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Results for “Systemic inflammation”

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At least 109 records · Page 6Linked to original sources

PubMed2005

[Large vessel vasculitis as cause of fever of unknown origin (FUO) or systemic inflammation. Diagnosis using 18-F-fluor-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)].

BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.

Adult↗

PubMed2003

Independent association of various smoking characteristics with markers of systemic inflammation in men. Results from a representative sample of the general population (MONICA Augsburg Survey 1994/95).

AIMS: Aim of the study was to investigate the association between various markers of systemic inflammation and a detailed history of smoking in a large representative sample of the general population. METHODS AND RESULTS: The effects of chronic smoking on white blood cell (WBC) count, fibrinogen, albumin, plasma viscosity (PV), and high-sensitivity C-reactive protein (CRP) were measured in 2305 men and 2211 women, age 25-74 years, participating in the third MONICA Augsburg survey 1994/95. In men, current smokers showed statistically significantly higher values for WBC count, fibrinogen, PV, and CRP, compared to never smokers, with intermediate, but only slightly increased values for ex-smokers and for occasional smokers. No consistent associations were seen with albumin. Duration of smoking was positively associated with markers of inflammation as were pack-years of smoking. Conversely, duration of abstinence from smoking was inversely related to these markers. Except for WBC count, no such associations were found in women. CONCLUSION: Data from this large representative population show strong associations between smoking and various markers of systemic inflammation in men. They also show that cessation of smoking is associated with a decreased inflammatory response, which may represent one mechanism responsible for the reduced cardiovascular risk in these subjects.

Acute-Phase Proteins↗

PubMed2004

Cellular proteolysis and systemic inflammation during exacerbation in cystic fibrosis.

BACKGROUND: Weight loss indicates a poor prognosis in cystic fibrosis (CF). We hypothesised that fat-free mass (FFM) depletion and increased systemic inflammation would be associated with increased cellular proteolysis during an exacerbation of the respiratory symptoms. Patients were studied prospectively from the beginning of treatment with antibiotics when admitted to the Adults CF Centre. METHODS: Twenty six patients with CF were studied at the start and end of antibiotic treatment and 2 weeks later. Mean (95% CI) FEV1 when clinically stable was 54.1 (44.5, 62.6)% predicted. Urinary excretion of Pseudouridine (5-ribosyluracil, PSU) was determined as an indicator of cellular protein breakdown. Body composition was assessed by dual energy X-ray absorptiometry (DXA). RESULTS: Patients had increased concentrations of PSU at all assessments (p<0.01). Those with a low FFM had greater PSU (ratio to FFMI) than those with a normal FFM at all assessments. At the start of treatment, PSU was related to FFM, C-reactive protein (CRP) (p<0.05) and tumour necrosis factor (TNF)alpha soluble receptors (sr) I and II (p<0.01). Circulating inflammatory mediators were greater in patients than in healthy subjects at all assessments. CONCLUSION: Increased protein breakdown is associated with a low FFM and increased systemic inflammation and it may be a contributory mechanism of poor weight preservation in CF.

Absorptiometry, Photon↗

PubMed2006

Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation.

Apnea-induced hypoxia and reoxygenation, which generates reactive oxygen species, may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kappaB (NF-kappaB), increasing systemic inflammation in obstructive sleep apnea. We measured NF-kappaB activity in circulating neutrophils and plasma levels of NF-kappaB-controlled gene products, soluble E (sE)-selectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in control subjects and in obstructive sleep apnea (OSA) patients. To confirm a causal link with OSA, we reassessed these parameters after nasal continuous positive airway pressure (CPAP) therapy. Twenty-two subjects undergoing evaluation for symptoms of sleep-disordered breathing were grouped by apnea hypopnea index: control, less than 5/h; mild to moderate OSA, 11-40/h; severe OSA, more than 40/h. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kappaB activity was determined by electrophoretic mobility shift assay. Plasma sE-selectin and sVCAM-1 were assayed by enzyme-linked immunosorbent assay. Neutrophils in mild to moderate and severe OSA patients showed 4.8- and 7.9-fold greater NF-kappaB binding activity compared with control subjects (p<0.0001). The degree of NF-kappaB activation was positively correlated with indices of apnea severity. In five severe OSA patients, 1 month of CPAP therapy decreased neutrophil NF-kappaB activation to control levels. sE-selectin and sVCAM concentrations were reduced by CPAP in four of these five subjects. OSA leads to NF-kappaB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease.

