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

The administration of branched-chain amino acids (BCAAs) has been proved useful in reducing both urea nitrogen production and muscle proteolysis in trauma patients with sepsis, but the optimum infusion rate to achieve these effects is still in question. In this prospective randomized study, a group of 16 posttrauma patients with sepsis received a branched chain-enriched (BCAA = 49.4%) amino acid mixture (8 patients; 120 observations) or a standard amino acid infusion (BCAAs = 15.5%; 8 patients; 227 observations). Total calories, percent lipid calories, and amino acid nitrogen administration were not different in the two groups. Each patient was studied at 8-hour intervals for the plasma levels of amino acids, six hepatic acute-phase proteins, albumin, and other metabolic parameters, including urinary urea nitrogen and 3-methylhistidine excretion. The total intake of each amino acid and its clearance were calculated and the dose of leucine during each 8-hour period was related to the leucine clearance, plasma acute-phase protein levels, and the urinary production of urea and 3-methylhistidine, as an indicator of proteolysis. The results show a significant (r2 = 0.691; p less than 0.0001) reduction of urea nitrogen production and proteolysis as a function of the increase in leucine dose. The identification of a critical mean rate of leucine infusion has been derived from the analysis of the significant linear correlation between leucine intake and leucine clearance (r2 = 0.594; p less than 0.0001). Significant positive correlations between the leucine intake dose and the platelet count (r2 = 0.402; p less than 0.0001), the plasma fibrinogen level (r2 = 0.218; p less than 0.0001), and the regression-derived sum of six acute-phase proteins plus albumin (r2 = 0.696; p less than 0.0001) were found. The increase in leucine clearance was progressively less marked above a mean daily leucine intake rate of 1.4 mumol/kg/min, which also appeared to be the dose level that maximized the acute-phase protein and coagulation effects and reduced proteolysis and urea nitrogen production, suggesting that this is a critical BCAA infusion rate at which an optimum leucine effect occurs. From these data a BCAA (leucine) dose nomogram has been derived.
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PMID:Leucine dose response in the reduction of urea production from septic proteolysis and in the stimulation of acute-phase proteins. 171 Mar 95

Mechanisms of nutrient alteration of hepatic protein synthesis during sepsis are unclear. In vitro, arginine downregulates endotoxin-stimulated hepatocyte protein synthesis but in vivo effects are unknown. This study evaluated the effects of supplemental arginine or glycine on fibrinogen (acute-phase protein), histone, albumin, and liver protein synthesis after Gram-negative sepsis in the rat. Adult rats (225 g, n = 36) were randomized to receive isonitrogenous isocaloric total parenteral nutrition supplemented with 264 mg of N per kilogram per day as either arginine or glycine. On day 5, each group was further randomized to control or sepsis. Sepsis was induced by injection of 8 x 10(7) Escherichia coli per 100 g body weight, and then a continuous infusion of [1-14C]leucine was started. The rats were sacrificed 4 hours later. The fractional protein synthesis rates (percent per day) of histone, fibrinogen, albumin, and liver were determined. Supplemental arginine led to significantly increased histone (p less than 0.05, analysis of variance) and fibrinogen (p less than 0.01, analysis of variance) synthesis in the septic rats compared with all other groups. Histone and albumin synthesis were also significantly increased (p less than 0.05) in the arginine-supplemented control group compared with the glycine-supplemented control group. Arginine supplementation during sepsis significantly increased (p less than 0.05) albumin and liver protein synthesis compared with controls. Histones which are involved in DNA synthesis and are rich in arginine may play a role in the host response to stress and sepsis. These in vivo results appear to contradict hepatocyte-Kupffer cell coculture studies perhaps because of the hormonal and cytokine responses to nutrient substrate and acute septicemia.
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PMID:Harry M. Vars Research Award. Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat. 171 54

The clearance rate of endogenous and exogenous circulating lipids during the septic or inflammatory state remains a controversial subject. Thus, we have developed rat models of gram-negative and gram-positive sepsis and of sterile inflammation to study this problem. In addition to the febrile response, these stresses induced some of the following metabolic changes in the blood: decreased total protein, albumin, and ketone body levels and increased lactate, pyruvate, alanine, cholesterol, and triacylglycerol levels. The activities of heart, diaphragm, and adipose tissue lipoprotein lipase and of hepatic lipase decreased to differing extents depending on whether the enzyme substrate was a long-chain or a medium- and long-chain triglyceride-based emulsion. However, the latter emulsion was always hydrolyzed faster than the former. This observation suggests that, during infection/inflammation, the medium- and long-chain triglyceride-based emulsion would be cleared more quickly, would induce less hypertriglyceridemia, and would thus deliver lipid energy more rapidly than a traditional long-chain triglyceride-based emulsion.
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PMID:Decreased lipolytic activity in tissues during infectious and inflammatory stress. 180 2

