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.

We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes.

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 the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.

Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.

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.