Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia.

Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte-macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.

Neopterin in AIDs, other immunodeficiencies, and bacterial and viral infections.

An increase in total urinary neopterin was observed in 12 of 13 patients with acquired immunodeficiency syndrome (AIDS), seven of 13 patients with lymphadenopathy, one of six healthy homosexual males, seven of ten adult patients with staphylococcal pneumonia, 11 of 12 children with viral infections, four of seven children with bacterial infections, and 12 of 13 children with various immune defects. Extremely high values of total urinary neopterin and monapterin were observed in severely ill patients with AIDS and those with familial hemophagocytic lymphohistiocytosis. Neopterin excretion was normal in two AIDS patients with Kaposi's sarcoma, but without opportunistic infections at that time. On reexamination of one of these patients later on, elevated neopterin values were noted. Parallel increases in neopterin and monapterin were found, whereas biopterin was usually normal. The increase in total neopterin was mainly due to 7,8-dihydroneopterin and was accompanied by an increase in 3'-hydroxysepiapterin. Increased neopterin in urine is assumed to reflect the increase in GTP pool and GTP cyclohydrolase I activity as observed in stimulated monocytes. Thus, neopterin, as a measure of the activation of the nonspecific cellular immune system, may be used diagnostically to detect allograft rejection after transplantations and to follow-up HTLV-III positive patients.

Pharmacokinetics of heparin after a single intravenous or subcutaneous injection. / Pharmakokinetik von Heparin nach einmaliger intravenöser oder subkutaner Injektion.

In 2 groups of 4 probands the pharmacokinetics of heparin were investigated by a physiologic method (factor Xa inhibition) and an isotope method (35S-heparin) following a single intravenous injection of 5000 IU heparin and a single subcutaneous injection of 10000 IU heparin respectively. Following intravenous administration the anticoagulant effect and radioactivity fall exponentially. The half-life is about 50 min and the distribution volume 3000 ml (factor Xa inhibition) and 3800 ml (radioactivity). With subcutaneous injection peak concentrations above 0.2 IR heparin/ml were measured by both methods 2-4 h after administration; 9 h after administration, no further factor Xa inhibition was detectable in 2 probands. In the light of these and previously published results, some practical aspects of the conduct of therapy and prophylaxis of thromboembolism with heparin are discussed.