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)

Despite its potential advantages HDF has not gained large clinical acceptance among nephrologist due to its technical complexity and to the large quantity of pharmaceutical substitution fluid needed. HDF with on-line production of substitution fluid from dialysate simplifies the procedure and reduces the cost of treatment session. We treated regularly 13 high risk and/or non-compliant patients (9 males, 4 females) with HDF for 46 +/- 17 months. HDF program consisted of 3 sessions weekly lasting 210 +/- 10 mn with blood flow rate 350 +/- 20 ml/mn and fluid volume exchange of 20 liters/session. High flux dialyzers (HF80, Filtral 16) were reused 6 to 13 times automatically on a Renatron machine with peroxyacetic acid solution as sole cleaning and disinfecting agent. Microbiologic quality of infusate was assessed by membrane filtration culturing method and LAL endotoxin determination. 3937 HDF sessions were performed. 57.140 I of substitution fluid were infused IV to patients. Eight pyrogenic reactions were observed: 2 due to septicemia related to catheter infection and 6 from unknown origin. Adequacy of program was achieved in all patients. Blood pressure control was satisfactorily obtained without antihypertensive medication in 12/13 patients. Effective weekly integrated urea clearances was 150 +/- 15 l/wk, KT/V index was 1.50 +/- 0.10, urea TAC 20 +/- 2 mM/l and protein catabolic rate 1.40 +/- 0.10 g/kg/24 h. We conclude that HDF with on-line production of bicarbonate substitution fluid is a safe and highly efficient method cost-competitive with bicarbonate HD, which offers an interesting alternative for renal replacement therapy.
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PMID:[Hemodiafiltration with on-line production of bicarbonate infusate: 5 years of clinical experience]. 157 93

Lipid A is the toxic component of bacterial endotoxins (LPS) and LPS has been thought to be clinically important in Gram-negative bacterial sepsis, as well as in non-bacteremic states where endotoxemia of enteric origin may be deleterious. The presently accepted method of detecting both LPS and its common lipid A moiety is the Limulus lysate amebocyte assay (LAL), but this test cross-reacts with non-bacterial antigens and serum contains natural inhibitors to the reaction. As an extension of previous work using a polyclonal antibody, we have developed a rapid and sensitive monoclonal antibody assay for lipid A. This 3-step inhibition ELISA is reproducible in aqueous solutions and capable of detecting less than 10 pg/ml of this shared toxic endotoxin component. The assay does not detect intact LPS but acid hydrolysis releases the active lipid A for reaction. While already valuable in detecting lipid A in biological solutions, the presence of naturally occurring anti-lipid A immunoglobulins in serum interfere with the reaction and cause false positives in this inhibition assay. Clinical usefulness of the assay will depend on removal of these antibodies from serum prior to testing.
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PMID:A rapid sensitive monoclonal assay for lipid A in solution. 242 64

Patients with multiple organ failure secondary to intraabdominal sepsis are often blood culture negative despite exhibiting the features of septic shock. This study examined the possible central role of endotoxin in such patients. In 15 consecutive intensive care patients with the above clinical picture endotoxin was measured by a chromogenic limulus (LAL) assay; on admission and thereafter 4 hourly. Regular blood cultures and cultures of any primary septic focus were also performed and liver function was assessed by measurement of indocyanine-green clearance from plasma (ICGC). All 15 patients had significant endotoxaemia at least intermittently. No significant difference was observed between survivors (n = 5) and non-survivors (n = 10) in either initial or peak endotoxin levels, although the pattern of endotoxaemia differed with non-survivors exhibiting consistently high or steadily increasing levels. Of 5 patients with an intra-abdominal (I/A) septic focus only one had a positive blood culture while 5 of 10 patients with extra-abdominal (E/A) infection had positive cultures. Despite this the I/A group had higher initial and peak endotoxin levels. 3 patients with Gram-positive septicaemia had significant endotoxaemia in the absence of any gram-negative infection. Changes in ICGC appeared to be of useful prognostic significance. ICGC was significantly lower in the I/A group and in both groups there was a significant negative correlation between ICGC and the level of endotoxaemia. These results suggest that endotoxin may play a central role in the syndrome of multiple organ failure and further suggest that the endotoxin is endogenous (gut-derived) secondary to failure of hepatic filtration.
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PMID:Endotoxaemia in multiple organ failure due to sepsis. 339 65

