Biotransformation of acetophenone and its halogen derivatives by Yarrowia lipolytica strains.

The ability of 16 strains of Yarrowia lipolytica to biotransform acetophenone and its derivatives has been studied. Thirteen of these strains were derived from a wild-type strain Y. lipolytica A-101; six had the invertase gene (SUC2) from Saccharomyces cerevisiae integrated into their genome, as well as the damaged or undamaged gene encoding orotidine-5'-phosphate decarboxylase (URA3), three had integrated the damaged URA3 gene into their genome and three were UV acetate-negative mutants, not able to growth on acetate as the sole carbon source. The other tested strains included two wild strains, A-101 and PMR-1, and an adenine auxotroph ATCC 32-338A. All strains were capable of reducing acetophenone to the R-alcohol in high enantiomeric excess (80-89 %). In all of the cultures tested, reversibility of the reduction was observed, which led to an increase in the enantiomeric excess. nantioselective reduction of the acetophenone halogen derivatives revealed that the nature and location of the halogen atom had a significant influence on the enantioselectivity of the reduction. In the culture of ATCC 32-338A, after a 3-day biotransformation of 2,4'-dibromoacetophenone the enantiopure R-alcohol was obtained at a rate of 100 % of substrate conversion. In conclusion, using these invertase-containing strains or uracyl auxotrophs provided no additional benefit in terms of biotransformation capacity over the parental strain.

The BAG3 gene variants in Polish patients with dilated cardiomyopathy: four novel mutations and a genotype-phenotype correlation.

BACKGROUND: BAG3 gene mutations have been recently implicated as a novel cause of dilated cardiomyopathy (DCM). Our aim was to evaluate the prevalence of BAG3 mutations in Polish patients with DCM and to search for genotype-phenotype correlations. METHODS: We studied 90 unrelated probands by direct sequencing of BAG3 exons and splice sites. Large deletions/insertions were screened for by quantitative real time polymerase chain reaction (qPCR). RESULTS: We found 5 different mutations in 6 probands and a total of 21 mutations among their relatives: the known p.Glu455Lys mutation (2 families), 4 novel mutations: p.Gln353ArgfsX10 (c.1055delC), p.Gly379AlafsX45 (c.1135delG), p.Tyr451X (c.1353C>A) and a large deletion of 17,990 bp removing BAG3 exons 3-4. Analysis of mutation positive relatives of the probands from this study pooled with those previously reported showed higher DCM prevalence among those with missense vs. truncating mutations (OR = 8.33, P = 0.0058) as well as a difference in age at disease onset between the former and the latter in Kaplan-Meier survival analysis (P = 0.006). Clinical data from our study suggested that in BAG3 mutation carriers acute onset DCM with hemodynamic compromise may be triggered by infection. CONCLUSIONS: BAG3 point mutations and large deletions are relatively frequent cause of DCM. Delayed DCM onset associated with truncating vs. non-truncating mutations may be important for genetic counseling.

LMNA mutations in Polish patients with dilated cardiomyopathy: prevalence, clinical characteristics, and in vitro studies.

BACKGROUND: LMNA mutations are most frequently involved in the pathogenesis of dilated cardiomyopathy with conduction disease. The goal of this study was to identify LMNA mutations, estimate their frequency among Polish dilated cardiomyopathy patients and characterize their effect both in vivo and in vitro. METHODS: Between January, 2008 and June, 2012 two patient populations were screened for the presence of LMNA mutations by direct sequencing: 66 dilated cardiomyopathy patients including 27 heart transplant recipients and 39 dilated cardiomyopathy patients with heart failure referred for heart transplantation evaluation, and 44 consecutive dilated cardiomyopathy patients, referred for a family evaluation and mutation screening. RESULTS: We detected nine non-synonymous mutations including three novel mutations: p.Ser431*, p.Val256Gly and p.Gly400Argfs*11 deletion. There were 25 carriers altogether in nine families. The carriers were mostly characterized by dilated cardiomyopathy and heart failure with conduction system disease and/or complex ventricular arrhythmia, although five were asymptomatic. Among the LMNA mutation carriers, six underwent heart transplantation, fourteen ICD implantation and eight had pacemaker. In addition, we obtained ultrastructural images of cardiomyocytes from the patient carrying p.Thr510Tyrfs*42. Furthermore, because the novel p.Val256Gly mutation was found in a sporadic case, we verified its pathogenicity by expressing the mutation in a cellular model. CONCLUSIONS: In conclusion, in the two referral centre populations, the screening revealed five mutations among 66 heart transplant recipients or patients referred for heart transplantation (7.6%) and four mutations among 44 consecutive dilated cardiomyopathy patients referred for familial evaluation (9.1%). Dilated cardiomyopathy patients with LMNA mutations have poor prognosis, however considerable clinical variability is present among family members.

