It has been suggested that because propranolol decreases portal venous pressure, it may prevent gastrointestinal bleeding associated with portal hypertension. We randomly assigned 74 patients with cirrhosis, who were admitted because of gastrointestinal bleeding, to either oral propranolol given in doses that reduced the heart rate by 25 per cent (38 patients) or to a placebo (36 patients). The proportion of patients free of recurrent gastrointestinal bleeding one year after inclusion in this study was 96 per cent in the propranolol group and 50 per cent in the placebo group (P less than 0.0001). We conclude that continuous administration of propranolol by mouth is effective in preventing recurrent gastrointestinal bleeding in patients with cirrhosis.

We performed a double-blind study in 101 preterm infants who weighed less than or equal to 1500 g at birth, who had respiratory distress, and who survived for at least four weeks, to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. Weekly indirect ophthalmologic examinations begun when the infants were three weeks old revealed a significant decrease in the incidence of retrolental fibroplasia greater than or equal to Grade III (P less than 0.03) and greater than or equal to Grade II (P less than 0.05) (McCormick classification) in the 50 infants given 100 mg of vitamin E per kilogram of body weight per day as compared with 51 given 5 mg per kilogram per day (controls). When multivariate analysis was applied to the controls, five risk factors were identified: gestational age, level and duration of administration oxygen, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012).

This report summarizes morbidity in 151 patients in a cooperative trial designed to evaluate the clinical effects of different dialysis prescriptions. Four treatment groups were divided along two dimensions: dialysis treatment time (long or short), and blood urea nitrogen (BUN) concentration averaged with respect to time (TACurea) (high or low). Dietary protein was not restricted. There was no difference in mortality between the groups. Withdrawal of patients from the high-BUN groups for medical reasons was significantly greater than withdrawal from the low-BUN groups. Hospitalization was also greater in the high-BUN groups, but dialysis treatment time had no significant effects. The data indicate that the occurrence of morbid events is affected by the dialysis prescription. Increased morbidity appears to accompany prescriptions associated with a relatively high BUN. Conversely, morbidity may be decreased by prescriptions associated with more efficient removal of urea if the dietary intake of protein and other nutrients is adequate.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic, 41 patients with advanced cancer who were being treated with cisplatin were entered into two double-blind trials. In the first trial patients were randomly assigned to receive either metoclopramide or placebo, and in the second trial they received either metoclopramide or prochlorperazine. Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo (medians, 1.0 vs. 10.5; P = 0.001) or prochlorperazine (medians, 1.5 vs. 12.0; P = 0.005). Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis (P = 0.001 and P = 0.022, respectively) and was more effective than placebo in shortening the duration of nausea (P = 0.042) and vomiting (P = 0.028). Side effects from metoclopramide were minor, with mild sedation frequently observed; one patient had a brief extrapyramidal reaction. We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy.

To evaluate the use of antibiotics given prophylactically of colon surgery, we examined 26 trials published from 1965 to 1980 in which patients given various antibiotic regiments were compared with controls given no antibiotic treatment. In 22 (85 per cent of these trials) antibiotics reduced postoperative wound infection (p less than 0.05 in 14). Combining the results of the trials published from 1965 to 1975 reveals a 95 per cent confidence interval from the true difference in infection rates of 14 +/- 6 per cent (36 per cent for control group vs. 22 per cent for treatment group) and the true difference in death rates of 6.7 +/- 4.4 per cent (11.2 per cent for control group vs 4.5 per cent for treatment group). Yet trials employing control groups given no treatment continue to be reported. Since the use of such controls is justified only when no effective alternative therapy exists, we believe that any further trials of antibiotic prophylaxis in colon surgery should employ a previously proved standard. However, steadily increasing efficacy of treatment means that comparisons of new therapies with standard therapies will become prohibitively expensive because of the large number of patients required.

We concluded a prospective study of the value of maintenance therapy in disseminated testicular cancer after chemotherapy-induced complete remission or chemotherapy cytoreduction followed by surgical resection of residual teratoma. A group of 171 patients were randomized to treatment consisting of cisplatin, vinblastine, and bleomycin, or these drugs plus doxorubicin. There was no apparent difference between these two induction regimens. Complete remission was achieved in 113 patients (66 per cent), and 19 (11 per cent) were free of disease by surgical resection of residual tumor. Of the 171 who started, 113 were eligible to receive either maintenance doses of vinblastine (58 patients) or no further therapy (55 patients) after remission-induction therapy. There was a 9 per cent relapse rate during maintenance with vinblastine and a 7 per cent relapse rate with no maintenance therapy; the overall relapse rate was 8 per cent (nine of 113). Our data indicate that maintenance therapy is unnecessary in disseminated testicular cancer.

