml) with two tablets of either placebo, a mixture of atropine sulfate and diphenoxylate hydrochloride (Lomotil), an aspirin-phenacetin-caffeine (APC) combination or the latter with codeine, or an injection of saline with two placebo tablets. Gastrointestinal irritation was most prominent in subjects receiving lincomycin with atropine-diphenoxylate and lincomycin with APC plus codeine (P less than .05). Decreased intestinal motility from atropine-diphenoxylate or codeine may increase the contact time between the lincomycin (or its metabolites) or some developing toxic substances and the mucosal epithelium. The use of atropine-diphenoxylate or codeine in treating lincomycin-induced diarrhea may be questionable.

Twenty-eight infants and children hospitalized for severe shigellosis were treated orally either with ampicillin trihydrate (100 mg/kg/day administered in divided doses every six hours) or with trimethoprim-sulfamethoxazole (trimethoprim, 10 mg; sulfamethoxazole, 50 mg/kg/day in divided doses every 12 hours) for five days. Four patients with ampicillin-resistant shigellae continued to have diarrhea and positive stool cultures during therapy. Patients with susceptible shigellae treated with ampicillin and all patients treated with trimethoprim-sulfamethoxazole responsed promptly and comparably within an average of 1.6 and 1.7 days, respectively, until stool cultures were negative, and 3.1 and 2.9 days, respectively, until diarrhea stopped. Patients with ampicillin-resistant shigellae responded to treatment with trimethoprim-sulfamethoxazole. It is concluded that trimethoprim-sulfamethoxazole is the best currently available drug for treatment of shigellosis in areas where multiple antibiotic resistance of shigellae is common.

Bleomycin sulfate, doxorubicin hydrochloride, cyclophosphamide, and vincristine sulfate combination chemotherapy was given to 29 patients with small-cell undifferentiated lung cancer. Only four of these patients had limited disease, and in these patients there was 100% complete remission; two of these four patients remain in complete remission at more than 52 and 60 weeks. Of the 25 patients with generalized disease, 18 (72%) had neoplasm regression (greater than 50%), including two with complete remission (8%). The median duration of remission was 25 weeks. The median survival time from diagnosis was 39 weeks and that from initiation of therapy, 35 weeks. The drug regimen was well tolerated, and although substantial leukopenia was produced, there were only three patients in whom granulocytopenic infections developed. There was only one drug-related death.

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI-38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of other experimental vaccine. Clinical side effects were only minor.

Four hundred children with streptococcal pharyngitis were treated randomly with single injections in groups of 100 each (1) with 600,000 units of penicillin G benzathine, (2) 1.2 million units of penicillin G benzathine, (3) 600,000 units of penicillin G benzathine and 600,000 units of penicillin G procaine, or (4) 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine. Clinical response and severity of local reaction were judged in a double-blind manner at 24, 48, and 72 hours; throat cultures were taken then, and at 10, 21, and 42 days. Although the clinical response to 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine was equal to 1.2 million units of penicillin G benzathine, the former cleared the streptococci more quickly, greatly reduced the incidence and severity of local reactions, and offered optimal therapy for streptococcal pharyngitis in the pediatric age group.

Nitrous oxide in a concentration of 35% has been shown to ameliorate the pain of acute myocardial infarction. This conclusion was reached on the basis of a double-blind study in 69 patients and a clinical study in an additional 42 patients. The use of nitrous oxide was not accompanied by hemodynamic changes or significant adverse reactions.

The bronchodilator efficacy and safety of metaproterenol sulfate were evaluated by double-blind crossover tests against placebo at three intervals during a 90-day treatment period in 50 asthmatic children. One group of 25 patients was continuously treated with metaproterenol syrup, and the other 25 with placebo syrup. Pulmonary function tests showed statistically significant improvements in forced expiratory volume, forced expiratory volume in one second, and peak expiratory flow rate after metaproterenol administration as compared with those measurements after treatment with placebo. Biweekly global evaluations of responses to metaproterenol administration were consistently more favorable than responses to placebo. Tachycardia and blood pressure changes after metaproterenol administration were consistent with the pharmacologic properties of beta-sympathomimetic stimulants. Side effects during metaproterenol treatment were minimal and laboratory data remained normal.

Aspiration pneumonitis and lung abscess generally involve anaerobic bacteria, which normally colonize the upper respiratory passages. The therapeutic response of these infections to parenteral penicillin G (49 patients) and parenteral clindamycin (35 patients) was compared to determine relative efficacy. No difference was discerned between these two agents in terms of time required for defervescence, roentgenographic clearing, and ultimate outcome. Seven patients with infections including Bacteroides fragilis were treated with penicillin G, and all responded well. These data indicate that penicillin G is the preferred agent for pulmonary infections involving anaerobic bacteria. Clindamycin is a suitable alternative for patients in whom penicillin G is contraindicated.

Fify-seven Huichol Indians with a lifelong individual history and a 1,600-year cultural tradition of ingestion of peyote, a mescaline-containing cactus possessing hallucinogenic properties, were compared with 50 Huichol Indian controls and ten laboratory controls for effects on lymphocyte chromosomes. The frequency of abnormalities in the experimental and control groups did not differ significantly. Our results indicate that multigenerational ingestion of peyote is not associated with abnormalities in lymphocyte chromosomes.

The relative effectiveness of ephedrine, theophylline, and hydroxyzine hydrochloride and their combinations was studied in a two-part investigation of 16 youths who has asthma and exercise-induced asthma. The beneficial and adverse effects of the drugs in the control of asthma were studied in the first part of the investigation. Both theophylline and ephedrine were judged superior to placebo when given alone. When combined they were somewhat more effective than either agent alone, although adverse effects precluded their use in almost half of the subjects. The addition of hydroxyzine diminished the side effects sufficiently to make the combination acceptable to four subjects who refused to take ephedrine/theophylline. In the second part of the study, the relief of exercise-induced asthma was evaluated. Ephedrine had no effect, hydroxyzine had a weak effect on hastening recovery, but theophylline modified the postexercise response significantly. The three drugs together produced an additive effect superior to that of theophylline alone.

Ibuprofen is a nonsteroidal drug with analgesic, antipyretic, and anti-inflammatory properties that was recently introduced for use in antiarthritis therapy in the United States. In a year-long double-blind multiclinic trial in 885 patients with rheumatoid arthritis, ibuprofen was at least as satisfactory as aspirin, considering both efficacy and tolerance. In the majority of patients, daily doses ranged from 800 to 1,600 mg of ibuprofen and 3 to 6 gm of aspirin. The drugs did not differ greatly in providing relief from arthritis symptoms, but ibuprofen was definitely better tolerated, especially in regard to gastrointestinal complaints. Seven percent of the ibuprofen group dropped out of the study because of adverse reactions, as compared with 16% of the aspirin group; 17% of the ibuprofen group and 31% of the aspirin group had gastrointestinal symptoms.

A multicenter, prospective, double-blind, controlled study was performed to compare the efficacy of trimethoprim-sulfamethoxazole with that of ampicillin in the treatment of chronic urinary tract infections. The incidence of adverse clinical signs and symptoms as well as abnormal laboratory values were comparable in the two treatment groups. This study appears to establish the fact that trimethoprim-sulfamethoxazole is an acceptable alternative to ampicillin for the treatment of chronic urinary tract infections caused by susceptible Escherichia coli.