Adult↗

PubMed1999

Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation.

BACKGROUND: Increased levels of circulating von Willebrand factor (vWF) have been found in patients with inflammatory bowel disease (IBD); this increase may reflect either endothelial damage or systemic inflammation. Our aim was to evaluate serum vWF levels in patients with IBD and their correlation with clinical and biochemical disease activity. METHODS: We evaluated serum vWF levels in 32 patients with ulcerative colitis (UC) (10 active with increased acute-phase reactants (APR), 6 active with normal APR, 16 in remission), 27 with Crohn disease (CD) (10 active, 12 quiescent, and 5 quiescent with increased APR), and 31 healthy controls. RESULTS: Mean levels of vWF were 100.1 (standard deviation (s), 51.4) in IBD and 89.9 (s, 36.9) in controls (P = 0.33). Only five (8.47%) patients (three with active UC, one with active CD, and one with inactive CD but increased APR) showed circulating vWF levels higher than the upper limit of normal (150), compared with 1 (3.2%) of controls (P = 0.32). Among CD patients vWF levels were 80.0+/-25.4 in patients with quiescent disease and normal APR, 123.3+/-63.4 in patients with active disease (P = 0.04 versus inactive with normal APR), and 135.8+/-90.0 in patients with quiescent disease and increased APR (P = 0.059 versus inactive with normal APR). Among UC patients vWF levels were 82.7+/-35.6 in patients with quiescent disease and normal APR and 125.1+/-54.2 in those with active disease and increased APR (P = 0.002). Overall, mean vWF levels were significantly higher in patients with increased APR than in patients with normal APR (P = 0.0005) and controls (P = 0.009). CONCLUSIONS: Our data show slight but significant increases in serum vWF levels in patients with IBD, which are correlated with signs of systemic inflammation.

Acute-Phase Proteins↗

PubMed2002

[Systemic inflammation during exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: The circulating blood levels of several inflammatory cytokines and acute phase proteins are higher in patients with stable chronic obstructive pulmonary disease (COPD). However, whether or not these inflammatory markers increase during COPD exacerbation or are modified by corticosteroid treatment has not been investigated. The objective of this study was therefore 1) to describe changes in several inflammatory markers in systemic circulation during COPD exacerbation, and 2) to assess the potential effects of corticosteroid treatment during exacerbation. METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) were determined for 10 patients (65 2 years old) with severe COPD (FEV1 35 4% reference) who were hospitalized for acute respiratory failure (PaO2 57 2 mm Hg; PaCO2 48 3 mm Hg). Blood samples were obtained in the emergency room (before starting intravenous corticosteroid treatment), during the first 24 hours of admission, upon discharge and two months later. Eight healthy non-smokers of a similar age (54 3 years) were also studied as control subjects. RESULTS: The COPD patients had higher concentrations of IL-6 (5.1 1.6 vs. 1.8 0.5 pg/mL, p < 0.05) and CRP (2.2 0.4 vs. 0.6 0.2 mg/dL, p < 0.005) than did controls, but the concentrations of IL-8 were similar (29 11.3 vs. 34.7 10.3 pg/mL, p = ns). No statistically significant changes were seen either during recovery, in spite of intravenous corticosteroid treatment, or two months after discharge.The ELISA test used was unable to detect TNF-alpha in any of the samples obtained from either patients or controls. CONCLUSION: The results show that 1) there is evidence of systemic inflammation during exacerbation of COPD, and 2) such systemic inflammation does not appear to be influenced significantly by intravenous corticosteroid treatment.

Adrenal Cortex Hormones↗

PubMed2005

Blocking IL-1 in systemic inflammation.

