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.

To investigate hydroxocobalamin's role in preventing cyanide intoxication from sodium nitroprusside, we studied two groups of patients. One group received nitroprusside alone, and the other received nitroprusside and hydroxocobalamin. Red-cell and plasma cyanide levels were 83.44 +/- 23.12 and 3.51 +/- 1.01 microgram per 100 ml after nitroprusside alone and were 33.18 +/- 17.29 and 2.18 +/- 0.65 microgram per 100 ml after nitroprusside plus hydroxocobalamin. Acidosis developed in patients with red-cell cyanide levels higher than 75 microgram per 100 ml. When hydroxocobalamin infusion was stopped before sodium nitroprusside infusion was discontinued, blood cyanide levels and base deficit increased in a manner similar to that in the untreated group. The dose of nitroprusside used in each group did not differ statistically. These data show that hydroxocobalamin prevents cyanide transfer from red cells and plasma to tissue after nitroprusside metabolism, and thereby prevents cyanide toxicity from large intravenous doses of the drug.

Thirty-two asymptomatic patients with acute lymphocytic leukemia, who had received prophylactic cranial radiation (2400 rads) and either intrathecal methotrexate or cytosine arabinoside were studied by computed tomography of the brain 19 to 67 months after initiation of prophylaxis. Seventeen of 32 (53 per cent) had one or more abnormal findings. Dilatation of the ventricles (eight patients) and widening of the subarachnoid spaces (nine patients) were equally distributed among patients in both intrathecal-chemotherapy groups. Areas of decreased attenuation coefficient (hypodense, abnormally radiolucent regions) (four patients) and intracerebral calcification (one patient)--lesions previously described in methotrexate leukoencephalopathy--were found only in those who had received intrathecal methotrexate. Mild central-nervous-system dysfunction was detected in seven patients but did not correlate with the presence of tomographic abnormalities. Nevertheless, these tomographic findings may represent preclinical lesions. The unexpectedly high prevalence of such abnormalities contrasts with the essentially normal tomographic findings in a control group with acute lymphocytic leukemia who received no central-nervous-system prophylaxis. These results suggest that alternative approaches to such prophylaxis be considered.

We performed a randomized double-blind study to determine the efficacy of doxycycline (100 mg daily) in preventing travelers' diarrhea among 39 Peace Corps volunteers during their first five weeks in Kenya. The volunteers took either doxycycline or placebo for three weeks and were observed for an additional two weeks. Nine of 21 taking placebo and one of 18 taking doxycycline had travelers' diarrhea during the treatment period (P = 0.012). The protection seemed to persist for at least one week after the drug was stopped. Enterotoxigenic Escherichia coli was the only pathogen isolated from the placebo group, but was not detected in persons taking doxycycline. None of these organisms were resistant to doxycycline or tetracycline, whereas resistance to tetracyclines and other antibiotics was common among the nonenterotoxigenic Esch. coli. We conclude that doxycycline effectively prevented most episodes of travelers' dirrhea.

Urine specimens from 61 women with symptoms of cystitis who are infected with amoxicillin-sensitive organisms were examined by the antibody-coated bacteria assay. Patients with negative assays were randomized to receive either a single 3-g oral dose of amoxicillin or 10 days of amoxicillin, 250 mg, given by mouth four times per day (conventional therapy). Patients with positive assays received conventional therapy. All 43 patients without antibody-coated bacteria in the urine, 22 given single-dose therapy and 21 treated conventionally, were cured of their infection. Of 18 patients with antibody-coated bacteria, nine relapsed within one week of completion of conventional therapy. The results of the antibody-coated bacteria assay appear to predict the therapeutic response: both single-dose and conventional amoxicillin therapy are completely successful in patients with negative assays; in contrast, conventional therapy is ineffective in 50 per cent of patients with positive assays.

In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.

The Anturane Reinfarction Trial is a randomized, double-blind, multicenter clinical trial comparing sulfinpyrazone (200 mg four times a day) and placebo in the prevention of cardiac mortality among patients with a recent documented myocardial infarction. Results represent data accumulated on 1475 cligible patients entered 25 to 35 days after myocardial infarction and followed for an average of 8.4 months. The data reflect excellent randomization, compliance with therapy and tolerance of the drug. All 69 deaths were a cardiovascular nature (68 cardiac and one cerebrovascular). For cardiac deaths, the annual death rate was 9.5 per cent in the placebo group and 4.9 per cent in the sulfinpyrazone group, representing an observed reduction of 48.5 per cent (P = 0.018). The annual sudden-cardiac-death rate was 6.3 per cent for the placebo and 2.7 per cent for the sulfinpyrazone group, representing a 57.2 per cent reduction in sudden-cardiac-death rate (P = 0.015). Sulfinpyrazone appears to be effective in reducing cardiac deaths during the first year after myocardial infarction.

We conducted a prospective study in a prepaid primary-care practice (health-maintenance organization) of a system in which nurses and physician assistants used protocols, and compared the efficiency and costs of this "new-health-practitioner" protocol system to a physician-only nonprotocol system. In five months, we studied 472 patients with any of four common acute complaints--respiratory infections, urinary and vaginal infections, headache, and abdominal pain; a subset of 203 patients was randomly allocated between the two systems. In the new-health-practitioner system physician time per patient was reduced by 92 per cent, from 11.8 to 0.9 minutes, and average visit costs--including practitioner time and charges for laboratory tests and medications--were 20 per cent less (P = 0.01). We conclude that this protocol system saves physician time and reduces costs.

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.

Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.

Overweight patients with uncomplicated essential hypertension were followed up biweekly for six months: 24 not receiving antihypertensive-drug therapy (Group I) and 83 on regular but inadequate (despite drug manipulation) antihypertensive-drug therapy (Group II). All patients in Group I and 57 randomly selected patients from group II (IIa) participated in a weight-reduction program. The remaining 26 from Group II (IIb) did not receive a dietary program. Salt intake was in the normal range in all three groups. All patients on the dietary program lost at least 3 kg (mean, 10.5 kg), and all but two showed a meaningful reduction in blood pressure; 75 per cent of Group I and 61 per cent of Group IIa returned to normal blood pressure. The weight and blood-pressure reductions were highly significant (P less than 0.001), were present in both sexes and all ages, and were directly associated. In Group IIb, no significant change in blood pressure or weight occurred (P greater than 0.30).

In a randomized, double-blind, placebocontrolled study to evaluate the efficacy of trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk for this pneumonia over a two-year period. Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection P less than 0.01). Bacterial sepsis, pneumonia other than that caused by P. carinii, acute otitis media, upper-respiratory-tract infections, sinusitis and cellulitis occurred less frequently in recipients of the drug than in the placebo group (P less than 0.01 in each case). Oral candidiasis was the only adverse effect ecountered from trimethoprim-sulfamethoxazole administration. The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis.

Since the last comprehensive review of anticoagulation in acute myocardial infarction four additional randomized control trials have been reported. The overwhelming majority of all trials favored anticoagulation. Rates of thromboembolism were higher in the control, and hemorrhagic complications in the anticoagulated group. Pooling of all randomized control trials gives mean case fatality rates of 19.6% for the control and 15.4% for the anticoagulated group, a relative reduction of 21% (P less than 0.05 or less than 0.001, depending on the analytic method). Five of six randomized control trials reported "no effect" because the difference favoring anticoagulation was not statistically significant. However, sample sizes in these "negative" papers were too small to protect against missing a 21% reduction in true case fatality rate due to anticoagulation (beta greater than 0.10). All patients who present no specific contraindication should receive anticoagulants during hospitalization for infarction.