In a randomized crossover trial, 38 women with recurrent urinary tract infections were assigned to use either continuous prophylaxis with trimethoprim-sulfamethoxazole or intermittent self-administered therapy (single-dose trimethoprim-sulfamethoxazole taken for acute urinary symptoms). The infection rate for patients on prophylaxis was 0.2 episodes/patient-year compared with 2.2 infections/patient-year for patients on self-administered therapy (p less than 0.001). Thirty-five of thirty-eight symptomatic episodes diagnosed by patients as infection were confirmed microbiologically, and 30 of the 35 infections responded clinically and microbiologically to patient-administered therapy with single-dose trimethoprim-sulfamethoxazole. No complications were seen in the 5 patients in whom therapy failed. The annual costs of prophylaxis and self-therapy were similar ($256 and $239, respectively) and both were less expensive than conventional therapy in women having 2 or more infections per year. In selected women, self-therapy is efficacious and economical compared with conventional therapy or prophylaxis.

The amplitude of ventricular fibrillation found initially in 394 patients was compared to clinical and logistical findings at the time of cardiac arrest. Peak-to-peak amplitude averaged 0.55 +/- 0.25 mV; a very low amplitude (0.2 mV or less) or "fine" fibrillation was present in 66 patients (17%). The amplitude was not found to be related to clinical histories, but depended on the length of the period from collapse until start of basic life support (p = 0.004) and the delay until assessment by paramedics (p = 0.001). Survival rates were strongly associated with amplitude: only 4 patients (6%) with fine ventricular fibrillation survived, compared to 117 or 328 patients (36%) in whom the initial amplitude was higher (p less than 0.001). Patient outcome related to amplitude even after adjusting for clinical history and logistical delays (p less than 0.005). We conclude that fine ventricular fibrillation is in part the result of delay in initiation of treatment, and that fibrillation amplitude is a powerful indicator of outcome after cardiac arrest.

At six centers, 203 patients with stabilized hypoxemic chronic obstructive pulmonary disease were evaluated hemodynamically during a continuous or 12-hour oxygen therapy program. Neither oxygen therapy program resulted in correction or near-correction of the baseline hemodynamic abnormalities. The continuous oxygen therapy group did show improvement in pulmonary vascular resistance, pulmonary arterial pressure, and stroke volume index. The improvement in pulmonary vascular resistance was associated with improved cardiac function, as evidenced by an increase in baseline and exercise stroke volume index. The nocturnal oxygen therapy group showed stable hemodynamic variables. For both groups, changes in mean pulmonary artery pressure during the first 6 months were associated with subsequent survival after adjustment for association with the baseline mean pulmonary artery pressure. Continuous oxygen therapy can improve the hemodynamic abnormalities of patients with hypoxic chronic obstructive pulmonary disease. The hemodynamic response to this treatment is predictive of survival.

Impedance plethysmography is an accurate noninvasive method to test for proximal vein thrombosis, but it is insensitive to calf-vein thrombi. We randomly assigned patients on referral with clinically suspected deep-vein thrombosis and normal impedance plethysmographic findings to either serial impedance plethysmography alone or combined impedance plethysmography and leg scanning (which has been shown to be essentially as sensitive as venography) and compared the long-term outcomes. During the initial surveillance, deep-vein thrombosis was detected in 6 of 311 patients (1.9%) tested by serial impedance plethysmography alone and in 30 of 323 patients (9.3%) (most with calf-vein thrombi) tested by the combined approach (p less than 0.001). During long-term follow-up, no patient died from pulmonary embolism; but 6 patients (1.9%; 95% confidence limits, 0.7% to 4.2%) tested by serial impedance plethysmography developed deep-vein thrombosis compared with 7 patients (2.2%; 95% confidence limits, 0.9% to 4.4%) tested by the combined approach. Serial impedance plethysmography used alone is an effective strategy to evaluate such symptomatic patients.

Gentamicin and tobramycin were compared for cost effectiveness in the treatment of adult patients with serious infections in a general medical service. We used data from a randomized double-blind trial in which the only observed difference between the clinical effects of these aminoglycosides was the incidence of nephrotoxicity (26% with gentamicin and 12% with tobramycin). According to 1984 cost data, the combined average drug and nephrotoxicity costs per patient were $127 for tobramycin and $72 for gentamicin. An extensive sensitivity analysis--varying frequency and cost of nephrotoxicity, dialysis requirements, aminoglycoside acquisition costs, and length of hospitalization--showed gentamicin to be more cost effective than tobramycin, unless hospitalization is prolonged by an average of at least 15 days for patients with severe nephrotoxicity or at least 3 days for all patients with moderate or severe nephrotoxicity.

