Showing papers on "C-reactive protein published in 1997"

Inflammation, Aspirin, and the Risk of Cardiovascular Disease in Apparently Healthy Men

Abstract: Background Inflammation may be important in the pathogenesis of atherothrombosis. We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk. Methods We measured plasma C-reactive protein, a marker for systemic inflammation, in 543 apparently healthy men participating in the Physicians' Health Study in whom myocardial infarction, stroke, or venous thrombosis subsequently developed, and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years. Subjects were randomly assigned to receive aspirin or placebo at the beginning of the trial. Results Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infarction (1.51 vs. 1.13 mg per liter, P<0.001) or ischemic stroke (1.38 vs. 1.13 mg per liter, P = 0.02), but not venous thrombosis (1.26 vs. 1.13 mg per liter, P = 0.34), than among men without vascular events. The men in the quartile wit...

Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia.

Abstract: Background Complement activation during cardiopulmonary bypass (CPB) surgery is considered to result from interaction of blood with the extracorporeal circuit. We investigated whether additional mechanisms may contribute to complement activation during and after CPB and, in particular, focused on a possible role of the acute-phase protein C–reactive protein (CRP). Methods and Results In 19 patients enrolled for myocardial revascularization, perioperative and postoperative levels of complement activation products, interleukin-6 (IL-6), CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo, were measured and related to clinical symptoms. A biphasic activation of complement was observed. The ratio between the areas under the curve of perioperative and postoperative C3b/c and C4b/c were 3:2 and 1:46, respectively. IL-6 levels reached a maximum at 6 hours post-surgery. CRP levels peaked on the second postoperative day. Each complement-CRP complex had peak levels on the second...

Lifetime Smoking Exposure Affects the Association of C-Reactive Protein with Cardiovascular Disease Risk Factors and Subclinical Disease in Healthy Elderly Subjects

Abstract: Blood levels of C-reactive protein (CRP), a marker of inflammation, are related to cardiovascular disease risk. To determine cross-sectional correlates in the elderly, we measured CRP in 400 men and women older than 65 years and free of clinical cardiovascular disease at baseline as part of the Cardiovascular Health Study. Only 2% of the values were greater than 10 mg/L, the cut-point usually used to identify inflammation. CRP levels appeared tightly regulated, since there were strong bivariate correlations between CRP and the following: inflammation-sensitive proteins such as fibrinogen ( r =.52); measures of fibrinolysis such as plasmin-antiplasmin complex ( r =.23); pack-years of smoking ( r =.30); and body mass index ( r =.24; all P values≤.001). The association with pack-years was independent of the length of time since cessation of smoking. CRP levels were also associated with coagulation factors VIIc, IXc, and Xc; HDL cholesterol (negative) and triglyceride; diabetes status; diuretic use; ECG abnormalities; and level of exercise. Because of effect modification, two multiple linear regression prediction models were developed for CRP, one each for never smokers and ever smokers. An a priori physiologic model was used to guide these analyses, which disallowed the use of other inflammation-sensitive variables such as fibrinogen. In never smokers, the independent predictors were body mass index (+), diabetes status (+), plasmin-antiplasmin complex (+), and the presence of ECG abnormalities (+); this model predicted 15% of the CRP population variance. In ever smokers, the predictors were body mass index (+), plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL cholesterol (−), and ankle-arm blood pressure index (−); this model predicted 42% of the population variance. We conclude that levels of CRP in the healthy elderly are tightly regulated and reflect lifetime exposure to smoking as well as level of obesity, ongoing level of fibrinolysis, diabetes status, and level of subclinical atherothrombotic disease. Moreover, exposure to smoking affects the relation of CRP to these other factors.

Prognostic Influence of Increased Fibrinogen and C-Reactive Protein Levels in Unstable Coronary Artery Disease

Abstract: Background The prognostic influences of fibrinogen and C-reactive protein levels and their relations to myocardial damage in unstable coronary artery syndromes have not been well described. Methods...

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

Abstract: OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

C-Reactive Protein Colocalizes With Complement in Human Hearts During Acute Myocardial Infarction

Abstract: Background Rises in circulating C-reactive protein (CRP), the prototypical acute-phase protein in humans, correlate with clinical outcome in patients with myocardial ischemia and infarction. We hypothesized that these correlations might reflect active participation of CRP in the local inflammatory response ensuing in the jeopardized myocardium because on binding to a ligand, CRP is able to activate the classic pathway of complement, and in addition, complement activation has been shown to occur locally in infarcted myocardium. Methods and Results To verify our hypothesis, we investigated localization of CRP in relation to deposition of complement in tissue specimens of infarcted and healthy heart tissue obtained from 17 patients who had died after acute myocardial infarction. CRP was found to be deposited only in infarcted regions and not in normal-appearing areas of the myocardium, being colocalized with depositions of C4 and C3 activation fragments of the complement system. Deposition of CRP and complem...

Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants

Abstract: AIMS—To evaluate the commonly used markers—namely IL-6, TNFα, IL-1β, C-reactive protein and E-selectin for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment. METHODS—Very low birthweight infants in whom clinical sepsis was suspected when they were >72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined. RESULTS—One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNFα 17 pg/ml, IL-1β 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNFα on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection. CONCLUSIONS—Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNFα should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition. Keywords: C-reactive protein; E-selectin; interleukin 1β; interleukin-6; tumour necrosis factor α; very low birthweight

Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity.

Abstract: OBJECTIVE To investigate the difference in acute phase protein responses between patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and spondyloarthropathies (SpA). METHODS Circulating levels of cytokines inducing the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were measured in 2 cohorts of patients. The first cohort included 52 patients with SLE and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA. An examination at the time of blood collection and the Systemic Lupus Activity Measure (SLAM) index were used to assess disease activity in patients with SLE. Serum levels of IL-6 were measured using a biological assay, and concentrations of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by immunoassays. RESULTS Although C-reactive protein (CRP) levels were significantly lower in SLE than in RA or SpA, the concentrations of circulating IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF-sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF-sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75 levels correlated with disease activity in SLE. CONCLUSION The weak acute phase protein response in SLE may be explained by a decreased ratio between inducing cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological marker for the followup of SLE, where acute phase protein response is generally low during disease exacerbations.

Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti-tumour necrosis factor-alpha (cA2) therapy.

Abstract: Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum samples from rheumatoid arthritis (RA) patients undergoing a double-blinded placebo-controlled trial with the chimaeric anti-tumour necrosis factor (TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the commencement of the trial compared with normal control sera. Following cA2 therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10 mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10 mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reducing maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2 treated group. In a separate non-placebo-controlled study, we also evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the normal control range, but were significantly reduced (P < 0.035) 14 days after infusion to 72% of pre-infusion values. This study confirms previous reports that MMP-3 levels are elevated and correlate with measures of inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1 levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to and following anti-TNF-alpha antibody therapy, it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease.

Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity.

Abstract: Objective. To analyze the levels of the T cell regulatory cytokines interleukin 10 (IL-10) and IL-12 in plasma of patients with Behcet's disease (BD), and to assess the value of cytokines and cytokine antagonists as biological markers of disease activity. Methods. Sera/plasma of 66 consecutive outpatients with established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor necrosis factor-α (TNF-α), soluble (s) TNF receptor (R)-55, sTNFR-75, IL-10, and IL-12 using immunological methods. Additional laboratory measurements included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Data from the history and clinical examination were recorded to correlate cytokine levels with clinical markers of disease activity. Results. 18 patients had inactive (Group 1), 36 had mildly active (Group II), and 12 patients had active BD (Group III). IL-10 was elevated in 42 plasma samples (64%). The percentage of samples containing IL-10 and the median levels of IL-10 of the 3 patient groups did not differ significantly. IL-12 was detectable in plasma of 9 patients : One from Group I (5%), 3 from Group II (8%), and 5 from Group III (41%). IL-12 correlated with disease activity (difference between Groups I and III, p = 0.02, between Groups II and III, p = 0.008). ESR in patients with active disease and mildly active disease was significantly higher than values in patients with inactive disease (p = 0.03, p = 0.02, respectively), while median CRP levels were significantly different between Group I and Group III only (p = 0.006). sTNFR-75 levels were significantly different between Groups II and III (p = 0.003) and between Groups I and III (p = 0.008). Conclusion. The elevation of plasma IL-10 in the majority of patients and the correlation of IL-12 plasma levels with disease activity suggest a pathogenic role of a TH1-type immune response in active disease. In addition, the correlation of sTNFR-75 levels with disease activity indicates that sTNFR-75 may serve as a biological marker of disease activity in BD.

Treatment of ulcerative colitis with an engineered human anti-TNFalpha antibody CDP571.

