Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early postoperative infections and septic complications are predominant causes of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Prophylactic granulocyte colony-stimulating factor (G-CSF) administration after OLTx was found to decrease the number of sepsis episodes and sepsis-related mortality. Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defense, alteration of their functions may influence the development of sepsis in these patients. Therefore, we investigated in vitro whether or not priming with G-CSF affects the neutrophils' respiratory burst (RB) in immunosuppressed liver-transplanted patients. Venous blood was drawn from liver allograft recipients (n=12) between the 5th and 15th day postoperatively. Patients without clinical signs of infection or rejection were included in this study. Leukocytes were obtained as supernatant following sedimentation and incubated with 1000 IE ml-1 G-CSF. The RB was measured by the intracellular oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by flow cytometry. The results were expressed as a percentage of increasing stimulation compared to the control responses, which are made up of the percentage of cells with RB reaction after stimulation with phorbol ester (PMA), bacteria (E. coli), or the combination of a cytokine (TNF-alpha) and a bacterial peptide (FMLP) in the absence of G-CSF. In vitro priming with G-CSF resulted in significantly increased activity of the RB after PMA (from 71.7% to 85.6%) and TNF-alpha/FMLP (from 58.4% to 72.7%) stimulation. These data demonstrate that G-CSF in vitro augments the RB of PMNs, thereby suggesting a possible therapeutic role for G-CSF as immunomodulating agent during bacterial and fungal infections following OLTx.
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PMID:Neutrophil respiratory burst following liver transplantation: in vitro effects of granulocyte colony-stimulating factor. 1142 85

We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed (P = 0.06) increases in PMN (mean +/- SE change from baseline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 and +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/- 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors (P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN.
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PMID:Acute G-CSF therapy is not protective during lethal E. coli sepsis. 1155 26

Acute colonic pseudo-obstruction, the so-called Ogilvie's syndrome, is a rare and life-threatening digestive complication usually observed in critically ill patients. It is characterized by signs of large-bowel obstruction, without a mechanical cause, and has been reported in various settings, including acute leukemias as a complication of neutropenic enterocolitis after intensive chemotherapy. We describe the case of a young woman who, during the neutropenic phase following autologous bone marrow transplantation for relapsed acute myeloid leukemia, developed neutropenic enterocolitis complicated by an acute pseudo-obstruction of descendent colon and sigma. This process was associated with sepsis and resolved with conservative therapy of the underlying condition, using granulocyte colony-stimulating factor and intravenous neostigmine. We discuss the management of this rare syndrome.
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PMID:Ogilvie's syndrome in acute myeloid leukemia: pharmacological approach with neostigmine. 1173 75

This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m(2) over 96 h (days -12 to -8), etoposide 700 mg/m(2) every day x3 (days -6 to -4), and cyclophosphamide 4.2 g/m(2) on d -3 was followed by stem cells and granulocyte colony-stimulating factor. The median days of granulocyte count <500/microl was 14 (range 10-42) and platelets <20,000/microl was 13 (range 2-80). Median numbers of red cell and platelet transfusions were 15 (5-16) and 14 (4-103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values <50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0-56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1-68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal.
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PMID:Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer. 1178 46

No data on lipopolysaccharide-binding protein (LBP) in newborns with sepsis have been available up to now. We therefore determined levels of LBP and soluble CD14 (sCD14) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role. The study included prospectively collected patient samples of two recently published studies on cytokine expression in neonatal sepsis. Twenty-nine septic patients were enrolled in the present analysis. Samples--either cord blood or peripheral blood--from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood samples of a control group of 40 healthy mature infants delivered spontaneously were analyzed. For seven patients of the septic group, a second sample collected between 24 and 48 h of life was available. Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as standards. LBP and sCD14 were correlated to cytokine plasma levels. In septic neonates, LBP (median, 36.6 versus 7.8 microg/ml; P < 0.001) and sCD14 (median, 0.42 versus 0.28 microg/ml; P < 0.001) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor (G-CSF), interleukin-1beta (IL-1beta), IL-6, and IL-8 levels. LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to samples obtained at or shortly after delivery (median, 36.6 versus 60 microg/ml; P = 0.038). In summary, levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated; the elevated plasma levels seem to persist for more than 24 h, which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis.
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PMID:Elevated levels of lipopolysaccharide-binding protein and soluble CD14 in plasma in neonatal early-onset sepsis. 1187 91

