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Biomedical subjects

B Maisch

Publications and source records attributed to B Maisch.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1994

Clinical and genetical heterogeneity of familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease which has a benign clinical course in most patients but carries also the risk of sudden cardiac death. Initial genetic studies have revealed the beta-myosin heavy chain (beta-MHC) gene on chromosome 14q11-q12 as morbid gene. Several mutations have been identified, almost all of them are missense mutations of the area in the gene coding for the globular head region of the myosin. The codon 403 has been found to be a hot-spot for mutations. Both, mutant myosin messenger RNA and proteins have been found in cardiac and in skeletal muscle, indicating the presence of a normal protein synthesis of the mutant allele. Histological studies show that gross alterations in protein assembly do not occur (e.g. by introducing the 403Arg-->Gln mutation in cell expression systems) and in-vitro motility of distinct mutations may be reduced in comparison to wild type myosin. The exact mechanism, however, how myosin mutations cause FHC has not yet been elucidated. Three novel loci for FHC have been identified only recently on chromosomes 1q3, 11p13-q13, and 15q22. It can be hoped that the characterization of the morbid genes in these loci will provide valuable information for the clarification of the pathogenesis of FHC and possibly for future therapeutic approaches. The challenge for future studies is to identify the morbid genes of the new loci, their mutations and their proteins.

Calmodulin-Binding Proteins↗
PubMed1993

Renin-angiotensin system and myocardial collagen matrix remodeling in hypertensive heart disease: in vivo and in vitro studies on collagen matrix regulation.

The interstitial space of the myocardium is composed of nonmyocyte cells and a highly organized collagen network which serves to maintain the architecture and mechanical behavior of the myocardial walls. It is the myocardial collagen matrix that determines myocardial stiffness in the normal and structurally remodeled myocardium. In hypertensive heart disease, the heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for collagen synthesis and degradation, explains the appearance of diastolic and/or systolic dysfunction of the left ventricle that leads to symptomatic heart failure. Several lines of evidence suggest that circulating and myocardial renin-angiotensin systems (RAS) are involved in the regulation of the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In cultured adult rat cardiac fibroblasts angiotensin II was shown to directly stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation, that would lead to collagen accumulation. In the spontaneously hypertensive rat, an appropriate experimental model for primary hypertension in man, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness due to interstitial fibrosis could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.

Collagen↗
PubMed1993

Cardiocytolytic antimyolemmal antibodies in dilated cardiomyopathy following presentation: observations in 7 patients.

The prevalence of lytic activity of circulating antimyolemmal antibodies in dilated cardiomyopathy of recent onset is unclear. To obtain preliminary data we studied 7 consecutive patients with dilated cardiomyopathy (age 44 +/- 14 years) and symptoms for fewer than 6 months. The presence of antimyolemmal antibodies was determined in vitro using intact rat and human cardiocytes and indirect immunofluorescence. Serum cytolytic index for antimyolemmal antibodies was measured by microcytotoxicity assay and the data were compared with that from 70 controls (normal range 0.92 +/- 0.07, effective cytolysis < 0.75). Autoantibody screening was uniformly negative and only 1 patient had positive viral serology. Light microscopy of cardiac biopsies revealed non-specific histology in 2, focal myocarditis in 1 and healing or healed myocarditis in 4. Significant binding of IgG, IgM or polyvalent antibodies to antimyolemmal antibodies bound to rat or human cardiocytes was present in every patient and 5 of them were positive with all 3 markers. Cytolytic index for the group ranged from 0.47 to 0.60 indicating effective lysis in all patients (P < 0.01 versus controls). Cardiocytolytic antimyolemmal antibodies are commonly present in dilated cardiomyopathy following presentation. Their detection might reflect ongoing disease activity and help identify patients likely to benefit from immunomodulative therapy.

Adolescent↗
PubMed1993

De novo expression of MHC class I and class II antigens on endomyocardial biopsies from patients with inflammatory heart disease and rejection following heart transplantation.

Inflammation of the heart muscle is caused either by infection (i.e. coxsackie virus) resulting in myocarditis or by rejection following heart transplantation. These processes induce activation of the immune system. We examined endomyocardial biopsies from patients with myocarditis, perimyocarditis and rejection following heart transplantation and compared these to biopsies from patients with coronary artery disease. The biopsies were examined immunohistologically with specific monoclonal antibodies against class I and class II molecules of the major histocompatibility complex (MHC). MHC class I antigens on the normally negative myocytes were evident in myocarditis (38%) and in rejection after heart transplantation (68%). In the interstitium there was an increase of both MHC class I and class II antigens. MHC class II antigens, however, were never seen on myocytes. MHC class I antigens are required for the action of CD 8 positive cytotoxic T cells. Therefore myocytes which express MHC class I antigens are susceptible to cytotoxic effects of the immune system. MHC class II antigens are essential to T helper cells. By cytokine release, activated T helper cells play a central role in the initiation, regulation and mediation of an immune response in myocarditis and rejection following heart transplantation.

