UMLS:C0036690 - FACTA Search

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

Bacterial translocation/Acute radiation syndrome/Endotoxin/G-CSF/OK-432 Acute radiation induces bacterial translocation from the gut, followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterial translocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterial translocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation.
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PMID:OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice. 1159 85

In this experimental study, consist of 54 Sprague-Dawley rats, we tried to observe the effectiveness of haemopoietic growth factors such as G-CSF and GM-CSF in treatment of sepsis and see if they have any effects on phagocytic activity of macrophages when are administered after establishment of sepsis. In first phase of this study, twenty one rats were randomly divided into three groups of 7 animals each. Cecal ligation and perforation were carried out in each rat and sepsis made up. The Control group received 2 x 0.2 cc %5 dextrose injection subcutaneous (s.c.).. The G-CSF group received 2 x 1 g G-CSF with 0.2 cc %5 dextrose s.c. The GM-CSF received 1 x 2 g GM-CSF with 0.2 cc %5 dextrose s.c. Seventh day survival was considered as criterion in the three groups. In second phase of this study, thirty three rats were randomly divided into three groups of 11 animals each. The same procedures were carried out also in these groups. Leukocyte counts and peripheric spread were analyzed in postoperative 24th and 72th hours, alveolar and peritoneal macrophages were Investigated in postoperative 72nd hour. There was significantly neutrophilic leukocytosis in the G-CSF group according to the control group. Nevertheless, there was no change in the phagocytic activity of alveolar and peritoneal macrophages. GM-CSF brought about positive effect of phagocytic activity of macrophages without change of leucocyte count in the sepsis, but it caused neutrophilic, monocytosis and lymphocytopenia. The seventh day survival rates in control, G-CSF, GM-CSF groups were as; 42.8%, 71.4%, 28.5% respectively. As a result, we saw that G-CSF has no effect on the phagocytic activity of macrophages, while increases the survival by enhancing the count and probably the function of neutrophils. GM-CSF fails to increase survival while effects the phagocytic activities of macrophages positively and enhances the peripheral neutrophil and monosit counts without changing the total number of leukocytes.
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PMID:[The effectiveness of hemopoietic growth factors in sepsis]. 1170 42

Bacterial sepsis continues to be an important cause of morbidity and mortality in neonates. Neutropenia in the newborn, as a result of decreased bone marrow neutrophil storage pool reserves and myeloid committed progenitor cells, increases the risk of sepsis and is associated with a poor prognosis. The hematopoietic colony-stimulating factors G-CSF (granulocyte colony stimulating factor) and GM-CSF (granulocyte-macrophage colony stimulating factor) increase the number of circulating neutrophil number by stimulating neutrophil precursors proliferation. In a number of clinical trials in very low birthweight neonates and in neonates with preeclampsia-associated neonatal neutropenia, both hematopoietic growth factors significantly increased the circulating absolute neutrophil count. However, no larger study showed that prophylactic G-CSF or GM-CSF treatment resulted in a reduction of infectious complications or in an improved overall survival. Similar results were seen in studies evaluating G-CSF and GM-CSF as intervention therapy in septic neonates. Therefore, experts do not recommend the routine use of the expensive growth factors in preterm and term neonates. However, prospective clinical trials are still needed to evaluate whether specific treatment groups will benefit from the use of G-CSF or GM-CSF. In this regard, efforts must be directed at better defining the endpoints and in particular assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups of patients.
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PMID:[Hematopoietic growth factors in prevention and therapy of infectious complications in premature and newborn infants]. 1172 63

Pseudomonas aeruginosa infection, one of the major complications of burn wounds, may lead to sepsis and death. Using the Multi-Probe Template/RNase protection assay, we have compared the expression of different cytokine genes within the skin and livers of thermally injured mice infected with P. aeruginosa PAO1. Thermal injury alone enhanced or up-regulated certain cytokines, including macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1)RI, IL-1 beta, macrophage inflammatory protein (MIP)-1 beta and MIP-2; while PAO1 challenge alone up-regulated tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) expression. The combination of thermal injury plus PAO1 infection enhanced the expression of several pro-inflammatory and haematopoietic cytokines [stem cell factor (SCF), leukocyte inhibitory factor (LIF), IL-6 and TNF-alpha]; induced the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF by 5 h and the expression of additional cytokines, including TGF-beta, TNF-beta, lymphotoxin beta (LT-beta), interferon gamma (IFN-gamma), and IFN-beta by 40 h post-burn/infection. While the most intense cytokine expression occurred in the skin, the majority of cytokines tested were also expressed in the liver by 40 h post-burn/infection. These results suggest that in P. aeruginosa infection of burn wounds: (1) up-regulation of the expression of different cytokines, locally and within the livers of burned mice, is an indication of P. aeruginosa -induced sepsis; and (2) IL-6 and G-CSF play an important role in the host response mechanism.
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PMID:The effects of infection of thermal injury by Pseudomonas aeruginosa PAO1 on the murine cytokine response. 1179 26

Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+) enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was 83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44) months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients.
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PMID:Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia. 1183 25

Sepsis is still a major problem in human medicine with a high mortality rate. Nearly all attempts to improve the outcome of septic patients with immune modulators failed. In most of these trials only mechanistic endpoints such as mortality rate, complication rate, cytokine levels and physiological parameters were assessed. Only in a very few trials quality of life had been chosen as primary endpoint. In basic research and especially in animal experiments in the field of sepsis and oncology, only molecular investigations which explain drug and treatment interactions were in the focus of the scientific community. Animal models simulating clinical complexity and investigating outcomes like quality of life were very rare. The aim of this study was to demonstrate alterations in sickness behaviour -- the animal equivalent to quality of life in man -- in rats as a response to sepsis after prophylaxis with G-CSF and antibiotics. Sickness behaviour was assessed by measurement of core body temperature, food and water intake, locomotor activity and circadian rhythm of these parameters. Complex animal experiments in rats were performed including anaesthesia, antibiotic and cytokine (G-CSF) prophylaxis, volume substitution, laparotomy, contamination and infection with human faecal suspension and postoperative analgesia. In group A (sham) and D (antibiotic + G-CSF) the mortality rate was 0%, but in group B (no prophylaxis) 33% (3/9) and in group C (antibiotic prophylaxis) 11% (1/9) of the animals died. Before infection all rats showed clear circadian patterns of locomotor activity and body temperature with physiologically higher values during the night-time. Immediately after operation and infection temperature increased, water and food intake, locomotor activity decreased and circadian rhythms were lost. Body temperature and water consumption were already normalised at day 2 after infection in all groups. Normal food intake was re-established in group C and D at day 3 while one more day was needed for recovery in Group C. Restoration of locomotor activity occurred in group D at day 5, in group C at day 7. In group B locomotor activity remained suppressed during the whole observation period of 8 days postoperatively. In conclusion, in septic rats sickness behaviour, an equivalent to quality of life in humans, is improved rapidly by a prophylaxis with G-CSF in combination with antibiotics and can be used as a new outcome in preclinical surgical research.
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PMID:Quality of life in animals as a new outcome for surgical research: G-CSF as a quality of life improving factor. 1256 90

Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.
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PMID:Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy. 1189 27

The relationship between peaks of G-CSF serum concentrations and respiratory burst activity of polymorphonuclear cells (PMN) was investigated in patients with postoperative or post-traumatic severe sepsis and septic shock. Over a 12 month period, a longitudinal analysis of G-CSF, TNF-alpha and IFN-gamma serum concentrations, burst activity of PMN, and expression of CD64 on the surface of PMN, were performed by ELISA technique and flow cytometric analysis, respectively, in 58 patients admitted to the intensive care unit (ICU) on a daily basis until discharge from the ICU or death. Out of these 58 patients, 27 with proven infections were in septic shock for at least 4 days' duration. Seventeen of these patients survived, whereas ten died. In 15 out of these 27 patients, 26 episodes of G-CSF peaks were observed, which were followed in most patients (13/15) by an increase in PMN burst activity, from 28% up to 540% (median 188%). Following the G-CSF peaks, CD64 expression on PMN remained at an increased level, followed by a marked decline 3 days later. TNF-alpha serum concentrations were elevated in most episodes (22/26), whereas IFN-gamma serum concentrations were below the detection level in 23/26 episodes. Taken together, peaks in G-CSF serum concentrations are followed by enhanced CD64 expression and increased burst activity of PMN in most patients with severe sepsis and septic shock. Thus, endogenous G-CSF increases neutrophil function in patients with severe sepsis and septic shock, necessary for resolution of bacterial infections in these patients.
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PMID:Peaks of endogenous G-CSF serum concentrations are followed by an increase in respiratory burst activity of granulocytes in patients with septic shock. 1202 9

