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)

Tumor necrosis factor-alpha (TNF) is a cytokine released by mononuclear cells in response to inflammation and sepsis. Since the biological effects of TNF are consistent with the systemic and intestinal features of ulcerative colitis, the role of TNF was examined in a rabbit model of chronic colitis. Peripheral blood mononuclear cells were isolated, stimulated with lipopolysaccharide, and cultured supernatants assayed for TNF levels using a cytotoxic assay on mouse fibrosarcoma L929 cells. Basal levels of TNF production by mononuclear cells from 13 normal rabbits (124.3 units/ml +/- 27.1 units/ml, mean +/- SE) were not different from nine rabbits with colitis (83.6 units/ml +/- 24.4 units/ml, P > 0.05). Treatment with lipopolysaccharide (100 micrograms/ml) induced increased TNF production by mononuclear cells isolated from both normals (672.0 units/ml +/- 197.5 units/ml, P < 0.05) and rabbits with colitis (1114.0 units/ml +/- 489.6 units/ml, P < 0.05). However, at all lipopolysaccharide concentrations stimulated TNF levels were comparable in experimental and control groups (P > 0.05). In light of the role of leukotrienes in inflammation, a separate group of rabbits with colitis was investigated following treatment with an oral leukotriene B4 receptor antagonist. Serum TNF levels in 15 control rabbits (32.5 units/ml +/- 7.6 units/ml, mean +/- SE) were not significantly different from rabbits with colitis receiving either leukotriene B4 receptor antagonist (35.7 units/ml +/- 9.2 units/ml, N = 13) or vehicle alone (50.3 units/ml +/- 10.2 units/ml, N = 14) (ANOVA, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic tumor necrosis factor-alpha production in experimental colitis. 133 Apr 61

Acemannan, a complex carbohydrate shown to stimulate interleukin-1, tumor necrosis factor alpha and prostaglandin E2 production by macrophages, has also demonstrated antiviral activity in vitro against human immunodeficiency virus, Newcastle disease virus and influenza virus. A pilot study was undertaken to determine acemannan's effect in 49 feline immunodeficiency virus (FIV) infected cats with clinical signs of disease (Stage 3, 4 or 5), 23 of which had severe lymphopenia. Cats received acemannan either by intravenous (Group 1) or subcutaneous (Group 2) injection once weekly for 12 weeks, or by daily oral (Group 3) administration for 12 weeks. Upon entry into the study, cats were randomly assigned to one of the three groups. Laboratory analyses were performed at the beginning of the study and at Weeks 6 and 12. Cats were allowed to continue with a predetermined maintenance regimen of acemannan after completing the 12-week study. Thirteen cats died during the course of treatment. Upon necropsy, the most frequent histopathologic findings were neoplastic, kidney and pancreatic disease. Friedman's two-way ANOVA test showed no significant differences in efficacy among groups administered acemannan by the different routes. Therefore, groups were combined and a signed-ranks test was used to determine changes over time. A significant increase was seen in lymphocyte counts (P < 0.001). Neutrophil counts decreased significantly (P = 0.007), as did incidence of sepsis (P = 0.008). When cats entering with lymphopenia were analyzed separately, a much greater increase in lymphocyte counts was noted (235%) compared with non-lymphopenic cats (42%). A survival rate of 75% was found for all three groups. Thirty-six of 49 animals are alive 5-19 months post-entry. These results suggest that acemannan therapy may be of significant benefit in FIV-infected cats exhibiting clinical signs of disease.
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PMID:Pilot study of the effect of acemannan in cats infected with feline immunodeficiency virus. 133 96

Overwhelming sepsis continues to be a major source of morbidity and mortality in patients who have sustained severe traumatic injury. Recently, much interest has been focused on the role of the peripheral blood neutrophil (PMN) in infections in these patients. Two surface receptors, CD11b (CR3) and CD16 (Fc gamma RIII), are thought to participate in bacterial phagocytosis and are both present on greater than 85% of normal PMNs. We have previously shown that cells that lack both of these receptors have markedly reduced phagocytic function. The purpose of this study was to determine the effect of severe trauma on the expression of these PMN receptors. Twenty severe trauma patients, age 19-70 years, presenting with an initial APACHE II score of greater than or equal to 10 were arbitrarily divided into two groups to define severity of injury: Group A, initial APACHE II of 10-18 (n = 11) and Group B, initial APACHE II of 19-25 (n = 9). Blood was obtained on admission, on Day 3, and weekly thereafter. PMNs were stained with fluorochrome-labeled monoclonal antibodies directed against CD11b and CD16 and then analyzed by flow cytometry. Controls consisted of 14 normal adults, age 20-65 years. The percentage and absolute numbers of CD11b+/CD16+ PMNs were determined for each patient or control sample. ANOVA and multiple comparison of variables (P = 0.05) were performed for each week. Values for Group A were different from controls at Weeks 0, 1, and 3. Values for Group B were significantly lower than those of controls at all weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. 153 18