Biopsy↗
PubMed1993

Clinical and prognostic effect of a positive granulocyte scan in infective endocarditis.

Thirty patients with clinical signs of infective endocarditis and pathologic echocardiographic findings indicating vegetations underwent scanning with In-111 or Tc-99m hexamethylpropylene amineoxime (HMPAO) labeled granulocytes. Blood cultures were positive in 60% of the patients. The other cases were negative as a result of antibiotic pretreatment. The results of scintigraphy were correlated with the subsequent clinical course, and in 20 cases with data obtained by histologic examination of the valves. With regard to the degree of the inflammatory process, the nuclear medical procedure provided the following results: true-positive in 6 cases, false-positive in 1 case, true-negative in 19 cases, and false-negative in 3 cases. In this study, positive granulocyte scans correlate with high activity of the inflammatory process and predict a poor prognosis for the patients concerned.

Echocardiography↗
PubMed1993

Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyretin). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant transthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so far were heterozygotes for a single nucleotide change in the gene for TTR that resulted in amino acid substitutions in the mature protein. A new TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. Electrocardiography was suggestive of a pseudoinfarction pattern, and echocardiography and cardiac catheterisation showed signs of hypertrophic nonobstructive cardiomyopathy with increased ventricular filling pressures and a prominent "a" wave. Amyloid of the TTR type was identified by immunohistochemistry in the endomyocardial biopsy specimen. Hybrid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from all known TTR variants so far. The patient died in an accident before investigations were complete. Electrophoretic analysis of the plasma from his first degree relatives (son, daughter, brother, and mother) identified the asymptomatic 22 year old son as an apparently heterozygous carrier of the mutant TTR protein. Comparative tryptic peptide mapping and sequencing showed that isoleucine at position 68 of the amino acid sequence was replaced by leucine.

Amino Acid Sequence↗
PubMed1993

Renin-angiotensin system and myocardial fibrosis in hypertension: regulation of the myocardial collagen matrix.

The cardiac interstitium is composed of non-myocyte cells embedded in a highly organized extracellular matrix containing a three-dimensional collagen network which serves to maintain the architecture of the myocardium and determines myocardial stiffness. In hypertensive heart disease, a heterogeneity in myocardial structure, created by the altered behaviour of cardiac fibroblasts responsible for collagen synthesis and degradation, can explain the appearance of diastolic and ultimately systolic dysfunction of the left ventricle. In vivo, circulating and myocardial renin-angiotensin systems (RAS) were found to be involved in the regulation of the structural remodelling of the cardiac interstitium. In vitro, in cultured adult rat cardiac fibroblasts, angiotensin II was shown to stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation. In the SHR-model of primary hypertension, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness, due to interstitial fibrosis, could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.

Animals↗
PubMed1993

Value and limitations of transesophageal echocardiography in infective endocarditis.

Echocardiography has contributed considerably to the evolution in the management of patients with infective endocarditis. There is a clear hierarchy with respect to sensitivity of the different methods is superior when compared to 2-D and M-mode echocardiography in identifying both vegetations and perivalvular complications e.g. abscess formation, aneurysms, mural endocardial lesions. For patients with suspected endocarditis, in whom vegetations can not be clearly identified or in whom abscess formation is suspected with transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) with mono- or multiplane scans has become the standard diagnostic procedure. For the examination of prosthetic valves it is the method of choice. It has even been suggested that it is employed as routine measure in all patients with suspected infective endocarditis. TEE is a safe semi-invasive technique with an extremely low complication rate and high sensitivity. Its specificity depends largely on the patient group which is examined. In patients with indicative clinical symptoms the specificity and the predictive value of vegetations are high. When used as screening method to assess echodense formations at cardiac valves particularly in the elderly, in whom degenerative changes prevail, its specificity and positive predictive value of vegetation-like structures are much lower. The negative predictive value of a negative transesophageal echocardiogram remains high, however. Valve abscesses are detected rarely by transthoracic echocardiography. It is the domain of TEE to assess them particularly in the aortic and mitral valve area. For them the specificity and positive predictive value of TEE in the diagnosis of infective endocarditis is high again. Of further importance was the observation that patients with vegetations of > 10 mm were more likely to suffer embolic complications. It should be noted, however, that infective endocarditis remains a clinical diagnosis: neither is the demonstration of a vegetation already the equivalent of endocarditis, nor does missing vegetations completely rule out the possibility of it. But without doubt, the presence of vegetations, of abscess formation or a concomitant pericardial effusion add valuable information to clinical diagnosis of infective endocarditis, which still needs a "high index of suspicion".

