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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte and macrophage production after burn injury or burn wound infection is significantly reduced and further compromised by endotoxin (ET). Moreover, the macrophage seems to be the major source of this bone marrow suppression. We sought to determine if recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that is capable of improving survival after experimental burn wound sepsis, altered postburn macrophage-mediated marrow suppression. Groups of male BDF1 mice (n = 6 to 10) receiving a 15% total body surface area burn +/- infection (B or B + I) with Pseudomonas aeruginosa were injected with 100 ng rhG-CSF twice daily. On day 3, peritoneal-elicited macrophages (5 x 10(6) cells/mL) from either rhG-CSF-treated or control (5% dextrose in water) mice were incubated +/- ET (300 ng/mL). The resultant macrophage supernatant was added to cultures of target marrow granulocyte-macrophage progenitor cells (GM-CFC) at a volume of 1:10. The GM-CFC growth as a percentage of cultures not containing macrophage supernatant were compared and reductions in the number of GM-CFC taken as an index of marrow suppression. Macrophages obtained from B and B + I animals reduced target GM-CFC growth, compared with macrophages from normal animals (B vs. normal animals p < 0.05). In addition, ET-stimulated macrophages induced further bone marrow suppression for all three groups (p < 0.01). Macrophages from granulocyte colony-stimulating factor-treated animals caused significantly less bone marrow suppression, compared with untreated animals for all groups (p < 0.05 to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant human granulocyte colony-stimulating factor treatment improves macrophage suppression of granulocyte and macrophage growth after burn and burn wound infection. 750 Apr 9

Ethanol is a potent immunosuppressive agent that impairs neutrophil effector function. The purpose of this study was to determine whether granulocyte colony-stimulating factor (G-CSF), a cytokine that increases neutrophil number and functional activity, could prevent the ethanol-induced impairment of antibacterial host defense. Rats were injected with human recombinant G-CSF for 2 days. Eight hr after the last injection of G-CSF, animals were infused with ethanol (or saline) for 1 hr before the subcutaneous injection of live Escherichia coli. The infusion of alcohol was continued after the bacterial challenge and produced blood alcohol levels of 275-300 mg/dl. In control animals, the injection of E. coli resulted in a marked leukopenia. There was an influx of leukocytes into the subcutaneous space where the bacteria were injected, and neutrophil accumulation in tissues adjacent to the focus of infection (i.e., dorsal skin and muscle). Based on myeloperoxidase activity, there was no detectable accumulation of neutrophils in other soft tissues. In acutely intoxicated rats, leukocyte migration to the inflammatory site was impaired, and the number of viable bacteria isolated from the subcutaneous pocket was markedly increased. G-CSF prevented the sepsis-induced leukopenia, increased the influx of neutrophils in to the infection site, reduced the number of bacteria in the subcutaneous lavage fluid, and decreased the incidence of bacteremia in ethanol-treated rats when compared with rats not receiving G-CSF. These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil recruitment selectively to the site of infection and that can be used to ameliorate the ethanol-induced impairment in bacterial host defense.
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PMID:Granulocyte colony-stimulating factor prevents ethanol-induced impairment in host defense in septic rats. 750 76

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.
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PMID:Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation. 751 Aug 13

Impaired neutrophil responses contribute to the neonate's increased susceptibility to infection. Because granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance granulocyte and macrophage number and function, their use in the management of neonatal sepsis may be beneficial. Little is known about the endogenous levels of G-CSF and GM-CSF. In adults, raised values for G-CSF, but not GM-CSF, have been demonstrated in patients with infection, and conflicting data has emerged regarding CSF levels in neonates. We have used an ELISA to measure maternal and cord serum G-CSF and GM-CSF at the time of delivery, with gestational age between 25 and 42 wk. In mothers, an inverse linear relationship between gestational age and GM-CSF levels (p = 0.049) was found, but no association with G-CSF levels was observed. In neonates, a quadratic association was found between GM-CSF levels and gestational age (p = 0.019), whereas G-CSF levels showed an inverse linear association (p = 0.015). In addition, an association was found between maternal and cord GM-CSF (p = 0.007) but not G-CSF levels in paired samples. The effect of gestational age on the cytokine levels could not be explained by the white cell count, the absolute neutrophil count, pregnancy-induced hypertension, or the presence of infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte and granulocyte-macrophage colony-stimulating factors in cord and maternal serum at delivery. 751 77

