Blood
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The observation of low transcutaneous arterial oxygen saturation (SaO2) in otherwise well sickle cell patients has lead to questions about the interpretation of pulse oximetry values in these patients. We undertook a prospective study of children with sickle cell disease to (1) determine the prevalence of, and factors associated with, low transcutaneous SaO2 in clinically well patients, (2) develop an algorithm for the use of pulse oximetry in acutely ill patients, and (3) assess the accuracy of pulse oximetry in these patients. Eighty-six clinically well children with hemoglobin (Hb) SS had a lower mean transcutaneous SaO2 than 22 Hb SC patients and 10 control subjects (95.6% v 99.1% v 99.0%, respectively; p < .001). ⋯ The accuracy of pulse oximetry was shown by the correlation between SaO2 measured by pulse oximetry and calculated by using the patient's oxygen dissociation curve and PaO2 (r = .97). This study provides evidence that Hb oxygen desaturation is not a universal finding among children with sickle cell disease and identifies factors associated with Hb oxygen desaturation. We conclude that pulse oximetry may be useful to assess whether progressive pulmonary dysfunction begins at an early age in Hb SS patients, and to assess acutely ill patients for the presence of hypoxemia associated with acute chest syndrome.
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Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. ⋯ Because IL-2-induced GM-CSF release coincides with LAK lysis of IL-2-cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM-CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells.
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The treatment of cancer with lymphokine-activated killer (LAK) cells in conjunction with high-dose interleukin-2 (IL-2) has been limited by the toxicity of IL-2 and the narrow range of tumors that respond to therapy. Cytokines that are capable of augmenting lower doses of IL-2 are, therefore, a major focus of research. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF) can augment low-dose IL-2 LAK induction from murine splenocytes. ⋯ In contrast, depletion of both CD4+ and CD8+ T cells before culture inhibited the generation of LAK activity. However, depletion of only CD4+ T cells, or only CD8+ T cells, did not inhibit the generation of IL-2 or (IL-2 + GM-CSF) LAK activity. These results suggest that LAK precursors are present in both the CD4+ and CD8+ T-cell populations and suggest that the addition of GM-CSF to low-dose IL-2 may result in the generation of T-derived LAK cells.
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Multicenter Study
A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group.
The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. ⋯ In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)
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In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti-HPA-1a. ⋯ The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy.