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

In adults supplemental parenteral nutrition (PN) is advisable in burns over 40% especially when weight loss exceeds 10% of body weight. In children with smaller reserves and higher requirement of proteins and energy no rigid scheme for parenteral supplementation is used at our unit. In a young infant it may be added already at a 20-30% deep burn, especially with connected gastrointestinal tract problems, infection etc. Metabolic and protein requirements are estimated 50-100% in addition to their normal needs. Hypertonic glucose (gradually increased from 20-40%), covered with insulin in the early phase, is used as source of carbohydrates. L-amino acid mixture containing the "pediatric essential amino acids" histidine and cysteine is given as a nitrogen source. 20% Intralipid is given in a gradually increased amount of 2-4 g/kg per day to provide calories and essential fatty acids. Among electrolytes K, Ca, P and Mg must be added. Increased amounts of vitamin C and folate are needed by burned children. Vitamin E is also required during prolonged lipid administration. Trace elements (Zn. Fe, etc.) are supplied orally or i.v. with special solutions or fresh plasma infusions. Our experience with parenteral nutrition in severely burned children will be presented. There were no severe metabolic side-effects but sepsis represented the major problem. The concomitant heat preservation by warming the room and use of infra-red heaters is emphasized.
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PMID:Parenteral nutrition in severely burned children. 10 12

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.
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PMID:Plasma amino acids as predictors of the severity and outcome of sepsis. 38 83

There is considerable evidence to implicate aggressive species of oxygen in the pathogenesis of organ dysfunction consequent to sepsis and septic shock. The inflammatory process appears to participate ubiquitously in this setting. A characteristic of inflammation is the involvement of activated neutrophils and their generation of aggressive oxygen species. Such species may both directly injure cells proximal to the oxidant generating cells, and may inactivate any proteolytic mechanisms normally protective against proteolytic injury caused by neutrophil elastase and other proteolytic enzymes released during inflammation. The offending agent in sepsis is most commonly envisioned as bacterial lipopolysaccharide, or endotoxin. Infusion of endotoxin into animals can reproduce much of the pathophysiology of sepsis and septic shock. In addition, administration of endotoxin to cultured cells, particularly endothelial cells, can cause responses consistent with a sequence of events that occurs in intact animals and humans. In both experimental models, it appears that aggressive oxygen species are important actors in the scenario eventuating in cell or organ injury. Of importance, the toxic consequences of these free radicals probably occurs in relatively protected spaces, including microenvironments created by close adherence between inflammatory cells and endothelial cells and the cell interior. For those reasons, the potential for antioxidants as therapy should include consideration of the volume of distribution of such substances. It is probably important that antioxidants access excluded spaces including cell interiors in order to have their maximum effect in this setting. We have studied ina preliminary way the effects of n-acetyl-cysteine, a highly permeable free radical scavenger and anti-oxidant, in patients with established ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen radicals--an important mediator of sepsis and septic shock. 179 73

The response to injury and infection can be viewed as a mobilization of body protein, fat, and carbohydrate stores to ensure normal or above-normal circulating levels of substrate in the absence of dietary intake. The situation does not readily yield to nutritional manipulation, and inappropriate nutritional support can cause additional stress. Artificial nutrition is mainly a form of nutrient administration and not nutrient utilization. Modulation of neurohumoral and wound responses to trauma due to starvation and refeeding has not been delineated. The provision of adequate substrates alone does not necessarily guarantee their efficient use in metabolism. With a clear knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop more rational therapeutic approaches during critical illness. Determination of appropriate and optimal substrate support through parenteral and enteral nutrition remains of great clinical importance. The clinical application of branched-chain amino acids, dispensable amino acids, acetylated amino acids, dipeptides or tripeptides, cysteine, glutamine, and arginine has been explored in recent years. The idea that lipids are deleterious in sepsis and organ failure should be revised and documented, and recent studies suggest that fish oils as a lipid source may also favorably affect immune responses. Under stressful conditions, total parenteral nutrition can require large amounts of energy at a time when there are marked disturbances in glucose utilization. In this area, the use of nonglucose carbohydrates or oligosaccharides can be appropriate, despite the lack of broad acceptance. Existing conventional substrates should be studied beyond mere provision of energy and metabolic pathway support.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional and metabolic support: converging concepts. 180 4

High molecular weight kininogen (HMWK) is a multifunctional protein that is a parent molecule for bradykinin, a cofactor for coagulation, and an inhibitor of cysteine proteases. On immunoblot, nonreduced plasma HMWK is usually two bands at 140 kd and 120 kd; reduced plasma HMWK is a single band at 120 kd. In both concentration-dependent and time-dependent experiments kaolin-activated normal plasma HMWK becomes cleaved in an ordered sequence. When nonreduced, HMWK on immunoblot in kaolin-activated plasma changes in size from a 140 kd band through a 120 kd intermediate to result in a stable 100 kd protein. When reduced, HMWK on immunoblot in kaolin-activated plasma changes from a single 120 kd band through a 56 kd intermediate to result in a stable 46 kd protein. A similar sequence of cleavage of plasma HMWK occurs when the soluble activator dextran sulfate is used to stimulate the system. Cleavage of plasma HMWK after kaolin activation occurs similarly in factor XI-deficient plasma as in normal plasma but is decreased in prekallikrein-deficient plasma. Prolonged kaolin activation of prekallikrein-deficient plasma results in HMWK cleavage to bands below 120 kd. No band of plasma HMWK below 120 kd appears in prolonged kaolin-activated factor XII-deficient plasma. In some patients with sepsis, detectable cleavage of plasma HMWK to bands below 120 kd may not be seen, even though the patient has other evidence for contact system activation. In conclusion, these studies indicate that certain cleaved patterns of plasma HMWK on immunoblot indicate prior activation of the contact system. However, the absence of these cleaved forms of plasma HMWK in a single plasma does not exclude the occurrence of contact activation.
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PMID:Structural changes of plasma high molecular weight kininogen after in vitro activation and in sepsis. 245 60

Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in the BAL (Figs. 1, 2). Plasma concentrations of malondialdehyde were similar (Fig. 3). Only the levels of conjugated dienes were significantly higher on the 5th treatment day in the placebo group (Fig. 4). The organ function of the lung (FiO2, PEEP, PaO2), liver (SGOT, bilirubin), and kidney (creatinine) and coagulation parameters (PTT, prothrombin time, platelet count) were similar in the two groups during the time of investigation. We observed no clinically relevant differences in the tracheobronchial mucus (Table 2). CONCLUSION. The present data do not support routine use of NAC in ventilated patients, either as an antioxidant or as a mucolytic agent. Intravenous administration of 3 g NAC/day had no clinically relevant effect on glutathione levels, lipid peroxidation products, tracheobronchial mucus, and clinical condition.
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PMID:[The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study]. 748 27

Denutrition is often associated with poor postoperative outcome. However, a large body of evidence, from studies comparing perioperative parenteral (PN) or enteral (EN) nutrition to the absence of perioperative nutrition, suggests that perioperative nutritional support provides significant improvements in both nutritional status and postoperative clinical outcome in selected patients who are or will become malnourished. The aim of this study was to select and review all relevant articles comparing perioperative parenteral and enteral nutritional support, either in terms of clinical outcome, or risks and costs, or in pathophysiological terms. Twelve clinical reports were reviewed. All contained methodological flaws, mainly type II statistical error due to an insufficient number of patients, inaccurate primary diagnosis, absence of blinding, and lack of objective criteria of judgement. These concerns warrant caution in interpreting the results. Moderately strong (grade B) recommendations can only be drawn from these studies: PN (compared to early EN) is associated with a higher rate of sepsis in patients following abdominal trauma; EN is as efficient as PN in patients following surgery; EN is safe and cheaper than PN. PN formulae lack many important nutrients (glutamine, arginine, cysteine, peptides, fibers, n-3 polyunsaturated fatty acids, and nucleotides). Many experimental (animal) and some clinical (in non surgical patients) studies showed that PN (compared to EN) induces gut mucosal atrophy, liver dysfunction, gut bacterial translocation and immune dysfunction. The final aim of PN and EN would therefore strikingly differ. The qualitatively imperfect PN would only supply the fasting patient with quantitative amounts of calories and proteins. Due to initially limited digestive tolerance, EN provides less nutrition than PN does, but would finally lead to the same or even better outcome, due to its ability to counteract stress induced gut and immune dysfunction. Current evidence therefore suggests that early EN is superior to PN in trauma patients, and not different from but cheaper (and therefore more cost-effective) than PN in surgical patients. Further controlled, randomised, and blinded studies including sufficient sizes of groups are required, especially in the surgical setting, to address a large number of still unanswered questions.
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PMID:[Respective indications of enteral or parenteral nutrition during pre- and post-operative periods]. 748 29

The effects of endotoxin on the activities of the major Na(+)-independent amino acid transporters in rat liver (Systems n, asc, L, bo,+, and y+) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na(+)-independent amino acid transport systems y+ and bo,+ (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the Vmax of the high affinity carrier (System y+) and a 25% increase in the Vmax of the low affinity transporter (System bo,+). The data indicate selective stimulation of Na(+)-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis.
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PMID:Hepatic Na(+)-independent amino acid transport in endotoxemic rats: evidence for selective stimulation of arginine transport. 774 45

The effect of the antioxidant N-acetyl-L-cysteine was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. N-Acetyl-L-cysteine significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of N-acetyl-L-cysteine was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that N-acetyl-L-cysteine works as a direct antioxidant and scavenger of free radicals generated from other sources.
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PMID:Effect of N-acetyl-L-cysteine on sepsis in mice. 779 76

Nitric oxide reacts with superoxide to form peroxynitrite, a potential mediator of oxidant-induced cellular injury. The endothelium is a primary target of injury in many pathological states, including acute lung injury, sepsis, multiple organ failure syndrome, and atherosclerosis, where enhanced production of nitric oxide and superoxide occurs simultaneously. It was hypothesized that stimulation of endothelial cell nitric oxide production would result in formation of peroxynitrite. Immediate oxidant production was detected by luminol- and lucigenin-enhanced chemiluminescence from cultured bovine aortic endothelial cells exposed to bradykinin or to the calcium ionophore A23187. Luminol-enhanced chemiluminescence was efficiently inhibited by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester and by superoxide dismutase, implying dependence on the presence of both nitric oxide and superoxide for oxidant production. Inhibition of luminol-enhanced chemiluminescence by nitro-L-arginine methyl ester was partially reversed by L-arginine, but not by D-arginine. Cysteine, methionine, and urate, known inhibitors of peroxynitrite-mediated oxidation, inhibited luminol-enhanced chemiluminescence, while the hydroxyl radical scavengers, mannitol and dimethylsulfoxide, and catalase did not. Bicarbonate increased luminol-enhanced chemiluminescence in a concentration-dependent manner. Superoxide production, detected by lucigenin-enhanced chemiluminescence, was slightly increased in the presence of nitro-L-arginine methyl ester, suggesting that endothelial cell-produced superoxide was partially metabolized by reaction with nitric oxide. These results are consistent with agonist-induced peroxynitrite production by endothelial cells and suggests that peroxynitrite may have an important role in oxidant-induced endothelial injury.
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PMID:Agonist-induced peroxynitrite production from endothelial cells. 817 19


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