PubMed Health⌕ Search

Biomedical subjects

Carl-Erik Dempfle

Publications and source records attributed to Carl-Erik Dempfle.

33 records · Page 2Linked to original sources
PubMed2004

Coagulopathy of sepsis.

Disseminated intravascular coagulation (DIC) is a common phenomenon in patients with sepsis, but the clinical implications of this condition are not clear. Clinical trials with coagulation inhibitors have failed to show a significant benefit concerning survival. DIC is primarily a laboratory diagnosis, based on the combination of elevated fibrin-related markers (FRM), with decreased procoagulant factors and platelets. Non-overt DIC is observed in most patients with sepsis, whereas overt DIC is less frequent. Patients with overt DIC may display consumption coagulopathy and purpura fulminans. Consumption coagulopathy is a bleeding disorder caused by low levels of platelets and procoagulant factors associated with massive coagulation activation. Purpura fulminans is caused by widespread microvascular thrombosis, resulting in tissue necrosis. Treatment with drotrecogin alfa (activated) improves survival and other outcome parameters in severe sepsis, including a subgroup of patients fulfilling the laboratory criteria of overt DIC. No randomized trials demonstrating effective therapies in consumption coagulopathy have been published. Bleeding patients with consumption coagulopathy are most frequently treated with platelet transfusions and various plasma products including fresh frozen plasma and coagulation factor concentrates. Based on case reports, treatment with drotrecogin alfa (activated) or substitution of protein C have been recommended for adjuvant treatment of sepsis-related purpura fulminans.

Blood Coagulation Disorders↗
PubMed2004

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score.

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.

Adolescent↗
PubMed2004

Hypofibrinogenaemia associated with a novel heterozygous gamma289 Ala -->Val substitution (fibrinogen Dorfen).

The molecular basis of hypofibrinogenaemia was investigated in a 34-year-old woman and her 10-year-old daughter. DNA sequencing revealed a single heterozygous GCC-->GTC transition in exon 8 of the fibrinogen gamma ?gene in both subjects, predicting a novel gamma289 Ala-->Val substitution. Examination of fibrinogen gamma ?chains by electrospray ionization mass spectrometry failed to detect the variant chain in plasma fibrinogen. Further evidence for its non-expression came from tryptic peptide mapping. The mutation predicts a mass increase of 28 Da in peptide T32, but only the normal (M + 2H) ion was detected at 1418 m/z in the proposita. Our finding that gamma289 is an important determinant of plasma fibrinogen levels highlights the role of mutational analysis in defining structurally important regions of the fibrinogen molecule. This case suggests that the highly conserved Ala(289) is important in maintaining structure of the "a" polymerization site via hydrogen bonding to Thr(371).

Adult↗
PubMed2004

Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Calcific aortic stenosis, the major heart valve disease encountered in the elderly, leads to massive calcium deposition in the valve leaflets that morphologically resembles bone formation. Recent studies have demonstrated the expression of various bone-associated proteins in stenotic valves, suggesting that valvular calcification may be an actively regulated process. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, and bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor cytokine superfamily, are known to participate in the regulation of bone development and maturation. Their pathogenetic role in calcific aortic stenosis is unknown. METHODS: Using an immunoperoxidase technique and antibodies against BSP and BMP-2, the expression of BSP and BMP-2 was examined in 16 human aortic valves with calcific aortic stenosis obtained at valve replacement, and in seven normal autopsy controls without signs of aortic stenosis. RESULTS: By semiquantitative scoring, stenotic valves showed a significantly increased staining of BSP in cells and extracellular matrix as compared to control valves (2.7 +/- 0.1 versus 0.6 +/- 0.2 score units, p <0.001). Marked BMP-2 expression was detected in stenotic valves, mostly in cell-rich areas associated with focal calcium deposits, but no specific staining for BMP-2 was detected in control valves (1.5 +/- 0.2 versus 0.0 +/- 0.0 score units, p <0.001). CONCLUSION: These results demonstrate for the first time that BSP and BMP-2 are differentially expressed in normal aortic valves and in aortic stenosis, thereby supporting the concept that valvular calcification might be based on an actively regulated process involving BSP and BMP-2.

Aged↗
PubMed2003

Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis.

