Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro plasma perfusion experiments were performed using small columns containing either resin or charcoal adsorbents to assess the removal of cytokines and endotoxin. 125I-labelled tumor necrosis factor-alpha (TNF-alpha; 500 pg/ml) and interleukin-6 (IL-6; 10 ng/ml) were added individually to human plasma. Over 4 hr of perfusion, Amberlite XAD-7 resin removed 32.5% +/- 3.3% (n = 5) of the initial amount of TNF-alpha and 71.4% +/- 3.8% (n = 5) of the initial amount of IL-6. DHP-1 polyhema-coated activated charcoal removed 17.2% +/- 6.2% (n = 5) of TNF-alpha and 48.5% +/- 7.4% (n = 5) of IL-6. Preliminary experiments were performed with lipopolysaccharide (LPS; 100 ng/ml) and interleukin-1 alpha (IL-1 alpha; 500 pg/ml), which showed that, over 4 hr, Amberlite XAD-7 removed 10.3% of the initial LPS and 29.1% of IL-1 alpha, whereas DHP-1 charcoal removed 23.2% of the initial LPS and 65.3% of IL-1 alpha. In vitro plasma ultrafiltration with either polysulfone or polyacrylonitrile membranes, as used clinically in haemodialysis, was performed with recirculation of plasma containing LPS or TNF-alpha. Neither of the substances was filtered to a significant degree. In conclusion, direct removal of these inflammatory mediators from the circulation of patients with multiorgan failure due to fulminant hepatic failure or sepsis would be possible by perfusion of plasma through adsorbents but not by haemodialysis.
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PMID:In vitro plasma perfusion through adsorbents and plasma ultrafiltration to remove endotoxin and cytokines. 129 81

Multiple organ failure (MOF) is a serious condition that involves simultaneous or consecutive functional failure of several important organs. Furthermore, sepsis is known to play an important role in the occurrence of MOF. Hemoadsorption therapy with the endotoxin adsorption column containing polymyxin B immobilized fibers by direct hemoperfusion (PMX-DHP) is reportedly effective in the treatment of septic shock. This study examined the changes induced on cytokines upon PMX-DHP treatment in 25 patients who underwent emergency abdominal surgery and were immediately started on a postoperative regimen of continuous hemodiafiltration (CHDF) and PMX-DHP. Postoperative MOF was observed in these patients with a mean APACHE II SCORE of 25.5. Eighty percent of patients survived for more than 1 month. We were able to reduce the necessary dose of dopamine in 85.7% of patients because hemodynamic stability improved after administration of PMX-DHP. Interleukin 6 blood levels did not change significantly before or after PMX-DHP treatment in either the surviving or nonsurviving patients. Blood interleukin 1 receptor antagonist levels decreased in both groups. Intercellular adhesion molecular-1, NOx, and thrombomodulin did not change significantly during the course of treatment in either group. Decreased blood levels of PAI-1 levels were found in the surviving patients whereas increased levels of PAI-1 were found in the non-surviving patients. In conclusion, PMX-DHP treatment may be limited clinically in its ability to remove inflammatory cytokines and humoral mediators. However, PMX-DHP treatment is useful for hemodynamic stabilization, which prevents development of MOF.
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PMID:Changes of cytokines in direct endotoxin adsorption treatment on postoperative multiple organ failure. 1125 8

Despite the use of potent antibiotics and intensive supportive care, the mortality among patients with sepsis and Gram-negative bacteremia remains high. In recent years, endotoxin adsorption therapy (PMX-DHP, polymyxin-direct hemoperfusion) has been widely used in Japan to remove endotoxin, a causative agent of sepsis. In septic patients whose clinical condition may change at any moment, the decision of when to perform blood purification in addition to conventional intensive care is a critical factor in the therapeutic strategy and prognosis. In the present study, we investigated the effect over time of PMX-DHP in sepsis. The subjects were 16 patients with systemic inflammatory response syndrome (SIRS) who required surgical treatment including a surgical operation and drainage. The following six parameters were compared between the first and second PMX-DHP: mean blood pressure and time-restricted urine at four time points - at baseline and at 6, 24 and 72 h after PMX-DHP; and white blood cell count, platelet count, base excess and Septic Severity Score (SSS) at 24 and 72 h after PMX-DHP. Mean blood pressure improved over time up to 24 h after both the first and second PMX-DHP. Time-restricted urine volume improved only at 6 h after the first PMX-DHP. White blood cell count improved over time up to 24 h after both the first and second PMX-DHP. The SSS improved at all time points studied except for 3 days after the second PMX-DHP. We conclude that PMX-DHP is expected to have important implications in terms of (i) correction of clinical conditions (by severity assessment); (ii) improvement of hemodynamics; (iii) possible anti-inflammatory effect; and (iv) possible improvement of oxygen metabolism in tissues.
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PMID:Effect over time of endotoxin adsorption therapy in sepsis. 1582 24

To evaluate effects of polymyxin B direct hemoperfusion (PMX-DHP) on a neonatal sepsis cecal ligation and perforation (CLP) model, in 24 anesthetized and mechanically ventilated 3-d-old piglets, 16 were assigned to CLP and an arteriovenous extracorporeal circuit from 3 h until 6 h post-CLP, with a PMX-column in PMX-DHP-treated group (8 piglets) and 8 as sham. Plasma lipopolysaccharide (LPS) was measured at before CLP and at 3 and 9 h. Changes in mean systemic blood pressure (mSBP), mean pulmonary blood pressure, serum IL-6, tumor necrosis factor alpha, interferon gamma, and highly mobile group-1 box protein were measured before CLP and at 1, 3, 6, and 9 h. LPS was lower in the sham and PMX-DHP groups than in the control at 9 h. The mSBP was higher in the sham and PMX-DHP groups than in the control at both 6 h. IL-6 was lower in the sham and PMX-DHP groups than in the control at 6 h. HMGB-1 was lower in the PMX-DHP group than in the control at 6 h. IFN-gamma was only detected in the control group at 9 h. Survival times in the PMX-DHP group were longer than in the control. Thus, PMX-DHP improved septic shock in a neonatal septic model.
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PMID:Effect of hemoperfusion using polymyxin B-immobilized fiber on IL-6, HMGB-1, and IFN gamma in a neonatal sepsis model. 1600 26

Neutrophil activates and injures tissues and organs during sepsis or septic shock. Blood purification therapies such as continuous veno-venous hemofiltration (CVVH) and direct hemoperfusion with polymyxin-immobilized fiber (PMX-DHP) have been used for the treatment of sepsis and septic shock, however, the effects of such therapies on neutrophil activation have previously been poorly understood. We sought to evaluate neutrophil reactive oxygen species (ROS), especially H2O2 production, in the pathophysiology of sepsis or septic shock and the effect of CVVH or PMX-DHP on neutrophil ROS. Seven critically ill septic patients requiring CVVH (and 12 matched septic patients who did not require CVVH as control) and seven septic shock patients treated with PMX-DHP were studied. We found that patients with sepsis or septic shock had significantly higher levels of neutrophil ROS compared with normal volunteers (183 +/- 42, 292 +/- 90, and 103 +/- 30) (P < 0.05, and < 0.005). Neutrophil ROS did not change over time in patients treated either with CVVH or without CVVH. In contrast, neutrophil ROS significantly inhibited PMX-DHP treatment in patients with septic shock (pretreatment; 292 +/- 88 vs. post-treatment; 205 +/- 93, P < 0.05). In conclusion, neutrophil ROS was significantly enhanced in the sepsis or septic shock affected patients. CVVH did not affect neutrophil ROS while PMX-DHP significant inhibited neutrophil ROS.
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PMID:The effect of continuous veno-venous hemofiltration or direct hemoperfusion with polymyxin B-immobilized fiber on neutrophil respiratory oxidative burst in patients with sepsis and septic shock. 1655 30