A growing number of systemic inflammatory diseases characterized in part by recurrent fevers, leukocytosis, anemia, and elevated acute phase proteins are linked to interleukin (IL)-1 activity since rapid and sustained resolution is observed upon specific blockade of IL-1 receptors. Rapid resolution of systemic and local inflammation is now also reported in systemic onset juvenile idiopathic arthritis (SoJIA). Loss of control of the secretion of IL-1beta might be a common mechanism explaining the aberrant activity of IL-1 in these diseases.

Arthritis, Juvenile↗

PubMed2004

Dopexamine and cellular immune functions during systemic inflammation.

An immune-neuroendocrine interaction that is mediated via beta2-adrenergic receptors has been demonstrated previously. Dopexamine is a substance with strong beta2-adrenergic effects and is used in the treatment of critically ill patients. We therefore investigated the effect of dopexamine infusion on survival and cellular immune functions during systemic inflammation. Sepsis (CLP) was induced in male NMRI mice that received either 0.9% saline, dopexamine (0.05 mg/kg/hour ip, DPX), the selective beta2-adrenergic antagonist ICI 118.551 (0.5 mg/kg ip every 12 hours, ICI) or a combination of both drugs. 48 hours after onset of sepsis, survival rate, splenocyte apoptosis, splenocyte proliferation, splenocyte IL-2, IL-6 and IFN-gamma release, and leukocyte distribution were monitored. Dopexamine increased splenocyte apoptosis and normalized the distribution of circulating lymphocytes but did not affect sepsis-induced mortality. ICI 118.551 induced a dramatic increase of mortality paralleled by a decreased splenocyte proliferation and the strongest increase in splenocyte apoptosis. Co-administration of dopexamine abolished the ICI 118.551-induced alterations but this effect seemed to be mediated via a pathway other than adrenergic beta2-receptors. We conclude that dopexamine modulates cellular immune functions during systemic inflammation and that different receptor systems are involved in the mediation of this process. Furthermore, the immunomodulatory effect of beta2-adrenergic blockade was demonstrated.

Adrenergic beta-Antagonists↗

PubMed2001

Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill.

BACKGROUND: For many years, the intensivists are searching for an easily measurable and available parameter which might reflect the intensity of stress and/or systemic inflammation in critically ill patients following shock, multiple trauma, major surgery or sepsis. Recently, some authors have described the onset of significant lymphocytopenia after polytrauma, major surgery, endotoxaemia and sepsis. We investigate whether serial examination of white blood cell counts may reflect and clarify the immune response to stressful events in critically ill patients. GOAL: We have designed a prospective longitudinal observational study to investigate serial changes in circulating neutrophil and lymphocyte counts following major surgery, unscheduled surgery and sepsis. METHODS: We have investigated the differential white blood cell counts and the clinical course in 90 oncological ICU patients. We compared three groups: group A consisting of 62 patients who underwent scheduled colorectal surgery, group B consisting of 18 patients who underwent unscheduled surgery for abdominal sepsis, group C consisting of 10 medical ICU patients who were treated for severe sepsis and septic shock. The severity of clinical course was expressed by means of SOFA score (group A 0.3-1-1.3 point, group B 2.2-2.9-2.6 point, group C 7.4-8.3-7.7 point) and APACHE II score (group A 3.7-7.6-8.1 point, group B 8.6-11.1-10.5 point, group C 16.3-15.2-14.3 point). Differential white blood cell counts were investigated on blood cell counter SYSMEX SF 3000 in 4 consecutive periods: 1 day one before surgery, 0 the day of surgery or ICU admittance, 1 day one after surgery (or the 1st ICU day), 2nd day following surgery (or the 2nd ICU day). The measured values of neutrophils and lymphocytes were expressed as relative counts (%) of the whole all white blood cell population. RESULTS: The physiologic response of circulating leukocytes to surgical stress in group A is characterized by the onset of marked neutrophilia (62.5% before surgery up to 84.4% after surgery) and significant lymphocytopenia (28.1% before surgery to 10.3% following surgery). We observed a slow decline in neutrophil counts and an increase in lymphocyte counts since the 1st postoperative day. The patients with abdominal infection (group B) had elevated counts of neutrophils already before surgery (83.2%) and low values of lymphocyte counts (9.5%). A further increase in neutrophil counts (89.9%) and marked lymphopenia (7%) were recorded during the post-surgical period in group B. Critically ill patients with severe sepsis or septic shock (group C) had significantly highest values of neutrophil relative counts (94%-93.1%-92.5%, p < 0.05 against group A) and marked lowest values of lymphocyte counts (3.8%-4%-3.7%, p < 0.05 against group A). The severity of clinical course (according SOFA and APACHE II score) correlated with the divergence of neutrophil and lymphocyte counts in the white blood picture (marked neutrophilia and lymphocytopenia). CONCLUSION: In the population of 90 ICU oncological patients, we observed rapid serial changes in white blood cell populations, as a response of the immune system to surgical stress, systemic inflammation or sepsis. Preliminary results show the correlation between the severity of clinical course and the grade of neutrophilia and lymphocytopenia. The ratio of neutrophil and lymphocyte counts (in absolute and/or relative % values) is an easily measurable parameter which may express the severity of affliction. We suggest the term: neutrophil-lymphocyte stress factor, as a ratio of neutrophil to lymphocyte counts, which can be routinely used in clinical ICU practice in intervals of 6-12 and 24 hours. The prognostic value of neutrophil-lymphocyte stress factor should be evaluated in further studies. (Tab. 6, Fig. 5, Ref. 12.)

