PubMed Health⌕ Search

Biomedical subjects

Stephan B Felix

Publications and source records attributed to Stephan B Felix.

46 records · Page 3Linked to original sources
PubMed2003

Hemodynamic improvement and removal of autoantibodies against beta1-adrenergic receptor by immunoadsorption therapy in dilated cardiomyopathy.

The removal of beta(1)-adrenergic receptor (beta(1)AR) autoantibodies by immunoadsorption (IA) has been proposed as a potential mechanism for the improvement of the left ventricular function in dilated cardiomyopathy (DCM). In the present study, the possible association between removal of the autoantibodies against the human beta(1)AR with the hemodynamic improvement induced by IA was investigated.IA was performed in 22 DCM patients (n=22; NYHA III-IV, EF<30%, stable medication). The beta(1)AR autoantibodies from column eluents (CE) were detected by enzyme-linked immunosorbent assay (ELISA) and BIAcore methods. CE of 32% (7/22) of the patients was found to be antibody-positive with ELISA or BIAcore. In addition, a bioassay system was also used for the detection of this autoantibody. Seventy-three percent (16/22) of the patients were found to be antibody-positive by this method. However, independent of the beta(1)AR antibody detection method, both antibody-positive and antibody-negative groups showed similar acute and prolonged hemodynamic improvements during IA therapy. Furthermore, antibody-positive and -negative groups received a comparable improvement of left ventricular ejection fraction. These results suggest that different mechanisms are involved in the hemodynamic improvement induced by IA. The beneficial hemodynamic effects induced by IA are not directly associated with the removal of beta(1)AR autoantibodies.

Autoantibodies↗
PubMed2003

Identification and characterization of KAT, a novel gene preferentially expressed in several human cancer cell lines.

We describe the molecular characterization of a novel human gene on chromosome 1q23.3, termed KAT, which is highly conserved among mammals. The KAT gene spans a genomic region of approximately 1.6 kilobases and consists of 4 exons encoding a 115 amino acid protein with a molecular mass of about 12.5 kDa. The gene is expressed in several human tissues, including kidney, liver, skeletal muscle, heart, colon, thymus, spleen, placenta and lung. We identified an alternatively spliced form, lacking exon 2, in human and mouse tissues. In silico analysis of expressed sequence tags, derived from different types of human tumors, revealed another splice variant. This transcript is characterized by retention of the third intron, leading to a truncated translation product. The KAT protein is localized around the nuclear membranes. It was found to be expressed in several breast, colon and lung carcinoma cell lines, but not in normal breast epithelial cell lines. In addition, KAT protein was detected in invasive ductal carcinoma, but not in adjacent tissues. This suggests a role of this gene in tumorigenesis.

Alternative Splicing↗
PubMed2002

Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy.

BACKGROUND: Immunoadsorption capable of removing circulating autoantibodies represents an additional therapeutic approach in dilated cardiomyopathy (DCM). The role played by autoantibodies belonging to the immunoglobulin (Ig) subclass G-3 in cardiac dysfunction remains to be elucidated. METHODS AND RESULTS: Patients with DCM (left ventricular ejection fraction <30%) participated in this case-control study. Nine patients underwent immunoadsorption with protein A (low affinity to IgG-3), and 9 patients were treated with anti-IgG, which removes all IgG subclasses. Immunoadsorption was performed in 4 courses at 1-month intervals until month 3. In the 2 groups, immunoadsorption induced comparable reduction of total IgG (>80%). IgG-3 was effectively eliminated only by anti-IgG adsorption (eg, during the first immunoadsorption course; protein A, -37+/-4%; anti-IgG, -89+/-3%; P<0.001 versus protein A). The beta1-receptor autoantibody was effectively reduced only by anti-IgG (P<0.01 versus protein A). Hemodynamics did not change in the protein A group. In the anti-IgG group during the first immunoadsorption course, cardiac index increased from 2.3+/-0.1 to 3.0+/-0.1 L x min(-1) x m(-2) (P<0.01 versus protein A). After 3 months, before the last immunoadsorption course, cardiac index was 2.2+/-0.1 L x min(-1) x m(-2) in the protein A group and 3.0+/-0.2 L x min(-1) x m(-2) in the anti-IgG group (P<0.01 versus protein A). Left ventricular ejection fraction increased only in the anti-IgG group (P<0.05 versus protein A). CONCLUSIONS: Autoantibodies belonging to IgG-3 may play an important role in cardiac dysfunction of DCM. The removal of antibodies of the IgG-3 subclass may represent an essential mechanism of immunoadsorption in DCM.

