Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple organ failure (MOF) following major trauma occurs in response to perfusion deficits, a persistent inflammatory focus, or a persistent focus of dead and/or injured tissue. Several pathophysiologic aspects are considered relevant to current clinical practice. Their application in settings of trauma and surgical sepsis reduces overall mortality and incidence of multiple organ failure. With regard to the pathophysiologic background (I) microcirculatory resuscitation, (II) source control, and (III) metabolic support appear to be important therapeutic principles. (I) Microcirculatory Resuscitation: Since time is a critical factor in damage control, resuscitation and restoration of microvascular perfusion needs to occur as soon as possible if multiple system organ failure is to be avoided during the later time course. (II) Source control: The best treatment for multiorgan failure appears to be prevention. With early, aggressive control or removal of risk factors for multiple organ failure, namely early surgical intervention for control of hemorrhage, control of potential septic sources, decompression, and early fracture stabilization reductions in the incidence and mortality of MOF have been observed. Metabolic support: Malnutrition appears to be an important cofactor in morbidity and mortality. (III) Metabolic support needs to be started early and prior to the phenomenon of nitrogen retention during the hypermetabolic state of multiple organ failure.
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PMID:[Multiple trauma: definition, shock, multiple organ failure]. 158 21

The 'flow' phase response to head injury is characterized by hypermetabolism and catabolism of lean body mass. In order to measure the contribution of protein oxidation (CPO) to resting metabolic expenditure (RME), 11 severely head injured patients (AIS 5) were studied. All patients had 24 h urine collections for at least 10 days after injury and RME was determined at intervals by indirect calorimetry. No patient received exogenous steroids. Peak urinary nitrogen excretion was 11.63 +/- 1.28 g/m2/day occurring between days 6 and 9 after injury. Fat oxidation was the greatest component of the RME at all times after head injury and the CPO to RME was 26.4 +/- 2.9 per cent during days 1-2, 31.8 +/- 3.3 per cent during days 3-5, 28.6 +/- 3.4 per cent during days 6-9 and 23.3 +/- 3.8 per cent during days 10-20 after injury. These figures are higher than those previously reported for burns, musculoskeletal injury or sepsis. The mechanism for the increased CPO is unclear. It may be related to such conditions of management as paralysis and fasting, but more likely it is an idiosyncratic feature of the metabolic response to head injury.
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PMID:Substrate oxidation and the contribution of protein oxidation to energy expenditure after severe head injury. 158 69

Insulin-like growth factor 1 (IGF-1) is regulated by nutritional intake independently of growth hormone and may be a better nutritional indicator than the plasma proteins. This possibility was investigated in six malnourished inpatients, who suffered sepsis, surgical trauma, or both and who received total parenteral nutrition (TPN) for 10-35 days. Both plasma IGF-1 and pre-albumin showed (P less than 0.05) increases during TPN from baseline values of 0.042-0.42 U/mL (median, 0.11) and 59-156 mg/L (median, 108), respectively, to maxima of 0.19-1.12 U/mL (median, 0.63) and 140-363 mg/L (median, 203). Statistically significant (P less than 0.05) positive correlation occurred between nitrogen balance (range, -7.5 to +11.0 g/day) and IGF-1 or pre-albumin. Correlation between nitrogen balance and IGF-1 is preserved during the acute phase response to tissue injury when C-reactive protein (CRP) varies in the range 40-248 mg/L. Under these circumstances, the correlation between nitrogen balance and pre-albumin is, in contrast, abolished. These results suggest that IGF-1 behaves as a valid index of nutritional adequacy during parenteral feeding whereas pre-albumin reflects mainly the acute phase response.
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PMID:Insulin-like growth factor 1: a valid nutritional indicator during parenteral feeding of patients suffering an acute phase response. 162 15

Metabolic effects of a commercially available amino acid infusate were investigated in five preoperative patients with abdominal sepsis and five healthy subjects. Oxygen consumption (VO2) was measured continuously during the 3-h study, and blood samples were taken regularly for hormone and metabolite analyses. During 1 h of preinfusion measurements, VO2 was 15% higher (P less than 0.05) in the septic patients. Preinfusion plasma cortisol, glucagon, and catecholamines were also significantly elevated in the septic group. The amino acid solution (9 g nitrogen; 950 kJ; 227 kcal) was infused into each subject through their central venous catheter during the 2nd and 3rd h of the study. VO2 increased similarly in both groups by approximately 21% during the infusion (P less than 0.05), whereas respiratory quotient increased significantly in only the controls (P less than 0.05). Plasma insulin and glucagon concentrations rose significantly in both groups during the infusion, despite little change in glucose levels. Plasma norepinephrine increased in both groups, although the response was significant in only the control subjects. In summary, the amino acid infusate stimulated metabolic rate similarly in the septic and nonseptic subjects.
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PMID:Thermogenic and hormonal responses to amino acid infusion in septic humans. 163 90