Abstract: Background: Tumour Necrosis Factor-alpha (TNFα) is a pro-inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFα antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis. Methods: Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGγ4 antibody CDP571 and monitored for 8 weeks. Results: Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left-sided disease, four extensive disease and six patients were steroid-unresponsive. The treatment was well tolerated and plasma half-life of CDP571 was ≈7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell–Tuck score by 1 week post-infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin-6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance. Conclusion: A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.

Serum C-reactive protein as a marker for infection and inflammation in regular dialysis patients.

Abstract: Serum C-reactive protein (CRP) concentration was measured in 98 hemodialysis (HD) patients and 68 continuous ambulatory peritoneal dialysis patients (CAPD). The effect, if any, of a HD session on serum CRP level and the usefulness of CRP in diagnosing and monitoring proven inflammatory disease were studied. Seventy-five percent of CAPD patients without evidence of inflammation had CRP levels within the quoted normal range ( 50 mg/l. These increased CRP levels fell with treatment. A CRP level of > 50 mg/l proved highly suggestive of a significant inflammatory process and a value of 50 mg/l or serial/baseline measurements are available for comparison. Whether any relationship exists between elevation of CRP and the well-documented increased risk of cardiovascular death in dialysis patients is currently unknown.

Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus.

Abstract: SUMMARY The objective was to study the relationship between the levels of interleukin-1 receptor antagonist (IL-1Ra) and disease activity and the acute-phase response in SLE patients with and without renal involvement. Twenty SLE patients who had distinct active clinical manifestations (eight glomerulonephritis, four systemic vasculitis without kidney involvement, nine skin rash, 12 arthritis, five serositis, four neuropsychiatric manifestations, three thrombocytopenia, one myositis and one haemolytic anaemia) were studied during a period of 8‐12 months. Serum and plasma samples were taken at intervals of 6 weeks‐ 4 months and tested for IL-1Ra, IL-1b, IL-6, IgG and anti-dsDNA, C1q, C3, C4 and C-reactive protein (CRP). IL-1Ra serum concentrations were increased in most SLE patients with active disease when compared to normal blood donors. However, at the time of flare, significantly higher levels of IL-1Ra were observed in patients with extra- renal disease as compared to other patients (median [range]: 363 [202‐3041] and 4847 [268‐27180] pg/ml for patients with and without renal involvement, respectively). This diAerence was not due to proteinuria. IL-1Ra levels did not correlate with SLEDAI score during flares, but they were elevated during flares in patients with extra-renal manifestations. When disease activity was at its highest, IL-1Ra concentrations correlated with IL-1b (r = 0.76; P<0.001), IL-6 (r = 0.60; P<0.01) and CRP (r = 0.61; P<0.01), but not with C1q, C3, C4 and anti-dsDNA levels. The study showed that the pattern of inflammatory cytokines in active SLE varies in a manner that is dependent on which organs are involved. A relative absence of IL-1Ra response appears to be a feature characteristic of kidney involvement. IL-1Ra elevation clearly correlates with flares involving other organs. CYTOKINES transmit information between cells and are particularly important as mediators in inflammatory diseases. Under physiological conditions, proinflammatory and anti-inflammatory cytokines are controlled by inbuilt mechanisms of defence [1]. Several such mechanisms are known and include receptor antagonists, soluble cytokine receptors, inhibitory actions of diAerent cytokines, and autoantibodies against cytokines. Interleukin-1 (IL-1) plays a central role in inflammatory processes, and its biological activities are regulated by a naturally occurring specific receptor antagonist (IL-1Ra) which was originally found in biological fluids of patients with high fever and inflammatory diseases [2‐4]. IL-1Ra, structurally related to IL-1, is secreted by monocytes/ macrophages and neutrophils, and binds to IL-1 receptors competitively without inducing any biological response [5]. IgG-containing immune complexes stimulate the production of IL-1Ra by monocytes [6], and various cytokines (IL-4, IL-10, IL-13) enhance IL-1Ra production but inhibit IL-1 production [7]. An IL-1Ra gene polymorphism has been described and been related to disease severity, but not to disease susceptibility in systemic lupus erythematosus (SLE) [8]. Although inflammation is evidently important in the pathogenesis of SLE, the response of acute-phase proteins such as C-reactive protein (CRP) is weak, especially in patients with mainly kidney and skin involvement [9]. IL-6 is know to be the main CRP inducer, but IL-1 has also been shown to be involved in this process [10]. A recent cross-sectional study showed overall elevated IL-1Ra levels in SLE, but did not explore clinical correlates or include IL-1b determinations [11]. We now report on these variables in a longitudinal study in which blood specimens were collected over 8‐12 month periods surrounding flares of the disease.