Morphologic and clinical aspects of Danon disease in a patient with a mutation c.137G > A in the LAMP-2 gene.

BACKGROUND: Danon disease is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). MATERIALS AND METHODS: Our study describes a 19-year-old man with isolated hypertrophic cardiomyopathy, in whom we performed DNA analysis and compared results of microscopic analysis of skeletal and cardiac muscles. RESULTS: Sequencing of the LAMP-2 gene revealed a novel point mutation c.137G > A in exon 2, leading to premature stop codon. Ultrastructural analysis of cardiac and skeletal muscles revealed the presence of unusual autophagic vacuoles in both. Although some vacuoles in skeletal muscle reacted strongly with dystrophin, ß-sarcoglycan, and laminin, those in cardiomyocytes showed no immunoreactivity. CONCLUSION: Our immunohistochemical and ultrastructural findings reinforce the claim that in Danon disease the pathomechanism of chaperone-mediated autophagy in cardiomyocytes differs from that in skeletal muscle.

Remodeling of mitochondrial interior in cardiac lipofuscinosis.

Ultrastructural analysis was performed in cardiac ceroidlipofuscinosis to confirm the presence and the nature of storage material. Granular osmophilic deposits characteristic of GROD structures coincidented with particularly aberrant mitochondria. Remodeling of mitochondrial interior with the appearance of several form of abnormal inclusions was never observed in cardiac ceroidlipofuscinosis. The presence of dense osmophilic bodies, glycogen conglomerates, balloon-like and onion-like structures in mitochondrial interior seem to be early events of this storage process.

Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience.

BACKGROUND: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant. AIMS: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM. METHODS: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA. RESULTS: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001). CONCLUSIONS: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

Association between the acquisition of antibodies against Lyme disease and the risk of atrial arrhythmias.

INTRODUCTION: The impact of antibodies against Borrelia burgdorferi (BB) on the occurrence of cardiac arrhythmias in patients without typical symptoms of Lyme disease (LD) is largely unknown. OBJECTIVES: We aimed to assess the risk of atrial fibrillation (AF) and other atrial arrhythmias (AAs) in patients who tested positive for anti-LD antibodies. PATIENTS AND METHODS: We included consecutive patients referred for the diagnosis and treatment of AAs who had no history of erythema migrans or other symptoms of LD. The presence of anti-BB antibodies (immunoglobulin [Ig] M and IgG) was assessed in each patient, and the diagnostic workup of cardiac arrhythmias was performed. RESULTS: Of the 527 patients enrolled in the study, 292 (55%) were diagnosed with AAs, and we detected BB antibodies in 131 individuals (24.8%). The patients with a serological history of Borrelia infection were older (mean [SD], 55.6 [15.7] vs 50.3 [18.6] years; P = 0.01), had a higher probability of developing AF or other supraventricular arrhythmias (SAs) (66.4% vs 51.8%; P = 0.03), and had elevated levels of N­terminal pro-B ­type natriuretic peptide (NT­proBNP) (58% vs 47.5%; P = 0.04). We also found an as-sociation between the occurrence of AF and other SAs in patients with anti-BB antibodies and elevated NT­proBNP values, and the risk of AAs in these patients increased almost 3­fold (P = 0.01). CONCLUSION: Our data indicated an association between the exposure to Borrelia infection and the risk for AF and other AAs in the patients with elevated levels of NT­proBNP, suggesting the need for a more efficacious diagnostic approach to patients with SAs, especially in LD­endemic regions.

An increasing trend of the delay in asthma diagnosis after the discontinuation of a population-based intervention.

