Biomedical subjects

B Maisch

Publications and source records attributed to B Maisch.

At least 73 records · Page 4Linked to original sources

PubMed2000

Strategies to optimize CAD prevention in modern cardiology. The "Marburg CAD Prevention Project".

In recent years we identified numerous cardiovascular risk factors and had been able to reduce cardiovascular events by a variety of different interventions. There is no question that we can improve the course of coronary artery disease (CAD) in patients with a high-risk profile by modifying these factors. Despite this knowledge, many patients with known CAD or myocardial infarction are not treated for secondary prevention as recommended by well established guidelines (http:¿www.chd-taskforce.com). In order to improve secondary prevention in our patients we started a project, the so called "Marburg CAD Prevention Project". By this we combine our computer data base of the CAD preventional routine laboratory with the computer program CARDDAS. Individual risk factors and the angiographic findings were analyzed. Patients as well as local physicians were informed on the need to treat the important risk factors. This approach ensures that at least all of our patients with documented CAD receive the appropriate preventional recommendations and treatment.

Adolescent↗

PubMed2000

Restenosis after percutaneous coronary interventions and infection.

Infectious agents may directly or indirectly (through the response of the host's immune system) modulate the growth of vascular cells. Local and/or systemic increase of cytokines could influence the extent of (re-)stenosis in the vascular tree. Further studies in this field may identify patients at a high risk for atherogenesis and restenosis. Their results should be helpful in treating restenosis after percutaneous coronary interventions.

Angioplasty, Balloon, Coronary↗

PubMed2000

Arrhythmias in acute pericarditis. An endomyocardial biopsy study.

It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40 patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/- 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II degree AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis.

Acute Disease↗

PubMed2000

Flexible percutaneous pericardioscopy: inherent drawbacks and recent advances.

Pericardioscopy enables endoscopic inspection and aimed biopsy of the parietal and visceral pericardium. To elucidate possible technical modifications contributing to the feasibility, diagnostic value and safety of the procedure, pericardioscopy with an Olympus HYF-1T flexible endoscope was performed in 32 patients (53.1% males, mean age 46.2 +/- 13.1 years) with pericardial effusions. In all patients, the initial step of the procedure was subxiphoid fluoroscopically controlled pericardiocentesis and drainage of the pericardial effusion. An Olympus FB-41ST biopsy forceps was applied for endoscopically guided pericardial biopsies. Standard sampling was used in 22/32 patients (3 to 6 samples/patient) and extensive sampling in 10/32 patients (18 to 20 samples/patient). In additional 12 patients pericardial biopsy was performed without pericardioscopy, under fluoroscopic control. Endoscopic visualization was clearly superior when pericardial effusion was partially replaced with 100 to 300 ml of air (29/32 procedures) in comparison to 3/32 procedures in which the pericardial effusion was replaced with warm normal saline (37 degrees C). In patients with hemorrhagic effusion (12/32), we either repeatedly injected and removed 100 to 150 ml volumes of normal saline (37 degrees C), or postponed pericardioscopy for 2 to 3 days of active drainage. The specificity of endoscopic findings is low and not decisive for the diagnosis. However, pericardioscopy is significantly contributing to the diagnostic value of pericardial biopsy, especially regarding establishing the new diagnosis and etiology of the pericardial disease. Sampling efficiency was also significantly higher for procedures using aimed pericardial biopsy with standard and extensive sampling compared to procedures performed under fluoroscopy: 86.2%, 87.3%, and 43.7%, respectively. No major complications directly related to the procedure were encountered. Minor complications included: short-run ventricular tachycardia (6.3%), pain at the sheath entry site (75%) and transient fever (37.5%). In conclusion, pericardioscopy with Olympus HYF-1T, after air instillation, is a technically complex, but safe procedure that enables excellent visualization and extensive pericardial sampling with improved diagnostic value of pericardial biopsies.

Adult↗

PubMed2000

Cytokine activation in pericardial fluids in different forms of pericarditis.