C-reactive protein elevation and early outcome in patients with unstable angina pectoris.

Abstract: C-reactive protein, a reactant of the acute phase of inflammation, has been shown to be increased in patients with unstable angina. Moreover, it has recently been found that increased C-reactive protein is associated with a poor outcome during hospitalization in selected patients with severe unstable angina. The aim of this study was to investigate the prognostic value of C-reactive protein elevation in a large population with unstable angina. We measured serum levels of this marker in 140 patients hospitalized with unstable angina (class IIIB of the Braunwald classification, mean time from last anginal episode 5 ± 5 hours). Thirty-nine of them (28%) had increased serum levels on hospital admission and 33 (24%) experienced an adverse out-come (myocardial infarction or refractory angina) during hospitalization. Kaplan-Meier analysis showed that the probability of developing cardiac events during hospitalization was not different between patients with and without abnormal C-reactive protein levels. Furthermore, the incidence of ischemia at Holter monitoring during the first 72 hours after hospitalization was not different between patients with and without abnormal C-reactive protein. In a representative population of patients with unstable angina, a sizable proportion had increased serum C-reactive protein levels; however, abnormal concentrations of C-reactive protein do not predict an adverse outcome in the early phase after the acute episode.

Are serum inflammatory markers age dependent in acute appendicitis

Abstract: BACKGROUND Preoperative measurement of body inflammatory agents reduces unnecessary appendectomies by up to 30 percent. A decline in the formation of blood leukocytes and C-reactive protein with aging may hinder the correct diagnosis of appendicitis. STUDY DESIGN White cell count and C-reactive protein were determined before appendectomy in 600 patients aged 0 to 5 years, 6 to 19 years, 20 to 39 years, 40 to 59 years, 60 to 79 years, and older than 80 years. Their records were analyzed. The sensitivity, specificity, diagnostic accuracy, and receiver-operating characteristic curves for C-reactive protein and white cell count to predict appendicitis were calculated separately for each age group. RESULTS The rates of negative explorations and perforations were highest at both extremes of age. In uncomplicated appendicitis, the diagnostic potential of white cell count was better than C-reactive protein in all age groups except infants. The C-reactive protein was elevated similarly throughout human life, but only in those with perforated appendicitis. The receiver-operating characteristic curves confirmed that the performance of white cell count was better than C-reactive protein in the correct diagnosis in every age group except infants and octogenarians. CONCLUSIONS The leukocyte response declines in 0- to 5-year-old children with appendicitis, but the C-reactive protein response is well preserved in all other age groups.

Acute phase proteins, C-reactive protein and serum amyloid A protein, as prognostic markers in the elderly inpatient

Abstract: Aim: to study the clinical significance and potential utility of measuring serum amyloid A protein (SAA) compared with the classical acute phase protein, C-reactive protein (CRP). Method: a 3 month prospective study on 66 women, mean age 83 years (range 69-106) and 33 men, mean age 84 years (range 69-95), admitted to the geriatric medicine unit at Hammersmith Hospital. CRP and SAA were determined on admission and at intervals throughout hospital stay; outcome end-points were death during the study, detection of infection, duration of admission and early re-admission to hospital after discharge. Results: CRP and SAA responses were highly correlated (r = 0.75, P — 0.0001). However, the SAA response was greater than that of CRP in most individuals, with a median ratio of initial SAA to CRP of 2.2 in patients with infective pathology and 1.6 in those with inflammatory pathology. Median (range) SAA on admission was 98 (0.1-940) mg/ml in patients with infection and was twice that observed in patients with other causes of inflammation, median value 50 (0.6-699) mg/1. There was no difference between median CRP on admission in patients with infection or inflammation, median value 53 (0.1 - 235) and 51.5 (5 - 246) mg/1 respectively. Initial and peak levels of CRP, but not of SAA, were significantly greater in patients who subsequently died, whereas high levels of both proteins predicted length of admission and early re-admission. Conclusion: major elevations of the serum concentrations of CRP and SAA indicated serious disease and predicted poor outcome. Measurement of SAA as well as CRP enhanced the clinical utility of monitoring the acute phase response in 7% of patients with a diagnosis of infection.

C-reactive protein as a marker for acute coronary syndromes.