Because of its low sensitivity, the conventional measurement method for endotoxin (ET) is not the most appropriate for monitoring the effect of ET adsorption therapy. Thus, the efficacy of ET adsorption therapy was investigated using a newly developed high-sensitivity ET assay method. The changes in the cytokine production capacity of whole blood were also examined. We treated 24 peritonitis patients who had developed postoperative septic shock with ET adsorption therapy using a column of polymyxin B-immobilized fibers (PMX) and their serum ET levels were measured using the high-sensitivity ET assay based on the kinetic turbidimetric Limulus assay. In addition, the changes in the tumor necrosis factor-(TNF-alpha) production capacity of whole blood following lipopolysaccharide (LPS) stimulation and clinical outcome in the study patients were also examined. The 28-day mortality rate was 12%. PMX-direct hemoperfusion (PMX-DHP) was associated with elevation of the mean arterial pressure and urine output, reduction in the mean dose requirement of vasopressor agents, and recovery from the shock state in all the patients. The PaO2/FIO2 ratio also showed significant improvement. Using the high-sensitivity ET assay, ET was detected in the blood of 20 out of the 24 patients (80%) before the PMX-DHP, and a significant reduction in the ET level was noted after the PMX-DHP. The TNF-alpha production capacity of whole blood, which was found to be lower in the septic shock patients than in healthy subjects, was significantly increased after PMX-DHP. Elimination of ET by PMX-DHP in septic shock patients was confirmed by the high-sensitivity ET assay. PMX-DHP is thus considered to be a useful adjuvant therapeutic technique in the treatment of septic shock. Also, PMX-DHP might alleviate the immunosuppression associated with severe sepsis.
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PMID:Endotoxin adsorption therapy for septic shock using polymyxin B-immobilized fibers (PMX): evaluation by high-sensitivity endotoxin assay and measurement of the cytokine production capacity. 1655 31

Toxic shock-like syndrome (TSLS) is a form of rapidly progressing septic shock that can lead to multiple organ failure and has a high mortality rate of 30%. We report a rare case of TSLS affecting the head and neck. A 40-year-old man complained of redness and swelling of the neck with vomiting and diarrhea. His blood pressure dropped, and multiple organ failure occurred. Streptcoccus pyogenes, Group A, was identified in a blood culture, and he was diagnosed as having TSLS. He was treated with high-dose carbapenem, clindamysin, and gamma globulin. Continuous hemodiafiltration (CHDF) and PMX-DHP was applied to prevent sepsis and multiple organ failure. Debridement of the neck was performed on day 16. He recovered gradually and was discharged from hospital on day 45. A total resection is required to treat TSLS, but such a procedure is difficult to perform in the head and neck region. Our case improved without resection but after debridement and general control. TSLS should be first treated by medication and then by surgery, consisting of either debridement or resection.
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PMID:[Case of toxic shock-like syndrome affecting the neck]. 1702 21

In the present study, we examined whether the performance of hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) reduces circulating interleukin-8 concentration in patients with sepsis. Fifteen patients with sepsis satisfying the following criteria were enrolled in the study: (i) signs of systemic inflammatory response syndrome caused by infection; and (ii) mean arterial blood pressure > or =60 mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for appropriate intravenous infusion, and the DHP-PMX was carried out twice at 24 h intervals (for 3 h each time). Circulating interleukin-8 concentration was measured seven times. The sequential organ failure assessment (SOFA) score was calculated twice. Circulating interleukin-8 concentration was 55 +/- 15.7 pg/mL before DHP-PMX, while it was 101 +/- 58.8 pg/mL immediately after the first session of treatment. It was 24 +/- 9.0 pg/mL before the second session of DHP-PMX, and it was 28 +/- 8.0 pg/mL immediately after the second session. The IL-8 level was 17 +/- 4.3 pg/mL at 48 h afterward, and 18 +/- 4.3 pg/mL at 72 h afterward, showing a significant decrease from 48 h onwards, compared with before treatment (P < 0.05). The SOFA score was 9 +/- 1.5 and the APACHE II score was 19 +/- 2.0 before DHP-PMX, while the SOFA score was 7.0 +/- 0.9 at 72 h afterward, showing a significant decrease compared with before treatment (P < 0.05). The present findings indicate that DHP-PMX indirectly reduces circulating interleukin-8 concentration and improves SOFA score.
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PMID:Hemoperfusion with an immobilized polymyxin B fiber column reduces circulating interleukin-8 concentrations. 1709 97

