No abstract

Cellular drug resistance is one of the main causes of the frequent ultimate failure of chemotherapy in childhood acute myeloid leukemia (AML). We here summarize the results of a literature review on in vitro drug resistance in childhood AML, focusing on studies using so-called cell culture assays. We also briefly describe some results of an ongoing collaborative study between the Research Laboratory of Pediatric Oncology in Amsterdam (University Hospital Vrije Universiteit) and the German BFM-AML Group. In general, the literature and our preliminary data on in vitro cellular drug resistance in AML are promising in terms of clinical relevance. Cell biological features and clinical response to chemotherapy are related to in vitro drug resistance. However, a large study including multivariate analysis is required to more firmly establish the clinical value of cellular drug resistance testing in childhood AML, and the collaborative study will therefore be continued. Possible applications of cell culture assays include risk-group stratification, rational improvements of current treatment protocols for subgroups of patients based on specific drug resistance profiles, individualised tailored therapy, the study of cross-resistance patterns between drugs, the study of possibilities to modulate or circumvent drug resistance, the study of drug interactions, selection of patients for clinical phase II studies and drug screening.

IFN-g inhibits tumor cell proliferation and diminishes the invasive properties of glioma cells via reduction of HA binding capacity. Our results support the use of IFN-g in the therapy of malignant gliomas.

The concentration of plasma fibronectin was determined by Laurell's electroimmunoassay in 75 preterm or term newborns within the first 2 days of life, in 97 healthy infants aged from 3 days to 12 months, in 40 septic infants and in 38 healthy adult subjects. The mean fibronectin concentration in citrated plasma of normal adults was 318 +/- 84 ml/l. Healthy eutrophic term newborns 1-2 days old had approximately one-third of the fibronectin concentration of adults. There was no significant difference in the values between healthy term and eutrophic preterm newborns or between eutrophic and hypotrophic newborns. The plasma fibronectin increased strongly over the 1st month of life. No significant difference was observed between fibronectin levels in infant boys and girls. The values in septic newborns and septic older infants were significantly lower when compared with those of age-matched healthy controls. It is speculated that this deficiency, because of linkage to fibrin in disseminated intravascular coagulation or due to increased utilisation as a nonspecific opsonin and sequestration at sites of tissue injury, may contribute to organ failure in septicaemia.

ABSTRACT. Weissbach, G., Domula, M., Lenk, H. and Schneider, P. (Paediatric Clinic of the Medical Department, Karl‐Marx‐University, Leipzig, DDR). The progressive anti‐thrombin activity and its relations to other factors of the coagulation system in newborns. Acta Paediatr Scand, 63: 555, 1974.—The progressive antithrombin and its relations to other factors of the coagulation system have been studied in chronically asphyxiated newborns. The progressive antithrombin activity was determined in 44 healthy and in 40 chronically asphyxiated newborns according to the method described by Gerendas & Monkhouse. The activity was clearly depressed in the asphyxiated group as compared with healthy full‐term newborns. Only within the group of asphyxiated newborns did the statistical analysis reveal close correlations between progressive antithrombin and the factors fibrinogen, plasminogen, thromboplastin time value, factor II, and thrombocytes. Furthermore, most of these were also closely correlated among themselves. The partly very close relations can be explained only by a simultaneous consumption of these constituents by disseminated intravascular coagulation processes and secondary hyper‐fibrinolysis. The decrease in progressive antithrombin is due to an irreversible binding of the antithrombin III to thrombin, liberated within the vessels.