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

The agranulocytosis associated with clozapine is, indeed, a serious medical disorder. Patients experience prolonged and profound severe granulocytopenia--often with absolute neutrophil counts of less than 100/cu mm. Patients suffer neutropenic sepsis and often are as sick as patients undergoing induction chemotherapy for lymphoma or leukemia. Thus, it is important to evaluate the state-of-the-art management of such patients and to define the role of growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Early use of G-CSF or GM-CSF can shorten the duration of granulocytopenia from a mean of 16 to 8 days and reduce the morbidity of the disorder. Such intervention can potentially decrease the total cost of agranulocytosis. Further issues under consideration are the early use of hematopoietic growth factors prior to the onset of agranulocytosis and the use of these factors for the outpatient management of this disorder.
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PMID:G-CSF and the management of clozapine-induced agranulocytosis. 752 42

Serum samples from 76 patients with neutropenia and 34 control subjects were analyzed for levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 1 alpha, and tumor necrosis factor beta. Clinical correlates and duration of neutropenia were determined insofar as possible. Systemic acute inflammatory disease was present in only two patients. In most cases, the neutropenia was considered idiopathic or medication related. Significantly elevated serum granulocyte colony-stimulating factor levels were found in the patient group, regardless of the apparent cause of the neutropenia. Increased levels of granulocyte-macrophage colony-stimulating factor, interleukin 1, and tumor necrosis factor were seen in only one patient with sepsis.
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PMID:Serum cytokine levels in patients with neutropenia. 752 20

Invasive fungal infections have become an increasing problem in severely immunocompromised hosts. We here report a case of septicemia, caused by Trichosporon beigelii, an unusual pathogen of systemic infections. This infection was acquired during a period of severe neutropenia after chemotherapy for relapsed acute myelogenous leukemia following allogeneic bone marrow transplantation. The patient recovered from a life-threatening T. beigelii septicemia due to early intensified treatment with amphotericin B and a rapid neutrophil recovery, enhanced by granulocyte colony-stimulating factor (G-CSF). According to the current literature, amphotericin B is the treatment of choice for systemic T. beigelii infections. In patients with severe granulocytopenia, the rapid recovery of neutrophils remains the most important factor for the outcome of this infection.
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PMID:Successful treatment of a Trichosporon beigelii septicemia in a granulocytopenic patient with amphotericin B and granulocyte colony-stimulating factor. 752 73

The granulocyte colony-stimulating factor (G-CSF) has been shown to accelerate recovery from severe neutropenia and to decrease the incidence of documented infections after intensive chemotherapy in cancer patients. However, the routine prophylactic use of G-CSF is expensive. This study was conducted to determine the role of G-CSF as adjunct therapy for septicemia following neutropenia caused by chemotherapy in children with acute leukemia. Fifty consecutive episodes of septicemia were studied involving 34 episodes of Gram-negative, 7 episodes of Gram-positive, 5 episodes of polymicrobial bacterial septicemia, one episode of fungemia, and 3 episodes of disseminated fungal infection. In the first 25 episodes, G-CSF was not used (group A). For the next 16 episodes, G-CSF 200 micrograms per square meter per day subcutaneously was given immediately after the septicemia was documented until the absolute neutrophil count was maintained at more than 1,500 per cubic millimeter (group B). Thereafter, G-CSF at the same dose as that of group B was prophylactically used in all the children who received high-dose cytosine arabinoside-containing regimens. Nine episodes of septicemia occurred (group C). The incidences of mortality per episode of septicemia in groups A, B, and C were 12.0% (3/25), 12.5% (2/16) and 0% (0/9), respectively. Statistically, there was no difference between the three groups overall and in pair-wise comparisons (all P > 0.5). The durations of G-CSF administration in group B ranged from 6 to 26 days with a median of 12 days and the durations of G-CSF administration in group C ranged from 10 to 23 days with a median of 19 days. With or without G-CSF, there may be no significant difference in the mortality of septicemia following neutropenia caused by chemotherapy in children with acute leukemia.
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PMID:Role of granulocyte colony-stimulating factor as adjunct therapy for septicemia in children with acute leukemia. 753 94

A study was carried out to investigate the efficacy of therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 patients with granulocytopenia and sepsis who had failed to respond to antibiotics. The mean leukocyte count at the start of the study was 911 +/- 334/microliter. Patients were injected subcutaneously with 75 micrograms rhG-CSF once daily for a mean of 5.2 days. The plasma G-CSF concentration was measured by ELISA. The leukocyte count increased approximately 9-fold after 1 week in 19 patients and the percentage of granulocytes rose from 46.2% to 78.9%. These 19 patients survived, while the 5 patients with no leukocyte response to rhG-CSF died. High plasma G-CSF levels were found in patients with granulocytopenia. Plasma G-CSF levels decreased as levels of granulocyte increased in survivors. A high plasma G-CSF concentration persisted in the 5 non-responding patients resulting in a fatal outcome. This study suggests that rhG-CSF both increased the leukocyte count and was a useful therapeutic manoeuvre for sepsis.
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PMID:Evaluation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in granulopoetic patients complicated with sepsis. 753 91


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