The role of neutrophil oxidative burst activation (OBA) in the development of fulminant post-trauma adult respiratory distress syndrome (ARDS) was studied in 30 patients. Neutrophil (PMN) chemiluminescence (LE) was used as the index of OBA. Serially, for 8 days post-trauma, patient neutrophils (Pc) were studied in their own serum (Ps) normal serum (Ns), or Gey's solution (G). Ps was checked against normal neutrophils (Nc) for inhibition. LE was initiated by the addition of preopsonized zymosan to 1 x 10(6) PMN, the LE response monitored by luminometer, and the peak of the integral of LE recorded. Seven developed ARDS within the first 4 days; 12 patients developed sepsis (TS) but no ARDS, and 11 patients had uncomplicated trauma (TR). All ARDS showed increased LE (P less than 0.0001), at 48-96 hr. Patients without ARDS showed no significant increase in LE, although their mean injury severity (ISS) was the same. The ARDS LE response was mediated by activation of Pc [74%] with only a small but significant additional effect (6%) by ARDS serum (Ps): LE = 0.672 (Pc) + 0.24 [ARDS(Ps)] + 1343; N = 146, r2 0.733, P less than 0.0001. However, sera (Ps or Ns) was required, as incubation in G inhibited LE; [cells + s] greater than [cells + G], P less than 0.0001. LE is a biologic marker of ARDS, and the delay between injury and the LE indicated that initiation of ARDS may have therapeutic importance. Neutrophil activation in ARDS requires sera, but the ARDS effect appears mainly due to cells with only a small ARDS-specific serum-mediated role. The physiologic response to ARDS was evaluated by serial 8-hr studies of blood gases and pH; the respiratory index (RI) to pulmonary shunt (QS/QT) relationship, compliance (COMPL), and net fluid balance (DFLUID) PMN and platelet (PLAT) counts were also measured. Compared with TR and TS, the ARDS patients at 48-96 hr, showed increased RI, QS/QT, and DFluid requiring increased FiO2 and PEEP as COMPL and PLAT fell and LE rose. These changes were all simultaneously significant (P less than 0.05 to P less than 0.0001) by Bonferroni t-statistic applied to ANOVA. The clinical importance of these physiologic and biochemical responses was emphasized by the significantly (P less than 0.005) increased mortality in the ARDS patients. These data suggest that PMN LE and simple measures of respiratory function are early biologic markers of the development of fulminant post-traumatic ARDS and can be used to predict ARDS severity.
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PMID:Neutrophil oxidative burst activation and the pattern of respiratory physiologic abnormalities in the fulminant post-traumatic adult respiratory distress syndrome. 184 56

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

Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.
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PMID:Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents. 200 51

Sepsis produces profound hypothyroidism. This hypothyroid state is associated with altered lung metabolism and structural integrity. We studied the respiratory function of rats during sepsis-induced hypothyroidism with or without T3 treatment. Forty-four male Holtzman rats underwent cecal ligation and puncture (CLP). Treatment was administered at six hours after surgery consisting of intraperitoneal injection of T3 (15 micrograms/kg, n = 19) or saline (n = 25). At 20 hours (Group A) or 30 hours (Group B) following CLP, respiratory drive was assessed by serial occlusion pressure technique (P0.1). The rats were killed and static elastance determined by serial air inflation to 10 cc. The lungs were excised for weight determination. The P0.1 values were significantly greater in T3-treated animals over controls in Group A (9.3 +/- 0.7 vs. 6.6 +/- 2.2, p less than 0.05 by t test); elastance was significantly improved by T3 treatment in Group B (p less than 0.05 by two-way ANOVA). Lung weight, pH, pO2, pCO2, respiratory rate (RR), and mortality were not significantly different between groups. Control animals were hypothyroid by 20 hours after CLP (T3 less than 12.5 ng/dL) whereas T3-treated animals were euthyroid (T3 = 145 +/- 43 ng/dL). Pulmonary dysfunction frequently accompanies sepsis; the euthyroid state appears protective. We found a significantly improved respiratory drive in septic animals with T3 treatment. Lung elastance was similarly improved in late sepsis with T3 treatment. The data suggest that T3 treatment preserves respiratory function in septic rats as evidenced by respiratory drive and compliance.
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PMID:T3 preserves respiratory function in sepsis. 205 39

