Chlorambucil, in combination with prednisone, was compared with prednisone alone in a randomized controlled trial in 21 children with either steroid-dependent or frequently relapsing nephrotic syndrome to assess its effect on the duration of remission and the rate of relapse. All control patients treated with prednisone alone continued to relapse at the same rate, with all patients experiencing a return of proteinuria by seven months. Conversely, those who received the same prednisone therapy along with chlorambucil for six to 12 weeks remained in complete remission, without further medication, during 12 to 34 months of follow-up observation. Complications were minimal. Immediate side effects commonly reported with cyclophosphamide were not seen with chlorambucil. Comparison with published reports also suggests that remission induced by chlorambucil is more stable than that after cyclophosphamide. Chlorambucil appears to be of value in the frequently relapsing nephrotic patient, adding an effect that is unattainable with prednisone alone.

In spite of the controversy over the role of randomized clinical trials in medical research, the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-randomized studies such as those relying on the use of historical controls and adjustment technics. Others have suggested that recent statistical innovations for improving clinical trials, including adaptive allocation of treatment to patients and sequential stopping procedures, are underutilized. These innovations, though theoretically interesting, are not easily adapted to large-scale, complex medical trials in which there may be multiple end points and delayed response times. Ethical considerations suggest that randomized trials are more suitable than uncontrolled experimentation in protecting the interests of patients. Randomized clinical trials remain the most reliable method for evaluating the efficacy of therapies.

We studied the antihypertensive effect of propranolol alone and in combination with diuretics in 13 patients with high, 18 with normal and nine with low-renin essential hypertension whose blood-pressure response to diuretics was previously established. Propranolol (160 mg daily) significantly lowered mean arterial pressure in high-renin (129 +/- 2.6 to 114 +/- 2.1 mm Hg) and normal-renin (131 +/- 2.7 to 119 +/- 3.5 mm Hg) patients but not in low-renin patients. A positive correlation (r = 0.36, P less than 0.05) between fall in pressure and fall in plasma renin activity occurred at this dose when the whole group was considered. An antihypertensive effect occurred in both high-renin and low-renin hypertension during large-dose (320 to 960 mg daily) propranolol therapy. This effect was independent of changes in plasma renin activity. The antihypertensive effects of propranolol and diuretics were additive in normal-renin and high-renin hypertension. These data suggest that propranolol's pressure-lowering activity is due to both renin-dependent and renin-independent effects.

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.