Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany

Br J Haematol. 1998 Dec;103(3):842-5. Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany. Nielsen P, Carpinteiro S, Fischer R, Cabeda JM, Porto G, Gabbe EE. Abteilung für Medizinische Biochemie, Universitätskrankenhaus Eppendorf, Hamburg, Germany. Abstract Mutation analysis was performed for two HFE mutations (C282Y, H63D) in unrelated patients with hereditary haemochromatosis (n = 92), family members of patients (n = 34), and unrelated controls (n = 157) from Northern Germany, 87/92 patients (94.6%) revealed the C282Y mutation in homozygous form, five were heterozygous. No H63D mutation was found in 174 chromosomes of patients homozygous for C282Y, whereas four of the heterozygote patients also carried the H63D mutation. Among the control group, 9.6% were heterozygotes for C282Y. 2/157 subjects were homozygous, 37/157 were heterozygous for the H63D mutation, but showed no signs of iron overload. PMID: 9858243 [PubMed - indexed for MEDLINE

Utility of pace-matching mapping in the ablation of idiopathic ventricular tachyarrhythmias

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.Introduction: The electroanatomical mapping of idiopathic ventricular tachyarrhythmias (iVT) - premature ventricular contractions (PVC) and idiopathic ventricular tachycardia (VT) - is dependent on the recording of spontaneous PVC or induction of the clinical VT during the procedure to obtain the iVT activation map. The presence of infrequent and non-inducible iVT may preclude ablation. Pace-matching (PM) mapping of the anatomical region on interest, using the PaSo™ algorithm, may allow to circumvent this limitation. Purpose: Determination of the utility of the PaSo™pace-matching mapping for iVT ablation Methods: A single-center retrospective study was made, with inclusion of consecutive patients undergoing iVT ablation between October 2013 and October 2016. It was collected electroanatomical data, including the highest correlation obtained by PM (PaSo™). Success of the procedure was assessed (defined as the elimination of spontaneous PVC during the electrophysiological study and non-inducible iVT at the end) and the ability of the PaSo™ pace-matching mapping to guide effective ablation was determined. Results: 29 patients were studied (62.1% women, mean age 52.8±14.7 years). 65.5% presented symptomatic frequent PVC and 34.5% VT. The most frequent anatomic origin was the right ventricular outflow tract (58.6%), followed by the left coronary cusp (20.7%), mitro-aortic continuity (13.8%) and papillary muscles (6.9%). The ablation was successful (PVC elimination during the procedure) in 75.9% of the cases. In 79.3% of the cases it was possible to obtain an activation map; in 20.7% (6 cases) it was only possible to obtain a pace-matching map, because ocurred suppression of PVC during the procedure, and success was achieved in 5 of these cases. There was no relationship between success and anatomical region of origin of the iVT. The mean value of the better pace-matching correlation was 94.45% ± 3.95%, being significantly higher when the zone of interest was located in the right ventricle (95.71±3.23 vs. 92.68±4.3, p=0.04). There was a positive and significant association between the PaSo™ correlation value and success (r=0.554; p=0.007). Significantly higher correlations were observed in successful ablations [95.9% vs 92%; p=0.006), and the PaSo™ correlation value was a good predictor of success (AUC: 0.874, 95% CI 0.74–1.0, p=0.003). The pace-matching threshold of 93.55% predicted ablation success with 86.4% sensitivity and 85.7% specificity. Conclusion: In patients with iVT, pace-matching mapping provides a suitable method for performing ablation procedure, and it is essential in patients where spontaneous suppression of PVC occurs during the procedure. The achievement of a pace-matching correlation>93.55% conveniently identifies the dysrhythmic focus, allowing increasing of ablation success.info:eu-repo/semantics/publishedVersio

Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia

Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals

Electroanatomic characterization and ablation of scar-related isthmus sites supporting perimitral flutter

Objectives The authors reviewed 3-dimensional electroanatomic maps of perimitral flutter to identify scar-related isthmuses and determine their effectiveness as ablation sites. Background Perimitral flutter is usually treated by linear ablation between the left lower pulmonary vein and mitral annulus. Conduction block can be difficult to achieve, and recurrences are common. Methods Patients undergoing atrial tachycardia ablation using CARTO3 (Biosense Webster Inc., Irvine, California) were screened from 4 centers. Patients with confirmed perimitral flutter were reviewed for the presence of scar-related isthmuses by using CARTO3 with the ConfiDense and Ripple Mapping modules. Results Confirmed perimitral flutter was identified in 28 patients (age 65.2 ± 8.1 years), of whom 26 patients had prior atrial fibrillation ablation. Scar-related isthmus ablation was performed in 12 of 28 patients. Perimitral flutter was terminated in all following correct identification of a scar-related isthmus using ripple mapping. The mean scar voltage threshold was 0.11 ± 0.05 mV. The mean width of scar-related isthmuses was 8.9 ± 3.5 mm with a conduction speed of 31.8 ± 5.5 cm/s compared to that of normal left atrium of 71.2 ± 21.5 cm/s (p < 0.0001). Empirical, anatomic ablation was performed in 16 of 28, with termination in 10 of 16 (63%; p = 0.027). Significantly less ablation was required for critical isthmus ablation compared to empirical linear lesions (11.4 ± 5.3 min vs. 26.2 ± 17.1 min; p = 0.0004). All 16 cases of anatomic ablation were reviewed with ripple mapping, and 63% had scar-related isthmus. Conclusions Perimitral flutter is usually easy to diagnose but can be difficult to ablate. Ripple mapping is highly effective at locating the critical isthmus maintaining the tachycardia and avoiding anatomic ablation lines. This approach has a higher termination rate with less radiofrequency ablation required

A large outbreak of Legionnaires’ Disease in an industrial town in Portugal

Background We describe the investigation and control of an outbreak of Legionnaires’ disease in Portugal in October, November and December 2014. Methods Confirmed cases were individuals with pneumonia, laboratory evidence of Legionella pneumophila serogroup 1 and exposure, by residence, occupational or leisure to the affected municipalities. 49 possible sources were reduced to four potential sources, all industries with wet cooling system, following risk assessment. We geo-referenced cases’ residences and the location of cooling towers defining four study areas 10 km buffer centered on each cooling tower system. We compared the number of cases with expected numbers, calculated from the outbreak's attack rates applied to 2011 census population. Using Stones’ Test, we tested observed to expected ratios for decline in risk, with distance up to 10 km four directions. Isolates of Legionella pneumophila were compared using molecular methods. Results We identified 403 cases, 377 of which were confirmed, 14 patients died. Patients became ill between 14 October and 2 December. A NE wind and thermal inversion were recorded during the estimated period of exposure. Disease risk was highest in people living south west from all of the industries identified and decreased with distance (p < 0.001). 71 clinical isolates demonstrated an identical SBT profile to an isolate from a cooling tower. Whole genome sequencing identified an unusual L. pneumophila subsp. fraseri serogroup 1 as the outbreak causative strain, and confirmed isolates’ relatedness. Conclusions Industrial wet cooling systems, bacteria with enhanced survival characteristics and a combination of climatic conditions contributed to the second largest outbreak of Legionnaires’ disease recorded internationally.info:eu-repo/semantics/publishedVersio

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013