Biomedical subjects

Irene Portig

Publications and source records attributed to Irene Portig.

8 recordsLinked to original sources

PubMed2006

Familial inflammatory dilated cardiomyopathy.

BACKGROUND: Systematic family screening has recently identified dilated cardiomyopathy as an inherited disorder in up to 30% of cases. Mutations in genes encoding proteins responsible for myocardial architecture have been identified, but additional pathophysiological mechanisms including inflammatory reactions have been proposed. AIMS: Identification and characterization of familial DCM, where at least one affected family member fulfils the criteria for inflammatory DCM may lead to a better understanding of the aetiology and pathogenesis of (inflammatory) DCM. METHODS AND RESULTS: Ten families were examined. In six families, clinical characteristics and mode of inheritance were compatible with pure fDCM, fDCM with conduction defect and autosomal recessive fDCM. In four families, (auto-)immune features were diagnosed in affected and non-affected family members. CONCLUSIONS: Familial DCM with an inflammatory component was identified as a specific subgroup of familial DCM. In most cases, the inflammatory process seems to modify, i.e. aggravate, the "classic, cytoskeletopathic" familial DCM, but in some, especially when taking clinical and genetic aspects into account, inflammatory (auto-)immune features can be addressed as the leading pathogenetic principle. Further elucidation of these families may provide a better insight into pathophysiologic processes and may aid in the development of specific therapeutic strategies.

Adult↗

PubMed2005

[Women and autoimmune diseases with cardiovascular manifestations].

Women's greater susceptibility to autoimmune diseases has been recognized for more than 100 years. And although the basic immune response (including a more vigorous immune response and increased antibody production) has been known to differ between men and women, conclusive pathophysiological explanations for this phenomenon are still lacking. Experimental work done in animal models have revealed a profound influence of sex hormones on the susceptibility to autoimmune diseases and on clinical disease via direct and indirect signaling pathways. Apart from sex hormones additional factors seem to participate in the pathogenesis of autoimmune diseases, which remain to be elucidated ("so far, you cannot explain autoimmunity [only] with estrogen" [lockshin]).

Animals↗

PubMed2005

Inflammatory dilated cardiomyopathy (DCMI).

Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma. The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci. Therefore, the authors started their investigation with the search for MHC class 2 DQ polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected.

Cardiomyopathy, Dilated↗

PubMed2004

[Noninvasive methods in the diagnosis of macro- and microangiopathy of peripherial and carotid arteries].

PURPOSE: Indications and diagnostic value of the most important noninvasive procedures for the diagnosis of peripheral arterial disease and diseases of the supraaortic arteries are reviewed in this article with particular emphasis on cardiologic questions. PERIPHERAL ARTERIAL DISEASE: As compared to coronary artery disease, peripheral arterial disease has long been addressed as being negligible in number and importance, a view that had to be reassessed in recent years. The prevalence of claudication and critical leg ischemia has increased. Earlier diagnosis and specific therapeutic regimens will be able to prevent or at least slow progression of the disease and, thereby, major amputation. The patient's history and physical examination in addition to measurement of the ankle-brachial index (ABI; determined by dividing the systolic pressure measured by Doppler ultrasonography of the A. dorsalis pedis or A. tibialis posterior by that of the A. brachialis) usually allows for the diagnosis of peripheral arterial disease (ABI < 0.9). If in doubt (ABI > 0.9, but presence of typical claudication), a treadmill test or additional tests such as pressure-pulse recording (mechanical oscillography), toe pressure measurements, or duplex ultrasonography should be performed. When peripheral arterial disease has been diagnosed, duplex ultrasonography or treadmill testing aids in planning additional diagnostic procedures and the adequate therapeutic regimen. Transcutaneous oxymetry is of prognostic value in assessing the tendency of wound healing in distal limb ulceration and can distinguish between critical limb ischemia and complicated claudication. Thermography is used to document functional and organic peripheral arterial occlusions and capillaroscopy to directly view nail fold capillaries in order to distinguish between primary and secondary Raynaud's phenomenon. Noninvasive radiologic techniques in the diagnosis of peripheral arterial disease are also discussed in this journal. SUPRAAORTIC ARTERIES: Noninvasive diagnostic procedures in assessing disease of the supraaortic arteries include history-taking, physical examination, continuous-wave-(cw-)Doppler and color-coded ultrasonography. Cw-Doppler ultrasonography is still widely used and sufficient in diagnosing moderate to severe stenosis or occlusion of the carotid artery. B-mode and color-coded ultrasonography has several advantages over cw-Doppler ultrasonography through direct visualization of the vascular membrane, perivascular structures, and intravascular blood flow. Carotid stenosis < 50% and plaque morphology can be assessed, inflammatory processes, aneurysms, and dissections diagnosed. Increase in intima-media thickness and echolucent plaques are associated with cerebral ischemic events and can be diagnosed via duplex sonography. These findings have great implications in the consultation of patients with atherogenic risk factors.

Arterial Occlusive Diseases↗

PubMed2004

Detection of anti-hsp70 immunoglobulin G antibodies indicates better outcome in coronary artery bypass grafting patients suffering from severe preoperative angina.

