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)

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.
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PMID:Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial. 211 8

In this study, an experiment was performed to investigate the optimal concentration of branched chain amino acid (BCAA) in hyperalimentation to be administered when protein catabolism is accelerated by sepsis or bodily injury. Amino acid solutions containing BCAA 25%, 30%, 40%, 45% and 50% were prepared and were administered iv for three days with other essential amino acid-containing nitrogen in the same volume into rats with peritonitis which had been developed by ligature and puncture at the cecum, and the results were compared. After observing for three days, the influence over nitrogen balance, improvement of 3-methyl-histidine/creatinine in urine, weight loss in muscles, and aminogram in serum and muscles indicated that the hyperalimentation under stress is utilized most effectively when amino acid contains 45% of branched-chain amino acid.
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PMID:Optimum branched-chain amino acids concentration for improving protein catabolism in severely stressed rats. 211 47

It has been suggested that lipid is a preferred fuel in stressed patients. We evaluated glucose oxidation in 20 patients (sepsis, cancer of the colon, multiple trauma, controls) while they received TPN (5.65 mg glucose/kg/min). Respiratory quotient (RQ) was measured by indirect calorimetry and the percent VCO2 arising from the oxidation of glucose was measured using [U-14C] glucose. Since RQs were 1.0 or greater in all patients, the nonprotein energy utilized by them was calculated to be derived completely from glucose. However, the kinetic data showed that glucose contributed only 55-60% of the VCO2. Protein oxidation contributed less than 20% of the VCO2, as calculated from urinary nitrogen. The difference must have been derived from fatty acid oxidation. The glucose turnover that was not oxidized was presumed to be converted to lipid at an RQ of 8.6. The net oxygen consumption and carbon dioxide production from this overall distribution resulted in an RQ of about 1.0 with only 60% coming from glucose oxidation. Since all patients responded in the same manner, it appears that the proper ratio of glucose and lipid was dictated on a physiologic basis and not on the type of disease.
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PMID:A physiologic basis for the provision of fuel mixtures in normal and stressed patients. 212 Apr 66

The etiology and mechanisms by which severe trauma or sepsis induce hepatic failure are unknown. Previously we showed that Kupffer cells (KC), the fixed macrophages of the liver, induce a profound decrease in hepatocyte (HC) total-protein synthesis when exposed to endotoxin. Furthermore we demonstrated that endotoxin-activated KCs induce these changes in HC protein synthesis through the induction of a novel L-arginine-dependent biochemical pathway within the HC. In this pathway, the guanido nitrogen of L-arginine is converted to the highly reactive molecule nitric oxide (NO.). To identify the KC factors that act as signals for induction of HC NO. biosynthesis, recombinant cytokines were added to HC cultures and HC nitrogen oxide production and protein synthesis levels were determined. We found that no single cytokine, but rather a specific combination of tumor necrosis factor, interleukin-1, interferon-gamma, and endotoxin, were required for maximal induction of HC nitrogen oxide production. This specific combination of cytokines induced a 248.8 +/- 26.0 mumol/L (micromolar) increase in HC nitrogen oxide production and simultaneously inhibited HC total protein synthesis by 36.1% +/- 3.1%. These data demonstrate that multiple cytokines, produced by endotoxin-activated KC, induce the production of NO. within HC, which in turn leads to the inhibition of HC total-protein synthesis.
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PMID:Multiple cytokines are required to induce hepatocyte nitric oxide production and inhibit total protein synthesis. 212 Nov 10