BACKGROUND: We have previously analyzed the delay in asthma diagnosis in children from the cohort of Asthma Prevention Program in Lodz Province, Poland. That community-based intervention focused mainly on the improvement in access to specialists. The aim of this study was reevaluation of the timelines of all recent asthma diagnoses (N = 500) in children referred to our clinic after the discontinuation of the program, that is, in the time span from 2004 to 2009. METHODS: Subjects with no previous diagnosis of asthma but a positive asthma predictive index were labeled as having undiagnosed asthma. The time from the first medical appointment when asthma could have been diagnosed the earliest until the final diagnosis of asthma was calculated for each subject and defined as the duration of undiagnosed asthma (years). All data were obtained from children's medical documentation and through phone interviews. RESULTS: During the intervention program, the duration of undiagnosed asthma significantly decreased. However, it showed a significant upward trend after the discontinuation of the program. After 6 years since the program was abandoned, the average undiagnosed asthma duration returned to its initial length from before the intervention. The independent statistical predictors of the delayed asthma diagnosis were the absence of atopy and suboptimal initial antiasthma therapy. CONCLUSION: Our results revealed the following: first, general practitioners do not follow the recommended guidelines for early detection of asthma in children; and second, a greater accessibility of specialists could enhance chances of early asthma diagnosis, especially in nonatopic children.

Tick-borne infections as a cause of heart transplantation.

Many bacterial species can be a cause of various heart diseases, such as: Borrelia burgdorferi sensu lato, Coxiella burnetii and Bartonella spp. The aim of the present studies was to establish if any tick-borne infections can contribute to serious heart disorders resulting in the need for heart transplantation. Myocardium, aortic and mitral valve samples from hearts removed from patients undergoing heart transplantation were tested. The presence of Bartonella spp., Borrelia afzeli and C. burnetii bacteria in malfunctioning human hearts has been shown. DNA of Bartonella spp., B. burgdorferi and C. burnetii were detected in various parts of tested hearts. DNA of B. afzelii and Bartonella spp. were found in the aortic valves. DNA of C. burnetii was detected in the myocardium. Mixed infections with Bartonella spp. and C. burnetii were also observed. Obtained results indicate that diagnosis of Bartonella spp., B. burgdorferi C. burnetii and Rickettsia spp. infections should be considered in cases of infectious endocarditis with negative blood cultures.

[Variability in clinical profile of asthmatic child referred from allergy clinic--ten years of observation]. / Zmiennosc danych u dzieci chorych na astme kierowanych do poradni alergologicznej--10-letnia obserwacja.

INTRODUCTION: Asthma is the most frequent chronic respiratory disease in children. Underdiagnosis is frequent, which results in undertreatment and, consequently, in rising asthma morbidity and mortality rates. The delay in the diagnosis of asthma seems to precisely reflect problems with a proper realization of the goals of the diagnostic part of the Global Initiative for Asthma guidelines. We attempted to assess the clinical profile of children who were referred to allergy clinic followed by asthma diagnosis, we consider especially demographic and social data. MATERIAL AND METHODS: We analyzed the group of 907 children with diagnosis of asthma between 2000 and 2009. This was cross-sectional study assessing demographic, social and clinical characteristic. All variables were tested over time. RESULTS: We observed change in clinical profile of children checking into the clinic over time. The new profile includes: younger age of patient, higher frequency of recurrent infections, lower frequency of wheezes and atopy. CONCLUSIONS: New clinical profile of patients referred to allergist reveals the need of costly differential diagnosis of asthma in specialized centers. This should be included in new strategies in the health care system in Poland.

Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption.

