Effects on anginal symptoms of sudden withdrawal of large doses of propranolol or placebo were evaluated in 20 patients in a double-blind crossover efficacy trial requiring sudden cessation of the agent. With propranolol, 160 to 320 mg per day for six and 12 weeks, no patients had increased angina or nitroglycerin use, and there were no hospitalizations or deaths. However, within two weeks of discontinuance of propranolol, untoward ischemic events developed in 10 patients. Six had serious withdrawal complications: intermediate coronary syndrome in three, and ventricular tachycardia, fatal myocardial infarction, and sudden death in one each. In four patients discontinuance of placebo increased anginal symptoms; in the remaining 10, ischemic symptoms were not provoked. The rebound phenomenon was related to degree of pre-propranolol angina and relief of pain by the agent. Thus, chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal.

Forty patients, randomly assigned to an experimental and a control group, participated in a double-blind study to assess the effectiveness of acupuncture in reducing chronic pain associated with osteoarthritis. The experimental group received treatment at standard acupuncture points, and the control group at placebo points. Analysis before and after treatment showed a significant (P less than 0.05) improvement in tenderness and subjective report of pain in both groups as evaluated by two independent observers and in activity by one observer. Comparison of responses to treatment between the two groups showed no significant (P greater than 0.05) difference. Thus, both experimental and control groups showed a reduction in pain after the treatments. These results may reflect the natural course of illness, and various attitudinal and social factors.

Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.

The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), "atypical angina" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients.

We compared the surgical and medical managements of reflux esophagitis in a prospective managements of reflux esophagitis in a prospective clinical trial. Patients wissigned to surgical (15 patients) and medical (16 patients) groups. A non-randomized medical group (20 patients) was also studied. Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response. A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients. Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy. The histologic appearance of the squamous mucosa, however, remained abnormal in all but one patient. In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux. The relative increases in pphincter pressure to graded increases in gastric pressure, however, remained abnormal in all but one patient.

Improved nitrogen sparing was demonstrated in 20 patients undergoing either head-and-neck operations or abdominal explorations, who were randomized to receive intravenously either 3 per cent amino acids or 5 per cent dextrose. Infusions were started immediately after operation and continued for a minimum of six days. In patients receiving amino acids, as compared with those receiving dextrose, mean cumulative six-day nitrogen losses were significantly lower (42 plus or minus 5 g [S.E.M.] and 74 plus or minus 7 g, respectively--P smaller 0.005), as were serum glucose and insulin levels, but beta-hydroxybutyrate, acetoacetate and blood urea nitrogen were significantly elevated. No adverse effects of the amino acid solution were observed. The presumed mechanism for improved nitrogen sparing is a decrease in serum glucose and insulin levels, allowing greater endogenous fat mobilization and utilization, thus sparing lean body mass.

Two neuropsychologic studies were performed to determine the long-term effects of "prophylactic" cranial or craniospinal irradiation on the psychologic and neurologic functions of children with acute lymphocytic leukemia. In a prospective study, 34 patients with leukemia who received either craniospinal irradiation or cranial irradiation combined with intrathecal methotrexate were evaluated by standardized neurologic and psychologic examinations before and after irradiation. Their performance was compared with that of 27 controls who received irradiation to parts of the body other than the cranium. In a retrospective study, 11 patients with leukemia receiving prophylactic craniospinal irradiation and 12 controls with the disease not receiving such therapy were followed from the second year after either irradiation or the initial hematologic remission. Eighteen months after irradiation in the prospective study and four years after irradiation in the retrospective study, no noteworthy neurologic or psychologic differences were found between subjects and controls.

To develop an intravenous bile acid tolerance test that might be useful for detecting impaired liver function or liver injury, the plasma disappearance of intravenously injected cholyglycine was characterized in healthy man by a radiommunoassay, specific for conjugates of cholic acid, on serial samples of venous blood. Cholylglycine disappearance was rapid (mean half-life plus or minus S.E. equals 2.6 plus or minus 0.1 minutes) and of first-order kinetics; the rate of disappearance was independent of dose between 2 and 15 mumoles per kilogram of body weight. A dose of 5 mumoles per kilogram was selected as an optimal dose, and its clearance was defined in 45 healthy subjects. After intravenous injection of this dose, conjugates of cholic acid increased 10-fold, but in all subjects the concentration of these bile acids had returned to 1 muM (the upper limit of normal, fasting state) by 10 minutes. No side effects were observed.

Serum Haemophilus influenzae Type b (HITB) anticapsular antibodies were induced in adult volunteers by feeding of either of two strains of a cross-reacting Escherichia coli 075:K100:H5. In all the fed volunteers colonization for a finite period lasting up to eight weeks occurred, without adventitious reactions. Nine of 14 normal volunteers and one of two volunteers previously immunized with the Type 6 H.influenzae polysaccharide responded with a greater than twofold increase in serum Type 6H. influenzae antibodies. These antibodies induced by Esch. coli were specific for the capsular polysaccharide and had bactericidal activity. The safety of this procedure, the comparable results in laboratory animals and the identification of other cross-reacting strains of Esch. coli with meningococcal and pneumococcal capsular polysaccharides suggest that colonization with these nonpathogenic organisms at birth may provide a general method of preventive immunization to diseases caused by encapsulated bacteria.

Among 100 consecutive patients receiving heparin in therapeutic dosage, major bleeding occurred in 21, and minor bleeding in 16. Two patients died from bleeding, and two had recurrent pulmonary embolism. Major bleeding occurred in 21% when therapy was regulated with whole-blood clotting time and in 20% when heparin was given without clotting tests. In a subsequent prospective trial patients received heparin by intermittent intravenous injection with or without laboratory control according to the partial thromboplastin time or continuously by intravenous infusion. Recurrent thromboembolism occurred once in each group. Major bleeding was seven times more frequent with intermittent injection than with continuous infusion. Control with the partial thromboplastin time did not prevent major bleeding in patients receiving intermittent injections. With continuous infusion, one-fourth less heparin was required than with intermittent injections. Administration of heparin by continuous infusion appears safer than intermittent injection with or without laboratory control and is no less effective for prevention of thromboembolism.

Thirty-five infants weighing less than 1500 g at birth were fed four commercial formulas (A-D) varying in polyunsaturated fatty acid composition (32 per cent linoleic acid in A and B and 12 per cent linoleic acid in C and D) and in iron content (smaller than 1.0 in A and B; 12 to 12 mg per liter in B and D). Infants receiving formula B showed significantly lower hemoglobins (p smaller than 0.01) and higher reticulocyte counts (p smaller than 0.005) than infants fed the other three formulas. Infants receiving the two formulas with higher concentrations of unsaturated fatty acids (A and B) showed significantly greater hydrogen-peroxide-induced hemolysis (p smaller than 0.001) than those given diets containing lower amounts. Infants in groups A and B also had lower serum tocopherol concentrations. Infant red-cell membranes are altered by the increased amounts of polyunsaturated fatty acids and iron in the diet. It appears that the development of vitamin E deficiency anemia occurs in infants receiving iron supplementation.