Showing papers by "Per Venge published in 2006"

Troponin I as a Predictor of Coronary Heart Disease and Mortality in 70-Year-Old Men A Community-Based Cohort Study

Abstract: Background— Cardiac troponin I (cTnI), a standard for detection of myocardial damage, has recently been reported to predict acute myocardial infarction or death in patients with unstable coronary heart disease (CHD). Cardiac TnI concentrations increase with age in subjects free from clinical signs of CHD, suggesting silent myocardial damage. We investigated the association between cTnI and future CHD and mortality in a community-based cohort of men. Methods and Results— A community-based study was conducted from August 1991 to May 1995 among 1203 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10.4 years with the use of registry data (National Board of Health and Welfare, Sweden). CHD was defined with the use of data taken from the Cause of Death Registry or from first-time hospitalization for CHD as recorded in the Hospital Discharge Registry. Cardiac TnI concentrations were measured blinded for outcome, in frozen baseline plasma samples, with the use of the AccuTnI from Beckm...

The Antibody Configurations of Cardiac Troponin I Assays May Determine Their Clinical Performance

Abstract: Background: Previous studies have shown superior clinical performance of the cardiac troponin I (cTnI) assay from Beckman-Coulter Diagnostics. This assay had a unique combination of monoclonal antibodies with 2 monoclonal antibodies directed against epitopes near the NH 2 terminus of the heart-specific region of troponin I. The approach has been adopted by the new cTnI assay from Abbott Diagnostics. The aim of our study was to investigate whether this approach affects the clinical performance of cTnI assays. Methods: Cardiac troponin concentrations were measured in a random sample of patients with unstable coronary artery disease included in the GUSTO IV trial (n = 696) by the AccuTnI (Beckman-Coulter Diagnostics), Architect cTnI (Abbott Diagnostics), Immulite 2500 cTnI (Diagnostics Products Corporation), and Elecsys 2010 cTnT (Roche Diagnostics) assays and related to the 1-year mortality. The primary cutoff concentrations were based on the 99th percentile upper reference limits and an imprecision (CV) ≤10%. Results: The sensitivities of the AccuTnI and Architect cTnI assays in identifying patients who died within 1 year were equal and were significantly higher ( P P P Conclusions: The Architect cTnI assay has clinical performance similar to that of the AccuTnI, probably as a result of the inclusion of a monoclonal antibody against troponin I epitope 41–49 in the assay.

A (G->C) transversion in the 3' UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP.

Abstract: Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted from human eosinophil granulocytes. ECP may be in- volved in the injury of epithelial cells in allergic diseases such as asthma. The objectives were to determine the prevalence of the ECP gene poly- morphism 562(G>C) in apparently healthy sub- jects and subjects with allergy and relate the prev- alence to clinical disease and to serum and cellular levels of ECP. The 562(G>C) ECP gene polymor- phism was determined by gene sequencing of the ECP gene from DNA prepared from 163 appar- ently healthy subjects and 151 subjects with aller- gic and nonallergic asthma or other diseases. ECP was measured by a sensitive radioimmunoassay. A polymorphism was detected at position 562, which mapped to the 3 untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty-nine per- cent of the population had the 562GG genotype and 4%, the 562CC genotype. The cellular con- tent of ECP in peripheral blood eosinophil granu- locytes was significantly lower in cells from subjects with the 562GC (4.61.5 g/10 6 eosinophils) and 562CC (3.20.7 g/10 6 eosinophils) genotypes as compared with those with the 562GG genotype (6.01.9 g/10 6 eosinophils; P C) ECP gene poly- morphism. Associations between the 562(G>C) polymorphism or haplotypes of the two polymor- phisms to allergy were not found. The 562(G>C) polymorphism in the 3-end of the UTR of the ECP gene may determine the ECP content in human eosinophils, but unlike the 434(G>C) polymor- phism, the 562(G>C) polymorphism is not related to allergy J. Leukoc. Biol. 79: 000-000; 2006.

Cystatin C as a marker of immune complex-associated renal impairment in a Sudanese population with visceral leishmaniasis.

Abstract: Renal function was studied in visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) by means of the specific marker cystatin C and related to circulating immune complexes and cytokine production. Forty patients with VL (23 with sub-acute disease and 17 with acute disease), 17 patients with PKDL, and 22 healthy controls were included. Cystatin C, but not creatinine, was significantly raised in VL (P = 0.004). The highest levels of cystatin C were found in those with acute disease (P < 0.0001). In VL, cystatin C levels were positively correlated to circulating immune complexes and production of granulocyte-macrophage colony stimulating factor (GM-CSF), but negatively correlated to aspartate aminotransferase and lactate dehydrogenase. We conclude that cystatin C is a superior marker of glomerular function in leishmaniasis and that immune complex deposition and GM-CSF are two functions that most likely are causally involved in the mechanisms leading to glomerular dysfunction in leishmaniasis.

Albumin stimulation of eosinophil migration involves PI3-kinases and is associated with diminished eosinophil CD49d and CD49f expression.