Adrenergic beta-Antagonists↗
PubMed2002

Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption.

OBJECTIVES: The objective of this study was to investigate whether immunoadsorption (IA) removes cardiodepressant antibodies from the plasma of patients with dilated cardiomyopathy (DCM), as well as to describe their effects on isolated rat cardiomyocytes. BACKGROUND: Immunoadsorption induces early hemodynamic improvement in patients with DCM. The mechanisms for this improvement remain to be elucidated. METHODS: Patients with DCM (n = 11; left ventricular ejection fraction < 30%, cardiac index [CI] < 2.5 l/min per m(2)) were treated with IA on three consecutive days, with one IA session daily, by application of specific antibody columns directed against human immunoglobulin (Ig). Immunoadsorption was also conducted on 500 ml of blood taken from nine healthy donors (control subjects). After passage of plasma, the IA columns were regenerated. Column eluent (CE) was collected and dialyzed (100 kD). Confocal laser scanning microscopy was used to analyze the effects of CE on cell contraction and on Ca(2+)-dependent fluorescence in isolated, field-stimulated adult rat cardiomyocytes loaded with cell-permeable Fluo-3. Immunoprecipitation with different preparations of myocardial protein fractions was used for characterization of cardiotropic antibodies. RESULTS: During IA, the IgG plasma level decreased from 10.7 +/- 0.6 to 2.4 +/- 0.1 g/l (mean +/- SEM), and the CI increased from 2.2 +/- 0.1 to 2.7 +/- 0.2 l/min per m(2) (p < 0.01). The CE obtained from control subjects did not influence Ca(2+) transients or cell shortening of cardiomyocytes. In contrast, in patients with DCM, the CE collected during the first regeneration cycle of the first IA session caused an immediate and dose-related decrease of Ca(2+) transients (dilution 1:5; -22.7 +/- 5.5%; p < 0.01) and cell shortening (dilution 1:5; -29.9 +/- 6.0%, p < 0.01). Early hemodynamic improvement among the patients correlated with the cardiodepressant effect of CE on the isolated cardiomyocytes. Purification of CE by protein A adsorption indicated that the cardiodepressant substances are antibodies. Immunoprecipitation revealed that the eliminated antibodies are capable of binding to various myocardial proteins. CONCLUSIONS: Cardiac autoantibodies play a functional role in DCM, and their removal may induce early hemodynamic improvement.

Animals↗
PubMed2002

Laser-facilitated thrombectomy: a new therapeutic option for treatment of thrombus-laden coronary lesions.

To overcome the adverse complications of balloon angioplasty in thrombus burden lesions (i.e., distal embolization, platelet activation, no-reflow phenomenon with persistent myocardial hypoxemia), mechanical removal of the thrombus or distal embolization protection devices is required. Pulsed ultraviolet excimer laser light at 308 nm can vaporize thrombus and suppress platelet aggregation. Clinical experience has already shown its efficacy in acute ischemic-thrombotic acute coronary syndromes. Unlike other thrombectomy devices, a 308 nm excimer laser can ablate thrombi as well as the underlying plaque, speed up thrombus clearing, and enhance thrombolytic and GP IIb/IIIa activity. It can also be employed in patients with contraindications for systemic thrombolytic agents or GP IIb/IIIa antagonists. Our report covers clinical data and technical aspects concerning three patients with acute myocardial infarction who presented with a large thrombus burden. After successful laser-transmitted vaporization of the thrombus mass in these patients, the remaining thrombus burden was evacuated, and normal antegrade coronary flow was successfully restored. This approach can be useful for selective patients with acute coronary syndromes.

Aged↗
PubMed2002

A randomized trial of 5 vs. 6 French transradial percutaneous coronary interventions.

Transradial coronary interventions (TCI) are occasionally limited by radial spasms and postprocedural radial occlusions, which are related to the radial diameter and which possibly may be reduced by the use of smaller guiding catheter. However, 5 Fr, 0.058" lumen diameter guiding catheter affords less strength, visibility, and backup. In a randomized study, we investigated procedural and clinical success and vascular access complications of 5 Fr in comparison to 6 Fr guiding catheter. One hundred seventy-one patients with coronary lesions suitable for at least 5 Fr transradial approach (i.e., normal Allen test, only balloon angioplasty and stent) were randomly assigned for 5 or 6 Fr TCI. The primary combined endpoint was procedural and clinical success, and secondary endpoints were vascular access complications and the occurrence of postprocedural radial occlusions at 1-month follow-up. Procedural success was achieved in 95.4% of 5 Fr and 92.9% of 6 Fr patients. Selective cannulation of the coronary ostium failed in 1.1% of 5 Fr and 4.8% of 6 Fr patients (P = 0.08). Minor hematomas without need for surgical repair or blood transfusions occurred in 1.1% (5 Fr) and 4.8% (6 Fr; P = 0.07); 1.1% of 5 Fr and 5.9% of 6 Fr patients (P = 0.05) suffered loss of radial pulse due to radial occlusion. Selected noncomplex coronary lesions can successfully and safely be treated either with 5 or 6 Fr guiding catheters. A tendency of higher procedural success rates and lower vascular access complications was documented after 5 Fr in comparison to 6 Fr TCI. This was particularly the case among patients with small radial diameters.