Two hundred twenty patients were randomly assigned to receive either ceforanide or cephalothin as perioperative antibiotic prophylaxis during cardiovascular surgery. More infections were seen among cephalothin recipients (8 deep, 32 total) than among ceforanide recipients (1 deep, 17 total). Among patients who had only coronary artery bypass grafting, more cephalothin recipients had infection than did ceforanide recipients (19 of 82 as opposed to 7 of 83; p = 0.001; relative risk, 2.7; 95% confidence interval, 1.22 to 6.18). The difference between the two regimens was attributable to fewer blood, wound, and urinary tract infections. Among patients who had other procedures, there was no difference in the efficacy of the two regimens. Cephalothin recipients who developed wound or blood stream infections had lower antibiotic levels in their atrial appendages than recipients not developing such infections (p = 0.02). If one assumes that cephalothin does not increase the risk of infection, then these data show that antibiotic prophylaxis prevents infection after coronary artery bypass surgery, and, in the dosages used, that ceforanide is superior to cephalothin.

We compared the outcome of marrow transplantation with that of continued chemotherapy for adults with acute nonlymphoblastic leukemia who achieve a first remission. From May 1977 to July 1982, 111 consecutive adults (ages 17 to 50) with newly diagnosed acute nonlymphoblastic leukemia were treated with induction chemotherapy. Ninety patients (81%) had a complete remission. Forty-four remission patients had available donors: 33 received a transplant and 11 did not. Forty-six patients in remission without matched donors were treated with continued chemotherapy. Kaplan-Meier estimates of 5-year, disease-free survival from complete remission are 49% +/- 18% for the transplant group and 20% +/- 13% for the chemotherapy group. When compared to the chemotherapy group, patients undergoing transplantation had a higher risk of dying during the first 6 months after remission induction but a lower risk of dying thereafter. Within the transplant group, only age influenced survival. Within the chemotherapy group, a leukocyte count of greater than 10 000 mm3 at diagnosis, a French-American-British (FAB) Cooperative Group morphologic status of M-4, M-5, or M-6, and the presence of infection at diagnosis were all associated with shorter survival.

One hundred randomly selected inpatients were examined with both double-contrast barium meal and endoscopy in a blinded prospective fashion. All studies were done by staff personnel, with equal clinical information available to both the radiologist and endoscopist. The final diagnosis was made by a review committee of participating radiologists and endoscopists. Endoscopy was more sensitive (92% versus 54%, p less than 0.001) and specific (100% versus 91%, p less than 0.05) than the double-contrast barium meal. Both procedures significantly affected the clinical outcome of the patient, the effect of endoscopy being significantly greater than that of the double-contrast barium meal. Although errors with the barium study related predominantly to an inability to show subtle lesions, poor patient cooperation and perceptual and technical failures were additional significant factors. Endoscopy is recommended for certain groups of patients.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Two chemotherapy regimens for treatment of patients with advanced Hodgkin's disease, BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone) and MOPP (mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone), were compared in a randomized prospective study. Two hundred ninety-three patients were evaluable in the induction phase of this study. The complete remission rate with BCVPP was 76% (112/147) and with MOPP, 73% (106/146) (p = 0.51). The duration of complete remissions for previously untreated patients given BCVPP was significantly longer than that for previously untreated patients given MOPP (p = 0.02). Although hematologic toxicities were similar, BCVPP caused less gastrointestinal (p = 0.0001) and neurologic toxicity (p = 0.01) than MOPP. Previously untreated patients achieving complete remission with BCVPP survived significantly longer than those receiving MOPP (p = 0.03). As primary induction chemotherapy for advanced Hodgkin's disease, BCVPP is an effective alternative to MOPP, having equal or greater therapeutic benefit with less toxicity.

The protective efficacy of pneumococcal vaccine against systemic pneumococcal infections in adults with the current indications for the vaccine was evaluated in a case-control study. Six (7%) of the 90 cases and 16 (18%) of the matched controls had received pneumococcal vaccine for an odds ratio of 0.33 (p less than 0.05). The vaccine's protective efficacy was 67%, which remained virtually unchanged after adjusting for potential confounding variables. The vaccine's efficacy was 77% for patients at moderately increased risk of pneumococcal infections, but 0% for patients who were severely immunocompromised. The vaccine's protective efficacy was 70% (p less than 0.05) for all patients 55 years or older after controlling for indications for the vaccine in addition to age. Pneumococcal vaccine confers substantial protection against systemic pneumococcal infections on the elderly and patients with illnesses associated with a moderately increased risk of pneumococcal infections.

