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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Microbicidal and cytocidal products of the respiratory burst and integrin adhesion molecule expression have been studied in monocytes from patients who received rHuGM-CSF during regeneration after high-dose chemotherapy. In this study, administration of rHuGM-CSF after high-dose chemotherapy significantly augmented the secretion of inducible products of the monocyte respiratory burst. Monocyte activation persisted for several weeks after the cessation of GM-CSF therapy. Under in vitro conditions that mimicked gram-negative (LPS) and gram-positive (opsonized Staphylococcus aureus) sepsis, the monocyte responded to such stimulation by exhibiting an enhanced release of hydrogen peroxide at both regeneration and several weeks later (P < 0.001). Similarly, GM-CSF administration significantly augmented the phenotypic expression of the beta 2-integrin adhesion molecules and allowed the leucocyte-specific selectin, LAM-1, and the beta 2-integrins to respond normally to inflammatory stimulation by LPS. We further present evidence that GM-CSF therapy restored the otherwise refractory status of monocytes to inflammatory stimulation that existed in those patients given chemotherapy alone. The restoration of monocyte responsiveness by GM-CSF following high-dose chemotherapy could be a potentially valuable and hitherto not described action of rHuGM-CSF on monocyte function. We conclude that administration of GM-CSF may have the potential for restoring as well as augmenting the anti-microbial and anti-tumour function of the monocyte after high-dose chemotherapy.
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PMID:Administration of rHuGM-CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high-dose chemotherapy. 754 Apr 15

Forty-six patients with urothelial cancer were treated with a systemic chemotherapeutic regimen consisting of methotrexate, vinblastine, 4'-epirubicin and cisplatin (M-VEC) in conjunction with glycosylated recombinant human granulocyte colony stimulating factor (rhG-CSF); then 33 were evaluated for response. Complete response was observed in 7 patients (21%) and partial response in 13 (39%). As far as the toxic effects of this treatment are concerned, mucositis of a minimum grade and leukopenia greater than grade 3 occurred in 5% and 10% of the patients, respectively; there were no cases of nadir sepsis and drug-related death. Minor toxicity such as nausea vomiting occurred in 81% of patients, and no patient required either dose-reduction or a delay of more than 5 d before starting of the second cycle. Thus, it may be concluded that M-VEC chemotherapy combined with rhG-CSF is useful in the treatment of urothelial cancer, especially when used as a neoadjuvant.
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PMID:M-VEC (methotrexate, vinblastine, 4'-epirubicin and cisplatin) combined with glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the treatment of transitional cell carcinoma of urothelium: reduction in toxicity produced by rhG-CSF. 754 54

Sepsis is a common cause of morbidity and mortality. Neutrophils are the major defense against bacterial invasion, and granulocyte colony-stimulating factor (G-CSF) augments both neutrophil number and function. In our study, 160 rabbits were inoculated transtracheally with 0.5 mL of a solution containing 10(4) colony forming units per milliliter of Pasteurella multocida. Twenty-four hours later, chest x-rays and quantitative blood cultures demonstrated pneumonia and bacteremia. Therapy was then begun with penicillin G and either recombinant human G-CSF (rG-CSF; 5 to 8 micrograms/kg subcutaneously) or placebo every day for 5 days. Arterial blood gases and 23 other parameters of organ function were performed before inoculation and serially thereafter. All rabbits underwent histologic examination of organs at the time of septic death or when sacrificed on day 6. A total of 149 rabbits survived long enough to initiate therapy. A significant increase in leukocytes by day 4 was found in the rG-CSF-treated group. There was a trend towards improved survival in the rG-CSF group (77% v 67%; P = .13, n = 149). Analysis of pretreatment variables revealed sepsis-induced leukopenia (< or = 2,800/microL) as the only predictor of significantly improved survival with rG-CSF treatment (57% v 39%; P = .04, n = 73). The majority of the survival benefit occurred within the first 24 hours of treatment. This was before the time that a significant difference in mean white blood cell (WBC) count was observed between the study groups, making intravascular leukocytosis an unlikely explanation for the survival advantage in the rG-CSF group. No significant difference in laboratory variables reflecting organ function was demonstrated between the groups. Histologic grading of inflammation (0, normal, to 6, necrosis) in seven organs revealed that the surviving rabbits had mild but statistically significant increased inflammation in the liver, spleen, and noninoculated lung in the rG-CSF versus placebo groups (liver: 2.6 v 1.5, P < or = .0001; spleen: 3.2 v 2.3, P < or = .0001; and noninoculated lung: 2.9 v 2.5, P = .04). Administration of rG-CSF, in addition to penicillin G, in immune competent rabbits with gram-negative sepsis complicated by leukopenia significantly improved survival over antibiotics alone. The administration of rG-CSF in early sepsis for a short therapeutic duration was not associated with any clinically evident toxicity. Clinical trials using rG-CSF in septic patients with leukopenia are indicated.
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PMID:Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in a randomized blinded study of gram-negative pneumonia sepsis: analysis of survival and multisystem organ failure. 754 3