We designed a double-blind trial to study the effect of an "activated" prothrombin-complex concentrate (FEIBA) on joint and muscle bleeding in hemophiliacs with antibodies to factor VIII. Fifteen patients received either FEIBA or the control preparation (a nonactivated prothrombin-complex concentrate) for a total of 150 bleeding episodes (four mucocutaneous bleeding, 117 joint bleeding, and 29 muscle bleeding). In 64 per cent of the episodes, FEIBA was judged by the physician to be effective; the control preparation was perceived as effective in 52 per cent of the episodes in which it was used. Pairwise comparison of FEIBA and the control preparation for bleeding in the same joint or muscle showed a significantly better result with FEIBA (P = 0.0085). Joint mobility after the use of FEIBA was significantly improved (P = 0.006). There was a high incidence of hepatitis (three of the 15 patients) and of transient disturbances of liver function (nine of 15) during the 15-month observation period.

To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.

We randomized 96 postmenopausal women with metastatic breast carcinoma to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone. Before randomization, women were stratified according to disease-free interval, site of dominant disease, and estrogen-receptor status. Of 40 evaluable women treated with AG and hydrocortisone, 53 per cent had objective responses, as compared with 45 per cent of 29 women undergoing surgical adrenalectomy (P value not significant). Responses lasted a mean of 17.2 months in the medical group and greater than 17.1 months in the surgical group (not significant). Estrogen levels fell similarly in response to either treatment, whereas AG and hydrocortisone preserved androgen production. A null hypothesis tested the single question asked by this study: "Is surgical adrenalectomy superior to treatment with AG and hydrocortisone?" Rejection at significance levels of P = 0.01 and P = 0.07 for differences of 20 per cent and 10 per cent, respectively, suggested that medical therapy with AG and hydrocortisone may be logically chosen in place of surgical adrenalectomy.

The antiarrhythmic efficacy and safety of oral flecainide acetate were assessed during a controlled, short-term dosage-maintenance study. Thirteen patients with chronic ventricular ectopy entered a placebo control period, and 11 with persistent, frequent (greater than 600 per 12 hours) premature ventricular complexes (PVCs) advanced to drug therapy. Of 10 patients completing a trial of different doses, nine responded completely, with a mean PVC suppression of 98,3 per cent. Repetitive PVCs were eliminated. The mean effective dose was 189 mg per 12 hours, and the effective plasma concentration before administration of a dose averaged 635 ng per milliliter. One patient responded partially (68 per cent of PVCs suppressed). Flecainide continued to be effective and well tolerated at the end of a two-week outpatient trial in the nine complete responders, maintaining an average PVC suppression of 94.6 per cent. The PR and QRS intervals were mildly prolonged. The echocardiographic ejection fraction was unchanged during treatment. The elimination half-life was long - 18.8 +/- 3.8 hours. Flecainide thus appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics.

Within the past 15 years, regional neonatal-intensive-care programs have been introduced and have expanded rapidly. The efficacy of some of the individual interventions that constitute neonatal intensive care has been validated in randomized, controlled clinical trials. It is therefore generally assumed that neonatal-intensive-care programs that incorporate these maneuvers are effective in reducing death and disability. However, the overall effectiveness of these programs has not been tested experimentally. Moreover, much of the non-experimental evidence supporting their value is based on the experience of referral units and does not measure the impact on the populations they serve. A definitive economic evaluation of neonatal intensive care has not yet been reported, despite the high cost of such programs. We conclude that neonatal-intensive care programs require further evaluation with rigorous scientific methods.

Prolonged bed rest after myocardial infarction is thought to result in deconditioning, manifested by increased heart-rate and blood-pressure responses to exercise and decreased functional capacity. We studied the effects of early, supervised exercises in preventing deconditioning after acute myocardial infarction. Eighty-four patients were randomized to a control group and 174 to an exercise group. Enrollment in the exercise program occurred an average of 4.5 days after admission (range, one to nine). Discharge from the hospital occurred an average of 10.3 days after admission in the control group and 10.4 days in the exercise group. Most patients had a low-level treadmill test on the day before hospital discharge. There were no differences between the two groups in the clinical, hemodynamic, or electrocardiographic responses to the treadmill test. Incidences of complications and deaths (one death in each group) during hospitalization were not significantly different in the two groups, although six patients (3 per cent, all in the exercise group) required cardiac surgery--four because of recurrent chest pain and two because of rupture of heart muscle. Thus, we were unable to demonstrate any significant beneficial or deleterious effects of an early, in-hospital exercise program.