Abstract: Background For several years, acute coronary syndromes have been perceived as causing the most hospital admissions, and even hospital mortality. The syndrome of unstable angina frequently progresses to acute myocardial infarction but its pathogenesis is poorly understood, and prognosis determination is still problematic. We tested the hypothesis that measurement of the C-reactive protein in patients admitted for chest pain could be a marker for acute coronary syndromes. Methods and Results We studied 110 patients admitted with suspected ischaemic heart disease, but without elevated serum creatine-kinase levels at the time of hospital admission. Patients were subsequently divided into two groups based on their final diagnosis: group 1 comprised patients with unstable angina; group 2 patients with acute myocardial infarction. We measured the C-reactive protein at the time of hospital admission. The concentration of C-reactive protein was elevated in 59% of the patients with a final diagnosis of acute myocardial infarction, and in 5% of the patients with a final diagnosis of unstable angina, ( P <0·001). Conclusion This study indicates that C-reactive protein levels measured at the time of admission in patients with suspected ischaemic heart disease could be a marker for acute coronary syndromes, and helpful in identifying patients at high risk for acute myocardial infarction. Measurement of C-reactive protein may have practical clinical significance in the management of patients hospitalized for suspected acute coronary syndromes.

Elevation of serum ferritin levels as a marker for active systemic lupus erythematosus.

Abstract: Objective To determine the clinical relevance of serum levels of ferritin in patients with systemic lupus erythematosus (SLE) vs controls, we assessed the correlations between such levels and clinical disease activity, anti-DNA antibody titer, and serum levels of complement Methods We evaluated 36 patients (3 males and 33 females) with SLE, including 21 patients with active disease A total of 52 patients (3 males and 49 females) with rheumatoid arthritis (RA) served as controls In a further study for reproducibility, 15 SLE and 21 RA patients were examined Serum ferritin levels were measured by a 2-site radioimmunometric assay Serum levels of C-reactive protein (CRP) were measured semiquantitatively by immunoprecipitation or quantitatively by laser immunonephelometry Anti-DNA antibody was measured by the Farr assay CH50 was measured by the hemolytic activity method Results The SLE patients exhibited higher serum levels of ferritin and lower serum levels of CRP than the RA patients Serum levels of ferritin at the active stage of SLE exceeded those at the inactive stage The levels of serum ferritin in SLE were positively correlated with the anti-DNA antibody titer and negatively correlated with CH50 values Conclusion Serum levels of ferritin appear to provide a useful marker of disease activity in SLE patients

Infection, inflammation, and cerebrovascular ischemia.

Abstract: Hemostatic and inflammatory pathways mutually interact with each other. Increased inflammatory parameters are a sequel of and also a risk factor for cerebral thrombosis and ischemia. Ischemic stroke is followed by an acute-phase response that is characterized by a transient rise in fibrinogen, leukocyte count, and several cytokines. This article focuses on inflammatory changes that precede cerebral ischemia and on inflammation/infection as a risk factor for stroke and transient ischemic attack (TIA). Inflammatory parameters and vascular diseases and risk factors. The leukocyte count is positively associated with the risk for ischemic stroke and myocardial infarction.1,2 The granulocyte count appears to contribute mainly to such elevated risk. A recent epidemiologic study found that the monocyte count also correlated with an increased risk for myocardial ischemia.3 High plasma fibrinogen levels are a risk factor for stroke and myocardial infarction(MI).4 Moreover, several serum glycoproteins, mostly acute-phase reactants, were shown to be correlated with the severity of coronary atherosclerosis.5 Although the above inflammatory parameters appear to independently predict the risk of ischemic diseases, several vascular risk factors are themselves correlated with an increase in inflammatory parameters. We studied the association of leukocyte count, fibrinogen, and C-reactive protein (CRP) with vascular risk factors in the control group of our recent case-control study investigating acute infection as a risk factor for stroke.6,7 These control subjects were randomly selected from the population and were matched to stroke patients for sex and age. Subjects with the following conditions were excluded from the analysis: malignancies, acute or chronic inflammatory diseases; recent trauma, surgery, and vascular diseases. In an ANOVA model with several risk factors and ischemic diseases, diabetes mellitus was associated with higher leukocyte count, fibrinogen and CRP. High age was correlated with increased leukocyte count and fibrinogen; Smoking and a history of stroke …

