One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(- 7)M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at greater or equal to 2.5 x 10(-5)M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.

No abstract

The possible influence on blood polymorphonuclear (PMN) granulocyte functions of the small intestinal shunt operation for obesity was studied in 10 massively overweight patients. They were investigated prior to operation and for 9 months afterwards, when they had lost an average of 32 kg body weight. Preoperatively they showed reduced PMN bactericidal capacity and increased PMN adherence compared with controls of normal weight. During the first 2--4 months postoperatively all patients displayed a gradually increasing bactericidal capacity, which then reached levels similar to the controls and remained so for the rest of the follow-up period. This enhancement was more easily assessed by a new in vitro assay in which each PMN was provided with 30--40 bacteria, than by a standard assay using 2--4 bacteria per granulocyte. PMN adherence decreased during the first postoperative months and then returned to preoperative levels. The changes in PMN functions were not statistically related either to each other or to the continuous loss of body wieght. Thus, impairment of PMN killing function occurring in extremely obese patients became normalized after small bowel shunt operation, while the high adherence remained unchanged.