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

Beta 2-microglobulin (beta 2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. Beta 2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T = toxoplasmosis, O = others, R = rubella, C = cytomegalovirus and H = herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF beta 2m levels compared to neonates with sterile culture (6.24 +/- 2.66 vs 1.74 +/- 0.5 mg/l; P < 0.0001). CSF beta 2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF beta 2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98 +/- 2.5 vs 3.2 +/- 0.25 mg/l; P < 0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF beta 2m was accurate in distinguishing between neonates with and without CNS infection. Conclusion. CSF beta 2m may be a useful ancillary tool in neonates when CNS infection is suspected.
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PMID:Cerebrospinal fluid beta 2-microglobulin in neonates with central nervous system infections. 760 83

Thymoma has been associated with a variety of autoimmune disorders. We report a case of agranulocytosis and anemia in a 68-year-old woman with a spindle cell thymoma. She was unresponsive to treatment with antibiotics, granulocyte-colony stimulating factor (G-CSF), prednisone, and high-dose intravenous immunoglobulin. Serial bone marrow examinations on this therapy showed progression from a cellular marrow with mild myeloid and erythroid hyperplasia and lymphocytosis, to granulocyte aplasia and severe erythroid hypoplasia. Her serum contained granulocyte-specific antibodies and inhibited the growth in culture of her own marrow cells and marrow cells from a normal donor. An IgG fraction from her serum also inhibited the growth of marrow cells. Although the patient's spindle cell thymoma was surgically removed, she remained neutropenic. She was treated with six plasma exchanges followed by 1,000 milligrams of intravenous cyclophosphamide 2 days after the final plasma exchange and daily G-CSF. Three weeks later her peripheral blood showed marked leukocytosis with pronounced neutrophilia and a left shift. Although her agranulocytosis resolved, she died of fungal sepsis. This case demonstrates that aggressive plasma exchange and immunosuppressive therapy may benefit patients with agranulocytosis associated with thymoma.
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PMID:Immune mediated agranulocytosis and anemia associated with thymoma. 763 79

We presented a case of critical illness polyneuropathy after bacterial peritonitis. A 62-year-old male was received an emergency colectomy because of perforation of the sigmoid colon five days after the endoscopic polypectomy. He developed sepsis from peritonitis after operation in spite of the antibiotics therapy. On 15-th hospital days he developed muscle weakness and numbness of all limbs. He needed an artificial ventilator due to respiratory failure. Hematological and blood chemical findings showed a leukocytosis and metabolic acidosis with renal dysfunction because of sepsis. Serum anti-Campylobacter antibody was negative. Serial CSF examinations failed to show any abnormalities including albuminocytologic dissociation. Electrophysiological studies revealed a primary axonal degeneration, mainly in the motor, but also in the sensory nerve. Compound muscle and sensory action potentials were not elicited or markedly reduced without conduction velocity prolongation. Microscopic findings of the left sural nerve biopsy showed a primary axonal degeneration without evidence of inflammation. His prognosis was poor and three months later, he still required ventilatory assistance. Because of these clinical findings this patient was thought to have a critical illness polyneuropathy after excluding various etiologies of polyneuropathies. This case suggests that sepsis may be one of a cause of primary axonal polyneuropathy. The certain mechanism of this disease is still unknown. However cytokine, tumor necrotic factor(TNF) and/or Platelet activating factor(PAF) that secreted during sepsis may have an important role for the primary axonal degeneration.
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PMID:[A case of critical illness polyneuropathy in association with peritonitis after sigmoid colon perforation]. 766 19

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM-CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils. 767 96

Granulocyte colony-stimulating factor (G-CSF) stimulates the production and function of neutrophils (PMNs). Administration of G-CSF to non-neutropenic animals has been shown to improve survival in experimental models of infection, but PMNs have been implicated as mediators of acute lung injury induced by lipopolysaccharide (LPS) or bacteremia. Thus G-CSF-induced neutrophilia might be deleterious in sepsis. To investigate this possibility, we studied four groups of pigs: G+E50 (n = 6) were pretreated for 5 days with recombinant bovine (rb) G-CSF (5 micrograms/kg/day) and then challenged with LPS (50 micrograms/kg); NS+E50 (n = 6) were similarly pretreated with saline and challenged with LPS (50 micrograms/kg); E250 (n = 6) were not pretreated and were infused with a larger dose of LPS (250 micrograms/kg); RL (n = 7) were controls infused with lactated Ringer's solution. Pretreatment with rbG-CSF increased the peripheral absolute neutrophil count approximately fivefold (p < 0.05 vs. RL group). Comparisons of the NS+E50 and G+E50 groups showed that pretreatment with rhG-CSF did not affect LPS-induced alterations in mean arterial blood pressure or arterial oxygenation. Indices of pulmonary injury also were similar in these two groups, although pulmonary edema and protein leakage into alveoli were greater in the E250 group. We conclude that G-CSF-induced neutrophilia does not adversely effect physiologic responses to LPS in pigs.
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PMID:Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs. 768 31


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