In vitro characterization of antithrombin III concentrates--a single-blind study.

Twenty-three lots of five antithrombin III (AT III) concentrates from four manufacturers were analyzed in a single-blind study. All the preparations had been virus-inactivated by pasteurization, and one concentrate had also been treated with solvent/detergent (S/D). AT III activities were determined using two thrombin-based and one factor Xa-based chromogenic substrate assays. AT III antigen was measured by kinetic nephelometry. All AT III assays were tested against the first international reference preparation coded 72/1. In addition, AT III was characterized by crossed immunoelectrophoresis in the presence of heparin and by gel filtration. The following were quantified: heparin cofactor II activity and antigen content, heparin activity, thrombin-AT III complexes, AT III-protease complexes, total protein, albumin, immunoglobulins, glucose and pH. The AT III concentrates differed markedly in terms of their purity and potency. The specific activities of AT III and the ratios of AT III activity to antigen content ranged from 3.4 to 6.9 and from 0.63 to 0.84, respectively. The highest values were found in five lots of the concentrate that had been treated by both pasteurization and S/D. This preparation was the only one that was virtually free of denaturated AT III, as judged by crossed immunoelectrophoresis. Marked batch-to-batch variation in AT III potencies was found in two out of the five preparations analyzed. In two out of five lots from one manufacturer, the measured potencies were more than 10% lower than the declared potencies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chemotherapy of nonendemic Burkitt's lymphoma]. / Chemotherapie des nicht-endemischen Burkitt-Lymphoms.

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

Inhibition of proliferation and differentiation of mouse erythroleukemia cells by hydroxamic acids.

The effect of several hydroxamic acids on cell growth and differentiation was studied in vitro in cultures of Friend erythroleukemia cells, line F4-6. Terminal differentiation in F4-6 cells can be induced by exposure to a variety of structurally unrelated compounds or to conditions which inhibit cell growth. Hydroxamic acids do not induce erythroid differentiation but interfere with both cell growth of F4-6 cells and the induction of differentiation by DMSO in these cells. DMSO-induced terminal differentiation is inhibited even when F4-6 cells are pretreated for 24 h with hydroxamates followed by removal of the hydroxamates and transfer to fresh medium containing 1% DMSO. Reduction of cell growth by hydroxamates is completely and immediately reversible upon removal. In contrast, the inhibition of DMSO inducibility is not reversible within 24 h. Cell pretreated with hydroxamates for 24 h prior to a 96 h-exposure to DMSO show the same reduction in synthesis of hemoglobin as cells simultaneously exposed to DMSO and hydroxamates.