APACHE↗

PubMed2004

Signaling the brain in systemic inflammation: role of sensory circumventricular organs.

The sensory circumventricular organs (CVOs) are specialized brain regions that lack a tight blood-brain barrier. A role for these brain structures in signaling the brain during systemic inflammation is based on the following sets of observations. In spite of some conflicting data from literature, lesions of CVOs have been shown to block several components of brain controlled illness responses (i.e. fever or neuroendocrine modifications). Receptors for inflammatory cytokines and for bacterial fragments are constitutively expressed in cells within the sensory CVOs. The expression of most of these receptors is upregulated under conditions of systemic inflammation. Cellular responses in theses brain areas can be recorded and documented after stimulation of these respective receptors. Such responses include changes in electrical activity of neurons, induction of transcription factors leading to modifications in gene expression during inflammation and to a localized release of secondary signal molecules. These molecules may influence or even gain access to neural structures inside the blood-brain barrier, which can normally not directly be reached by circulating cytokines or bacterial fragments.

Animals↗

PubMed2004

Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X.

Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.

C-Reactive Protein↗

PubMed2004

Transforming growth factor-beta1 (TGF-beta1) in plasma is associated with preeclampsia risk in Peruvian women with systemic inflammation.

BACKGROUND: In a case-control study of 100 preeclamptics and 100 controls, we assessed plasma transforming growth factor-beta1 (TGF-beta1) concentrations in relation to preeclampsia risk among Peruvian women with and without systemic inflammation. METHODS: Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The OR of preeclampsia increased across quartiles of TGF-beta1 concentrations. Women with elevated TGF-beta1 and a proinflammatory profile experienced the highest risk of preeclampsia (OR = 15.4, 95% CI 4.7-50.4). CONCLUSIONS: Our results confirm an association between TGF-beta1 and risk of preeclampsia and extend the literature by indicating a strong association in women with systemic inflammation.

Adolescent↗

PubMed2000

Seropositivity to chlamydial lipopolysaccharide and Chlamydia pneumoniae, systemic inflammation and stable coronary artery disease: negative results of a case-control study.

