We used "high-dose" metronidazole, an "in vitro" and "in vivo" specific radiosensitizer of hypoxic cells, in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas. Thirty-six patients were stratified according to functional level and randomly allocated within two weeks of operation to one of two therapeutic groups: Group 1, radiation alone; and Group 2, radiation as in Group 1 but with high-dose metronidazole. We examined survival with the Kaplan-Meier probability plot and non-parametric tests. Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death (P = 0.02). This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant. Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors.

To investigate whether "prepared-childbirth" courses offer measurable physical advantages, we compared the labor and delivery characteristics of 129 primiparas who had completed ante-partum Lamaze-training psychoprophylaxis classes with an equal number of matched controls who had not. The former were given narcotics less frequently during labor (P less than 0.001), received conduction anesthesia less often (P less than 0.001), and had a higher frequency of spontaneous vaginal deliveries (P less than 0.001) than the control patients. However, these differences had no apparent effects on the length of labor, number or type of maternal complications, frequency of fetal distress, mean Apgar scored, or neonatal problems.

We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.001). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia (P = 0.001) and are less than 38 years of age (P = 0.001).

We compared methods of classifying hypertension according to plasma renin activity in 54 patients with essential hypertension and examined the validity of using these classifications to choose between two hypotensive drugs. A prospective, double-blind crossover study was used. Normal values for plasma renin activity were established from 111 control subjects. Plasma renin activity was related to race and inversely to age in hypertensive patients (P less than 0.05) but not in normal subjects. Three methods of classification correlated well but did not identify exactly the same renin-suppressed patients. Chlorthalidone produced a greater reduction in blood pressure and restored blood pressure to normal in a larger percentage of patients in both low-renin (59 per cent) and normal-renin (32 per cent) subgroups than propranolol (12 and 16 per cent). Renin determinations are of limited benefit in the choice of therapy for most patients with essential hypertension.

A clinical controlled trial was designed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes. Three strata comprising 574 families (lower-income group enrolled in health maintenance organization, lower-income not enrolled in such a project, and a middle-income group employed by a utility company) were interviewed to obtain information on utilization, morbidity, health status, and attitudes. Sixty percent of adults in each stratum were then screened. All families were interviewed again one year later. The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects. Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians. Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment.

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.