In patients with severe underlying disease and in polytraumatized patients, clinical signs of septicemia caused by infections with gram-negative bacteria are observed postoperatively with increasing frequency. Using a photometric LAL test, a longitudinal assessment of LAL reactivity on 41 intensive care patients was performed. Postoperatively, all patients developed a septicemia of different severity with body temperatures greater than 38.5 degrees C. Dividing the individual disease course, related to body temperatures, into three phases (A-C) it was found that independent of the severity of septicemia, the majority of patients (38/41) yielded a positive LAL reactivity. In phase B (body temperature greater than 38.5 degrees C) more plasma samples contained LAL-reactive material than in phase A and C (body temperature less than 38.5 degrees C). A decline of fever (phase B to C) correlated significantly (P less than 0.05) with the change from positive to negative LAL reactivity. In patients with high leukocyte counts (15-50 X 10(9)/l) a positive LAL reactivity was found more frequently. The majority of patients (21/27) who survived were transferred with negative LAL reactivity to the general wards. The results suggest that single determinations of LAL reactivity are of limited clinical validity. Using the individual profile of LAL reactivity gained through a longitudinal assessment, data upon the development of the disease course can be obtained.
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PMID:Endotoxemia in intensive care patients: a longitudinal study with the limulus amebocyte lysate test. 643 89

Both the PEG-N technique and the PACIA were applied to determine ICLM in sera from patients with liver cirrhosis and gram-negative septicemia, that have been shown to yield positive reactions for endotoxemia with the LAL test. The precision of the PEG precipitation technique, with a stabilized fraction of human HAG of known molecular size used as a calibrator, was satisfactory. In liver cirrhosis, the detectable ICLM was mainly composed of IgG and C3, whereas in gram-negative septicemia IgM, IgG, and C3 were found. PACIA also measured significantly elevated levels of ICLM with rheumatoid factor-binding activity in both patient groups, although the two assay systems did not correlate. PEG precipitates from both patient groups analyzed by gel-chromatography and passive hemolysis test contained large immune aggregates and various amounts of immunoglobulins with specificity directed toward lipid A, the least variable portion of endotoxin. These compositional differences of detected substances may imply the presence of different types of ICLM in patients with liver cirrhosis and gram-negative septicemia.
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PMID:The polyethylene glycol precipitation technique and the particle-counting immunoassay for detection of circulating immune complex-like material in liver cirrhosis and septicemia. 707 26

Systemic sepsis and multiple organ failure are frequent and often fatal complications after major surgery and trauma. In contrast to the biphasic hemodynamic pattern characteristically seen in patients, most experimental animal models have failed to reproduce the early, hyperdynamic phase of sepsis and endotoxemia. We have designed a standardized model of endotoxemia, which is elicited by continuous IV infusion of Salmonella abortus equi endotoxin in anesthetized juvenile pigs (age 8-12 weeks). The plasma concentration of endotoxin--as evaluated by the LAL test--is significantly elevated within less than half an hour following the start of endotoxin administration and is accompanied by a rapid fall of the leukocyte count in peripheral blood. High cardiac output and low systemic vascular resistance reflect a hypercirculatory state, during which left ventricular filling pressure is maintained by carefully monitored volume substitution (6% dextran 60). In the present investigation, different doses of endotoxin (3.8 and 11.4 micrograms/kg, respectively) were infused intravenously and investigated for their effect on respiratory, macrocirculatory, and regional blood flow alterations. The development of respiratory deterioration depended on the duration of endotoxin administration and on the height of endotoxin plasma levels. In all animals, a high cardiac output was maintained throughout 3.5 hr of endotoxemia. Regional blood flow to the myocardium and liver increased, whereas blood flow to the gastrointestinal tract and the spleen was compromised without difference between both groups. It is concluded that this porcine model should provide the potential for further insight into the early pathophysiological mechanisms involved in the development of multiple organ failure in patients with sepsis and endotoxemia.
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PMID:A porcine model of hyperdynamic endotoxemia: pattern of respiratory, macrocirculatory, and regional blood flow changes. 851 88