Intravenous immunoglobulin (Gammagard 5%), 500 mg/kg, was given over 3 hours to 10 acutely ill infants with proven or suspected sepsis (treatment group) and 10 clinically stable preterm infants less than 1750 gm birthweight as prophylaxis for sepsis (prevention group). No differences were found in heart rate, respiratory rate, mean arterial blood pressure, or urine output in either group during or following the infusion compared with preinfusion values, except for a small but significant decrease in heart rate postinfusion in the prevention group. Likewise, serum glucose, sodium, serum glutamic oxaloacetic transaminase, and osmolality were unchanged 15 minutes and 6 hours following infusion. Urea nitrogen rose a small but significant amount in both groups. Hemoglobin concentration declined a small but significant amount 15 minutes postinfusion in the prevention group, but returned to baseline by 6 hours postinfusion. There were no changes in white blood cell count or platelet counts in either group. These data indicate that intravenous immunoglobulin in the dose given was associated with no adverse effects. Additional studies are warranted to evaluate the efficacy of these preparations in the treatment and prevention of neonatal septicemia.
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PMID:Safety of intravenous immunoglobulin infusion in neonates at risk for sepsis. 212 Nov 51

The administration of a single mixture of the components of total parenteral nutrition (TPN) constitutes total nutritional admixture (TNA), the safety and efficacy of which in a variety of clinical settings have been confirmed by controlled trials. According to the nitrogen balance and stable isotope methods, TNA is as efficacious as the old system of three bottles with piggyback intravenous fat emulsion in maintaining body nitrogen mass, visceral protein, and liver function. Also, serum concentrations of electrolytes, trace elements, and vitamins can be maintained adequately using the TNA system. The other advantages are the timesaving to the nursing staff, with its hidden savings in cost; the avoidance of a peripheral catheter solely for the infusion of lipid emulsion in addition to the central catheter for TPN in hospitalized patients; and the facility of use in home nutrition programs. The ease of home use has resulted in a greater degree of patient compliance; thus patients receive a mixed-fuel system while avoiding the hazards of a piggyback infusion, with all its potential complications. Among the perceived disadvantages of TNA are a supposed higher frequency of catheter-related sepsis, a view based on in vitro studies that is not borne out by in vivo studies; catheter occlusion by precipitation of calcium salts; and enhanced ability to clear fat and thus fat tolerance with continuous infusion of lipids. Numerous studies have shown that these concerns are unwarranted.
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PMID:Clinical use of total nutritional admixtures. 213 56

The purpose of this study was to determine the efficacy of treatment with anti-TNF monoclonal antibody in preventing the deleterious effects of sepsis in a nonhuman primate. Experiments were carried out on anesthetized baboons intravenously infused with a lethal dose of Escherichia coli (E. coli). Twelve baboons (six control and six experimental) received 2 hr infusions of E. coli. The experimental group was administered a bolus of anti-TNF antibody, 15 mg/kg, 30 min after beginning the E. coli infusion. Control baboons lived an average of 19 hr (12-34 hr). All antibody-treated baboons survived more than 7 days with a significantly improved quality of life compared to the control group. Although some adverse changes occurred during the monitoring period in surviving baboons, they maintained nearly normal arterial pressures, and serum urea nitrogen and creatinine concentrations. The severe histopathologic changes in lungs, liver, adrenals, kidneys, and spleen documented at death in baboons receiving E. coli only were absent after 7 days in baboons given E. coli and early post-treatment with antibody to TNF.
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PMID:Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF alpha). 217 1

Nitric oxide (NO.) is a short-lived intermediate in a biochemical pathway where L-arginine is converted to L-citrulline and nitrite/nitrate (NO2-/NO3-). This highly reactive molecule is the biologically active component of this inducible pathway in macrophages. Using a rat Kupffer cell:hepatocyte (KC:HC) coculture model, we have previously shown that this combination of cells produces large quantities of both citrulline and NO2-/NO3- if exposed to lipopolysaccharides (LPS) but we did not determine whether nitric oxide was produced or released. We had also shown that this L-arginine metabolism was associated with a profound decrease in total protein synthesis. In these experiments, we show that KC:HC cocultures release nitric oxide into the culture supernatant if exposed to LPS. NO. production by these cells requires L-arginine and is inhibited by NG-mono-methyl-L-arginine. In addition, the time course for NO. release by KC:HC cocultures parallels the previously reported time course for NO2-/NO3- synthesis and the decrease in protein synthesis, supporting the hypothesis that NO. is the reactive nitrogen intermediate of the pathway responsible for this inhibition of protein synthesis. Finally, we show that KC:HC cocultures release more NO. than KC alone in response to LPS, and we propose that the combination of KC and HC acts as a functional unit capable of generating large amounts of NO. from L-arginine in gram-negative sepsis.
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PMID:Kupffer cell:hepatocyte cocultures release nitric oxide in response to bacterial endotoxin. 218 13

