To evaluate the interaction between the antibiotic rifampin and the anticoagulant warfarin during chronic therapy, eight normal subjects were given daily doses of warfarin for 21 days to achieve therapeutic hypoprothrombinemia. Daily blood samples were analyzed for one-stage prothrombin activity and for warfarin content spectrophotometrically and chromatographically. One month later, the same warfarin dose was repeated plus rifampin, 600 mg a day orally. For the last 10 days of every experiment, there was a highly significant lessening of both the hypoprothrombinemic effect (P less than 0.001) and the blood levels of warfarin (P less than 0.001). No significant difference in the warfarin levels was found between the spectrophotometric and chromatographic methods. It is concluded that rifampin markedly decreases the hypoprothrombinemic effect of warfarin during long-term therapy by enhancing its elimination from plasma. This conclusion was reinforced by finding increased amounts of warfarin metabolites in urine and stool.

Response to therapy, renal function, and mortality were analyzed in a prospective study of 249 men with bacteriuria followed for up to 10 years. All patients received initial organism-specific antibiotic therapy followed by 2 years of continuous treatment with sulfamethizole, nitrofurantoin, methenamine mandelate, or placebo. Continuous therapy with active drugs delayed recurrence of bacteriuria and reduced acute clinical exacerbations of infection. Patients with pure Escherichia coli bacteriuria, normal intravenous pyelogram, no previous therapy, and a normal prostate had a good prognosis with short-term antibiotic therapy alone. The presence of prostatic or upper urinary tract calculi, pyelonephritic scars, or mixed or enterococcal infections predicted a poor bacteriologic prognosis. In the absence of severe urologic disease or concomitant noninfectious renal disease no patients with persistent bacteriuria developed renal failure. Continuous antibiotic therapy is of value in selected male patients with bacteriuria in reducing recurrence and acute clinical exacerbations of urinary tract infection.

Cytosine arabinoside (cytarabine) was evaluated in a randomized double-blind controlled study for the treatment of localized herpes zoster. Cytarabine was administered subcutaneously in a dose of 50 mg/m-2 body surface area once daily for 4 days, always within 14 days of onset of the first symptom and usually within 7 days. Thirty patients given cytarabine and 30 patients given placebo were well matched with respect to age, sex, and length and severity of presenting rash and pain as well as underlying disease. There was no difference in the rate of disappearance of pain or rash in either treatment group. More patients given cytarabine than patients given placebo had minimal pain and significantly more cytarabine-treated patients had persistence of neurological symptoms at 6 months' follow-up. Acute side effects, though mild, were significantly increased in the cytarabine-treated patients especially with respect to nausea and vomiting and decrease in platelet count. Cytarabine administered in this dose subcutaneously had no beneficial effect and was associated with mild side effects and persistence of neurological symptoms.

Automated feedback control methods were applied to a medical problem, in a computer program that used measured serum digoxin concentrations (as feedback) to predict future concentrations and to achieve desired concentrations. The system was validated by comparing its ability with the corresponding ability of physicians to regulate digoxin dosage. The prospective, randomized study included 51 patients. In the presence of varying amounts of feedback (serum digoxin concentration) information, the computer always predicted future digoxin concentrations as accurately as did physicians. For both computer and physician, the decrease in the prediction errors when two concentrations were known against that when no concentrations were known was significant: mean absolute error decreased from 0.40 to 0.25 ng/ml for the physicians and from 0.45 to 0.27 ng/ml for the computer. Thus the computer system is capable of simulating and reproducing a sophisticated aspect of physician behavior: "learning" about individual patient responses. The computer achieved desired concentrations more accurately than did physicians, especially when two or more previous digoxin concentrations were abailable (mean absolute achievement error for computer, 0.28 ng/ml; for physicians, 0.50 ng/ml).

Alternate-day corticosteroid therapy was compared with two daily corticosteroid regimens for the treatment of giant cell arteritis. In a prospective study 60 patients with this disease were randomly assigned to three treatment groups: group A, 15 mg of prednisone every 8 hours; group B, 45 mg of prednisone every morning; and group C, 90 mgof prednisone every other morning. After 1 month of treatment, the arteritis seemed to be completely suppressed in 18 patients in group A and 16 in group B but in only 6 in group C. In the 14 other patients in group C, the continuing symptoms were cyclic and developed during the day steroids were not given. By changing to a daily regimen, the arteritis was controlled in most patients in group C. Adverse reactions to prednisone were noted frequently in groups A and B but rarely in group C.

Reverse isolation and prophylactic oral nonabsorbable antibiotics were evaluated among 64 consecutive noninfected adults with acute nonlymphocytic leukemia admitted for remission induction. Patients were randomly allocated to laminar air flow room reverse isolation with oral nonabsorbable antibiotics (LAF plus A), routine hospital ward care with antibiotics (W plus A), or ward care alone (W). The LAF plus A patients had a significantly decreased incidence of total infection, bacteremias, pneumonias, rectal abscesses, urinary tract infection, and pharyngitis. Infectious deaths were reduced in the LAF plus A group and the time to the first infection or to fatal infection was delayed. The W plus A patients who regularly ingested the antibiotics had a reduction in infections similar to that of the LAF plus A patients but those who could not tolerate the antibiotics had an incidence of infection comparable to the ward patients. The LAF plus A and the W plus A patients also had higher complete remission rates and longer median survival than the unprotected ward patients.

Thirty-four patients with severe delirium tremens were allocated randomly to treatment with paraldehyde (10 ml rectally very 30 minutes) or diazepam (10 mg then 5 mg intravenously every 5 minutes) until they were calm but awake. Diazepam-treated patients became calm in one half the time needed to calm patients with paraldehyde. Half of the patients had delirium tremens in association with pneumonia, pancreatitis, or alcoholic hepatitis; these patients required twice as much paraldehyde or diazepam for initial calming as patients with delirium tremens alone. Maintenance of a calm state was accomplished easily with either diazepam, intramuscularly, or paraldehyde, rectally. Adverse reactions occurred in nine patients, all of whom had been treated with paraldehyde; these patients had greater degrees of fever, tachypnea, and tachycardia and required three times longer for initial calming than patients without adverse reactions. Diazepam given under this regimen is a safe and effective sedative for management of combative patients with severe delirium tremens.