Distribution of T-cell signalling molecules in human myeloma

Abstract: It is controversial whether altered levels of TCR/CD3-associated signalling molecules play a role in the T-cell dysfunction of cancer patients. In multiple myeloma (MM), peripheral blood T (PBT) lymphocytes are functionally impaired by prolonged exposure to tumour cells, and so we investigated the organization of the TCR/CD3-associated signal transduction machinery. The aim of this study was two-fold: first, to investigate the levels of CD3zeta, p56(lck), p59(fyn), ZAP-70, protein kinase C-alpha (PKC-alpha) and phospholipase C-gamma (PLC-gamma) in MM PBT cells; second, to determine whether levels of expression were correlated with clinical or prognostic factors. Forty-four MM patients were studied and 25 age-matched normal donors served as controls. On average, PKC-alpha was the only significantly decreased (P<0.001) signalling molecule, whereas levels of CD3zeta, p56(lck), p59(fyn), PLC-gamma and ZAP-70 were not statistically different. However, there was wide variation between individual patients, and levels for each single protein also varied. A 75% or greater decrease in protein expression was observed, ranging from 8% (p59(fyn)) to 68% (PCK-alpha) of MM patients. When patients were grouped according to the cut-off values of prognostic factors such as the serum levels of C reactive protein (CRP), beta2-microglobulin (beta2M), neopterin (NPT) and the labelling index (LI%) of bone marrow (BM) plasma cells, the only difference observed was the lower PKC-alpha expression in patients with high serum NPT values. None of the T-cell signalling molecule levels was affected by the duration of tumour exposure, calculated on the number of years and/or months that had elapsed since diagnosis, or by disease status. In conclusion, there was a significant decrease of PCK-alpha in MM T cells; however, neither this decrease nor the heterogenous levels of the other T-cell signalling molecules were clearly correlated with prognosis, duration of tumour exposure, and disease status.

White blood cell count, leucocyte elastase activity, and serum Concentrations of interleukin-6 and C-reactive protein after open appendicectomy

Abstract: But: Etudier la cinetique de l'interleukine-6 (IL-6), du complexe elastase leucocyte (elastase), de la proteine reactive-C (CRP) et de la leucocytose (GB) apres appendicectomie par voie de Mac Burney. Type d'etude: Prospective. Provenance: Hopital universitaire Suede. Patients: Vingt et un patients ayant eu une appendicectomie pour suspicion d'appendicite. Principaux criteres de jugement: Les modifications postoperatoires de la CRP et de la leucocytose et leur correlation avec la survenue de complications. Resultats: Les concentrations les plus eleves d'IL-6 et les hyperleucocytoses les plus importants ont ete observees en preoperatoire, tandis qu'en postoperatoire la concentration de l'elastase etait maximale a J1 et celle de la CRP a J2. La concentration d'IL-6, la leucocytose et la CRP ont reaugmente a J6 chez un patient chez lequel on suspectait la survenu d'une infection profonde. Deux patients quie avaient une appendicite perforee avaient des concentrations d'IL-6, d'elastase et une leucocytose preoperatoire elevees. Conclusions: Les concentrations d'IL-6, d'elastase, et de CRP, et la leucocytose augmentent apres un traumatisme chirurgical, et peuvent rester elevees jusqu'au dixieme jour postoperatoire. Il est important de comprendre la cinetique postoperatoire de chaque test. La mesure de l'IL-6, de la CRP et la leucocytose permettraient de detecter plus facilement des complications postoperatoires.

C-Reactive Protein—Undervalued, Underutilized

Abstract: Tissue injury or infection leads to an increase in the serum concentration of a number of analytes, and to a decrease in the serum concentration of several others (1)(2). The change in concentration is referred to as the acute-phase response. Serum analytes that increase in concentration include C-reactive protein (CRP), serum amyloid A, fibrinogen, haptoglobin, ceruloplasmin, copper, interleukin-6, polypeptide-specific antigen, neopterin, and ferritin (3)(4)(5)(6). Analytes that decrease in concentration include transferrin and iron (6). CRP is a noteworthy member of this group because of the speed and degree to which its concentration increases after a variety of inflammatory states or injuries to tissues—including myocardial injury or infarction (2). CRP was discovered in 1930 by William Tillet and Thomas Francis at the Rockefeller Institute (7). They extracted a protein from the sera of patients with pneumococcal pneumonia that coprecipitated with the C polysaccharide derived from the cell wall of the pneumococcus. Because the reaction between the protein and the polysaccharide was so specific they named the protein C-reactive protein. The original test was a simple precipitin test, usually in …