Poruchy autonomní funkce srdce asociované s komorovými extrasystolami (KES) jsou často spojeny se snížením ejekční frakce a se zvýšenou kardiovaskulární morbiditou a mortalitou. Standardní zobrazovací techniky jako magnetická rezonance srdce (CMR) a koronární angiografie zajišťují vyloučení jiných příčin komorových extrasystol jako ischemie a neischemické fibrózy myokardu, ale nejsou schopny zobrazit narušení autonomního nervového systému srdce. Toto lze studovat pomocí scintigrafie myokardu (SPECT) s použitím 123 I-metajodbenzylguanidinu (MIBG). Vyšetřili jsme pilotní soubor šesti pacientů, z nichž u tří pacientů byla zjištěna porucha v adrenergní inervaci myokardu levé komory, a ty prezentujeme jako kazuistiky.
Disturbances of autonomic function in the heart associated with premature ventricular complexes (PVC) are associated with a decrease in ejection fraction as well as increased cardiac morbidity and mortality. Standard imaging techniques such as cMRI and coronary angiography secure the exclusion of other causes of PVC as ischemia and progressive fibrosis. These methods are not suitable for cardiac autonomic nervous system imaging and can't describe the cause of related PVCs. This may be described by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. We examined a pilot group of 6 patients, in which 3 individuals presented a disorder in the adrenergic innervation of the left ventricular myocardium and we present these as case reports.
- MeSH
- 3-jodobenzylguanidin farmakologie terapeutické užití MeSH
- autonomní nervový systém diagnostické zobrazování MeSH
- diagnostické zobrazování metody MeSH
- kazuistiky jako téma MeSH
- komorové extrasystoly * diagnostické zobrazování diagnóza etiologie MeSH
- lidé MeSH
- multimodální zobrazování * klasifikace metody MeSH
- myokard patologie MeSH
- pilotní projekty MeSH
- senioři MeSH
- zobrazování myokardiální perfuze metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8-18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.
- Publikační typ
- časopisecké články MeSH
FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.
- MeSH
- adenosin metabolismus MeSH
- alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 * genetika metabolismus MeSH
- buněčná diferenciace MeSH
- embryonální vývoj MeSH
- gen pro FTO * genetika metabolismus MeSH
- myši MeSH
- RNA metabolismus MeSH
- stárnutí genetika MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- tisková chyba MeSH
Methoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER - prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox's relative IC50 at 19 mmol L-1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.
- MeSH
- adrenalin * MeSH
- adrenergní receptory MeSH
- endonukleasy MeSH
- lidé MeSH
- methoxamin MeSH
- oprava DNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Aims: Gross pathology inspection (patho) is the gold standard for the morphological evaluation of focal myocardial pathology. Examination with 9.4 T magnetic resonance imaging (MRI) is a new method for very accurate display of myocardial pathology. The aim of this study was to demonstrate that lesions can be measured on high-resolution MRI images with the same accuracy as on pathological sections and compare these two methods for the evaluation of radiofrequency (RF) ablation lesion dimensions in swine heart tissue during animal experiment. Methods: Ten pigs underwent radiofrequency ablations in the left ventricle during animal experiment. After animal euthanasia, hearts were explanted, flushed with ice-cold cardioplegic solution to relax the whole myocardium, fixed in 10% formaldehyde and scanned with a 9.4 T magnetic resonance system. Anatomical images were processed using ImageJ software. Subsequently, the hearts were sliced, slices were photographed and measured in ImageJ software. Different dimensions and volumes were compared. Results: The results of both methods were statistically compared. Depth by MRI was 8.771 ± 2.595 mm and by patho 9.008 ± 2.823 mm; p = 0.198. Width was 10.802 ± 2.724 mm by MRI and 11.125 ± 2.801 mm by patho; p = 0.049. Estuary was 2.006 ± 0.867 mm by MRI and 2.001 ± 0.872 mm by patho; p = 0.953. The depth at the maximum diameter was 4.734 ± 1.532 mm on MRI and 4.783 ± 1.648 mm from the patho; p = 0.858. The volumes of the lesions calculated using a formula were 315.973 ± 257.673 mm3 for MRI and 355.726 ± 255.860 mm3 for patho; p = 0.104. Volume directly measured from MRI with the "point-by-point" method was 671.702 ± 362.299 mm3. Conclusion: Measurements obtained from gross pathology inspection and MRI are fully comparable. The advantage of MRI is that it is a non-destructive method enabling repeated measurements in all possible anatomical projections.