BACKGROUND: Recent findings indicate that molecular chaperones actively participate in myocardial cytoprotection. Moreover, ischemic tolerance can be induced in humans by brief ischemic events. Therefore, we investigated patients with severe angina attacks before coronary artery bypass grafting. We focused on appearance of anti-hsp70 antibodies as an immunologic response to heat shock protein induction by ischemia followed up by hemodynamic measurements perioperatively. We correlated these clinical findings with the presence of antibodies against hsp70 and the antioxidative capacity of patients' sera. METHODS: Thirty-five consecutive patients with coronary artery disease scheduled for coronary artery bypass grafting were included. Seventeen patients had severe angina, and 18 patients suffered from chronic stable angina preoperatively. In the patients' sera, antibodies against hsp70 were detected by enzyme-linked immunosorbent assay, and antioxidative capacity was detected using the chromogen assay. Cardiac output and pulmonary capillary wedge pressure were measured using a thermodilution catheter. We also evaluated C-reactive protein and creatine kinase MB isoenzyme, and performed a conventional leukocyte count. RESULTS: The sera of the 17 patients with severe angina attacks before surgery contained antibodies against hsp70 and a low antioxidative capacity. The interval between a severe angina attack and anti-hsp70 antibody titer are inversely correlated. These patients had better cardiac output and lower pulmonary capillary wedge pressure values after surgery. CONCLUSIONS: Severe angina before cardiac surgery coincided with an improved outcome as measured by hemodynamic variables as compared with chronic stable angina. This finding correlated significantly with a low antioxidative capacity and the presence of antibodies against hsp70. These pathophysiologic mechanisms might therefore play a role in myocardial protection.

Aged↗

PubMed2003

Human viral cardiomyopathy.

Viral infection of the heart is relatively common, usually asymptomatic and has a spontaneous and complete resolution. It can, however, in rare cases, lead to substantial cardiac damage, development of viral cardiomyopathy and congestive heart failure. Viral cardiomyopathy is defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (<14 lymphocytes and macrophages/mm ) the term viral cardiomyopathy or viral persistence in dilated cardiomyopathy should be applied. The diagnosis of myocarditis and viral cardiomyopathy can be made only by endomyocardial biopsy, implementing the WHO/WHF criteria, and PCR techniques for identification of viral genome. The most frequent cardiotropic viruses detected by endomyocardial biopsy are Parvo B19, enteroviruses, adenoviruses, cytomegalovirus, and less frequently Epstein-Barr virus, and influenza virus.

Animals↗

PubMed2003

Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens.

Although enteroviruses have long been considered the most common cause of inflammatory heart muscle diseases, parvovirus B19 (PVB19) is emerging as a new and important candidate for myocarditis and dilated cardiomyopathy with inflammation (DCMi) and without inflammation (DCM). We investigated left ventricular endomyocardial biopsy specimens from 110 patients with suspected inflammatory heart disease for the presence of PVB19, Coxsackie virus (CVB), and adenovirus (Ad2) genome by polymerase chain reaction. Diagnosis of myocarditis (36 patients), DCM (18 patients), DCMi (13 patients), and perimyocarditis (12 patients) was made by immunohistochemical and histopathological investigation of endomyocardial biopsy specimens. A control group consisting of patients with arterial hypertension was also investigated. Prevalence of the PVB19 genome in endomyocardial biopsy specimens was highest in patients with DCMi (3 of 13) and patients with myocarditis (7 of 36); in patients with DCM and perimyocarditis, prevalence was 3 of 13 and 2 of 12, respectively. In patients with resolved myocarditis, no PVB19 DNA was detected; in patients with no inflammation and controls, prevalence was only 4% and 7%, respectively. CVB-RNA was detected in endomyocardial biopsy specimens from 3 of 37 patients with myocarditis; Ad2-DNA was found in 1 patient with DCM and 1 patient with perimyocarditis. These findings suggest an association of the PVB19 genome in endomyocardial biopsy specimens of adults with the development of DCM, DCMi, and chronic myocarditis more frequently than previously expected. PVB19 should therefore be recognized as a potential cardiotropic pathogen in patients of all ages.

Adult↗

PubMed2002

Pathophysiology of cardiac inflammation: molecular mechanisms.

BACKGROUND: Inflammatory processes induced by rival infection are believed to be one of the major pathogenetic mechanisms in inflammatory dilated cardiomyopathy. Although the reason for progression to myocardial failure is not fully understood, postulated mechanisms include persistent viral infection alone or in combination with autoimmune processes. PATHOPHYSIOLOGY: Murine models of myocarditis have provided insight into the mechanisms by which autoimmune responses to cardiac antigens, probably in response to viral infection of the myocardium, arise and cause tissue pathology. Organ-specificity, cross-reactivity between microbial agents and cardiac tissue, and induction of tolerance to self-antigen are issues still at stake. In addition, cytokines mediate activation and effector phase of innate and specific immunity, which are both important in controlling viral infection. The innate immune response not only has an important protective function but also serves to initiate and regulate subsequent specific immune responses. In man, on the one hand specific T cells and antibodies against different cardiac tissue components have been demonstrated in myocardium and sera of patients with inflammatory cardiomyopathy, and on the other hand viral genome has been identified in endomyocardial biopsies due to the rapid development of new molecular biological techniques such as polymerase chain reaction (PCR), southern blot analysis and in-situ hybridization. But it is still a mater of debate whether virus infection itself, the ensuing immune response, or both, contribute to the deterioration of left ventricular function. CONCLUSION: Taking these mechanisms into account, screening for viral genome by PCR and detection of inflammatory infiltrates by immunohistochemistry are considered crucial for the establishment of a definite diagnosis thereby allowing for the initiation of specific therapeutic strategies.

Adult↗