Calcific aortic valve stenosis (AS), the main heart valve disease in the elderly, is characterized by extensive remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are upregulated in calcific AS and might modulate matrix remodeling. The regulatory mechanisms are unclear. As recent studies have suggested that calcific AS might result from an inflammatory process involving leukocyte invasion and activation, the present study aimed to elucidate the role of the pro-inflammatory cytokine interleukin (IL)-1 beta on MMP expression and cell proliferation in human aortic valves. Immunohistochemistry for leukocytes, IL-1 beta and MMP-1 was performed on aortic valves with (n=6) and without (n=6) calcification obtained at valve replacement or autopsy. Stenotic valves showed marked leukocyte infiltration and associated expression of IL-1 beta and MMP-1. In control valves only scattered leukocytes, low staining for MMP-1 and no staining for IL-1 beta were present. Double-label immunostaining localized IL-1 beta expression mainly to leukocytes and MMP-1 expression to myofibroblasts. Stimulation of cultured human aortic valve myofibroblasts with IL-1 beta lead to a time-dependently increased expression of MMP-1 and MMP-2 by Western blotting and zymography, whereas MMP-9 remained unchanged. Cell proliferation was increased by IL-1 beta as determined by bromodesoxyuridine incorporation. Thus, IL-1 beta may regulate remodeling of the extracellular matrix in calcific AS.

Aortic Valve Stenosis↗
PubMed2003

Time-dependent changes in the plasma concentration of matrix metalloproteinase 9 after acute myocardial infarction.

Matrix metalloproteinase (MMP)-2 and MMP-9 are believed to play a pathophysiologic role in acute myocardial infarction (MI). The time course of their plasma concentrations in correlation with the extent of myocardial damage is unclear. In a prospective study, 20 patients with proven acute MI underwent successful reperfusion within 6 h after the onset of symptoms. The patients were divided into two groups according to the size of their MI, i.e. large or moderate MI. Plasma concentrations of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined on admission, and after 24 h, 48 h, 1 week, 4 weeks, 3 months and 6 months. MMP-2 levels remained unchanged over time in both groups. The plasma concentration of MMP-9 was elevated on admission in patients with large MI versus moderate MI (195 +/- 190 versus 78 +/- 63 ng/ml, p < 0.01) as determined by left ventriculography, and returned to baseline (18 +/- 16 ng/ml) by 1 week after MI. TIMP-1 levels rose slowly in patients with large MI and returned to baseline at 6 months. The ratio of MMP-9 to TIMP-1 was significantly increased on admission in both groups and returned to baseline at 48 h. These data suggest that MMP-9 might play a pathophysiologic role during the early phase of acute MI.

Angioplasty, Balloon, Coronary↗
PubMed2003

Course of indicators of thrombin activity in the early phase of acute myocardial infarction: effect of fibrinolytic therapy and acute percutaneous coronary angioplasty.

We evaluated assay systems for detection of in vivo thrombin activity in patients with acute myocardial infarction. The study included 31 consecutive patients with acute myocardial infarction treated either with fibrinolytic therapy (FLT), or acute PTCA. Blood samples were drawn at admission, after 30 min, 1 h, 3 h, 6 h, 12 h, 24, and 48 h. Assays related to the enzymatic action of thrombin included fibrinopeptide A ELISA, a novel latex-enhanced photometric immunoassay for soluble fibrin complexes, fibrin monomer antigen, D-dimer antigen, and soluble platelet glycoprotein V, which is released from the platelet surface by thrombin cleavage. The soluble fibrin assay displayed a high degree of correlation with fibrinopeptide A, and no correlation with D-dimer antigen, indicating that this parameter allows monitoring of in vivo thrombin activity in patients with acute myocardial infarction. Fibrin monomer antigen, and D-dimer antigen, were influenced by FLT, indicating cross-reactivity with proteolytic fragments of fibrin. No significant changes in soluble glycoprotein V were observed. The results show that the novel soluble fibrin assay appears to be a promising method for measurement of in vivo fibrin formation in patients with acute myocardial infarction, irrespective of the primary treatment decision for FLT or acute PTCA.

Angioplasty, Balloon, Coronary↗
PubMed2003

Pathogenetic role of Chlamydia pneumoniae in calcific aortic stenosis: immunohistochemistry study and review of the literature.