- Publikační typ
- časopisecké články MeSH
Úvod: Thorakoskopická radiofrekvenční ablace technikou "single stage" je metodou léčby perzistující a dlouhodobě perzistující fibrilace síní (FS) nabízející možnost pro pacienty jinak neřešitelné konvenční katétrovou radiofrekvenční ablací. Prezentujeme úvodní soubor pacientů po zavedení nové metody na našem pracovišti. Metody: Celkem 52 pacientů ve věku 61,82 ± 9,7 roku podstoupilo v období září 2016 – březen 2019 single stage hybridní ablaci (thorakoskopická izolace plicních žil a „box lesion“ následovaná katétrovým ověřením efektu chirurgické části výkonu) pro symptomatickou perzistující a dlouhodobě perzistující FS s výrazně dilatovanou levou síní 57,9 ± 11,0 mm. Výsledky: Střední doba výkonu dosahovala 232 minut a střední doba hospitalizace byla 10 dnů. Při propuštění mělo 52 pacientů (100 %) sinusový rytmus. Šestiměsíční kontrolu absolvovalo 48 z 52 pacientů (92,3 %). Při první kontrole po třech měsících od výkonu bylo 41 ze 48 (85,4 %) pacientů bez záchytu FS, při druhé kontrole po 6 měsících bylo bez FS 38 ze 44 dále sledovaných pacientů (86,4). Akutní komplikace byla zaznamenána 1× perforace levé síně řešená úspěšně suturou a 1× tranzitorní ischemická ataka bez trvalých následků. Pozdní komplikace 1× masivní plicní embolizace, 1× atrioezofageální píštěl. Nebyl zaznamenán žádný periprocedurální infarkt myokardu ani cévní mozková příhoda s trvalými následky. Závěr: Hybridní thorakoskopická a katétrová ablace v jednom sezení je účinná a relativně bezpečná miniinvazivní metoda léčby dlouhodobě perzistující fibrilace síní.
Introduction: Single stage thoracoscopic radiofrequency ablation (RFA) is a treatment method for persistent and long-term persistent atrial fibrillation (AF) offering the possibility for patients otherwise inconsolable by conventional catheter RFA. We present a pilot group of patients after the introduction of the new method at our clinical center. Patients group: A total of 52 patients aged 61.82 ± 9.7 years underwent single stage hybrid ablation (thoracoscopic isolation of pulmonary veins and box lesion followed by catheter verification of the surgical procedure effectivness) for symptomatic persistent and long-term persistent AF with significantly dilated left atrium 57.9 ± 11.0mm in the period September 2016-March 2019. Results: The median duration of the procedure was 232 minutes and the median duration of hospitalization was 10 days. At discharge, 52 patients (100%) had sinus rhythm. 48 of 52 patients (92.3%) had a 6-month follow-up. 41 of 48 (85.4%) and 38 of 44 (86.4%) of patients were AF free at 3-month and 6-month follow-up, respectively. Acute complications were: one left atrial perforation resolved successfully by suture and one transient ischaemic attack without permanent sequelae. Late complications involved one massive pulmonary embolization and an atrioesophageal fistula. There was no periprocedural myocardial infarction or stroke with permanent sequelae. Conclusion: Hybrid thoracoscopic-catheter ablation performed during one procedure is an effective and relatively safe mini-invasive method of treatment for long-term persistent atrial fibrillation.
- Klíčová slova
- thorakoskopická ablace, hybridní single stage ablace,
- MeSH
- fibrilace síní * chirurgie MeSH
- katetrizační ablace metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Achondroplasia (ACH) is one of the most prevalent genetic forms of short-limbed skeletal dysplasia, caused by gain-of-function mutations in the receptor tyrosine kinase FGFR3. In August 2021, the C-type natriuretic peptide (CNP) analog vosoritide was approved for the treatment of ACH. A total of six other inhibitors of FGFR3 signaling are currently undergoing clinical evaluation for ACH. This progress creates an opportunity for children with ACH, who may gain early access to the treatment by entering clinical trials before the closure of their epiphyseal growth plates and cessation of growth. Pathophysiology associated with the ACH, however, demands a long observational period before admission to the interventional trial. Public patient registries can facilitate the process by identification of patients suitable for treatment and collecting the data necessary for the trial entry. RESULTS: In 2015, we established the prospective ACH registry in the Czechia and the Slovak Republic ( http://www.achondroplasia-registry.cz ). Patient data is collected through pediatric practitioners and other relevant specialists. After informed consent is given, the data is entered to the online TrialDB system and stored in the Oracle 9i database. The initial cohort included 51 ACH children (average age 8.5 years, range 3 months to 14 years). The frequency of selected neurological, orthopedic, or ORL diagnoses is also recorded. In 2015-2021, a total of 89 measurements of heights, weights, and other parameters were collected. The individual average growth rate was calculated and showed values without exception in the lower decile for the appropriate age. Evidence of paternal age effect was found, with 58.7% of ACH fathers older than the general average paternal age and 43.5% of fathers older by two or more years. One ACH patient had orthopedic limb extension and one patient received growth hormone therapy. Low blood pressure or renal impairment were not found in any patient. CONCLUSION: The registry collected the clinical information of 51 pediatric ACH patients during its 6 years of existence, corresponding to ~ 60% of ACH patients living in the Czechia and Slovak Republic. The registry continues to collect ACH patient data with annual frequency to monitor the growth and other parameters in preparation for future therapy.
- MeSH
- achondroplazie * epidemiologie genetika MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mutace MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- receptor fibroblastových růstových faktorů, typ 3 genetika MeSH
- registrace MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
