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Biomedical subjects

E H Estey

Publications and source records attributed to E H Estey.

114 records · Page 7Linked to original sources

Coagulation abnormalities induced by beta-lactam antibiotics in cancer patients.

The records of 714 neutropenic cancer patients who were treated with high doses of a combination of beta-lactam antibiotics were analyzed. In 268 patients, coagulation parameters were measured at least once before, during, and after therapy. Alterations on the prothrombin time, activated partial thromboplastin time, and thrombin time were found in those regimens containing a semisynthetic penicillin, cefamandole, and moxalactam. Mild and severe hemorrhage was observed in some patients receiving these regimens. After prophylactic administration of vitamin K to all patients treated with moxalactam, no further hemorrhage was noted. Alteration of the prothrombin time, with preservation of other parameters, was found in patients receiving antibiotic regimens containing semisynthetic penicillin and cefoxitin. No evidence of hemorrhage was found in this group of patients. In neutropenic cancer patients, the occurrence of another impairment in the clotting process, in addition to thrombocytopenia, greatly increases the risk of serious hemorrhage. Coagulation parameters must be routinely monitored when these patients receive antibiotics known to cause coagulation abnormalities.

Anti-Bacterial Agents↗

Phase II trial of mitoxantrone in refractory acute leukemia.

Mitoxantrone was administered to 41 adults with refractory acute leukemia. The initial dose employed was 4 mg/m2/day X 5 days. Eventually a starting dose of 10 mg/m2/day X 5 days was used, with some patients receiving a subsequent course at 12 mg/m2/day X 5 days. Three patients had a complete response, one a partial response, and one hematologic improvement. Although antileukemia effect was more frequent at the higher doses, so was death following treatment.

Acute Disease↗

Causes of initial remission induction failure in acute myelogenous leukemia.

One-hundred and sixty-one of 378 previously untreated patients with acute myelogenous leukemia (AML) failed to enter complete remission with a combination of anthracycline, cytosine arabinoside, vincristine, and prednisone between 1973 and 1979. Thirty-six of the failing patients (22%) were considered chemotherapy failures. As in the past, the remainder failed largely because of death from infection. However, despite the routine use of prophylactic platelet transfusions, hemorrhage was a major cause of death in 33%. Thirty-seven percent of the fatal infections were due to fungi and the incidence of fungal infection was as high during the second week of treatment as later. Age greater than 50 yr predisposed to fatal infection but not chemotherapy failure, while the presence of an antecedent hematologic disorder increased the risk of both fatal fungal infection and resistance to chemotherapy. Patients with an initial white blood cell count of greater than or equal to 25000/microliter were more likely to die of hemorrhage at all times during treatment. Improvement in supportive care remains crucial if improved complete rates are to be forthcoming in previously untreated patients.

Adult↗

Clinical pharmacology of moxalactam in patients with malignant disease.

Pharmacological studies of moxalactam were conducted with 37 cancer patients. Intramuscular administration of 500 mg of moxalactam to 10 patients produced a mean peak serum concentration of 12.4 micrograms/ml. The serum terminal-phase half-life was 3.9 h. Intravenous administration of 500 mg of moxalactam over 5 min to the same 10 patients produced a mean serum concentration of 42.0 micrograms/ml at 15 min, which decreased to 3.3 micrograms/ml at 6 h. A dose of 1 g of moxalactam was given in an identical manner to the same 10 patients. The mean serum concentration was 69.7 micrograms/ml at 15 min and 7.4 micrograms/ml at 6 h. The mean proportions of a drug recovered in the urine by 12 h after administration were 59% after the intramuscular dose and 61 and 55% after the single intravenous doses. Multiple-dose intravenous studies were also conducted. The serum terminal-phase half-life varied from 2.0 to 3.2 h. Continuous infusion studies were performed by up to 9 days by using a loading dose of 1 g over 0.5 h, followed by 2 g every 6 h. Serum concentrations were maintained at about 30.0 micrograms/ml during the study period.

Adult↗

Ceforanide kinetics.

Pharmacologic studies of the semisynthetic cephalosporin ceforanide were conducted in 29 cancer patients. Intravenous doses of 500 mg over 30 min every 6 hr to 10 patients induced mean peak serum concentrations between 44.7 and 51.5 micrograms/ml, while in 10 patients receiving 1 gm over 30 min every 12 hr mean peak serum concentrations varied from 73.4 to 91.8 micrograms/ml. Twelve hours after 1 gm of drug, mean serum concentrations varied between 5.6 and 6.5 micrograms/ml. After a 500-mg loading dose, continuous infusion of 500 mg every 4 hr, 10 patients maintained serum concentrations above 34.2 micrograms/ml for 7 or 8 days. Most of the drug was excreted in the urine in the initial 6 hr after administration and mean urinary concentration of 1,315 micrograms/ml were obtained during this time. Serum half-life ranged between 2.2 and 2.9 hr on all schedules and therefore wa longer than that of other cephalosporins. No serious toxicity was noted. The relatively broad spectrum of activity in addition to the long half-life suggests clinical utility for this drug.

Adolescent↗