BACKGROUND AND AIM OF THE STUDY: Non-rheumatic, calcific aortic stenosis (AS) is the most prevalent heart valve disease in the elderly. It is based on a chronic inflammatory process with infiltration and activation of leukocytes, and a rise in systemic inflammatory markers. An association with Chlamydia pneumoniae infection has been discussed, but previous studies have yielded divergent results. METHODS: Tricuspid aortic valves with calcific AS were obtained from patients undergoing aortic valve replacement. Control valves from patients matched for age and cardiovascular risk factors were obtained at autopsy. Immunohistochemistry was performed using monoclonal antibodies directed against C. pneumoniae and against leukocyte common antigen. Cultured HEp-2 cells infected with C. pneumoniae were used as positive controls. RESULTS: Positive immunostaining for C. pneumoniae was demonstrated in 12 of 14 (86%) stenotic valves and in six of nine (67%) control valves. Immunostained cells were located mainly in cell- and leukocyte-rich areas. Although stenotic valves showed a higher staining intensity as assessed by semiquantitative scoring (1.8 +/- 0.4 versus 0.8 +/- 0.2 units, p < 0.05), there was no statistically significant difference between stenotic and control valves regarding the presence of C. pneumoniae (p = 0.90). CONCLUSION: Positive immunostaining for C. pneumoniae was not associated with the presence of calcific AS. As in previous serologic and molecular biology studies, a high prevalence of C. pneumoniae in the adult population was demonstrated, irrespective of heart valve disease. Thus, C. pneumoniae is most likely not involved in the pathogenesis of calcific aortic stenosis.

Aged↗
PubMed2002

What role does the measurement of fibrinogen and its derivatives have in the diagnosis of disseminated intravascular coagulation?

Diagnosis of disseminated intravascular coagulation (DIC) is based on the detection of indicators of in vivo coagulation activation in patients without evidence of localized thrombus formation. DIC is a frequent finding in patients with sepsis and malignancy, as well as other conditions associated with the exposition of procoagulant cellular or non-cellular surfaces to the flowing blood. DIC may lead to microvascular occlusion, as well as to consumption of procoagulant activity. Early diagnosis of DIC is achieved by measurement of fibrin-related parameters such as D-dimer antigen, fibrin monomer antigen, soluble fibrin complexes, or fibrin degradation products. Quantitative assays allow diagnosis and monitoring of DIC. New assays using monoclonal antibodies directed against epitopes specific for elastase-mediated fibrin degradation may add valuable diagnostic information in patients with septic conditions.

Disseminated Intravascular Coagulation↗
PubMedDate not supplied

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.

Aortic Valve Stenosis↗
PubMedDate not supplied

Coagulation activation is associated with interleukin-6 plasma levels in patients with mechanical prosthetic heart valves.

BACKGROUND: The intensity of oral anticoagulant therapy in patients with mechanical heart valves is evaluated and controlled by the International Normalized Ratio (INR). However, intravascular coagulation activation can occur despite normal INR values and is related to clinical events. Here, anticoagulation efficiency was assessed by sensitive techniques and potential determinants of coagulation activation were identified. PATIENTS AND METHODS: Forty patients were enrolled after they had undergone mechanical aortic valve replacement. As markers of coagulation activation, plasma concentrations of the D-dimer antigen were prospectively measured. The patients were classified into quartiles according to the D-dimer plasma antigen level. Serum concentrations of the inflammatory markers C-reactive protein (CRP) and Interleukin (IL)-6 were also assessed. RESULTS: The D-dimer levels varied significantly despite therapeutic INR values. In patients with high D-dimer levels, the serum concentrations of IL-6 were significantly increased (top vs. bottom quartile, median, 1.35 versus 0.80 pg/ml; p<0.05), suggestive of subclinical inflammation. There was no association between the D-dimer levels and age, sex, cardiovascular risk factors or time since valve replacement. CONCLUSION: Coagulation activation and inflammation are associated with mechanical heart valves. The D-dimer antigen and IL-6 may be more sensitive than INR and CRP to detect these states and, therefore, could prove valuable additional markers, e.g., in determining the efficacy of new anticoagulant drugs.

Aged↗