Prospective evaluation were made of 45 patients with postoperative small bowel fistulas treated with total parenteral nutrition (TPN) and enteral nutrition (EN) between 1971-1988. The administration of TPN in the early treatment of enteric fistulas decreased the mean fistula output significantly (p < 0.05-0.001) and provided an effective tool in the control of high-output fistulas. The electrolyte contents of different fistula secretions were unchanged and the losses through the fistulas depended on the daily output. In patients with high-output fistulas acid-base balance disturbances had to be corrected. When comparing two parenteral nutrition regimens (carbohydrate+amino acids /CH + AA/ versus carbohydrate + amino acids + fat /CH + AA + F/) both facilitated the reduction of fistula secretion (in high-output fistulas. CH + AA = -50.2%; CH + AA + F = -49%). Positive nitrogen balance was achieved in non septic patients after 13 days of treatment. Improvement of serum protein and albumin occurred by the time of fistula healing. In non surviving patients significant decrease in protein synthesis was observed. Out 7 of 75 central venous catheters yielded positive bacterial cultures (9.3%). In 5 patients autopsy proved generalized sepsis. The use of parenteral and enteral nutrition proved to be a powerful method for controlling the enterocutaneous fistulas and maintaining the nutritional integrity of patients.
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PMID:Parenteral and enteral nutrition and the enterocutaneous fistula treatment. I. Investigations on fistula output, nutritional status complications. 184 21

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock. 187 10

This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.
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PMID:Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. 190 Oct 82

The influence of total parenteral nutrition (TPN) was studied in 67 patients with severe acute pancreatitis having three or more criteria according to Ranson (mean +/- SD = 3.8 +/- 0.21). Although TPN has been reported to not be of benefit in the progress and severity of the disease, we have found that the time TPN is started is important in influencing the course of the disease and in the development of local complications, as well as in the mortality rate. Patients whose TPN was started within the first 72 hours of the disease had a 23.6% complication rate and 13% mortality, in comparison with patients whose TPN was started later in the course of the disease, who had a 95.6% complication rate (p less than 0.01) and a mortality rate of 38% (p less than 0.03). The nutritional status of the patients during TPN administration of 28.4 days was maintained either steady or was improved, as assessed by nitrogen balance, serum levels of transferrin (p less than 0.05), and albumin (p less than 0.05). The administration of fat solution, either to prevent essential fatty acid deficiency or to provide part of the caloric requirements, was found to cause neither clinical nor laboratory worsening of the disease. All pancreatic fistulae that developed during the course of the disease spontaneously closed in patients receiving TPN without operation in a mean period of 33.3 days, and all pseudocysts subsided in an average of 18.3 days. Those who died (overall mortality rate 24%) had had uncontrollable sepsis, which resulted in hypercatabolism and multiple system organ failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Total parenteral nutrition in severe acute pancreatitis. 157 3

The metabolic response to sepsis is characterized by increased proteolysis and gluconeogenesis, reduced protein synthesis, and negative nitrogen balance. The effects of a solution with a high proportion of branched-chain amino acids (BCAA) on the nutritional state of septic patients were evaluated. Eighty patients with peritonitis were divided into two groups of 40 patients; group 1 was administered a solution with 22.5% BCAA and group 2 with 45% BCAA. The following parameters were evaluated: anthropometrics, creatinine/height index, urinary 3-methylhistidine, nitrogen balance, stress index, albumin, prealbumin, transferrin, retinol binding protein, lymphocytes, delayed cutaneous sensitivity tests, studies of hepatic function, and plasma aminogram. In group 2 a more positive nitrogen balance, a greater drop in the stress index, a rise in plasma prealbumin and retinol binding protein levels, an increase in the creatinine/height index, and a more marked fall in the urinary excretion of 3-methylhistidine were found. When solutions with a high BCAA content were administered, there was an increase in the plasma concentrations of these amino acids in the BCAA/aromatic amino acid quotient and a decrease in the aromatic amino acids. Plasma concentrations of leucine and valine achieved very high, potentially toxic, levels at 15 days when solutions with high BCAA content were used. It is concluded that solutions with BCAA are advisable for use in the septic patient in the increased protein catabolic phase, where positive nitrogen balance, a reduction in muscle protein catabolism, and faster recovery of muscle and visceral protein were obtained.
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PMID:Prospective study on the efficacy of branched-chain amino acids in septic patients. 190 75

Interferon-gamma (IFN-gamma) has been proposed for use following severe trauma to reverse depressed macrophage (M phi) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by M phi s and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis-induced MOFS by stimulating M phi s and leukocytes (WBC). This study addresses the following question: Does IFN-gamma predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits (n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO2, and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 micrograms/kg of Escherichia coli LPS iv, Group III (IFN-gamma alone) was given recombinant rabbit IFN-gamma (5.0 micrograms/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-gamma + LPS) received 3 days of IFN-gamma followed by LPS. One hour prior to sacrifice 5.0 microCi of 125I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO2, and WBC counts, and increased lavage/plasma ratio of 125I-albumin when compared to all other groups (P less than 0.05 by ANOVA, t test). Neither LPS alone nor IFN-gamma alone had a significant effect on measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon gamma increases sensitivity to endotoxin. 190 23

Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study. The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score. A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls. The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.
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PMID:Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater. 199 98


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