Aged↗
PubMed2002

Area ablation: a new lasing concept provides significantly enhanced acute and long-term results for treatment of in-stent restenosis.

BACKGROUND AND OBJECTIVES: Debulking is still a technique of choice for in-stent restenosis (ISR). Excimer laser debulking has enabled high procedural success with very low complication rates, but has demonstrated markedly heterogeneous results owing to differences in lasing and laser technology, and selected patient populations. Since new area-ablation technique enables ablation of larger areas than its own device size, we have evaluated their effectiveness and safety in an uncontrolled study. STUDY DESIGN/MATERIALS AND METHODS: Fifty-three patients with diffuse ISR were treated by laser area ablation, followed by adjunctive balloon angioplasty. Primary endpoint was percent of binary stenosis at 6-month follow-up; secondary endpoints were procedural success; target lesion revascularization (TLR); major adverse cardiac events (MACE); diameter stenosis (DS); and minimal lumen diameter (MLD) before and after laser debulking, and at 6-month follow-up. RESULTS: Laser debulking was feasible (as defined as < or =30% residual stenosis) in 98.1% of patients. At 6-month follow-up, binary stenosis was 26.4%; angiographic TLR, 20.7%; and MACE, 3.7%. DS decreased from 87+/-17% to 20 +/- 9% after laser debulking, and to 9+/-7% after PTCA; it was 29+/-14% at follow-up (P-values in comparison to baseline: 0.0047; 0.0036; 0.0064). MLD increased from 0.6+/-0.3 to 2.4+/-0.5 mm after laser debulking, to 2.8+/- 0.6 mm after adjunctive PTCA, and to 1.9 +/- 0.4 mm at follow-up (P-values in comparison to baseline: 0.0059; 0.0031; 0.0088). CONCLUSIONS: Owing to a significantly greater MLD, area ablation facilitates significantly enhanced immediate and follow-up results for diffuse ISR, including a simpler and more effective laser-debulking procedure than former lasing techniques.

Aged↗
PubMed2002

[Cytokines--causes, players or bystanders in heart failure].

BACKGROUND: Cytokines are important mediators of the immune system and are of pathophysiological relevance for different cardiac diseases. Currently, 18 cytokines carrying the name interleukin (IL) are known; they can be subdivided into pro- and anti-inflammatory interleukins. CARDIAC CYTOKINES: They partly act in a negative inotropic manner and cause destruction of cardiomyocytes resulting in myocardial fibrosis. The proinflammatory cytokine tumor necrosis factor (TNF-)alpha induces cardiodepressive effects and causes apoptosis. TNF-alpha, IL-6, soluble TNF-receptor-1 and -2 are independent predictors of increased mortality of patients with heart failure. Experimental and clinical evidence has shown that plasma and tissue levels of TNF-alpha were elevated to such extent as to explain at least some of the symptoms of heart failure due to the actions of this cytokine. CLINICAL TRIALS: Two multicenter studies (RENAISSANCE, RECOVER), based on promising pilot studies, have disclosed no effect for the TNF-alpha antagonists (Etanercept) on mortality and morbidity. It is not possible, however, to draw the conclusion from the data of these studies that TNF-alpha plays no significant pathophysiological role in the etiology and progression of heart failure.

Animals↗
PubMed2002

Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion.

The heart responds to ischaemic stimuli with release of negative inotropic mediators such as cytokines, platelet-activating factor, oxygen free radicals, arachidonic acids, nitric oxide, adenosine, and still unidentified "cardiodepressant factors" that modulate myocardial performance via autocrine and paracrine coupling. This review summarises experimental and clinical data on the role of negative inotropic mediators that are released from cardiac cells (including cardiomyocytes, endothelial cells, and resident mast cells) after myocardial ischaemia-reperfusion.

Adenosine↗