We undertook a randomized clinical trial to evaluate the efficacy of chest physiotherapy and intermittent positive-pressure breathing in the treatment of pneumonia. The diagnosis of pneumonia required a compatible clinical history and x-ray confirmation. A total of 54 patients were assigned to treatment and control groups and were similar in age, smoking history, underlying lung disease and prior antibiotic treatment. Antibiotic therapy, guided by Gram stain and sputum and blood cultures, was similar in both groups. Chest physiotherapy, consisting of postural drainage, percussion and vibration, was given concurrently with intermittent positive-pressure breathing with use of racemic epinephrine every four hours. There was no statistically significant difference in duration of fever, extent of radiographic clearing, duration of hospital stay and mortality between the control and treated groups. Chest physiotherapy and intermittent positive-pressure breathing do not hasten the resolution of pneumonia.

We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P less than 0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions.

We studied the effect of vitamin E on the development of bronchopulmonary dysplasis in neonates with respiratory-distress syndrome. Twenty infants received vitamin E administered intramuscularly during the acute phase of the syndrome, and 20 infants served as controls. Administration of vitamin E significantly increased the serum vitamin E concentration. Nine vitamin-treated and 13 control patients required supplemental oxygen for longer than 250 hours; all were treated with positive-pressure ventilation and endotracheal continuous distending airway pressure. Six of those 13 controls had x-ray changes consistent with bronchopulmonary dysplasia, and four died. None of the nine vitamin-treated patients had changes characteristic of bronchopulmonary dysplasia (P = 0.046), and all survived. Administration of vitamin E during the acute phase of the respiratory-distress syndrome appears to modify the development of bronchopulmonary dysplasis.

To investigate the efficacy of antibiotic irrigation in preventing catheter-associated urinarytract infection, we carried out a randomized controlled trial of a neomycin-polymyxin irrigant administered through closed urinary catheters. Eighteen of 98 (18 per cent) of the patients not given irrigation became infected, as compared with 14 of 89 (16 per cent) of those given irrigation, yielding a mean daily incidence of 5 per cent in each group. The distribution of organisms and their antibiotic sensitivities differed in the two groups, the organisms from the patients with irrigation being more resistant. Disconnections of the catheter junctions were associated with high rates of infection. The rate of disconnections of the junctions in the group given irrigation was almost twice that of the control group because of the presence of the extra junction on overall infection rate represents the result of two opposing phenomena: the increased entry of organisms and the suppression of a portion of them.

The role of glucagon in diabetes was studied in four patients with juvenile-type diabetes during continuous insulin infusion and a diet containing 150 g per day of carbohydrate. During insulin alone, plasma glucagon, measured at two-hour intervals, averaged 182 +/- 34 pg per milliliter, glucose 269 +/- 11 mg per deciliter, glucose excretion 52 +/- 8 g per 24 hours, ketone excretion 1.3 +/- 0.3 mmol per 24 hours, and urea nitrogen 12 +/- 2 g per 24 hours (mean +/- S.E.M.). Somatostatin (2 mg per day) lowered glucagon to 60 +/- 13 pg per milliliter, glucose to 111 +/- 17 mg per deciliter, glucose excretion to 1 +/- 0.7 g per 24 hours, ketone excretion to 0.5 +/- 0.2 mmol per 24 hours and urea nitrogen excretion to 8 +/- 2 g per 24 hours. Replacement of glucagon raised glucagon to 272 +/- 30 pg per milliliter, glucose to 202 +/- 20 mg per deciliter, glucose excretion to 14 +/- 7 g per 24 hours, ketone excretion to 0.8 mmol per 24 hours and urea nitrogen excretion to 11 +/- 2 g per 24 hours. In a subsequent study, similar improvement occurred on a diet of 30 g of carbohydrate daily, when absorption of dietary glucose was negligible. Hyperglucagonemia has an important role in diabetes; its correction reduces diabetic abnormalities to or toward normal.

Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively. Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy (P less than 0.01). The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy; one reacted to a subsequent sting. We conclude that venom immunotherapy is clinically superior to therapy on whole-body extract or placebo.

Five hundred and eighty-five patients with threatened stroke were followed in a randomized clinical trial for an average of 26 months to determine whether aspirin or sulfinpyrazone, singly or in combination, influence the subsequent occurrence of continuing transient ischemic attacks, stroke or death. Eighty-five subjects went on to stroke, and 42 died. Aspirin reduced the risk of continuing ischemic attacks, stroke or death by 19 per cent (P less than 0.05) and also reduced risk for the "harder," more important events of stroke or death by 31 percent (P less than 0.05), but this effect was sex-dependent: among men, the risk reduction for stroke or death was 48 per cent (P less than 0.005), whereas no significant trend was observed among women. For sulfinpyrazone, no risk reduction of ischemic attacks was observed, and the 10 per cent risk reduction of stroke or death was not statistically significant. No overall synergism or antagonism was observed between the two drugs. We conclude that aspirin is an efficacious drug for men with threatened stroke.