To evaluate the efficacy of supplemental arginine with nutritional support in the presence of sepsis, eighty-eight gastrostomized female Hartley guinea pigs were implanted with osmotic pumps effusing an Eschericia coli/Staphylococcus aureus mixture. Animals were randomized and infused for two weeks with isocaloric and isovolumetric diets containing 0%, 2%, 4%, or 6% supplemental arginine as arginine hydrochloride. Survival was 12/22 (54%) in 0%, 9/22 (41%) in 2% and 4%, and 2/22 (9%) in 6%. Analysis by chi-square test of independence was significant (p = 0.0141) with 6% survival lower than the others. Median survival was 11 days in 0%, 8 days in 2% and 6%, and 9 days in 4%. Median survival was longer in 0% than in 2% or 6% (Kruskal-Wallis ANOVA: p = 0.02). Nitrogen balance was significantly lower in 6% compared to 0% on days 2 through 10, and lower than 2% and 4% on days 6 and 9. Nitrogen balance was higher in 0% than in 2% on days 4, 6, 10, and 13. Serum albumin and C3 were lower in all experimental groups than normal controls (ANOVA: p = 0.01). Comparison of liver, spleen, adrenals, gastrocnemius, and carcass weights, cell-mediated immunity as determined by contact sensitivity to DNFB, and transferrin showed no significant differences. There was a positive dose-response effect seen amongst the experimental groups for the amino acids arginine, ornithine, and citrulline in relation to the amount of supplemental arginine. This study suggests that dietary arginine supplementation does not enhance survival in a guinea pig model of established peritonitis.
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PMID:Arginine supplementation and its effect on established peritonitis in guinea pigs. 211 35

Analysis of 185 consecutive patients admitted to a trauma center (1983-1986) with blunt traumatic injury to the liver classified by severity of hepatic injury (I-V) has demonstrated that the pattern of associated organ injuries is a major determinant of the immediate resuscitation requirements, complications, and the ultimate outcome of patients with hepatic injury. When the significance of all injuries and major complications was evaluated using simultaneous ANOVA techniques, only brain and chest trauma together were significant (p less than 0.03) as injuries occurring in subsequently fatal cases for all classes of blunt hepatic injury. Sepsis (p less than 0.05) and ARDS (p less than 0.005) were significant complications associated with death in the patients who survived the initial operative intervention, and only brain deterioration and exsanguinating hemorrhage were significant (p less than 0.0001) as direct causes of death in all groups of patients. It was of interest that neither associated bowel, spleen, stomach, or pancreatic injuries had a significant difference in incidence between survivors and deaths. Overall, the most important single injury determining ultimate outcome was blunt traumatic injury of the brain. Review of the resuscitation and operative intervention strategies, postoperative complications, and causes of death shows that the interactions between the class of liver injury and the injuries to other organs, primarily brain and lung, are the determinant of the optimization of postinjury therapy of both a surgical and critical care nature.
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PMID:Patterns of organ injury in blunt hepatic trauma and their significance for management and outcome. 281 Apr 18

The effect of sepsis in modifying post-surgical fuel utilization in critically ill patients was determined from 374 observations (246 septic [S] and 128 nonseptic [N] in 12 intubated ICU patients studied serially. Patients received TPN (values/24 hrs: Septic, N2, 9.1 +/- 2.2 gm; glucose, 543 +/- 211 kcal/m2, Nonseptic, N2, 8.3 +/- 3.6 gm; glucose, 550 +/- 346 kcal/m2). In some periods, intravenous lipid (L) was given to raise total caloric intake to 826 +/- 223 kcal/ 24 hr/m2. The VO2, VCO2, respiratory rate, minute volume, and blood gas levels were measured, and respiratory quotient (RQ) and metabolic rate (MR) computed. Statistics were performed by 2-way ANOVA and analysis of covariance. Without lipid, mean VCO2 for S (126 ml/min/m2) and N (128 ml/min/m2) were not significantly different, but VO2 in S (146 ml/min/m2) and N (132 ml/min/m2), and the RQ values S (0.88) and N (0.97), were different (p less than 0.0001). In 360 studies RQ was shown to be increased by the total caloric intake, but reduced in the presence of sepsis: RQ = 0.00014 (kcal/m2) - 0.09 (sepsis effect + 0.878 N = 360; r2 = 0.304; F2,357 = 78; p less than 0.0001; but both administered glucose and lipid calories contribute to the RQ in sepsis: RQ = 0.00017 (glucose kcal/m2) + 0.266 X 10(-3) (lipid kcal/m2) + 0.732 n = 114; r2 = 0.260; F2,111 = 19.5; p 0.0001. Sepsis increased VO2 with little change in VCO2, thus RQ fell, suggesting increased use of lipid fuels for oxidation. During hypercaloric lipid infusion in septic patients (SL) VO2 and VCO2 increased but VO2 was still greater, so RQ remained low (SL RQ = 0.89). As sepsis worsened VO2 remained high but VCO2 fell producing RQ less than 0.8, while plasma glucose levels were increased. These data suggest that septic patients are more dependent than nonseptics on lipid fuels for oxidative metabolism, and that IV lipids can be used to increase oxidative metabolism in sepsis at a time when glucose metabolism appears reduced.
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PMID:Increased lipid fuel dependence in the critically ill septic patient. 642 May 77


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