To evaluate hyaluronidase's effect in reducing post-infarction myocardial necrosis, we randomized 91 patients with anterior infarction to control (45) or to hyaluronidase-treatment (46) groups. A 35-lead precordial electrocardiogram was recorded on admission and seven days later. Hyaluronidase was administered intravenously after the first electrocardiogram and every six hours for 48 hours. QRS-complex changes were analyzed to assess the drug's effect. Precordial sites with ST-segment elevation (larger than or equal to 0.15 mV) on the initial electrocardiogram that retained an R wave were considered vulnerable for the development of electrocardiographic signs of necrosis. The sum of R-wave voltages of vulnerable sites fell more in the control group than in the hyaluronidase group (70.9 +/- 3.6 per cent [+/- 1 S.E.M.] vs 54.2 +/- 5.0 per cent P less than 0.01). Q waves appeared in 59.3 +/- 4.9 per cent of the vulnerable sites in control versus 46.4 +/- 4.9 per cent in hyaluronidase-treated patients (P less than 0.05). Thus, hyaluronidase reduced the frequency of electrocardiographic signs of myocardial necrosis.

Spectinomycin and tetracycline are alternative drugs to penicillin in the treatment of gonorrhea. To compare the efficacy of these agents and their propensity to select resistant gonococci, we treated 4043 patients randomly with either 2 or 4 g of spectinomycin once or 9 g of oral tetracycline for four days. Minimum cure rate for anogenital gonorrhea was 94 per cent with either drug. Oropharyngeal infection responded poorly to spectinomycin in men, with failure of therapy in six of 11. Postgonococcal urethritis in men was less common after tetracycline than after spectinomycin (P less than 0.005). Spectinomycin failure was not related to drug resistance. Tetracycline failure correlated with resistance (P less than 0.0002); one fifth of the isolates resistant to 1.0 mug per milliter of tetracycline were not eradicated. For several reasons, including the appearance of beta-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea. Spectinomycin and tetracycline are equally acceptable alternatives, each with distinct advantages and disadvantages.

In a double-blind, single-dose study, dextroamphetamine combined with morphine was compared with morphine alone to determine the relative efficacy of the combination given intramuscularly for postoperative pain. Each of 450 patients received one treatment of morphine sulfate (3, 6 or 12 mg) with dextroamphetamine (0, 5 or 10 mg). Analgesia, as measured by the patients' subjective responses to questions about relief of pain, was augmented when dextroamphetamine was given with morphine; the combination of dextroamphetamine, 10 mg, with morphine was twice as potent as morphine alone, and the combination with 5 mg was 1 1/2 times as potent as morphine. In simple performance tests, and in measures of side effects, dextroamphetamine generally offset undesirable effects of morphine (sedation and loss of alertness) while increasing analgesia. Effects on blood pressure, pulse and respiratory rate were minimal.

In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.

We prospectively randomized 27 granulocytopenic patients who experienced a total of 30 episodes of gram-negative septicemia. The control group received an appropriate antibiotic regimen alone, whereas the "transfusion" group received infusions of granulocytes in addition to the antibiotics. Five of 14 controls survived, and 12 of 16 in the transfusion group survived, and 12 of 16 in the transfusion group survived (P less than 0.04). An important factor in the outcome of treatment was the recovery of bone-marrow function (return of peripheral granulocyte count greater than or equal to 1000 per microliter). Eighty-three per cent (five of six) of the control group and all (four of four) of the transfusion group with recovery of granulocyte levels survived the episode of sepsis. In contrast, none of the eight control patients, as compared to 67 per cent (eight of 12) of the transfusion group, survived persistent granulocytopenia (P less than 0.005). Granulocyte transfusions appear to complement appropriate antibiotic treatment of gram-negative-septicemia due to granulocytopenia.