Elderly patients have a higher incidence of morbidity and mortality due to infectious diseases. Because most immune functions in the elderly differ compared with those in younger subjects, we studied the effect of the immunomodulating agent G-CSF on endotoxic liver injury and cytokine release in an aging animal model of acute sepsis. Young (3-month-old), mature (12-month-old), and senescent (24-month-old) male Sprague-Dawley rats (n = 6 each) were treated with bacterial endotoxin for 6 h. Age-matched groups of animals (n = 6 each) received G-CSF (200 microg/kg i.v.) 1 h prior to endotoxin. LPS-induced hepatic toxicity, as assessed in vivo by nutritive perfusion failure, intravascular leukocyte accumulation, biliary excretion dysfunction, and liver enzyme release, was significantly more pronounced in mature and old animals when compared with young animals. Concomitantly, mature but, in particular, senescent endotoxic animals exhibited 2- to 14-fold higher plasma levels of TNF-alpha, IL-1beta, IL-6, IL-10, and Rantes than young endotoxic rats. The percentage of G-CSF receptor surface expression on neutrophils did not significantly differ between young, mature, and senescent animals (36%-46%) and was found comparably down-regulated at 6 h after LPS exposure (15%-19%). Kupffer cell activation, i.e., clearance of intravascularly applied fluorescent latex beads, did not differ between the LPS-exposed age groups. G-CSF dampened LPS-induced Kupffer cell activation, and significantly reduced plasma cytokine levels in young and mature, but not in senescent animals. Thereby, G-CSF caused attenuation of hepatic tissue injury in all except the senescent endotoxic animals. In summary, our results show an age-dependent increase in hepatic LPS toxicity. Because flow cytometric analysis of G-CSF receptor expression disproved that cytokinemia-induced down-regulation of G-CSF receptors might account for the unresponsiveness to G-CSF in the senescent animals, other homeostatic regulatory mechanisms appear to undergo changes with age that bring out a disrupted balance between inflammatory cytokines with unresponsiveness to G-CSF and, thus, compromised host defense mechanisms in the elderly.
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PMID:Age-associated loss of immunomodulatory protection by granulocyte-colony stimulating factor in endotoxic rats. 1239 79

A randomized, double-blinded, placebo-controlled trial was conducted of early administration of recombinant granulocyte colony-stimulating factor (rGCSF) to 40 non-neutropenic, preterm infants between 33 and 36 weeks of gestational age with the diagnosis of presumed sepsis. The treatment group (n = 20) received 5 microg/kg per day of intravenous rGCSF once daily for 3 d and the control group (n = 20) received the same volume of physiological serum. Immediately before the first dose and on the 4th day, plasma levels of GCSF and tumour necrosis factor-alpha (TNF-alpha), absolute neutrophil counts (ANC), immature neutrophil count (INC), immature/total neutrophil (I/T) ratios and platelet counts were determined. At study entry, the plasma GCSF and TNF-alpha levels were similar. On day 4, there was no significant change in GCSF levels in either groups, whereas there was a significant decrease in TNF-alpha levels in the treatment group. ANC and INC of the treatment group also increased significantly. The I/T ratio continued at the same level in the treatment group, but decreased significantly on days 4 and 7 day in the control group. The length of time on the neonatal intensive care unit (NICU) was significantly shorter in the treatment group. In conclusion, early administration of 3 daily doses of rGCSF (5 microg/kg per day) to non-neutropenic, preterm infants who had presumed sepsis increased circulating ANC and INC, decreased plasma TNF-alpha levels and shortened the length of time on the NICU.
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PMID:Randomized, double-blinded, placebo-controlled trial of early administration of recombinant human granulocyte colony-stimulating factor to non-neutropenic preterm newborns between 33 and 36 weeks with presumed sepsis. 1258 21

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