Abscess↗
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

Increased nuclear proto-oncogene expression in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by an unexplained hypertrophy of the left ventricle, particularly the interventricular septum. Although point mutations in the beta-myosin chain gene have been found in several US families in familiar hypertrophic cardiomyopathy, the pathogenetic pathways leading to myocyte hypertrophy, the most important feature, are still not clear. To examine whether activation (expression) of nuclear proto-oncogenes may play a role in hypertrophic cardiomyopathy, endomyocardial biopsies from 13 patients with hypertrophic cardiomyopathy were examined using monoclonal antibodies against c-myc, c-fos and c-jun. The nuclear proto-oncogenes c-fos, c-jun and c-myc were expressed in 53, 60, and 50%, respectively, of patients with hypertrophic cardiomyopathy. In control biopsies, c-myc was detectable in only 10% of the patients, while c-fos and c-jun were always undetectable. These results show that nuclear proto-oncogenes are induced in patients with hypertrophic cardiomyopathy, although the triggering mechanisms remain unknown.

Antibodies, Monoclonal↗
PubMed1993

Cytolytic cross-reactive antibodies directed against the cardiac membrane and viral proteins in coxsackievirus B3 and B4 myocarditis. Characterization and pathogenetic relevance.

BACKGROUND: Coxsackievirus B3 and B4 (CVB) myocarditis was assessed by a more than twofold change in titer of the microneutralization tests against enteroviruses within 3 weeks in all patients, by an endomyocardial biopsy indicative of active myocarditis in eight cases, and by pericardial effusion and acute cardiomegaly in two patients. In all endomyocardial biopsies, immunoglobulin binding to the sarcolemma and to the interstitial tissue was demonstrated irrespective of an infiltrate being at the same focus or not. IgG binding was found in nine, IgM and IgA in seven, C3 in C1q in three, and C5b9 in three of 10 patients. In addition, circulating antimyolemmal antibodies (AMLAs) were demonstrated regularly. METHODS AND RESULTS: In this study, for the first time adult human myocytes isolated from atrial appendages during open-heart surgery were used as antigen in the indirect immunofluorescence test: nine of 10 sera of patients with CVB myocarditis demonstrated AMLAs of the homologous type in titers of 1:40-1:320, whereas eight of 10 reacted with rat myocytes (heterologous type) only. Circulating AMLAs fixed complement component C4 in the majority of cases. During the in vitro assay of antibody-mediated cytolysis with vital heart cells, fixation of components C3, C4 to the myolemma in all, of C1q in seven, and of the C3b9 complex in eight of 10 sera was demonstrated after addition of a fresh complement source, indicating the potential of a complement-mediated cytolysis being operative. In vitro cardiocytolysis of isolated adult rat heart cells is present in the untreated sera of patients with enteroviral myocarditis and is abolished after adsorption of sera with CVB and with isolated rat heart cells. This indicates functional cross-reactivity of the antimembrane antibodies. To analyze further the cross-reactive epitopes, sodium dodecyl sulfate gel electrophoresis of human and rat sarcolemma and consecutive immunoblots were performed. Cross-reactivity between viral (CVB) and sarcolemmal epitopes could be demonstrated to bands of 220 kd in 10%, 110 kd in 50%, 48 kd in 40%, 35 kd in 40%, and 31 and 28 kd in 30% each. Cardiospecific non-cross-reactive epitopes for antisarcolemmal antibodies or AMLAs were membrane proteins of 90 kd and 78 kd in 50%, 72 kd in 90%, 67 kd in 40%, and 45 kd in 50%. Virus-specific antibody binding sites for sera included proteins of 33 and 34 kd. CONCLUSIONS: Western blot analysis of sera incubated with cardiac membranes or enteroviral proteins demonstrated that the antibodies are directed to defined epitopes of the sarcolemma. Some antibodies were cross-reactive to enteroviral proteins, indicating that enteroviral infection may be the etiological trigger of an autoreactive myocarditis. The cytolytic property of the patients' sera in vitro suggests in addition that humoral autoreactivity and antigenic mimicry are major pathogenetic principles operative in human enteroviral myocarditis and its sequelae.

Adsorption↗
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

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization.

Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms governing the release of BNP and ANP.

Atrial Natriuretic Factor↗
PubMed1992

Myocardial collagen matrix remodelling in arterial hypertension.

The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