Abstract: Background: Albumin is known to induce chemokinesis and facilitate chemotaxis of human granulocytes in the Boyden chamber assay, but its mechanisms of action remain obscure. We have previously found that IL-2 inhibits albumin-stimulated eosinophil migration. The aim of this study was to identify the mechanisms behind the effects of albumin and IL-2 on the migration of human eosinophils. Methods: Purified eosinophils were preincubated with inhibitors of signal transduction molecules before incubation with or without albumin and IL-2. The migration assay was performed in a 48-well microchemotaxis chamber. The effect of albumin and IL-2 on cell size and on the surface expression of adhesion molecules was studied with flow cytometry. Results: Albumin-stimulated migration was inhibited by the PI3-kinase inhibitors wortmannin and LY-294002, but not by the PKC inhibitor RO-31-8220. IL-2 had no effect after preincubation with wortmannin or LY-294002. In contrast, the inhibitory effect of IL-2 remained after preincubation with RO-31-8220. Albumin increased the cell size as measured by forward scatter, and the expression of CD49d and CD49f decreased after incubation with albumin. IL-2 affected neither the expression of adhesion molecules nor the forward scatter. Conclusions: The stimulation of eosinophil migration by albumin is mediated by PI3-kinase, and the increase in cell size caused by albumin indicates activation of the cells. Decreased expression of CD49d and CD49f by albumin may diminish the adhesiveness of the cells, which in turn may facilitate migration. These are novel findings that indicate an active role for albumin in eosinophil migration.

Selective priming of peripheral blood eosinophils in patients with idiopathic hypereosinophilic syndrome.

Abstract: The idiopathic hypereosinophilic syndrome (HES) is characterised by blood eosinophilia associated with organ involvement. Elevated numbers of blood neutrophils have been observed during episodes of active HES. However, an increased responsiveness of eosinophils to chemotactic and chemokinetic stimuli may explain the selective eosinophil infiltration of the tissue. We have studied the migratory responses of blood eosinophils and neutrophils from 9 patients with HES and from 13 healthy control subjects. Chemokinetic and chemotactic responses to factors acting on both cell types were analysed by means of a modification of the Boyden chamber technique. We found increased migratory responses of the eosinophils, but not of the neutrophils, from the patients with HES. Increased blood neutrophil counts in three of the patients did not coincide with alterations of the neutrophil migratory responses. Our finding of increased migratory responses of eosinophils from patients with HES towards non-specific chemoattractants suggests selective priming of eosinophils in this disease. Interleukin (IL)-5 has previously been shown to prime eosinophils for migratory responses, and successful anti-IL-5 therapy of patients with HES indicates an important role for this cytokine in the development of hypereosinophilia.

[BNP or NT-proBNP should be analyzed in suspected heart failure. Guidelines for analysis and interpretation].

Abstract: [BNP or NT-proBNP should be analyzed in suspected heart failure. Guidelines for analysis and interpretation]

Abstract 2060: Persisting Troponin I Elevations Predict Adverse Outcome in Stabilized Patients After an Episode of Acute Coronary Syndrome.

Abstract: Introduction: In patients with acute coronary syndrome (ACS), any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persisting troponin elevations in stabilized patients after an episode of ACS is not known. We therefore measured troponin I (TnI) in stabilized patients participating in the FRISC II trial, in which patients with nonSTE-ACS were randomized to an invasive vs. a non-invasive strategy and to long-term treatment with dalteparin vs. placebo. Method: TnI was measured in blood samples obtained 3 months after inclusion in 1017 patients without a myocardial infarction (MI) or coronary procedure within the last 14 days. TnI was analyzed using the Access AccuTnI assay (Beckman-Coulter). The 99 th percentile of healthy subjects below 60 years of age, 0.02 μg/L, was chosen as prognostic cut-off. The 10% CV level of the assay was found to be at 0.012 μg/L. All patients were followed for at least 5 years. Results: TnI at 3 months was elevated > 0.02 μg/L in 17.1% of the patients. TnI > 0.02 μg/L predicted 5-year cardiac mortality (11.5% vs 3.4%; p 0.02 μg/L was an independent predictor of long-term cardiac mortality (OR 2.8; 95% CI 1.5–5.3; p=0.001) and, to a lesser extent, of MI (OR 1.5; 95% CI 1.0 –2.4; p=0.049). Conclusion: Persisting TnI elevations can frequently be detected in patients with stabilized ACS with the use of a sensitive assay. TnI >0.02 μg/L in patients with stabilized ACS predicts adverse cardiac events during long-term follow-up. Our results emphasize the importance of further troponin testing in ACS patients after discharge. The occurrence of minor TnI elevations in a large proportion of patients with stabilized ACS also cast doubts on using a very low troponin level as a criterion for the diagnosis of acute MI.

BNP eller NT-proBNP bör analyseras vid misstänkt hjärtsvikt : Riktlinjer för analys och tolkning

Abstract: Available data indicate that the use of B-type natriuretic peptide (BNP) or N-terminal-proBNP (NT-proBNP) improve the diagnostics of suspected heart failure as compared to the currently used clinic ...

Eosinophilia and the Hypereosinophil Syndromes

Abstract: Eosinophilia denotes the increased number of eosinophil granulocytes in blood or tissue and is associated with a large number of human diseases. Hypereosinophilia is the condition when excessive numbers of eosinophils are produced and which often leads to serious organ damage by the eosinophils. Keywords: eosinophil; eosinophilia; allergy; asthma; parasite