There are many causes of pericardial effusion and it is useful to classify them etiologically, since this disorder is the most common pathologic process involving the pericardium. This report details our experience with pericardioscopy and epicardial biopsy in 101 patients with pericardial effusions in whom pericardioscopy was performed. By means of clinical data and polymerase chain reaction we tried to elucidate the etiology of the pericardial effusion which were classified as follows: we found 41 effusions to be induced by primary malignant tumors or tumors metastatic to the pericardium. Specific diagnosis of viral and bacterial pericarditis was established in 17 patients by examination of the pericardial effusion with PCR, where we found 3 patients positive for adenovirus, 5 patients positive for cytomegalovirus, 2 patients positive for enterovirus-RNA and 5 patients positive for borrelia Burgdorferi-DNA. Additionally, idiopathic effusions (lymphocytic and autoreactive) were seen in 35 patients. In summary immunological and molecular biology investigations seem to provide an additional tool in the diagnostic of pericardial effusion with unknown etiology. If we focus on the ELISA results, there is some evidence, that the demonstration [table: see text] of activation markers and soluble mediators of inflammation such as Il-6, Il-8 and IFN-gamma in pericardial effusion and the simultaneously lack of these mediators in sera of the patients first may be helpful in the discrimination of autoreactive and lymphocytic effusion. Second, this cytokine pattern or distribution indicates a possible local inflammatory process, where these cytokines were all released from activated T lymphocytes present in lymphocytic effusion. In the future, this may have therapeutic implications.

Bacterial Infections↗

PubMed2000

New directions in diagnosis and treatment of pericardial disease. A project of the Taskforce on Pericardial Disease of the World Heart Federation.

New directions in the diagnosis and treatment of pericardial diseases synthesize the achievements of modern imaging with molecular biology and immunology techniques. Comprehensive and systematic implementation of new techniques of pericardiocentesis, pericardial fluid analysis, pericardioscopy, epicardial and pericardial biopsy, as well the application of comprehensive molecular biology and immunology techniques for pericardial fluid and biopsy analyses have opened new windows to the pericardial diseases, permitting early specific diagnosis and creating foundations for etiologic treatment in many cases. In patients with recurrent pericarditis, resistant to conventional treatments, as well as in patients with neoplastic pericarditis an alternative intrapericardial treatment regimen was suggested by the Taskforce on Pericardial Diseases of the World Heart Federation. Intrapericardial application of medication avoids systemic side effects with increased local efficacy. The following protocols are proposed: CIRP (colchicine in recurrent pericarditis)--colchicine vs placebo in chronic/recurring pericarditis without pericardiocentesis; TRIPE (triamcinolone in pericardial effusion)--intrapericardial instillation of triamcinolone + 6 months colchicine vs pericardial puncture without instillation + 6 months colchicine; NEPIN (neoplastic effusion and pericardial instillation)--pericardiocentesis and drainage + intrapericardial instillation of cisplatin or thiotepa.

Chronic Disease↗

PubMed2000

Intrapericardial treatment of autoreactive myocarditis with triamcinolon. Successful administration in patients with minimal pericardial effusion.

A major clinical drawback in the treatment of autoreactive pericarditis is its inherent feature to relapse. Intrapericardial treatment with triamcinolone was reported to be efficient in patients with large, symptomatic autoreactive pericardial effusions, avoiding side effects of systemic treatment as well as compliance problems. Intrapericardial treatment with 300 mg/m2 triamcinolone was for the first time performed in patients with autoreactive myopericarditis and minimal pericardial effusions (75 to 110 ml). After 12 months of follow-up both patients are asymptomatic and there were no further recurrences of pericardial effusion. Pericardiocentesis in these patients was performed with the application of the PerDUCER device, guided by pericardioscopy. This device has a hemispherical cavity at the top of the instrument connected with a vacuum-producing syringe. In this cavity the pericardium is captured by vacuum and tangentially punctured by the introducer needle. Pericardium that can be captured, must be up to 2 mm thin to fit into the hemispherical cavity. Pericardioscopy performed from the anterior mediastinum significantly contributed to the success of the procedures enabling visualization of the portions of the pericardium free of adipose tissue or adhesions, suitable for puncture with the PerDUCER. In conclusion, intrapericardial treatment of symptomatic autoreactive myopericarditis with minimal pericardial effusion was safely and efficiently performed in 2 patients. Pericardiocentesis was enabled by means of the PerDUCER device, facilitated by pericardioscopy.

Adult↗

PubMed2000

Mitochondrial DNA deletions in cardiomyopathies.

Structural changes in the mitochondrial DNA (mtDNA) have been implicated in the pathogenesis of a number of diseases. In this study we report on deletions in the mtDNA of patients with dilated cardiomyopathy (DCM) and post mortem control samples. Total DNA was extracted from left ventricular tissue and nearly the whole mtDNA was amplified using the long PCR technique. For quantitative analysis of the PCR-products with mtDNA deletions the fragments were scanned by a laser densitometer. With the method of long PCR we could detect wild-type and deleted mtDNA in 1 reaction. A total of 14 different deletions ranging from 3.3 to 12.6 kb could be detected. The highest rate of deleted as compared to wild-type mtDNA was 12% in 1 control and 9% in a patient with dilated cardiomyopathy. The number of mitochondrial deletions increase with age in the control group. Additional deletions appear sooner in cardiomyopathic hearts than in control hearts. With regard to the low quantity of the deleted mtDNA and the cumulative nature of these deletions by ageing, we conclude that they may be relevant in individual cases only. A general pathogenic effect on the development of dilated cardiomyopathy is less likely. The mutations may be a sign of increasing stress to the heart, however, thus promoting consecutive damage of mtDNA by initiating a vicious circle.

Adult↗

PubMed2000

Cardiac rhythm and conduction disturbances: what is the role of autoimmune mechanisms?

The immunopathogenesis of cardiac rhythm and conduction disorders has been underestimated. Therefore, the aim of this review is to analyze the current data and controversial issues in this area. The incidence of autoantibodies to human conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies (ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to age-matched controls. The risk of acquiring an atrioventricular block was up to 3-fold in patients with anti-atrioventricular node antibodies (AAVNab) in comparison to controls. The incidence of anti His antibodies (AHISab) was low both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab) seemed to be an epiphenomenon and not a pathogenetic marker of conduction disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a possible prerequisite in the pathophysiology of the disease, although transplacental passage of various antibodies and immune complexes is widely recognized. The main autoantibodies detected both in children with congenital heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The cross-reactivity of laminin with anti-La antibodies could be important in the initiation of the autoimmune process. Autoantibodies against adrenoceptors and muscarinic cholinergic receptors of neonatal heart and human endogenous retrovirus-3 expressed in fetal cardiac tissue could also play a role in the pathogenesis of the congenital heart block. Of note, apoptosis could be one of the possible mechanisms of the progression of the congenital conduction disturbances to the complete heart block. In addition, evidence is compiling that cellular activation and cellular cytotoxicity specific for a given target tissue appears to be at least equally important in the pathogenesis of the disease as the humoral response. In conclusion, the immunopathogenesis of certain cardiac rhythm and conduction disorders is well established in sick sinus syndrome, congenital heart block, and connective tissue diseases. ASNab, AAVNab, anti-Ro/SS-A, and anti-La/SS-B antibodies can be regarded as diagnostic and prognostic markers.

Adult↗

PubMed2000

Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics.

The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study designed to determine the value of the following potential non-invasive arrhythmia risk predictors in more than 200 patients with idiopathic dilated cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association functional class, left ventricular end-diastolic diameter and ejection fraction, left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on 24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This report describes the rationale of MACAS as well as the clinical characteristics of the first 236 patients enrolled between March 1996 and October 1999. The prognostic significance of the potential arrhythmia risk predictors in MACAS will be determined by multivariate Cox analysis at the end of 5-year follow-up. Primary endpoints are total mortality and major arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation or sudden cardiac death. The results of MACAS will have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in idiopathic dilated cardiomyopathy.

Adolescent↗

PubMed2000

Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report.

This article reviews the current state of consensus reached for the diagnosis of myocarditis and dilated cardiomyopathy on the basis of conventional histopathological and immunohistochemical methods for inflammatory infiltrates in addition to molecular biological methods for persistence of viral genome in endomyocardial biopsies. Additionally, a brief overview is presented stating the current knowledge on effector mechanisms of the immune system in myocarditis and dilated cardiomyopathy.

Autoantibodies↗

PubMed2000

Prevalence of viral genome in endomyocardial biopsies from patients with inflammatory heart muscle disease.

In the report of the 1995 World Health Federation/International Society and Federation of Cardiology (WHF/ISFC) Task Force on the Definition and Classification of Cardiomyopathies, the definition of heart muscle diseases was updated. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy are now recognized in this definition. Enteroviruses, adenoviruses and cytomegaloviruses are considered as main etiopathological factors in the pathogenesis of inflammatory heart disease. A wide range of different assays have been and are currently being used, either alone or in combination, to assay for the presence of enteroviral RNA and/or DNA of cytomegalo- and adenoviruses in endomyocardial biopsy and explanted heart samples. The prevalence of cardiotropic viruses in endomyocardial biopsies of patients with clinically suspected inflammatory cardiomyopathy varies widely: enteroviral genome was detected in endomyocardial biopsies of 3 to 53% of patients, cytomegaloviral DNA was detected in 3 to 40% of patients with inflammatory heart disease and adenoviruses in 3 to 23% of the patients. This report summarizes the methods that have been used and the results of molecular biological investigation with polymerase chain reaction, which were reported by several groups over the last years. Taking this together it seems to be clear that the improvement of molecular biological techniques and the experience of people working with these methods will lead to more reliable results on prevalence, persistence and the diagnostic value of these investigations. These findings have to be taken into account in future diagnostic and therapeutic studies in the field of cardiomyopathies.

Adenovirus Infections, Human↗

PubMed2000

Detection of viral and bacterial protein in endomyocardial biopsies of patients with inflammatory heart muscle disease?

The development of highly sensitive molecular biological methods such as in-situ hybridization and polymerase chain reaction (PCR) made it possible to detect viral/bacterial nucleic acid in human endomyocardial biopsies. However, only a few investigations addressed the problem of latent persistence of viral and bacterial genome and the detection of the corresponding proteins, which could have important consequences for the clinical course of the disease. The purpose of this study was to determine whether protein of various viruses (adenovirus, enterovirus, cytomegalovirus, influenza A and B virus, herpes simplex virus 1 and 2) and bacteria (chlamydia pneumonia) can be detected in endomyocardial biopsies of patients with myocarditis and dilated cardiomyopathy with and without inflammation by use of an immunofluorescence assay and to compare the frequency of its detection with the results of PCR, immunohistology and serology. Thirty-nine patients with myocarditis and dilated cardiomyopathy with and without inflammation were examined by a direct immunofluorescence assay using the endomyocardial biopsy as antigen. Each of the samples was additionally studied by immunohistological methods and PCR for the detection of infiltrating cells and the genome of cardiotropic viruses or bacteria. Fourteen of patients were considered to have myocarditis (group 1), 9 dilated cardiomyopathy with inflammation (group 2), 10 dilated cardiomyopathy (group 3), 6 to have no myocarditis or dilated cardiomyopathy (group 4). Using a direct immunofluorescence assay we could show only that 1 patient without histological myocarditis or dilated cardiomyopathy (group 4) was positive for influenza B and chlamydia pneumonia antigens in the endomyocardial biopsy. In addition we have determined influenza B-specific antibodies, such as IgG (marginal titer) and IgA (high titer) and chlamydia pneumonia-specific antibodies, such as IgG (marginal titer) in serum of this patient. A second patient with dilated cardiomyopathy was found to be positive for protein of chlamydia pneumonia, who was shown to have chlamydia pneumonia-specific antibodies, such as IgG (high titer) in serum. There was no correlation with PCR results, but good correlation with influenza B and chlamydia pneumonia-specific antibodies in sera of these patients. In this investigation we have determined viral/bacterial-specific antibodies using serological methods and proteins of these agents using immunoflourescence. Despite the detection of virus or bacteria-specific antibodies in the sera and detection of viral and/or bacterial protein in the biopsies of some of the patients viral and/or bacterial genome was not found in the biopsy. This may be explained by the focal character of myocarditis and sampling error, because for technical reasons we use different biopsies for immunohistochemical and molecular biological investigations.