Major nuclear envelope abnormalities, such as disruption and/or presence of intranuclear organelles, have rarely been described in cardiomyocytes from dilated cardiomyopathy (DCM) patients. In this study, we screened a series of 25 unrelated DCM patient samples for (a) cardiomyocyte nuclear abnormalities and (b) mutations in LMNA and TMPO as they are two DCM-causing genes that encode proteins involved in maintaining nuclear envelope architecture. Among the 25 heart samples investigated, we identified major cardiomyocyte nuclear abnormalities in 8 patients. Direct sequencing allowed the detection of three heterozygous LMNA mutations (p.D192G, p.Q353K and p.R541S) in three patients. By multiplex ligation-dependant probe amplification (MLPA)/quantitative real-time PCR, we found a heterozygous deletion encompassing exons 3-12 of the LMNA gene in one patient. Immunostaining demonstrated that this deletion led to a decrease in lamin A/C expression in cardiomyocytes from this patient. This LMNA deletion as well as the p.D192G mutation was found in patients displaying major cardiomyocyte nuclear envelope abnormalities, while the p.Q353K and p.R541S mutations were found in patients without specific nuclear envelope abnormalities. None of the DCM patients included in the study carried a mutation in the TMPO gene. Taken together, we found no evidence of a genotype-phenotype relationship between the onset and the severity of DCM, the presence of nuclear abnormalities and the presence or absence of LMNA mutations. We demonstrated that a large deletion in LMNA associated with reduced levels of the protein in the nuclear envelope suggesting a haploinsufficiency mechanism can lead to cardiomyocyte nuclear envelope disruption and thus underlie the pathogenesis of DCM.

Ultrastructural evidence of myocardial capillary remodeling in peripartum cardiomyopathy.

BACKGROUND: The etiology of peripartum cardiomyopathy (PPCM) is not well understood. Potential causal mechanisms include infection, autoimmune disease, and abnormal response to the hemodynamic stress of pregnancy. Recently it was shown that the development of PPCM in an experimental model is associated with the generation of a cleaved antiangiogenic and proapoptotic 16-kDa form of the nursing hormone prolactin, which impairs the cardiac capillary network and its function. The purpose of this study was to evaluate the ultrastructure of the myocardium in a patient with PPCM and in a comparative group of patients and to identify structural characteristics that may predispose to myocardium dysfunction. CASE REPORT: A 28-year-old woman with PPCM had fulminant heart failure leading to the implantation of a biventricular assist device, but no myocarditis was found on histological examination of her myocardial tissue. An ultrastructural study of myocardial tissue taken from three patients (mean age: 22 years, 2 females) with fulminant heart failure not related to PPCM (2 myocarditis, 1 dilated cardiomyopathy) served as a comparison. The ultrastructural analysis revealed the presence of small capillary damage. Vascular lumen occlusion, endothelial cell remodeling, and apoptosis with the appearance of mast cells, plasma cells, and preadipocytes were the most characteristic features of the damaged myocardial tissue with secondary interstitial fibrosis. No vascular pathology of cardiac capillaries was observed in the comparative group. CONCLUSIONS: A myocardial tissue study in PPCM revealed ultrastructural remodeling of small capillaries with the presence of endothelial cell apoptosis and impairment of the microcirculation.

Autophagy in transition from hypertrophic cardiomyopathy to heart failure.

Endomyocardial biopsy of a patient in transition stage from hypertrophic cardiomyopathy to heart failure was investigated. The tissue showed hypertrophy, atrophy of myocytes and an increased amount of fibrosis. In addition, numerous cardiomyocytes revealed ubiquitin positive inclusions. Ultrastructural analysis indicated that cardiomyocytes contained typical autophagic vacuoles including mitochondria, glycogen granules, degraded remnants and myelin structures. The most obvious ultrastructural finding was the presence of amorphous plaques and tubulofilamentous inclusions. Such ultrastructural abnormalities allow us to conclude that degeneration of myocardial cells by autophagy mechanisms leads to cardiomyocyte death, loss and heart failure.

[Pulmonary microscopic lesions in drug addicts--a preliminary report]. / Zmiany mikroskopowe pluc u narkomanów--doniesienie wstepne.