Since metoclopramide increases lower-esophageal-sphincter pressure in patients with gastroesophageal reflux, we compared the effects of metoclopramide, 10 mg four times daily, with those of placebo on symptoms in 31 patients with chronic heartburn. Eighteen patients completed a random-order, double-blind crossover study of two consecutive eight-week periods. The final 13 patients crossed over only if their symptoms were not substantially improved after the first eight weeks. Response of low-esophageal-sphincter pressure to metoclopramide did not correlate significantly with symptomatic improvement. After the metoclopramide treatment period, mean basal pressure was unchanged from values before study. In both treatment periods, metoclopramide-treated patients had significantly more symptomatic improvement than the control group (P less than 0.05).

Amikacin or gentamicin was used to treat 174 patients with suspected severe gram-negative infections in a prospective, randomized, double-blind trial. Enteric gram-negative bacilli were pathogenic in 71 cases (39 treated with amikacin, and 32 with gentamicin). Amikacin was effective in 10 to 12 bacteremias, 21 of 24 urinary-tract infections, two of five pneumonias and four of six other serious tissue infections. The toal favorable response rate was 77 per cent for amikacin and 78 per cent for gentamicin. Nephrotoxicity and auditory toxicity could be evaluated in 124 and 67 cases respectively. Definite nephrotoxicity developed in five of 62 (8 per cent) receiving amikacin and seven of 62 (11 per cent) given gentamicin, and possible nephrotoxicity developed in four patients in both groups. Definite ototoxicity developed in four patients in both groups. Definite otoxicity developed in two of 34 (6 per cent) and three of 30 (10 per cent) respectively. These differences were not statistically significant (by chisquare analysis, P greater than 0.05). The results indicate that amikacin is effective against severe gram-negative infections and is not more and not less ototoxic or nephrotoxic than gentamicin.

Danazol, an androgen derivative, was evaluated for its effectiveness in preventing attacks of hereditary angioedema in a double-blind study with nine patients. Of 47 placebo courses, 44 ended with attacks, but during 46 danazol courses only one attack occurred. Side effects were minimal, and virilization was not observed in the women studied. C1 esterase inhibitor levels increased three to four times, and levels of the fourth component of complement (C4) increased 15 times. These changes began during the first day of therapy and were maximal by one to two weeks. After therapy was stopped, C1 esterase inhibitor and C4 levels rapidly decreased. Danazol effectively prevents attacks in hereditary angioedema and acts to correct the underlying biochemical abnormality.

Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).

To determine whether intravenous 3.5 per cent amino acid solution enhanced the rate of albumin synthesis in postoperative patients, we measured the albumin synthesis rate by the (14C) carbonate technic in 10 patients on the fourth day after elective gastrointestinal-tract operations. Five patients were randomized to receive a 3.5 per cent solution of essential and non-essential amino acids, and five to receive 5 per cent glucose. A mean (+/-S.E.M.) of 75.0+/-2.0 per day of amino acids or 111.0+/-12.4 glucose was given. In the amino acid group the mean (+/-S.E.M.) albumin synthesis rate was 237+/-24 mg per kilogram per day, in comparison to 157+/-23 in the glucose group (P less than 0.05). The infused amino acids were apparently more effective than plain glucose in promoting albumin synthesis.

To evaluate earlier observations, including our own, showing usefulness of vitamin C for managing the common cold, we performed a double-blind trial of vitamin C versus placebo in 868 children. There was no difference in number becoming ill (133 versus 129), number of episodes (166 versus 159) or mean illness duration (5.5 versus 5.8 days) between the groups. Children receiving vitamin C had fewer throat cultures yielding beta-hemolytic streptococcus (six versus 13, P less than 0.10), but no difference in overall complicated illness rate (24 versus 25). Plasma ascorbic acid levels were higher in the vitamin group 24 to 26 hours after supplementation (1.28 versus 1.04 mg per 100 ml, P less than 0.01). Children with high plasma ascorbic acid concentrations had longer mean illness (6.8 versus 4.0 days, P less than 0.05) than those with low levels. Vitamin C does not seem to be an effective prophylactic or therapeutic agent for upper respiratory illness.