Nocturnal pain and gastric hypersecretion are common in duodenal ulcer. Therefore, we investigated the antisecretory effects of a new H2-receptor antagonist, cimetidine, in 200-, 300- or 400-mg doses, taken orally at bedtime. The 200-mg dose did not cause a statistically significant change in nocturnal (midnight to 7 a.m.) acid output and had only a borderline effect on pH. However, the 300-mg and 400-mg doses significantly (P less than 0.001) lowered acid output and increased (P less than 0.01) intragastric pH. All doses caused substantial decreases in secretory volume output. After a 400-mg dose, half the patients remained anacidic for eight hours. Dose-related increases of drug blood levels were observed and correlated with the degree and duration of inhibition of acid output. Serum gastrin levels were unaffected. Cimetidine appears to be a potent inhibitor of nocturnal gastric secretion.

The efficacy of corticosteroid therapy in severe viral hepatitis has never been demonstrated in a controlled clinical trial. For this reason, patients with severe viral hepatitis were randomly assigned to methyl-prednisolone or placebo treatment groups. The two groups were comparable in clinical findings, laboratory results and the presence of bridging necrosis on liver biopsy. Seven of the 14 patients assigned to methyl-prednisolone and two of the 15 assigned to placebo died during the 16-week study period. Although the apparent excess mortality in the steroid-treated patients is not quite statistically significant (P = 0.08), the trend persists when only patients positive for hepatitis B surface antigen (P = 0.04) are analyzed separately. Methyl-prednisolone does not enhance survival in patients with severe viral hepatitis, and it may be detrimental.

To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporpine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P less than 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of alpha-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful in the treatment of Parkinson's disease.

We investigated possible associations of HL-A types and antibody-response patterns during clinical trials with a live, attenuated intranasal influenza A vaccine. After vaccination, subjects with HL-A type W16 had, as a group, a mean convalescent-phase hemagglutination-inhibiting antibody titer of 14, which was significantly lower (P less than 0.001) than the mean titer of 36 in subjects without Type W16. Of 25 subjects with a poor antibody response, 32 per cent had HL-A type W16, whereas only 5 per cent with a good response had Type W16. The mean titers in nasal secretions of five W16 subjects at 13 and 30 days were less than 3; in contrast, similar titers of 22 subjects without W16 were 8 and 9 respectively. The results suggest that the lower antibody response in W16 subjects is due to increased cellular resistance to infection rather than to a suppressed immune response because other subjects with W16 had normal antibody responses after vaccination with killed influenza vaccine.

To monitor the efficacy of the 1972 United States Public Health Service recommended treatment regimens for uncomplicated gonorrhea, we studied 9008 patients who were randomly assigned either to aqueous procaine penicillin G, 4.8 million units intramuscularly plus 1 g of oral probenecid, or to one of the three other recommended regimens. Among the 3871 patients re-examined within three to seven days after therapy, the penicillin-probenecid regimen was successful in 96.8 per cent, whereas the cure rates of the ampicillin-probenecid, tetracycline, and spectinomycin regimens were 92.8, 96.2, and 94.8 per cent, respectively. In clinics comparing the regimens, penicillin G-probenecid was as effective as tetracycline, but more effective than ampicillin-probenecid (P less than 0.05) and spectinomycin (P less than 0.01). However, in patients re-examined three to 14 days after treatment, only the ampicillin-probenecid regimen was significantly less effective than penicillin probenecid (P less than 0.01). Despite these differences in results, all four regimens recommended by the Public Health Service provided effective therapy for uncomplicated gonorrhea.

A randomized double-blind study was carried out in 26 patients with multiple myeloma to compare the therapeutic effect of sodium fluoride (50 mg twice daily) plus calcium carbonate (1 g four times daily) and placebo. All patients also received melphalan and prednisone for one week every six weeks. Bone biopsies for microradiography and histology, and videodensitometry as well as conventional roentgenograms, 99mTc-polyphosphate bone scans, and bone densitometry of the mid and distal radius, were done initially and one year after therapy. Microradiography and videodensitometry studies revealed significant increases in bone formation (P less than 0.01) and bone mass (P less than 0.005) in the fluoride-calcium group. Bone trabeculae appeared thickened on roentgenograms of six of 13 fluoride-calcium-treated patients (P less than 0.02). Technetium bone scans and bone densitometry determinations proved insensitive for detection of skeletal changes. Fluoride calcium should be considered a useful adjunct in the treatment for multiple myeloma.

Forty patients with acute coronary insufficiency, including continued angina at rest and reversible ischemic electrocardiographic changes after hospitalization ("high-risk" subgroup), were randomly allotted to medical therapy or urgent surgical coronary bypass groups. In four months there were no deaths and two myocardial infarctions in 19 medical patients and one death and three myocardial infarctions in 21 surgical patients. Left ventricular ejection fraction did not change significantly in either group. The surgical patients had significantly higher functional capacities at four months as judged by lower symptomatic functional class (P less than 0.01), higher exercise angina threshold (P less than 0.001), higher pacing angina threshold (P less than 0.0001), and higher myocardial lactate extraction during pacing (P less than 0.0001). Initial medical management of patients with acute coronary insufficiency followed by elective coronary bypass in patients with continued disabling angina pectoris is a reasonable alternative to emergency bypass.

We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes.

This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P less than 0.005) one year, and 9.2 mg per dl higher (P less than 0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P less than 0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed.