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U Schönian

Publications and source records attributed to U Schönian.

At least 19 recordsLinked to original sources
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↗
PubMed1996

[Indications for transmyocardial laser therapy].

In symptomatic endstage coronary artery disease after full medical therapy (antianginal drugs, betablockers and ACE-inhibitors) further therapeutical options both for the interventional cardiologist with little hope for improvement by PTCA, stent, rotablation and atherectomy and for the cardiac surgeon with bypass surgery and endarterectomy are not available by definition due to the diffuse arteriosclerotic vessel morphology. In those patients one can therefore consider transmyocardial laser therapy (TMR) as the ultimate treatment option. It then is primarily a palliative measure to reduce the patient's symptoms. Improving perfusion and prognosis remains the most important goals, however. TMR can be utilized as the only revascularizing treatment measure or in combination with CABG or PTCA. According to data from international registries, few controlled and several non controlled studies and our own registry in Marburg with now 101 patients improvement of angina and/or dyspnoea can be expected in more than 60% of patients with end stage coronary artery disease (CAD). The patient cohort comprises symptomatic individuals after CABG or multiple PTCAs or with diffuse CAD in diabetes mellitus or with most severe hypercholesterinemia. We consider these above mentioned criteria as the only validated criteria to enter patients with endstage CAD in our controlled study. Hypothetical options for treatment by TMR such as vasculopathies after heart transplantation, cardiomyopathies under the notion of a possible but not proven microangiopathy are not accepted in our institution at present. Before TMR all patients are assessed for their angina class according to the Canadian Cardiac Society (CCS I-IV)) and their exercise capacity according to the New York Heart Association classification (NYHA I-IV) and reassessed regularly after 3, 6 and 12 months. Thallium/Te MIBI scans at rest- and whenever possible at exercise as well as stress echocardiography are carried in the patients to assess symptomatic improvement, alterations in myocardial perfusion and functional efficacy by TMR. By intermediate analysis the 101 patients of our registry more than 60% of the patients had improved their angina class by at least one classe, some patients have improved perfusion as assessed by scintigraphy, which makes at present a trend but not yet a significant difference, whereas central hemodynamics and ejection fraction remained virtually unchanged in most patients reassessed after TMR. In our analysis mortality of the 101 TMR patients was assessed and plotted on Kaplan Meier survival curves. Mortality at 6 months was 11%. When compared to a historical group of patients with identical CCS and comparable NYHA classes, who were worked up in the manner of a case control study, the TMR mortality was marginally but not yet significantly lower than one would expect from these control patients with terminal CAD treated purely by medication: Their 6 months mortality was 14%. Remarkably but not unexpectedly patients with comparable CCS classes, who could still be treated by PTCA and/or CABG had a significantly lower 6 months mortality than TMR patients or patients on antianginal drugs only. The pathophysiological mechanisms for the symptomatic improvement by laser therapy are not yet fully understood. The 1 mm transmyocardial channels created by the CO2 laser have been postulated to permit perfusion from the ventricular cavity and to seek connection to capillaries and vessels present in the malperfused myocardium thus improving the perfusion by newly created connections and sinusoids from the ventricular cavity. Although there is clear evidence for the presence of open channels acutely and within a few days after TMR therapy little evidence in man is as yet available on the question whether the channels remain open in the long run and, if so, whether they can actually improve perfusion to a substantial degree...

Angioplasty, Balloon, Coronary↗
PubMed1995

Immunosuppressive treatment for myocarditis and dilated cardiomyopathy.

This overview examines the immunological rationale for immunosuppressive and immunomodulating therapy in man and experimental animals. The controversy of whether immunosuppressive treatment is beneficial in myocarditis will continue even after the Myocarditis Treatment Trials has been published. It is known that in viral heart disease immunosuppressive drugs should be avoided, but in autoreactive forms of myocarditis with proven humoral and cellular effector mechanisms they may be used in controlled randomized trials to validate or refute their benefit. Immunomodulating factors, e.g. immunostimulatory or antiviral substances such as ribaverin, the interleukins and interferons have demonstrated some effect in experimental animal myocarditis but proof of their benefit in man is still lacking. Hyperimmunoglobulin therapy appears to be of particular interest because it incurs few side effects and has positive results in cytomegalovirus-associated myopericarditis in man and suspected myocarditis in children.

Adjuvants, Immunologic↗
PubMed1995

The European Study of Epidemiology and Treatment of Cardiac Inflammatory Disease (ESETCID).

Diagnosis of myocarditis has improved with the application of new techniques such as immunohistochemistry, polymerase chain reaction, in situ hybridization and Southern blot in endomyocardial biopsies. Treatment of inflammatory heart disease is still difficult and not yet validated by a study with patient numbers sufficient to allow statistical analysis. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Disease (ESETCID) addresses problems of aetiology, pathogenesis and specific treatment of myocarditis. It is the first multicentre, double-blind placebo-controlled randomized study, apart from the Myocarditis Treatment Trial, to discriminate between different forms of myocarditis. Patients with cytomegalovirus-induced myocarditis are treated by hyperimmunoglobulin compared to placebo. Patients with enterovirus-positive myocarditis will receive interferon alpha vs placebo. Patients with virus-negative myocarditis, which is considered autoimmune, will be treated with immunosuppression compared to placebo. The primary endpoint of this study is an improvement in ejection fraction of more than 5%. This trial may give a better understanding of the course of myocarditis, leading to more specific treatment which may in turn reduce the number of patients with post-myocardial heart muscle disease who require heart transplantation as a final therapeutic remedy.

Autoimmune Diseases↗
PubMed1995

Cytomegalovirus-associated heart muscle disease.

Human cytomegalovirus (CMV) can persist in many organs after primary infection. Not only is it suspected to cause morbidity during reactivation in patients under immunosuppression, but it may also induce long-term latency by chronic disease, e.g. in the myocardium. Endomyocardial biopsies of 27 patients with active myocarditis, 35 patients with healing, 41 patients with healed and 25 patients with ongoing myocarditis according to the Dallas Criteria and 52 patients with dilated cardiomyopathy (DCM) and the biopsies of 25 healthy heart donors were studied for persisting CMV-DNA by polymerase chain reaction (PCR) and in-situ hybridization (ISH). CMV-DNA could be assessed in 5-14% of patients in the different stages of myocarditis and in 22% of patients with DCM. Although two biopsies of the control group showed a positive result, studies by in-situ hybridization demonstrated that in patients with heart muscle disease CMV persists in all cell types including myocytes, whereas in the controls it is only found in interstitial cells. CMV antigens could not be detected in the myocardium with our methods. It must be assumed that infection by CMV is more a persistent or latent than an active infection.

Adult↗
PubMed1995

[The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction].

The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoantibodies↗
PubMed1994

Pericardioscopy and epicardial biopsy--new diagnostic tools in pericardial and perimyocardial disease.

Pericardioscopy is a new diagnostic tool for macroscopic visualization of alterations in both the epicardium and pericardium. We report on 35 patients with pericardial effusion due to inflammatory perimyocardial disease. After puncture of the pericardial effusion, an 8F sheath was introduced over a guidewire under X-ray control. The pericardial pressures were measured; the fluid was removed by aspiration and exchanged with 100 ml of body-warm saline until the pericardial fluid was clear. To visualize the peri- and epicardium, for video- and photo documentation, two sorts of 8F endoscope were used, either a flexible fibreglass version or a rigid 110 degree one--both made by Storz. Cytology of the fluid and optically guided and controlled epicardial and pericardial biopsies were performed to classify the form of pericarditis. A specific diagnosis of viral pericarditis could thus be established in seven cases--by in situ hybridization for cytomegalovirus (n = 3) and by microneutralization test for enteroviruses and/or coxsackievirus B4 isolation (n = 4); of lymphocytic perimyocarditis in 16; of bacterial pericarditis in seven and antibody-mediated autoreactive pericarditis in five cases.

Adult↗
PubMed1994

[Löffler endocarditis fibroplastica with simultaneous infectious endocarditis].

The clinical and immunological 8-year follow-up of a 45-year old female with hypereosinophilic syndrome and cardiac involvement of Löffler's fibroplastic endocarditis which was complicated by infective endocarditis during immunosuppressive treatment is presented. All 3 stages of the disease were documented by clinical and histologic data: stage 1 by biopsy proven eosinophilic myocarditis and arteritis, stage 2 with Berlin blue positive parietal thrombosis, and the fibrotic features of stage 3 both by fibrosis in the latest biopsies and by echocardiography. It was remarkable, however, that this classic clinical case of Löffler's endocarditis lacked a few serological markers postulated to be found regularly, e.g., a positive staining for the cationic protein and major ribonucleases. Instead, the patient demonstrated all the immunological features of autoreactive myocarditis with cytolytic, complement fixing antimyolemmal antibodies. After an initial loading dose of 120 mg prednisolone per day for 6 weeks (11/1986), the steroid dosage was reduced to 40 mg (12/1986) and diminished to 15 mg/day in 1988 to 1989. Finally, the patient was on 4 mg prednisolone per day for almost 4 years. In 1987, azathioprine was added in the dose of 150 mg/day for 6 weeks. In 3/1994 the patient developed infective endocarditis with streptococcus sanguis and presented with dyspnoea. By echocardiography a large floating structure was diagnosed on the anterior mitral leaflet and the left atrium was enlarged by severe mitral regurgitation. Infective endocarditis was successfully treated with antibiotics, but mitral regurgitation made valve replacement obligatory.

Autoantibodies↗
PubMed1994

[Eosinophilic endomyocarditis post partum or pregnancy-related cardiomyopathy].

We report the case of a 28-year old asthmatic female patient, who developed an acute heart failure beginning with diarrhea, fever, and dyspnea 5 weeks after delivery. After improvement of all vital functions and dismissal from hospital care unit a marked blood hypereosinophilia, left ventricular congestive heart failure, pericardium effusion and fever up to 40 degrees C followed. Endomycardial, bone marrow and skeletal muscle biopsies and the pericardial fluid showed a marked eosinophilic infiltration or polymyositis, respectively, which could be treated successfully with steroids and azathioprin. During steroid medication cytomegalovirus-associated myocarditis developed and was diagnosed by in situ hybridization. CMV hyperimmunoglobulin treatment (Cytotect, Biotest) was started (2 ml/kg bw on day 1 and 3, and 1 ml/kg on days 5, 7 and 9), which led to the eradication of the residual infiltrate and CMV-DNA in the myocardium. After discontinuation of all medication, eosinophilia and asthma recurred so that immunosuppressive treatment was continued.

Adult↗
PubMed1994

Immunosuppressive treatment in autoreactive myocarditis--results from a controlled trial.

It is still a matter of controversy whether immunosuppressive therapy is beneficial in patients with acute myocarditis, although autoimmune mechanisms play an important role in the development of myocarditis and its sequelae, for example, in dilated heart muscle disease, particularly because it is postulated that in man immunosuppression may aggravate the viral cell damage that is proposed to trigger the myocarditis. We report the clinical (NYHA-class), haemodynamic (improvement of left ventricular ejection fraction, left ventricular end-diastolic volume index), histological (infiltrate, fibrosis, myocyte hypertrophy) and immunohistological (immunoglobulin and C3-binding) findings in a controlled study including 17 patients with active myocarditis or acute perimyocarditis who were treated with a combination of prednisone and azathioprine for 3 months. We compared them with 21 patients of comparable clinical and haemodynamic compromise who underwent conventional treatment. Follow-up examinations were performed after 3 months. There was significant improvement of ejection fraction and NYHA-classification under immunosuppressive treatment. Infiltrates were reduced significantly in the immunosuppressed patients group only. Binding of IgG and IgM in the endomyocardial biopsy was diminished slightly but not significantly by both regimens. Fibrosis and myocyte hypertrophy were augmented in both treatment arms. There was no difference with respect to prognosis: four patients died or underwent heart transplantation in the immunosuppressive treatment group compared to five conventionally treated patients.

Acute Disease↗
PubMed1993

Cytomegalovirus associated inflammatory heart muscle disease.

Cytomegaloviruses(CMV) belong to a group of cardiotropic DNA-viruses with well-documented but sporadic cardiac involvement. By in situ hybridization with a biotinylated cDNA probe CMV-DNA was analysed in 2 different series of patients(1982-1988; 1989-1991) in the endomyocardial biopsy specimens of 35 patients with active myocarditis as defined by the Dallas criteria, and of 35 patients with acute perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality and/or an endomyocardial biopsy positive for active myocarditis) were analysed. 51% of patients with active myocarditis, 65% positive findings were observed in patients with perimyocarditis when all positive signals in the myocardium were taken into account. Since in interstitial cells and the vascular endothelium HCMV-DNA was also detected in controls we conclude that only HCMV-DNA in the nuclei are specific for HCMV-associated myocarditis. The incidence of positive signals in the myocytes was lower: 14% of all myocarditis patients and 8.5% of all pericarditis patients demonstrated this pattern. The results from in situ hybridization were compared to circulating anti-CMV antibodies from by an ELISA. As possible predisposing immunologic factors or associated alterations of effector functions we found a shift from normal to reduced natural killer cell activity and a marginal increase in B- and activated T-cells in the peripheral blood.

Adult↗
PubMed1993

Immunomodulating factors and immunosuppressive drugs in the therapy of myocarditis.

This review examines the immunologic rationale for immunosuppressive and immunomodulating therapy in man and experimental animal. The controversy if immunosuppressive treatment is beneficial in myocarditis will continue even after the American myocarditis trial. It is obvious that in viral heart disease immunosuppressive drugs should be avoided, in autoreactive forms of myocarditis with proven humoral and cellular effector mechanisms they may be used in controlled randomized trials to validate or negate their benefit. Immunomodulating factors e.g. immunostimulatory or antiviral substances like ribaverin, the interleukins and interferons have demonstrate some effect in experimental animal myocarditis but proof for the efficiency in man is still lacking. Hyperimmunoglobulin therapy appears to be of particular interest because of the little side effects and positive results in CMV associated myopericarditis in man.

Animals↗
PubMed1992

[Cytomegalovirus associated diseases of the heart].

Latent cytomegalovirus (CMV) infection is not uncommon in the juvenile and adult population. The full blown disease is mostly restricted to immunosuppressed and immunodeficient patients, but may also occur in healthy individuals. The acute CMV-myocarditis often takes a mild course with only transient changes of left ventricular hemodynamics or a pericardial effusion as assessed by echocardiography. In our patient population it was characterized by the presence of anti-interfibrillary antibodies. In acute myocarditis the virus genome can be detected by in-situ hybridization in 42% (40% in the myocytes, 21% in the interstitial cells and 41% in endothelial cells). In patients with perimyocarditis CMV-DNA is found in 24% of patients in the myocytes, in 24% of patients in the interstitial cells and in 50% of patients in the endothelium. In healthy controls CMV-DNA could be assessed only in interstitial and endothelial cells (70% and of the infected 30% of positive cases) but not in the myocytes. In dilated cardiomyopathy (DC) CMV-DNA can be found in 48%. Particularly in myocytes in 45% of cases, in interstitial cells in 50% and in the endothelium of small vessels in 68%. An induction of the disease by a chronic local stimulation of the immune system is a likely pathogenetic explanation of the immuno phenomena observed in parallel to the viral persistence. Additive damage by chronic CMV infection can be caused by the infection of the endothelium and smooth muscle cells of the intima of coronary arteries. There are some reports of CMV-DNA detection in the arterial walls or atherosclerotic plaques of patients with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Cytolytic anticardiac membrane antibodies in the pathogenesis of myopericarditis.

Antisarcolemmal (ASAs) and antimyolemmal antibodies (AMLAs) are serological hallmarks of inflammatory heart muscle disease. They occur in a similar incidence in postcardiac injury syndromes, sarcoid heart disease or in dilated and hypertrophic cardiomyopathy. Rarely but still notably they are found with increasing age or in coronary artery disease. We therefore examined whether they are truly pathogenetic or whether they also possess properties of 'natural antibodies'. AMLAs and ASAs, like natural antibodies, have specificity for preserved structures on the membrane; they possess cross-reactivity and increase with age. In contrast to natural antibodies, however, they occur frequently after viral stimulation or other forms of trauma, are more often of the IgG and IgA than of the IgM isotype and fix complement in the acute stage of the disease. They also possess cytolytic and cytotoxic properties when incubated in vitro with isolated heart muscle cells. Antigenic mimicry has been demonstrated to be operative, since they are cross-reactive to viral proteins.

Adult↗
PubMed1991

Are antisarcolemmal (ASAs) and antimyolemmal antibodies (AMLAs) "natural" antibodies?

Antisarcolemmal (ASAs) and in particular antimyolemmal antibodies (AMLAs) are a serologic hallmark of inflammatory heart muscle disease and its sequelae. Since they may also occur to a much lesser incidence with increasing age, it was examined whether they also possess properties of "natural antibodies". As natural antibodies, AMLAs and ASAs have specificity for conserved structures on the membrane. They possess cross-reactivity and increase with age. In contrast to natural antibodies, however, they occur most frequently after viral stimulation, and are more often of the IgG- and IgA- than of the IgM-isotype and fix complement in the acute stage of the disease. They also exhibit cytolytic and cytotoxic properties when incubated in vitro with isolated heart muscle cells. In addition, antigenic mimicry has been demonstrated to be operative, since they are cross-reactive to viral proteins.

Adult↗