In the critically ill surgical patient a variety of therapeutic maneuvers is required to maintain a "healthy gut." Provision of adequate amounts of glutamine to the gastrointestinal mucosa appears to be just one of these maneuvers. Other methods utilized to protect the gut from becoming a wound include: (a) minimizing additional systemic insults (such as hypotension, sepsis, multiple operative procedures); (b) aggressive pulmonary care; (c) the judicious use of antibiotics; and (d) aggressive enteral or parenteral feedings. The concept that the gut is an organ of quiescence following surgical stress merits reconsideration. The intestinal tract plays a central role in interorgan glutamine metabolism and is a key regulator of nitrogen handling following surgical stress. Critically ill patients are susceptible to developing gut-origin sepsis, the incidence of which will be diminished by instituting measures and providing treatments which support intestinal structure, function, and metabolism. Provision of glutamine-enriched diets to such patients may be one of these therapies.
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PMID:The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. 218 15

The application of autologous bone marrow transplantation (ABMT) in treating acute leukemias in children has been limited by the presence of residual occult viable leukemic cells in the marrow cell suspension. One approach to this problem is the ex vivo treatment ("purging") of the autograft to eradicate these tumor cells yet spare the normal lymphohematopoietic stem cells. Initial studies of acute myeloid leukemia (AML) in a rodent model demonstrated that incubation with 4-hydroperoxycyclophosphamide (4HC), a congener of cyclophosphamide and an active alkylating agent in aqueous solution, could effectively eliminate viable AML cells from marrow cell suspensions without apparent toxicity to normal stem cells. We have conducted clinical trials of ABMT with 4HC-treated marrow in children with acute leukemia in remission; marrow was collected, treated ex vivo with 4HC (100 micrograms/ml), and cryopreserved in liquid nitrogen until reinfusion. Children received pre-ABMT conditioning with either high-dose cyclophosphamide and total body irradiation (CY-TBI) for acute lymphocytic leukemia (ALL) or high-dose busulfan and cyclophosphamide (BU-CY) for AML. Of nine children who underwent ABMT with 4HC-treated marrow for ALL in second complete remission (CR2), all relapsed (eight in the marrow, one in the central nervous system) at a median of 5 months (range, 2-17) after ABMT and all have died with relapsed ALL or as a consequence of its treatment. Twenty-nine children with AML (five in CR1, 24 in CR2) received autografts with chemopurged marrow at a median remission duration of 3 months (range, 2-15). Three patients died from sepsis during aplasia; 10 children (one in CR1 and nine in CR2) relapsed with AML at a median of 7 months (range, 2-23) after ABMT, for an actuarial relapse rate of 47%. Sixteen patients with AML (four in CR1, 12 in CR2) are in unmaintained remission at a median of 16 months (range, 6-102) after ABMT, for an actuarial disease-free survival of 49%. Although ABMT with 4HC-treated marrow appears to have a limited role in the treatment of children with ALL who lack a suitable related donor, the results in AML are encouraging and compare favorably with both syngeneic and allogeneic BMT in similar groups of patients.
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PMID:Ex vivo chemopurging of autologous bone marrow with 4-hydroperoxycyclophosphamide to eliminate occult leukemic cells. Laboratory and clinical observations. 224 Apr 70


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