To determine the effect of variations in blood ionized calcium (Ca2+) on myocardial contractility independent of changes in loading conditions and other biochemical variables.

We evaluated the development of anemia as part of a trial of zidovudine therapy in patients with the acquired immunodeficiency syndrome (AIDS) with Kaposi sarcoma. Patients were randomized to one of three treatment groups or a placebo group. Transfusion-requiring anemia (hemoglobin less than 100 g/L) developed in 6 of 15 patients on zidovudine therapy at a mean of 6 weeks after starting treatment. A fall in the reticulocyte count was the earliest peripheral blood indicator of toxicity. Mean corpuscular volume increased markedly in patients on zidovudine therapy not developing anemia yet remained stable or only slightly increased in those who became anemic. Bone marrow examination showed pure red cell aplasia in 2 patients, erythroid maturation arrest in 1, and erythroid hypoplasia in 3. Megaloblastic erythropoiesis was present in 2 of the 6 anemic patients. Erythropoietin levels measured at the time of first transfusion were increased. Thus, the anemia associated with zidovudine therapy is due to red cell hypoplasia or aplasia.

To compare single-dose and 10-day treatment regimens of trimethoprim-sulfamethoxazole in women with acute dysuria, urgency, or urinary frequency.

To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus.

Twenty-five patients with active left-sided ulcerative colitis were randomly assigned to receive either 2 g of 4-aminosalicylic acid (para-aminosalicylic acid) or placebo in a 60-mL volume as a nightly retention enema. The duration of treatment was 8 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histologic inflammation in rectal biopsies. At 8 weeks, 10 of 12 patients (83%; 95% confidence interval [CI], 55% to 97%) who received 4-aminosalicylic acid showed improvement in clinical, sigmoidoscopic, and histologic variables. In contrast, only 2 of 13 patients (15%, 95% CI, 4% to 38%) who had received placebo showed clinical improvement (P less than 0.005). The 11 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid enemas. Of the 11, 9 showed clinical, sigmoidoscopic, and histologic improvement. No adverse effects were seen. 4-Aminosalicylic acid enemas are a safe and effective means of treating left-sided ulcerative colitis.

Infection with human immunodeficiency virus (HIV) may cause viral antigenemia, detected primarily as p24 viral core protein. Among 16 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex studied serially, 12 had or developed antigenemia ranging from 16 to 3006 pg/mL in plasma. The level could be categorized as high (greater than 100 pg/mL) or low (15 to 65 pg/mL). Three patients with anti-p24 antibody had no antigenemia. Zidovudine (AZT), 200 or 250 mg every 4 hours, reduced antigenemia by about 90%; other regimens were less effective. Leukocyte cultures were positive for HIV from patients with antigenemia, and in one third of samples in the absence of antigenemia. High levels of antigenemia correlated with symptoms, CD4 cell count, and prognosis. Drug toxicity requiring a lower dose was followed by increased antigenemia, recurrent symptoms, and decreased CD4 cells, suggesting lymphocyte toxicity. Monitoring antigenemia can be useful in evaluating patients with HIV infection and in evaluating the effect of antiviral chemotherapy.

The occurrence, outcome, and predictors of myocardial infarct extension were determined in 848 patients with acute myocardial infarction. An increase in the level of plasma MB creatine kinase activity was used to detect extension, which occurred in 71 of 848 patients (8.4%). For these patients, hospital mortality was more than four times higher than for those without extension (30% versus 7%, P less than 0.01). However, for patients surviving the initial hospitalization, there was no significant difference in mortality during the following year (12% compared with 9%). Multivariable analyses indicated that extension was more likely to occur in patients with recurrent ischemic pain during the second hospital day, a history of previous myocardial infarction, and ST segment depression on the admission electrocardiogram. The occurrence of extension in patients with two of these risk factors was more than twice that of patients without any of the risk factors (15.1% compared with 5.8%). Patients with these risk factors should be considered for early coronary angiography and possible intervention to prevent infarct extension and its sequellae.

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

To determine the efficacy of prophylactic interferon for prevention of cytomegalovirus infection and relapse of leukemia after allogeneic marrow transplantation.

To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia.

To compare the effectiveness and adverse effects of air-fluidized beds and conventional therapy for patients with pressure sores.

To assess the effects of ibuprofen on blood pressure control in patients being treated with antihypertensive drugs.

To determine the effect of displaying previous results of diagnostic tests on the ordering of selected outpatient tests.

To evaluate the effect of 1-desamino-8-D-arginine vasopressin (desmopressin) on blood loss in surgery, we conducted a randomized, double-blind trial of the drug in 35 patients with normal hemostatic function who were having spinal fusion with Harrington rod instrumentation. Seventeen patients were designated to receive 10 micrograms/m2 of desmopressin, and 18, to receive a placebo. Preoperative testing showed that desmopressin increased factor VIII coagulant activity, von Willebrand antigen concentrations, glass bead platelet retention, and prothrombin consumption and decreased the partial thromboplastin and bleeding times (p less than or equal to 0.0003). During surgery, desmopressin reduced blood loss by 32.5% (547 mL; 95% confidence interval [CI], 19 to 1075; p = 0.015) and reduced the need for concentrated erythrocyte transfusions by 25.6% (0.86 units; 95% CI, 0.08 to 1.65; p = 0.022). After surgery, desmopressin reduced the duration of treatment with analgesic agents by 13.1% (34.0 hours; 95% CI, -5.2 to 72.7; p = 0.105), presumably by decreasing bleeding in the surgical wound. When adjusted for the origin of the scoliosis by two-way analysis of variance, this effect was even more evident (p = 0.014). Multiple regression analysis showed that the best three predictors of blood loss in surgery and transfusion requirements were the bleeding time, glass bead platelet retention, and the use of desmopressin.

To determine if the more rapid absorption of subcutaneously administered human insulin, as compared with animal insulin, would result in an improved postprandial metabolic response, ten persons with type I diabetes mellitus were studied during a fixed meal. Plasma glucose and insulin concentrations were compared after subcutaneous injections of 0.2 U/kg body weight of regular biosynthetic human insulin or regular purified pork insulin in a double-blind randomized crossover trial. Meal glycemic excursions improved after the administration of biosynthetic human insulin, when compared with purified pork insulin (p less than 0.05 at 150, 180, and 210 minutes postprandially). Serum free immunoreactive insulin concentrations were significantly higher after injections of biosynthetic human insulin, and the rate of incremental rise during the first 30 minutes was also greater. Insulin antibody studies showed a strong negative correlation between peak insulin levels and the association constant for the high-affinity-binding insulin antibodies. We conclude that biosynthetic human insulin is more rapidly absorbed after subcutaneous injection than is purified pork insulin, a characteristic that results in improved postprandial metabolic control.

To determine the efficacy and safety of adjusted subcutaneous calcium heparin compared with continuous intravenous calcium heparin as the initial treatment for acute deep vein thrombosis.

To compare the efficacy of direct hepatic arterial chemotherapy with systemic chemotherapy in patients with liver metastases from colorectal carcinoma.

The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease.

To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B.