BACKGROUND: A sudden death of drug addicts is generally attributed to the depressive effect of substances in question on the respiratory center in the CNS. Microscopic morphology of lungs is relatively rarely dealt with. PURPOSE: This study probes into the morphology of individuals who were intoxicated by amphetamine and/or heroin and suddenly died. MATERIAL AND METHODS: The investigated group comprised lung specimens collected in the files of the Department of Forensic Medicine of Medical University of Warsaw in the years 2002-2004. A total of 41 autopsied drug addicts suddenly succumbed without any medical intervention. Formol-fixed paraffin blocks were stained with HE. The presence of opiates and/or amphetamine was investigated in body fluids at autopsy and recorded. The control group of 50 non-addicts originated from the files of the Department of Pathomorphology of the Rheumatologic Institute of Warsaw. Immunohistochemistry for alpha-1-antitripsin was performed in both groups. RESULTS: The microscopic image of the lungs in the investigated group showed a pronounced hyperemia of the thickened interalveolar septa. The alveoli and alveolar ductules were enormously expanded by fluid, which contained numerous air bubbles of variable, rather striking sizes. The fluid showed multiple hemosiderin-loaded macrophages. The reaction for alpha-1-antitripsin was negative. Microscopy of the lungs from the control group failed to demonstrate any essential abnormalities. The reaction for alpha-1-antitripsin was positive. CONCLUSIONS: Microscopy of the lungs of drug addicts is characteristic and attributed to drug. The pathologist facing such a picture is obliged to review and discuss with the clinician the possibility of drug addiction, if it has not been indicated so far. The investigation into the contribution of alpha-1 -antitripsin deficit should be continued.

Cardiovascular magnetic resonance findings in a case of Danon disease.

Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies.

Desmin expression in human cardiomyocytes and selected clinical and echocardiographic parameters in patients with chronic heart failure.

BACKGROUND: Desmin, one of the basic muscular-specific structural proteins, is believed to play an important role in the progression of heart failure (HF). The function of desmin in cardiomyocytes is still unclear. Mechanical, structural and regulatory functions are postulated. Regulatory function of desmin seems the most interesting. Desmin might be involved in the regulation of gene expression, myofibrillogenesis and intercellular signalling, and be responsible for shape and tension of the cell membrane and other organelles. Abnormal accumulation of desmin may disturb the function of myofibrils, lead to unusual tension of sarcolemma and atypical distribution of organelles (nucleus), and impair intra- and intercellular communication. AIM: Evaluation of desmin expression in specimens derived from right ventricular myocardium during endomyocardial biopsy (EMB). METHODS: The study population consisted of 135 patients (86.7% males, mean age 49.4 +/- 14.1 years) presenting with clinical symptoms of HF and LVEF < 45%. During EMB 3-4 samples were taken from the right ventricular myocardium. The immunohistochemical studies of the endomyocardial specimens included immunostaining with desmin-specific antibodies. The study population was divided into three groups: I - 48 patients with normal expression of desmin, II - 54 patients with increased expression and accumulation of desmin and III - 33 patients with low expression of desmin in cardiomyocytes. RESULTS: The LVEF was significantly higher in group I than in groups II and III. The LV diameter was significantly lower in group I than in groups II and III. Functional status according to NYHA class was the worst in group I compared to group II and III. These differences were statistically significant. CONCLUSION: Evaluation of desmin distribution in specimens derived from the right ventricular myocardium may be useful as an objective tool in the assessment of left ventricle status.

Cardiomyocyte desmin abnormalities - an accurate predictor of long-term survival in patients with chronic heart failure.

BACKGROUND: The proteins of cardiomyocytes are interesting targets for investigations as they may directly reflect intracellular changes within the heart. Desmin is one of the fundamental cytoskeleton proteins of cardiomyocytes, and has a mechanical, structural and regulatory function. In comparison with healthy individuals, patients with heart failure (HF) present different expression of desmin content, that can be associated with its abnormal structure, different distribution, localisation and disturbed function. Abnormal expression of desmin in cardiomyocytes plays a key role in progression of HF. AIM: To evaluate desmin expression in cardiomyocytes of patients with HF and to asses it's prognostic value during long-term follow-up. METHODS: Diagnostic endomyocardial biopsy (DMB) was performed in 135 patients (86.7% males, mean age 49.4 +/- 14.1 years) with clinical symptoms of HF (left ventricular ejection fraction %lt 45%). In each case four specimens were taken from the right ventricle. Desmin was detected with immunohistochemical staining of cardiomyocytes. The study population was divided into three groups: group I - 48 patients with normal expression of desmin; group II - 54 patients with abnormal accumulation of desmin; group III - 33 patients with low expression of desmin in cardiomyocytes. The ROC curves and Kaplan-Meier survival curves were constructed to analyse predictive value of examined parameters. RESULTS: The mean duration of follow-up was 33.2 +/- 14.6 (6-72) months. Cardiac cause of death was confirmed in 2.08% of cases in group I, 7.4% in group II and 22.86% in group III. Group I vs. group II: Cox's F test - p = 0.07647; log-rank test - p = 0.15047, group I vs. group III: Cox's F test - p = 0.007, log-rank test - p = 0.005, group II vs. group III: Cox's F test - p = 0.033, log-rank test - p = 0.079. CONCLUSIONS: Our results suggest that desmin content in cardiomyocytes directly affects the long-term prognosis in HF patients. The low expression of desmin in cardiomyocytes with immunohistochemical assay is associated with unfavourable clinical course.

Nuclear architecture remodelling in cardiomyocytes with lamin A deficiency.

We analysed the architecture of cardiomyocyte nuclei lacking lamin A activity in three patients with dilated cardiomyopathy. The diagnosis was established on the basis of clinical and electrophysiological examinations, chest radiography and electrocardiography. An ultrastructural study of affected cardiomyocytes showed dramatic alterations in nuclear distribution and organization affecting nuclear shape, lamina structure, chromatin and nuclear interior organization. The most specific hallmark of nuclei with lamin A deficiency was the reorganization of the nuclear interior, the appearance of a various number of mitochondria within the nuclear matrix, and focal or total lack of nuclear membrane.

[Morphological and clinical aspects of Danon disease]. / Morfologiczne i kliniczne aspekty choroby Danona.

BACKGROUND: Danon disease, an X-linked hypertrophic cardiomyopathy, is caused by primary deficiency of lysosome-associated membrane protein (LAMP-2). The pathological hallmark of the disease is the appearance of intracytoplasmic vacuoles containing autophagic material and the absence of LAMP-2 activity in the muscle. AIM: To define the LAMP-2 protein deficiency we investigated cardiac and skeletal muscle of a 19-year-old man with hypertrophic cardiomyopathy without clinically apparent skeletal myopathy or mental impairment, whose mother died suddenly at 46 years of age. METHODS: Clinical, morphological, immunohistochemical and ultrastructural analysis was performed. Paraffin sections of cardiac muscle were stained using routine histochemical methods. Frozen sections of skeletal muscle were stained using histochemical methods as well as using monoclonal antisera against N-terminal of dystrophin and antisera against LAMP-2. Ultrastructural examination of both cardiac and skeletal muscle specimens were performed. RESULTS: Cardiac and skeletal muscle revealed an excessive accumulation of early and late autophagic vacuoles containing various cytoplasmic debris. In immunohistochemical analysis the vacuolar membrane seen in skeletal muscle was decorated with antibody against dystrophin and such vacuoles were negative for LAMP-2. CONCLUSION: Ultrastructural and immunohistochemical analysis of skeletal muscle (less invasive than myocardial biopsy) may be used in diagnosis of Danon disease. Early diagnosis of Danon disease is important for timely cardiac transplantation, the only effective therapeutic option.

[RF ablation of longstanding persistent atrial fibrillation in patient with familial dilated cardiomyopathy]. / Ablacja RF podloza dlugotrwale przetrwalego migotania przedsionków u chorego z rodzinna kardiomiopatia rozstrzeniowa odwraca zaawansowany remodeling serca--opis przypadku.

A vicious circle of interactions between dilated cardiomyopathy and longstanding persistent AF/AFL may cause symptoms of advanced congestive heart failure. In a 31-year-old patient with diagnosis of familial dilated cardiomyopathy and permanent AF lasting for five years, gradually decreased left ventricular ejection fraction (LVEF) and increased diameter of heart chambers - left ventricular diastolic dimension (LVdD) 7.7 cm, left atrium (LA) 5.4 cm, and LVEF 15% were noted. Pharmacological treatment was ineffective Successful RF ablation of AF/AFL substrate (CTI block, PVs isolation, CFAE ablation, roof and MIG line, CS applications) reversed symptoms of significant heart remodeling (LVdD 5.9 cm, LA 4.3 cm, LVEF 50%).