In an open, uncontrolled pilot study, 5 men and 1 woman with suspected gram-negative sepsis were treated with a new whole-blood endotoxin adsorption system. Lipopolysaccharide (LPS) adsorption was carried out by hemoperfusion over high-affinity polymethacrylate-bound albumin (Fresenius Endotoxin Adsorber EN 500). All patients suffered from endotoxemia (>20 pg/ml LAL) and met at least two systemic inflammatory response syndrome (SIRS) criteria. Four patients suffered from pneumonia due to mechanical ventilation, one from peritonitis, and one from pneumonia and peritonitis. Endotoxin adsorption was very well tolerated, and efficient LPS removal was shown in all patients. Apache II score immediately before immunoadsorption was 23.5 and was 22.3 after the last treatment. All 6 critically ill patients improved substantially and were discharged from the intensive care unit. LPS whole blood immunoadsorption is a promising new method. No side effects have been observed thus far. A large controlled study to prove clinical efficacy in patients with severe sepsis is under way.
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PMID:A new endotoxin adsorber: first clinical application. 1177 16

Bartonella quintana has been reported as the cause of trench fever, persistent endocarditis, bacteriaemia and has been isolated with an increasing incidence in clinical specimens from AIDS patients. One of the main pathogenic factors of gram-negative bacteria, including B. quintana, is the lipopolysaccharide (LPS). However, very little information is available on the features of Bartonella LPS. The aim of the present study was to extract, purify and characterise B. quintana LPS. The effect of the LPS under scrutiny was also evaluated on TNFa release by means of the "in vitro" human whole blood model of sepsis. The Oklahoma strain of B. quintana was grown on sheep blood agar, at 37 C, in a moist atmosphere containing 5% carbon dioxide. Cells were harvested and washed in sterile and apyrogenic saline solution and LPS extracted following the procedure of Westphal e Jann (1965), modified by Minnick (1994). The LPS of B. quintana showed the migration pattern of a deep rough chemotype, and the chromogenic limulus amoebocyte lysate test (LAL test) revealed strong reactivity at low concentrations (6.2 pg/ml). Samples of human whole blood stimulated by 1000 ng/ml of B. quintana LPS released 1707 378 pg/ml of TNFa.
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PMID:[Extraction and characterization of the lipopolysaccharide of Bartonella quintana] 1275 89

In order to investigate the effect of carbapenems on systemic endotoxemia, 20 patients with severe sepsis due to ventilator-associated pneumonia and Gram-negative bacteremia were enrolled; 10 (group A) were administered 1 g t.i.d. of imipenem/cilastatin and 10 (group B) 2 g t.i.d. of meropenem. Blood was sampled at 0 time and after 1, 2, 4, 6, 12, 24, 36, 48, 60, 72, 84 and 96 hours for detection of endotoxins (LPS), interleukin-6 (IL-6), C-reactive protein (CRP) and drug levels. LPS were determined by the QCL-1000 LAL assay, IL-6 by an enzymeimmunoassay, CRP by nephelometry and carbapenem levels by a microbiological assay. We did not find that carbapenems had any effect on the kinetics of LPS and CRP; IL-6 of group A was lower than group B at 72 and 84 hours. No correlation was observed between drug levels of any carbapenem and LPS, IL-6 or CRP. It is concluded that in septic patients with Gram-negative bacteremia administration of either imipenem or meropenem did not affect systemic endotoxemia. The above data support the safe administration of both carbapenems in patients with severe sepsis.
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PMID:Impact of carbapenem administration on systemic endotoxemia in patients with severe sepsis and Gram-negative bacteremia. 1712 27

Many clinical experiments and studies have demonstrated that traditional Chinese medicines possess the capacity for being used in anti-sepsis. In this paper, we screened 78 herbs based on biosensor technology by targeting of lipid A. Terminaliachebula Retz was found to possess the highest capability of binding lipid A. With CER (cation-exchange resin) and HPLC, we obtained three active components extracted from Terminaliachebula Retz, and named them TCR1, TCR2 and TCR3 respectively. These three components were evaluated with the biosensor, and it was found that the TCR3 was the most capable candidate to bind lipid A. We also studied the biological activities of TCR3 against sepsis in vitro and in vivo. in vitro, TCR3 could significantly inhibit LPS (lipopolysaccharide)-induced LAL (Limulus amoebocyte lysate)) from agglutination and decrease TNFalpha (tumour necrosis factor alpha) release from RAW264.7 cells induced by LPS in a dose-dependent manner. in vivo, TCR3 could significantly protect mice against a lethal challenge with LPS and heat-killed Escherichia coli 35218 in a dose-dependent manner. These results demonstrate that Terminaliachebula Retz is an important herb to neutralize LPS and it has the potential to serve as a treatment for sepsis.
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PMID:Extraction of the anti-sepsis component from Terminaliachebula Retz and evaluation of its biological activities. 1920 50


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