Recently, direct hemoperfusion with a polymyxin B-coated fiber column (DHP-PMX) has been increasingly used for the treatment of sepsis, and an improvement in outcomes has been reported. However, the mechanism of the method is not known in detail. In the present study, we examined whether the performance of DHP-PMX improved tissue oxygen metabolism in patients with sepsis. Twenty-two patients with sepsis, satisfying the following criteria, were enrolled in the study: (i) signs of systemic inflammatory response syndrome caused by infection; and (ii) mean arterial blood pressure > or =60 mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for appropriate intravenous infusion, and the DHP-PMX was carried out twice within 24 h (for 3 h each time). Then, the gastric mucosal-arterial PCO(2) difference (PCO(2) gap) was calculated as the gastric mucosal PCO(2) minus arterial PCO(2). A PCO(2) gap > or =8 mm Hg was used to define abnormal tissue oxygen metabolism. PCO(2) gap was measured before PMX-DHP, as well as 24, 48, and 72 h afterward. PCO(2) gap was 20 +/- 4.9 mm Hg before DHP-PMX vs. 16 +/- 2.7 mm Hg (P = 0.189) at 24 h, 12 +/- 2.8 mm Hg (P = 0.046) at 48 h, and 11 +/- 2.2 mm Hg (P = 0.045) at 72 h afterward, showing a significant decrease from 48 h onward compared with before treatment. These findings suggest that DHP-PMX improves tissue oxygen metabolism.
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PMID:Hemoperfusion with an immobilized polymyxin B fiber column improves tissue oxygen metabolism. 1709 98

Endotoxin-removal direct hemoperfusion column containing polymyxin B immobilized fibers (PMX-DHP) is an effective procedure for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS). We investigated retrospectively the effects and appropriate timing of PMX-DHP induction for directly induced ARDS in 38 patients. PMX-DHP was carried out twice for two hours. Blood pressure, heart rate (HR) and PaO(2)/FIO(2) (PF) ratio, leukocytes, platelets, endotoxin, inflammatory cytokines and clusters of differentiated peripheral neutrophils and monocytes were measured before and after PMX-DHP. Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores and lung injury scores (LIS) were determined at the time of starting PMX-DHP. The underlying causes of ARDS were pneumonia in 29 patients and aspiration pneumonia in 9 patients. The patients were divided into Survivors (n = 21) and Nonsurvivors (n = 17). Mortality was 45% at 30 days after PMX-DHP. The APACHE II and SOFA scores and the LIS were not significantly different between the two groups. The time from the onset of ARDS to the start of PMX-DHP was significantly delayed between the two groups. PMX-DHP significantly improved the PF ratio, HR and systolic blood pressure in the Survivors compared to the Nonsurvivors. The function of active monocytes in the peripheral blood was significantly suppressed after PMX-DHP. This early induction of PMX-DHP is indicated for directly induced ARDS. In the Nonsurvivors, this delay could have led to undesirable responses to oxygenation and circulation after PMX-DHP.
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PMID:Effects of PMX-DHP treatment for patients with directly induced acute respiratory distress syndrome. 1738 35


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