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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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PMID:A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. 752 Jul 70

Therapy with myeloid colony-stimulating factors has been safely and effectively used in a wide variety of situations associated with neutropenia. We present a case of pseudoleukemia occurring in a patient with lymphoma and pancytopenia after 2 days of treatment with granulocyte colony-stimulating factor (G-CSF). Bone marrow aspirate and flow cytometry study results were consistent with acute myelomonocytic leukemia but were normal after G-CSF was discontinued for 4 days. As previous phase I studies of bone marrow morphology after G-CSF use have not described the extreme myeloid immaturity seen in this patient, it seems likely that the action of G-CSF was enhanced by factors associated with the patient's illness. We emphasize the clinical importance of this case in light of the widespread use of G-CSF.
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PMID:Pseudoleukemia after granulocyte colony-stimulating factor therapy. 753 47

Human umbilical cord blood (CB) is a rich source of hematopoietic stem cells for both research and stem cell transplantation. In clinical studies, it appears that recovery from myeloablative therapy using CB requires significantly fewer cells than a typical allogeneic marrow transplant. This suggests that CB may be enriched for early hematopoietic progenitors. The present studies were undertaken to determine the presence of CD34+ cells in CB with the phenotypic characteristics of multipotential stem cells. In 22 CB harvests, the average percentage of CD34+ cells was 1.33 +/- 0.21% (SE), a value similar to that in adult normal bone marrows (BM). However, the distribution of CD34+ cells was distinctly different from either BM or granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell harvests. CB contained a defined population of brightly staining CD34+ cells with low side scatter. These CD34 (bright) cells comprised a mean of 14.5 +/- 2.5% of the CB CD34+ cells, whereas < 1% of BM CD34+ cells has been shown to be CD34- bright. Eighty-five to ninety percent were negative for three antigens expressed at an early stage of stem cell maturation: CD38, HLA-DR and LFA-1. Fifty-five percent of these CD34 (bright) cells did not express the CD45RA isoform, an additional marker of immaturity. The antigen-bright cells also lacked lineage-specific antigens including CD33, CD56, CD19, CD10 and CD7 as well as CD71. Approximately 46% were Thy-1+, and 40% expressed c-kit receptors. These data suggest that, by phenotypic criteria, CB may be a particularly enriched source of primitive hematopoietic precursors.
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PMID:A unique population of CD34+ cells in cord blood. 754 Apr 69

Recombinant granulocyte colony-stimulating factor (G-CSF) was administered to healthy young (n = 32) and elderly (n = 19) volunteers (0 microgram/d, 30 microgram/d, or 300 microgram/d) to determine its effect on neutrophil production, blood kinetics, and tissue migration. Measurements included blood counts (daily), marrow neutrophil pool sizes and neutrophil tissue migration (baseline and day 5), blood kinetics (day 6), and marrow transit time while on drug (days 6 to 14). G-CSF markedly expanded the marrow neutrophil mitotic pool and shortened the transit time of the postmitotic pool (control, mean = 6.4 days; 300 microgram/d, mean = 2.9 d). G-CSF increased neutrophil production without significantly altering blood neutrophil half-life or margination. Compared to control, neutrophil accumulation in skin chambers decreased by about 50% in the 300 microgram/d group in both young and elderly subjects. G-CSF induced neutrophilia by stimulating proliferation of marrow neutrophil precursors and accelerating neutrophil entry into the blood. Decreased neutrophil inflammatory responses measured with the skin chamber technique may be because of the relative immaturity of the circulating cells or to alterations in neutrophil phenotype induced by G-CSF.
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PMID:Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. 870 92

The effects of rhG-CSF administration on fMLP-induced neutrophil CD11b and CD18 upregulation were studied in nine patients suffering from intermediate and high grade non-Hodgkin's lymphomas. Blood samples were obtained before recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration and 24 hrs after rhGSF interruption. The growth factor was administered subcutaneously for five days in a dosage of 5 microg/Kg/day. Nine normal subjects were studied as controls. Five patients showed an impaired baseline CD11b and CD18 upregulation, which was corrected by rhG-CSF therapy. Four patients showed a normal baseline CD11b and CD18 upregulation, but this function was reduced by rhG-CSF therapy. All patients showed a normal baseline fMLP-induced luminol-enhanced chemiluminiscence and significantly increased chemiluminescence values after rhG-CSF administration. We conclude that, while in some patients rhg-CSF is able to improve neutrophil CD11b and CD18 upregulation in response to chemotactic agents, in other patients a decrease of this function can occur, maybe due to a relative immaturity of the circulating neutrophils induced by rhG-CSF.
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PMID:fMLP-induced CD11b/CD18 upregulation on neutrophils from patients with non-Hodgkin's lymphomas treated with recombinant human granulocyte colony-stimulating factor. 938 5

The immaturity of neonatal phagocytic immunity contributes to increased mortality during neonatal sepsis. Neonates have both quantitative and qualitative neutrophil defects with decreased bone marrow neutrophil storage pool (NSP) reserves, an inability to increase neutrophil production, and defective neutrophil functional activity. Neonates respond to overwhelming sepsis with depletion of the NSP and the development of peripheral neutropenia. The myelopoietic cytokines granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been documented to induce neutrophilia in neonatal animals and human infants, increase the NSP, and upregulate neutrophils for improved functional activity. Preclinical studies in neonatal rats demonstrate increased survival with prophylactic G-CSF during experimental group B streptococcal sepsis. In pilot phase I/II human trials, G-CSF and GM-CSF were demonstrated to be both safe and well tolerated and to induce significant increases in absolute neutrophil count and NSP. Prophylactic GM-CSF in the very low birth weight neonate may reduce the incidence of nosocomial infections. Phase III trials are needed to further delineate the clinical usefulness of these myelopoietic cytokines in neonates with a high predisposition to sepsis.
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PMID:Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates. 966 63

The problems of immunologic adaptation during the transitional period from intra- to extrauterine life are responsible for the physiologic immaturity of the immune function in newborn infants. In preterm neonates the immunodeficiency is more severe and prolonged and is associated with a higher incidence of infections and sepsis. Furthermore, due to immaturity of the hematologic system, anemia, thrombocytopenia, and neutropenia are frequently observed in very low birth weight infants. The dysregulation of cytokine and hematopoietic growth factor synthesis is an important contributory factor to the complex deficiency of immunologic and hematologic function in the neonate and may explain the reduced incidence of acute graft-versus-host disease observed after cord blood transplantation in children. Human milk is a rich source of most of the cytokines that are reduced in the neonate. Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and erythropoietin are currently under evaluation in newborn infants with septic neutropenia or anemia of prematurity.
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PMID:Hematopoietic growth factor levels in term and preterm infants. 1022 41