Sepsis is an important cause of pediatric morbidity and mortality. Improving the outcome of pediatric sepsis requires diverse efforts, including prevention, early recognition, improvements in early management and transport, and physiology-directed care. Awareness that septic shock represents a pathophysiologic host response to infection has prompted investigation of immune mediators and coagulation factors as potential targets for anti-sepsis therapies. Advancements thus far include: the potential prevention of neonatal sepsis with granulocyte colony-stimulating factor; recognition of clindamycin as a potential inhibitor of endotoxin release; improved outcome from meningococcal disease in children treated with bactericidal/permeability-increasing protein (rBPI21); and improved outcome from sepsis in premature infants treated with pentoxifylline. Further randomized controlled studies of immunomodulatory agents are indicated and a few are in progress. Current studies on genetic propensities in cytokine and coagulation protein expression may explain variability in patient outcomes and eventually lead to genomics-based therapeutics.
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PMID:Improving the outcome of septic shock in children. 1196 95

To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not improved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P < 0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P < 0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy.
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PMID:Macrophage colony-stimulating factor (M-CSF) prevents infectious death induced by chemotherapy in mice, while granulocyte-CSF does not. 1198 93

Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.
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PMID:Cytokine modulation in sepsis and septic shock. 1215 Jul 2

Acute lymphocytic leukemia developed within 3 weeks after a fulminant case of varicella complicated by pneumococcal sepsis and severe bone marrow suppression in a child treated with filgrastim (human granulocyte colony-stimulating factor).
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PMID:Acute lymphocytic leukemia after fulminant varicella associated with severe neutropenia. 1294 Mar 35

Intravenous busulfan (i.v. BU) has demonstrated safety when administered at 0.8 mg/kg per dose i.v. every 6 hours x 16 doses. We evaluated the safety and pharmacokinetics (PK) of giving the same total daily i.v. BU dose (3.2 mg/kg) either divided as a twice-daily infusion or as a single infusion to patients undergoing hematopoietic stem cell transplantation (HSCT). Twelve patients with hematologic malignant disease were treated; 7 patients had non-Hodgkin's lymphoma, 4 patients had acute myeloid leukemia, and 1 patient had chronic myelogenous leukemia. The first cohort (group A) received, on the basis of actual body weight, i.v. BU at 1.6 mg/kg per dose over 4 hours every 12 hours for 4 days (day -7 to day -4). The second cohort (group B) received 3.2 mg/kg per dose of i.v. BU (same total dose as group A) as a single infusion over 4 hours daily for 4 days. In both groups the i.v. BU was followed by cyclophosphamide 60 mg/kg daily for 2 days (day -3 and day -2). Blood specimens were collected on the first, fifth, and seventh doses for group A and on the first and fourth doses for group B to determine the disposition of i.v. BU. Peripheral blood stem cells (autologous in 7 cases and HLA-matched allogeneic in 5 cases) were given 2 days after completion of cyclophosphamide administration (day 0), and granulocyte colony-stimulating factor 5 microg/kg was started on the same day. GVHD prophylaxis consisted of tacrolimus plus methotrexate for recipients of allogeneic stem cells. One patient developed presumed fungal pneumonia and died of multisystem organ dysfunction on day +21 before hematologic reconstitution could be evaluated. Another was reported to have sudden death of undetermined cause at home on day 40. The remaining patients had engraftment (absolute neutrophil count >500/microL) at a median of 11 days and sustained platelet counts >20,000/microL at a median of 14 days. Significant regimen-related toxicity (grade III-IV) was limited to hepatic toxicity (2 cases) catheter infection (2 cases), epistaxis (3 cases), diarrhea (1 case), anorexia (1 case), mucositis (1 case), hyperglycemia (1 case), pneumonia (1 case), and sepsis (1). In group B there was 1 case of mild venoocclusive disease, which resolved without sequelae. No central nervous system or pulmonary toxicity was noted. Pharmacokinetic parameters, including clearance, half-life, maximum concentration, and area under the curve, demonstrated that the first dose profile was highly predictive of later dose PK profiles. No accumulation of the drug was noted. The change in dosing schedule did not increase toxicity or end-organ damage despite higher plasma concentration-times. Although further study for long-term efficacy is warranted, i.v. BU can be given safely with reproducible results on a twice-daily divided or single-daily dosing schedule to patients undergoing HSCT.
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PMID:Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. 1237 50


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