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).

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.

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 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.

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.

The role of anti-HBs antibody in reducing the probability of hepatitis after accidental exposure to serum from patients with hepatitis or carriers of HBs Ag was studied prospectively among 712 medical workers. One fourth of the workers were anti-HBs positive and less than one per cent of them developed hepatitis, in contrast to 11 per cent among those who were anti-HBs negative. Three coded immune-serum globulin preparations of varying anti-HBs titer were randomly assigned. Among 251 persons passively immunized with globulin having a conventionally low anti-HBs titer, hepatitis developed in 17 (seven per cent) within six months. Comparative rates among those receiving intermediately high titer and high titer globulin, respectively, were five per cent (11 of 208) and two per cent (5 of 253). The significantly lower incidence among the latter (P less than 0.05) was offset by six additional cases, all in recipients of high titer globulin, detected when follow-up was extended to nine months.

A randomized, double-blind, multicenter study of hepatitis prevention by immune serum globulin with high anti-HBs titer ("hepatitis B immune globulin") was carried out among 318 new patients and 296 staff members of renal dialysis units. Three milliliters of high titer globulin, repeated at four months, was compared with equal doses of intermediate or normal titer globulin. Among staff members, the cumulative percentages developing hepatitis or HBs Ag, or both, within eight months were 6.9, 11.7, and 11.1 in the high, intermediate, and normal titer groups respectively. The lower incidence associated with high titer globulin was not significant (P greater than 0.05). However, among the patients the respective percentages were 7.9, 21.3, and 23.1 and the lower incidence in the high titer globulin group was significant.

Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials.

Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents. Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, "double-blind" experiment. All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable. For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001). No patient vomited while experiencing a subjective "high". Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.

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.