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.

Impaired right ventricular function as a predictor of early mortality in patients with light­ chain cardiac amyloidosis assessed in a cardiology department.

INTRODUCTION    Light­chain (AL) amyloidosis is the most common cardiac amyloidosis. Despite progress in treatment, early mortality remains a substantial problem in these patients. OBJECTIVES    The aim of this study was to determine a clinical profile of patients diagnosed with AL amyloidosis in a cardiology department, as well as to define the cut­off point for early mortality and identify predictors of early mortality in this population. PATIENTS AND METHODS    The study included 30 patients (14 women; median age, 61.5 years) with AL amyloidosis confirmed by echocardiography and biopsy of 2 organs. RESULTS    Six patients were diagnosed with stage II amyloidosis according to the Mayo 2004 classification, and 24 patients-with stage III. Early mortality was defined as death during 102 days after diagnosis and was observed in 14 patients. Patients who died earlier were younger and more frequently reported a weight loss of more than 10 kg and orthostatic hypotension than patients who died later. Moreover, they had higher concentrations of high­sensitivity troponin T and N­terminal pro­B­type natriuretic peptide (NT­proBNP) and worse left and right ventricular (RV) contractility. In the Cox models, the age of less than 64 years, NT­proBNP levels exceeding 4968 pg/ml, RV end­diastolic diameter of less than 34 mm, and tricuspid annular plane systolic excursion lower than 13 mm were significant predictors of mortality within 102 days after diagnosis. CONCLUSIONS    We presented the results of the first Polish prospective noninterventional study on AL amyloidosis diagnosed in the cardiology department. We found that patients have advanced disease at the time of diagnosis. Younger age, impaired RV function, and higher concentrations of cardiac markers are predictors of worse prognosis.

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.

Rapid progression of primary sclerosing cholangitis complicated with ulcerative colitis.

Primary sclerosing cholangitis is a cholestatic condition with unknown etiology and long-standing, progressive course, leading to cirrhosis and requiring orthotropic liver transplant. In approximately 80%, primary sclerosing cholangitis is accompanied by inflammatory bowel disease, and in most cases the recognition of bowel disease precedes the diagnosis of primary sclerosing cholangitis. We describe a case of 22-year-old male diagnosed simultaneously with primary sclerosing cholangitis and ulcerative colitis, with a medical history suggesting uncommon prior development of the liver disease. Five months after the initial diagnosis, we observed advanced lesions of bile tree due to progression of primary sclerosing cholangitis, which led to the unusually fast necessity for the orthotopic liver transplant.

Heterotopic pancreatic tissue in the gastric cardia: a case report and literature review.

The heterotopic pancreas, which is usually described as an untypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas, is relatively rare. Clinical manifestations may include bleeding, inflammation, pain and obstruction; however, in most cases it remains silent and is diagnosed during autopsy. Here, we report a case of ectopic pancreatic lesion located in the gastric cardia. The patient was a 73-year-old woman who had a history (over four months) of chronic epigastric pain accompanied by heartburn. Esophagogastroduodenoscopy revealed inflammatory changes throughout the stomach and lower esophagus, as well as a flat polypoid mass with benign features located in the gastric cardia, approx. 10 mm below the "Z" line, measuring approx. 7 mm in diameter. Endoscopic biopsy forceps were used to remove the lesion. Histological examination of the lesion revealed the presence of heterotopic pancreatic tissue in the gastric mucosa. On the basis of the presented case, we suggest that pancreatic ectopia should be a part of differential diagnosis, not only when dealing with submucosal gastric lesions, but also with those that are small, flat and/or untypically located.

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.

[Cardiac involvement in neuronal ceroid lipofuscinosis]. / Zajecie serca w przebiegu neuronalnej lipofuscynozy ceroidowej.

We present a case of a 58-year-old female with neuropsychiatric symptoms, followed by recurrent episodes of atrial flagellation and symptoms of heart failure. Based on intraoperative myocardial biopsy, neuronal ceroid lipofuscinosis was diagnosed.

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.

[Unclassified cardiomyopathy or Lyme carditis? A three year follow-up].

Lyme carditis can be a clinical manifestation of the early disseminated stage of Lyme disease caused by the tick-transmitted pathogen Borrelia burgdorferi. We present the case of a 41 year-old Caucasian woman referred to our hospital with symptoms of fatigue, progressive exertional dyspnoea, supraventricular cardiac arrhythmia, and an enlarged heart revealed on chest radiography. Following an untypical result of transthoracic echocardiography, cardiac magnetic resonance was performed. This showed structural cardiac changes and focus of late gadolinium enhancement in the midwall of the apex region. Further diagnostic processes, including endomyocardial biopsy and serology tests, made it possible to diagnose Lyme carditis. Clinical observation was followed-up for three years.