1. The effect of total parenteral nutrition with or without glutamine enrichment was studied in septic rats after 4 days of treatment. 2. Septic rats treated with glutamine-enriched total parenteral nutrition survived sepsis significantly better than other TPN-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with glutamine-enriched total parenteral nutrition was 25% compared with 55% in septic rats given total parenteral nutrition without glutamine and 70% in septic rats given glucose. 3. Glutamine-enriched total parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was the least negative as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P less than 0.001) in response to glutamine-enriched total parenteral nutrition in septic rats. 5. The rate of protein synthesis was increased (21.2%) and the rate of protein degradation was decreased (35.5%) in response to glutamine-enriched total parenteral nutrition in septic rats. 6. It is concluded that the administration of glutamine-enriched total parenteral nutrition is beneficial to septic rats and possibly to septic patients.
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PMID:Effect of glutamine-enriched total parenteral nutrition on septic rats. 165 66

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine and alanine metabolism in lungs of septic rats. 168 36

Continuing researches on the monitoring of acute phase proteins (A.P.P.) as markers of septic risk in the surgery patient, a series of 50 patients suffering from pathological processes classifiable as follows has been examined: 1) acute biliary pancreatitis 18 cases; 2) acute hepatobiliary pathology without pancreatic impairment 26 cases; 3) burn 2 cases; 4) particularly serious sepsis in immunodepressed subjects 4 cases. The constant finding of increased values of PCR, fibrin, cerul, alpha 1-Trip in the surgery patient at septic risk and their normalisation after treatment is, in single cases, particularly significant and perfectly consistent with the clinical entity of the infectious process. In immunodepressed surgery patients showing deficiency in nitrogen balance and suffering from endotoxin shock a marked, persistent decrease in alpha 2-Macro, Tranfs, Albu and Prealbu parameters was noted. The reduction in these four A.P.P. can, in the Authors' experience, be considered a diagnostic indicator of sepsis of extreme gravity and an unfavourable prognosis finding regarding the course of the disease process.
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PMID:[Our experience concerning acute phase proteins (A.P.P.) in the monitoring of surgical patients at risk of infection]. 169 40

Sixty-four patients aged 2 to 18 years with advanced-stage Hodgkin's disease (HD) were treated on a Children's Cancer Study Group (CCSG) pilot toxicity study (521-P). Therapy consisted of 12 courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (ABVD), followed by low-dose (2,100 cGy in 12 fractions) regional irradiation (RT). All patients were monitored for toxicity with particular attention to the pulmonary system. Six patients (9%) developed grade 3 or 4 pulmonary toxicity. Three had grade 3 toxicity based solely on changes in carbon monoxide diffusing capacity (DLCO) and remained well for more than 3 years after diagnosis. There was one fatality among the three symptomatic cases. In five cases, toxicity occurred prior to RT. One occurred after seven courses of ABVD, one after nine courses, and three after 10 courses. In one of these five cases, ABVD was stopped. The patient was given nitrogen mustard (mechlorethamine), vincristine, prednisone, and procarbazine (MOPP). This patient subsequently developed recurrence of HD and died of overwhelming sepsis. The other four continued on study and completed their chemotherapy. Three patients had no further bleomycin, and one continued bleomycin at 50% of the assigned dose. They all received mantle RT following chemotherapy, one with a boost dose to the mediastinum to 3,800 cGy and one with added RT to both lungs (1,050 cGy). In the sixth case of pulmonary toxicity, symptoms were first noticed 2 weeks after mantle RT to 3,500 cGy. This patient died of progressive respiratory failure. The event-free survival (EFS) and overall survival is 87% at 3 years. These early results indicate that this therapy is effective in advanced HD in children but has a 9% incidence of acute pulmonary toxicity.
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PMID:Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional radiation in advanced Hodgkin's disease in children: a report from the Children's Cancer Study Group. 170 80

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

Hypermetabolism and multiple organ failure syndrome (MOFS) after trauma, surgery, or sepsis is associated with accelerated catabolism, the rapid onset of malnutrition, and immune system failure. Current nutritional support, enteral or parenteral, can achieve an acceptable nutritional response but appears unable to improve immune function. Nutrients such as arginine, refined menhaden oil, and RNA have been found to have immune-stimulating properties. This randomized blind prospective trial compared two nutritionally complete enteral formulas, one supplemented with arginine, menhaden oil, and RNA, on the disease-specific effects of anergy and suppression of in vitro tests of immune function in intensive-care patients and the nutritional outcome of nitrogen balance. After 7-10 days of enteral nutrition in patients with persistent sepsis syndrome, both formulas were associated with the achievement of net nitrogen retention and improved visceral protein status but with nonresolution of anergy. However, the supplemented formula was associated with marked stimulation of in vitro lymphocyte proliferative responses and a significant reduction in 3-methylhistidine excretion. Six and 12-mo follow-up data demonstrated no long-term effects. Nutrients targeted to effect the disease-induced in vitro suppression of immune function in MOFS appear to achieve that end independent of the nutritional outcome of nitrogen balance and without adverse clinical outcome.
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PMID:Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance. 172 41


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