OBJECTIVES: We investigated the association between seropositivity to chlamydial lipopolysaccharide (cLPS) or Chlamydia pneumoniae (CP) and angiographically documented coronary artery disease (CAD), and we examined the relationship between serostatus and markers of systemic inflammation. BACKGROUND: The potential contribution of CP to atherogenesis is still a matter of debate, and inflammation has been suggested to represent the link between infection and atherosclerotic disease. METHODS: Subjects age 40 to 68 years were recruited for this case-control study between October 1996 and November 1997: 312 patients with at least one coronary stenosis >50% and 479 age- and sex-matched blood donors without manifest CAD or history of angina. Antibodies against cLPS and CP, C-reactive protein (CRP), fibrinogen, plasma viscosity, leukocytes and neutrophils were determined. The study had a power of >80% to detect an odds ratio (OR) of 1.55 or above for the prevalence of immunoglobulin (IgG) antibodies against cLPS at a significance level of alpha = 0.05. RESULTS: Prevalence of IgG antibodies against cLPS was not different between cases and controls (61% vs. 62%; p = 0.7). The adjusted OR for the presence of CAD given positive IgG serostatus against cLPS was 0.9 (95% CI; 0.6 to 1.3). Similarly, no difference in the prevalence of IgG antibodies against CP was seen (88% vs. 87%; p = 0.6); the adjusted OR was 1.0 (95% CI; 0.6 to 1.6). Markers of inflammation did not show any statistically significant difference between cLPS seropositives and seronegatives. CONCLUSIONS: Our results indicate no strong association between CP and CAD, and increased systemic inflammation in patients with CAD does not seem to be due to seropositivity to cLPS or CP.

Adult↗

PubMed2005

Systemic inflammation induces COX-2 mediated prostaglandin D2 biosynthesis in mice spinal cord.

Although prostaglandin (PG)D2 is one of the main metabolites of the cyclooxygenase (COX) pathway of arachidonate metabolism in the brain, relatively little is known about the regulation of PGD2 biosynthesis in the spinal cord during systemic inflammation. Therefore, the present study was aimed at investigating the effect of endotoxin treatment on spinal PGD2 biosynthesis in BALB/c mice. Spinal inflammatory response to systemic endotoxin was verified by determination of spinal TNFalpha and IL-1beta mRNA. COX-1, COX-2, membrane-bound prostaglandin E synthase-1 (mPGES-1), and lipocalin-type prostaglandin D synthase (L-PGDS) mRNA and protein were determined by RT-PCR and western blot, respectively. The concentrations of immunoreactive PGD2 and PGE2 were measured in superfusion media of spinal cord samples in-vitro. Endotoxin treatment (1 mg/kg; 24 h before) enhanced the expression of COX-2, mPGES-1, and L-PGDS mRNA and protein in spinal cord, while there was no significant effect on COX-1 mRNA and protein. In superfusion media of spinal cord samples obtained from endotoxin treated mice, the concentrations of immunoreactive PGE2 and PGD2 were higher than in the control group suggesting enhanced spinal PG biosynthesis after endotoxin treatment. Addition of the selective COX-2 inhibitor lumiracoxib (100 nM) to the superfusion medium did not significantly affect PGE2 or PGD2 release in spinal cord obtained from non-treated mice. In spinal cord of endotoxin-treated mice, lumiracoxib (100 nM) attenuated PGE2 and PGD2 release to values similar to those observed in tissue obtained from non-endotoxin-treated mice. These results show enhanced expression of spinal L-PGDS and increased spinal PGD2 biosynthesis during systemic inflammation whereby enhanced biosynthesis seems to be dependent primarily on COX-2 activity.

Animals↗

PubMed2006

Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury.