Sulfasalazine is metabolized by intestinal bacteria, resulting in the release of sulfapyridine and 5-aminosalicylate. The drug is useful in the treatment of active ulcerative colitis as well as in preventing relapses of the disease in remission. Although effective in active Crohn's disease as well, sulfasalazine appears to be of greater benefit to patients with colitis and ileocolitis than those with ileitis alone. 5-Aminosalicylate itself is efficacious when given in enema and suppository form; oral agents capable of delivering 5-aminosalicylate to distal disease sites are now under study. The drug's mechanism of action may relate to its effects on prostaglandin synthesis or interference with arachidonic acid metabolism by the lipoxygenase pathway. Common adverse reactions of sulfasalazine, including nausea, headache, and anorexia, as well as hemolysis, are associated with high serum sulfapyridine levels and often can be avoided by lowering the dose of sulfasalazine. Mild allergic reactions, such as rash and fever, may be overcome by gradual desensitization.

y composition was studied in 31 patients receiving chemotherapy for small-cell lung cancer. Patients were randomly assigned to receive either 4 weeks of total parenteral nutrition (study group) or to continue a self-regulated oral diet (control group). The relationship between height and total body nitrogen was altered initially for patients who had lost more than 5% of body weight. During the 4 weeks of parenteral nutrition, body weight, total body fat, and total body potassium, but not total body nitrogen, increased significantly in the study group (p less than 0.001). However, after parenteral nutrition was stopped, body weight and potassium levels in the study group fell significantly and to the same extent as in the control group. Nitrogen levels showed an overall fall in the 32 weeks of observation for both groups. After the period of parenteral nutrition, the decrease in body fat was significantly greater in the control group than in the study group (p less than 0.05). Thus, parenteral nutrition increased body fat and total body potassium, but not total body nitrogen.

In a double-blind study, 12 patients on chronic hemodialysis received daily an average of 1.3 meq/kg body weight of oral sodium citrate for 8 weeks and a placebo solution for 8 weeks. Sodium citrate corrected predialysis metabolic acidosis (plasma pH 7.41 compared to 7.35; serum bicarbonate, 21.1 compared to 17.0 meq/L) and the plasma arterial PCO2 was higher (33.8 compared to 31.2). Postdialysis serum bicarbonate was slightly higher, 22.7 compared to 21.0 but there was no significant difference in arterial pH. Weight gain between dialysis periods was 0.4 kg higher with sodium citrate (2.9 compared to 2.5 kg). There were no significant differences in other routine values, blood pressure, or symptoms during dialysis. Similar results were found in patients on acetate dialysate and in patients on bicarbonate dialysate.

Treatment records of 1800 patients with rheumatoid arthritis who were included in the clinical trials of auranofin in the United States were examined for data on development of proteinuria. Three percent (41) of 1283 auranofin-treated patients had an abnormal 24-hour urine protein level: 15 had mild (0.15 to 1 g/d), 17 had moderate (1 to 3.5 g/d), and 9 had heavy (greater than 3.5 g/d) proteinuria. Permanent renal impairment did not occur, and proteinuria did not persist beyond 12 months in most patients. Seven of eight patients who were rechallenged when the proteinuria had cleared were able to continue treatment without relapse. No clinically discernible risk factors were found. Biopsy specimens from 4 patients showed membranous glomerulonephritis, which indicates an underlying immunopathologic mechanism. In similar groups of patients, the risk of developing proteinuria with auranofin therapy is significantly less than that with parenteral gold therapy (p less than 0.05) and similar to that with background therapy with nonsteroidal antiinflammatory drugs (p = 0.92). The lower incidence and relatively benign nature of proteinuria seen in this review support previous findings that auranofin is better tolerated than injectable gold.

The indications for treating patients with subclinical hypothyroidism (normal serum thyroxine and free thyroxine levels, but elevated serum thyrotrophin levels) are poorly defined. In this study, 33 patients with subclinical hypothyroidism were randomly assigned in a double-blind manner to receive placebo or L-thyroxine therapy and were followed for 1 year with thyroid function tests, serum lipid measurements, basal metabolic rate and systolic time interval determinations, and a questionnaire on hypothyroid symptoms. The placebo group showed no changes in thyroid function or peripheral indices of thyroid hormone action. In the thyroxine-treated group, serum lipids and the mean systolic time interval did not change, but the systolic time intervals became normal in the 5 patients with the most abnormal baseline values. Symptoms improved in 8 of 14 patients receiving thyroxine and in 3 of 12 patients receiving placebo (p less than 0.05). L-Thyroxine therapy may be useful for patients with subclinical hypothyroidism with abnormal myocardial contractility or symptoms consistent with mild hypothyroidism, or both.