Adult↗

PubMed2000

The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results.

By including immunohistochemical parameters the WHF Task Force for the Definition of Acute and Chronic Myocarditis expanded the light microscopical Dallas criteria of myocarditis. The rapid development of new molecular biological techniques such as polymerase chain reaction (PCR) and in-situ hybridization has improved our understanding of the underlying etiological and pathophysiological mechanisms in inflammatory heart disease. Treatment of dilated cardiomyopathy with inflammation is still controversial, however. The American Myocarditis Treatment Trial could not demonstrate a significant difference in the improvement of ejection fraction between patients with active myocarditis in the cyclosporine/prednisolone treated group when compared to placebo. In the European Study of Epidemiology and Treatment of Inflammatory Heart Disease (ESETCID) patients with acute or chronic myocarditis are treated specifically according to the etiology of the disease. Patients are screened not only for infiltrating cells, but also for the presence of persisting viral genome (enterovirus, cytomegalovirus and adenovirus). By investigating endomyocardial biopsies of 3,055 patients ongoing inflammatory processes in the heart could be found in 17.2%. Only 182 showed a reduced ejection fraction below 45% fulfilling the entrance criteria for the ESETCID trial. These data imply that in symptomatic patients inflammatory heart muscle disease has to be considered regardless of left ventricular function and that endomyocardial biopsy can be an important tool for diagnosis. Virus could be detected in 11.8% (enterovirus 2.2%, cytomegalovirus 5.4%, adenovirus 4.2%). These first epidemiological results of this prospective randomized study demonstrate that viral persistence may contribute to the pathogenesis of inflammatory heart muscle disease, and that in chronic myocarditis viral persistence occurs in a smaller percentage of patients compared to previously published studies which were performed on highly selected patients.

Cardiomyopathies↗

PubMed2000

[Correlation between cardiac autonomic activity and compromise of left ventricular function in dilated cardiomyopathy].

In recent years, evaluation of cardiac autonomic activity by means of heart rate variability (HRV) determination and baroreflex sensitivity (BRS) testing has become readily available. The results of the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study showed that both diminished HRV and baro-reflex sensitivity are associated with poor outcome in patients after myocardial infarction. In contrast to patients with coronary disease little information is available concerning cardiac autonomic activity in idiopathic dilated cardiomyopathy (IDC). Therefore, HRV and BRS were assessed in 160 patients with IDC and preserved sinus rhythm in order to investigate the relationship between HRV, BRS, and left ventricular ejection fraction. Time domain indices of HRV were computed from 24-hour digital Holter recordings. BRS testing was performed using the noninvasive phenylephrine method. Mean standard deviation of all normal RR intervals (SDNN) of the whole study population was 112 +/- 46 ms. A well preserved HRV (SDNN > 105 ms) was found in 74 patients (46%), a moderately decreased HRV (SDNN 70-105 ms) in 59 patients (37%), and a severely decreased HRV (SDNN < 70 ms) in 27 patients (17%). Mean BRS was 7.5 +/- 5.0 ms/mm Hg. A well preserved BRS (> 6 ms/mm Hg) was present in 78 patients (57%), a moderately decreased BRS (3-6 ms/mm Hg) was present in 38 patients (28%), and a severely decreased BRS (< 3 ms/mm Hg) in 21 patients (15%). There was only a weak correlation between SDNN and BRS (r = 0.19; p < 0.05). A weak correlation was found for SDNN and left ventricular ejection fraction (r = 0.29; p < 0.05). There was no significant correlation between BRS and left ventricular ejection fraction (r = 0.14). In summary, there was only a weak correlation between the HRV, BRS, and left ventricular ejection fraction in patients with IDC suggesting that these 3 variables may be independent predictors of sudden death in IDC. The relative prognostic value of these variables and other potential risk predictors including the presence of arrhythmias on Holter, microvolt T wave alternans, QTc dispersion, and signal-averaged ECG is currently under investigation in a large prospective observational study (Marburg Cardiomyopathy Study (MACAS)) during 5-year follow-up at our institution.

Adolescent↗

PubMed2000

[Significance of matrix metalloproteinases in cardiovascular diseases].

The cardiovascular interstitial space is largely composed of type I and III fibrillar collagens. Tissue structure, form and function are determined not only by the collagen content but also by the ratio of different collagens to each other. Matrix metalloproteinases are members of a family of secreted and membrane-bound enzymes that are capable of degrading highly proteolytic resistant fibrillar type I and III collagens. Collagen tissue content is determined by balanced collagen synthesis and degradation. MMP activity and adverse tissue remodeling have been identified in coronary plaques in unstable angina. It has also been linked with the progression of aortic aneurysms and with left ventricular dilatation in congestive heart failure in patients with ischemic and non-ischemic cardiomyopathy. The role of MMPs in these cardiovascular diseases and possible therapeutic options are the focus of this review.

Animals↗

PubMed2000

[Impediment of cellular immune response under treatment with ticlopidine in a patient with Staphylococcus aureus endocarditis].

A 52-year-old male with coronary artery disease was admitted with acute aortic valve endocarditis and a temperature up to 39.5 degrees C caused by Staphylococcus aureus. The patient was treated with ticlopidine (Tiklyd) after percutaneous transluminal coronary angioplasties to reduce restenosis by inhibiting thrombocyte aggregation. Upon admission c-reactive protein (CRP) was 389 mg/l. Interleukin-6 (IL-6) and Interleukin-2-receptor (IL-2-rec) were distinctly increased. Monoclonal antimyocardial antibodies were found. Leukocyte count never exceeded 9.8 G/l; however, transesophageal echocardiography validated a soft vegetation of the aortic valve. Antibiotic therapy was initiated with imipenem, gentamicin and vancomycin; clarithromycin was added after five days. Temperature normalized after 24 days. The c-reactive protein decreased from 389 mg/l to 6 mg/l, and the elevated cytokine levels decreased accordingly. Agranulocytosis or pancytopenia by ticlopidine through a toxic mechanism have been described, which are normally reversible within three weeks; there has not yet been a description of a missing leukocyte response in endocarditis as in this case report. This is a special situation with lack of or impeded immunological response, which limits the use of ticlopidine, especially since a therapeutic alternative with clopidogrel is available.

Agranulocytosis↗

PubMed2000

Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis.

The concept of antigenic mimicry in autoimmune diseases such as rheumatic fever has been under investigation for decades and the range of cross-reactive tissue antigens for streptococcal-induced antibodies identified in rheumatic heart disease is still expanding. To identify heart tissue-reactive antigens which may be implicated in the secondary immunopathogenesis of rheumatic fever, sera from 56 patients with acute rheumatic heart disease were probed in two-dimensional Western blots for reactivity against heart tissue antigens. After two-dimensional immunoblot analysis, proteins were submitted to N-terminal amino acid sequence analysis. This analysis identified creatine kinase, two mitochondrial proteins and, at a low level, various stress proteins as cross-reactive myocardial antigens. Therefore, in addition to myosin, creatine kinase may represent another major antigen for autoreactive antibodies in rheumatic heart disease. Mitochondrial proteins have been implicated in the pathogenesis of inflammatory heart disease for some years, and in this study we have identified two mitochondrial proteins as relevant antigens in rheumatic heart disease.

Aconitate Hydratase↗