The relationship between local inflammation and the subsequent systemic inflammatory response is poorly described. In a burn injury model, the dermal inflammatory response may act as an ongoing trigger for the systemic inflammatory response syndrome (SIRS) and subsequent systemic complications. We hypothesized that topical attenuation of burn wound inflammatory signaling will control the dermal inflammatory source, attenuate SIRS, and reduce acute lung injury. Mice received a 30% total body surface area burn. Subgroups were treated with specific p38 MAPK inhibitor or vehicle, which was topically applied to wounds. Topical p38 MAPK inhibition significantly reduced burn wound inflammatory signaling and subsequent systemic expression of proinflammatory cytokines and chemokines. In vitro macrophage functional assays demonstrated a significant attenuation in serum inflammatory mediators from animals receiving the topical inhibitor. Topical p38 MAPK inhibition resulted in significantly less pulmonary inflammatory response via reduction of pulmonary neutrophil sequestration, pulmonary cytokine expression, and a significant reduction in pulmonary microvascular injury and edema formation. Although dermal activating transcription factor-2, a downstream p38 MAPK target, was significantly reduced, there was no reduction in pulmonary activating transcription factor-2 expression, arguing against significant systemic absorption of the topical inhibitor. These experiments demonstrate a strong interaction between dermal inflammation and systemic inflammatory response. Attenuating local inflammatory signaling appears effective in reducing SIRS and subsequent systemic complications after burn injury.

Animals↗

PubMed2006

Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.

BACKGROUND: Cancer cachexia is a multifactorial syndrome that is poorly defined. OBJECTIVE: Our objective was to evaluate whether a 3-factor profile incorporating weight loss (> or = 10%), low food intake (< or = 1500 kcal/d), and systemic inflammation (C-reactive protein > or = 10 mg/L) might relate better to the adverse functional aspects of cachexia and to a patient's overall prognosis than will weight loss alone. DESIGN: One hundred seventy weight-losing (> or = 5%) patients with advanced pancreatic cancer were screened for nutritional status, functional status, performance score, health status, and quality of life. Patients were followed for a minimum of 6 mo, and survival was noted. Patients were characterized by using the individual factors, > or = 2 factors, or all 3 factors. RESULTS: Weight loss alone did not define a population that differed in functional aspects of self-reported quality of life or health status and differed only in objective factors of physical function. The 3-factor profile identified both reduced subjective and objective function. In the overall population, the 3 factors, > or = 2 factors, and individual profile factors (except weight loss) all carried adverse prognostic significance (P < 0.01). Subgroup analysis showed that the 3-factor profile carried adverse prognostic significance in localized (hazard ratio: 4.9; P < 0.001) but not in metastatic disease. CONCLUSIONS: Weight loss alone does not identify the full effect of cachexia on physical function and is not a prognostic variable. The 3-factor profile (weight loss, reduced food intake, and systemic inflammation) identifies patients with both adverse function and prognosis. Shortened survival applies particularly to cachectic patients with localized disease, thereby reinforcing the need for early intervention.

Aged↗

PubMed1997

An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.

BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.

Acute Disease↗

PubMed2005

Systemic inflammation and reperfusion injury in patients with acute myocardial infarction.

Despite early recanalization of an occluded infarct artery, tissue reperfusion remains impaired in more than one-third of the acute myocardial infarction (AMI) patients owing to a process of reperfusion injury. The role of systemic inflammation in triggering this phenomenon is unknown. Proinflammatory factors (hs-CRP, TNF-alpha ) and anti-inflammatory mediators (IL-1 receptor antagonist, IL-10) were measured in 65 patients during the acute phase of a myocardial infarction as well as in 11 healthy control subjects. Myocardial reperfusion injury was defined as the presence of persistent ST-segment elevation despite successful coronary intervention (> or = 50 of the initial value) and was observed in 28 patients. Systemic proinflammatory mediators (particularly hs-CRP and leukocytes) were higher in AMI patients compared to control subjects. Within the group of AMI patients, only serum TNF-alpha differed significantly between patients with versus without reperfusion injury: a median value of 25 versus 13 pg/mL was observed, respectively. Logistic regression analysis identified a high level of TNF-alpha as the most important independent determinant of reperfusion injury (P = .001), beyond total ischemic time (P = .01) and extent of jeopardized myocardium (P = .08). There was no correlation between the TNF-alpha level and the total ischemic time (P = .8) or the extent of jeopardized myocardium (P = .6). Systemic inflammation, in particular high levels of TNF-alpha , is strongly associated with the occurrence of reperfusion injury after successful recanalization. Our findings suggest that TNF-alpha is involved in the triggering and/or amplification of local inflammatory responses related to ischemia-reperfusion injury.

Aged↗