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.

Psychological aspects of pain.

INTRODUCTION: Pain is defined "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Pain is a sensation of the body, and is always an unpleasant emotional experience. The role of psychology is auxiliary and supplemental to medicine. This is an aid addressed to the patient, physician and patient's caregivers: professional caregivers, family members and significant others. At each stage of the diagnostic and therapeutic process, psychology offers help, both from the cognitive and practical aspects. OBJECTIVE: The objective of the article is to present important psychological aspects of studies concerning pain, and the psychological methods and techniques of pain treatment. STATE OF KNOWLEDGE: Pain is the leading reason for patients seeking medical care and is one of the most disabling, burdensome, and costly conditions. Pain accompanies many diseases, each one of which generates unique/separate diagnostic, therapeutic and research problems. DEPRESSION AND RELATED PSYCHICAL DISORDERS: There is a significant relationship between depression and pain symptoms, as well as between pain and suicidal thoughts. Patients with a long history of pain disorders also have increased depression and anxiety symptoms, as well as suicidal thoughts. Patients with more severe depression and anxiety symptoms also have an increase in pain problems. The intensity of pain correlates with the intensity of psychopathological symptoms - both with mood lowering and with anxiety symptoms and worry. Active pain coping strategies strive to function in spite of pain, or to distract oneself from pain, are associated with adaptive functioning. Passive strategies involve withdrawal or relinquishing control to an external force or agent and are related to greater pain and depression. Pain catastrophizing is a negatively distorted perception of pain as awful, horrible and unbearable. Catastrophizing is strongly associated with depression and pain. Studies in which functional magnetic resonance imaging (fMRI) was used showed that pain catastrophizing, independent of the influence of depression, was significantly associated with increased activity in brain areas related to anticipation of pain, attention to pain, emotional aspects of pain and motor control. Pain behaviour is a conditioned pain. Care and concern on the part of others, secondarily enhance a patient's pain behaviours, which lead to an increase in the intensity of the pain experienced. A history of early life adversity (ELA) - rejection, neglect, physical or sexual abuse is related to the development of irritable bowel syndrome (IBS) in adulthood. Ovarian hormones have been shown to modulate pain sensitivity. IMAGING OF THE HUMAN BRAIN IN CHRONIC PAIN: Acute pain and chronic pain are encoded in different regions of the brain. Chronic pain can be considered a driving force that carves cortical anatomy and physiology, creating the chronic pain brain/ mind state. Cognitive-behavioural methods of pain treatment in domains of pain experience, cognitive coping and appraisal (positive coping measures), and reduced pain experience are effective in reducing pain in patients.

Simultaneous production of citric acid and invertase by Yarrowia lipolytica SUC+ transformants.

Simultaneous production of citric acid (CA) and invertase by Yarrowia lipolytica A-101-B56-5 (SUC(+) clone) growing from sucrose, mixture of glucose and fructose, glucose or glycerol was investigated. Among the tested substrates the highest concentration of CA was reached from glycerol (57.15 g/L) with high yield (Y(CA/S)=0.6g/g). When sucrose was used, comparable amount of CA was secreted (45 g/L) with slightly higher yield (Y(CA/S)=0.643 g/g). In all cultures amount of isocitrate (ICA) was below 2% of total citrates. Considering invertase production, the best carbon source appeared to be sucrose (72380 U/L). The highest yield of CA and invertase biosynthesis calculated for 1g of biomass was obtained for cells growing from glycerol (9.9 g/g and 4325 U/g, respectively). Concentrates of extra- and intracellular invertase of the highest activity were obtained from sucrose as substrate (0.5 and 1.8 × 10(6)U/L, respectively).

Are cardiomyocytes able to generate pre-amyloid peptides?

We performed ultrastructural testing of a cardiac biopsy taken from a heart with amyloidosis in which transthyretin mutation and light chain A amyloidosis were excluded. Cardiomyocytes of the affected heart showed accumulation of endosomal-like structures in which soluble amyloid oligomeric conformation was deposited. Intracellular accumulation of ß -amyloid as well as phosphorylated tau protein seen in the immunohistochemical study suggest that the heart tissue may generate an amyloidogenic peptide leading to cardiomyocyte destruction and heart dysfunction.

[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.

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.

[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.