To assess the cause of nonspecific vaginitis, we performed a prospective case-control study of vaginal flora and a randomized unblinded trial of different therapies. Haemophilus vaginalis was isolated from 17 to 18 women with signs of vaginitis but only one of 18 normal matched controls (P less than 0.002). The concentration of anaerobic bacteria in vaginal washings also was increased in patients. Clinical improvement and eradication of H. vaginalis occurred in one of seven patients given sulfonamide vaginal cream, two of 15 given oral doxycycline, nine of 27 given oral ampicillin, and 80 of 81 given oral metronidazole. On the seventh day of therapy signs of nonspecific vaginitis persisted in 31 of 31 with, and in two of 92 without, persistent H. vaginalis infection (P less than 0.001). These data suggest the causal role of H. vaginalis in nonspecific vaginitis, possibly in concert with vaginal anaerobes. The widespread use of sulfonamide creams is inappropriate. Metronidazole is effective, but its efficacy must be weighed against its possible toxicity.

We tested the hypothesis that donor blood containing antibody to hepatitis B core antigen (anti-HBc) but lacking detectable hepatitis B surface antigen (HBsAg) and antibody (anti-HBs)might transmit Type B hepatitis by examining donor and recipient serums from a Veterans Administration study of post-transfusion hepatitis. Donor blood was available from three patients with Type B hepatitis and from one patient with hepatitis B virus infection (development of anti-HBs and anti-HBc) without symptomatic disease. All four had received 1 unit of blood with high titer of anti-HBc but lacking HBsAg and anti-HBs. In contrast, no such units had been transfused into nine patients with "immunization-like" response (development of anti-HBs without anti-HBc) or into 26 control patients. These data stress the importance of anti-HBc as an indicator of hepatitis B virus infection and support the hypothesis that high-titer anti-HBc-positive blood might be infectious.

To test the feasibility and effects of incorporating concurrent quality assurance (CQA) into the concurrent utilization reviews required by PSRO's, adherence to essential criteria of medical care and attainment of expected immediate outcomes were monitored prospectively in 5604 cases of seven conditions in 24 experimental and 26 control hospitals in five PSRO areas. CQA was not consistently associated with improved documentation in records, but was associated with slightly better adherence to treatment criteria in all five PSRO areas (P less than 0.03). Adherence to pooled documentation or treatment criteria was unrelated to outcomes. However, failure to adhere to disease-specific scientifically validated treatment criteria was associated with unsatisfactory outcomes in bacterial pneumonia (P less than 0.01) and acute myocardial infarction (P less than 0.02). CQA was professionally acceptable, technically feasible and compatible with PSRO reviews. Given adequate physician support, CQA can produce slightly greater adherence to treatment criteria. If the criteria are valid, adherence may lead to improved immediate outcomes in some diseases.

Prophylaxis by granulocyte transfusions against infection associated with granulocytopenia was studied in 69 patients receiving bone-marrow transplants for the therapy of hematologic neoplasia or aplastic anemia. Patients were randomized to receive or not to receive granulocyte transfusions when their circulating granulocyte levels fell to less than 200 per cubic millimeter during the period between transplantation and the development of graft function. During the first 21 posttransplant days, there were two local infections and no septicemias in 29 transfused patients. Seven local infections and 10 septicemias developed among the 40 controls. This protection was afforded by granulocytes collected by reversible leukoadhesion as well as by cells collected by continuous-flow centrifugation.

We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis and gastrointestinal bleeding. Twelve of the 49 control patients bled (P less than 0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory, failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration.

We tested the effect of human leukocyte interferon on early localized herpes zoster infections in three placebo-controlled, randomized double-blind trials involving 90 patients with cancer. There were no significant differences in pretreatment severity of infection or nature of underlying disease in the groups. Higher dosages of more purified interferon in the second and third trials produced a significant (P less than or equal to 0.01) decrease in cutaneous dissemination. No dissemination occurred in those receiving the highest dosage (5.1 x 10(5) U per kilogram per day) (P less than or equal to 0.025). The number of days of new-vesicle formation in the primary dermatome decreased (mean, 2.3 days, P less than or equal to 0.05) in this group. Treated patients had a trend toward less acute pain, and significantly (P less than or equal to 0.05) diminished severity of post-herpetic neuralgia, at the two highest dosage levels. Visceral complications were six times less frequent in interferon recipients. High-dosage interferon appeared effective in limiting cutaneous dissemination, visceral complications and progression within the primary dermatome.

To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine other had, in addition, a serum urea nitrogen level of over 100 mg per diciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P less than 0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia.