Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation

IntroductionThere are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long‐term recurrence of AF after catheter ablation, depending on AF type.MethodsAF patients who underwent point‐by‐point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni‐ and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence.ResultsIn total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence‐free time of 22.7 (9.3–43.1) months. Patients with persistent AF had significantly higher body surface area‐indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38–3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01–1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF.ConclusionThe current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.     

Morphological and photosynthetic acclimation of Potamogeton perfoliatus to different environments in Lake Balaton

Comparative significance and synchronicity of morphological and photosynthetic adjustments of Potamogeton perfoliatus to shore-specific environments were examined on plants growing at the maximum depth of colonisation of the northern and southern shores of Lake Balaton. The shore-specific environments did not affect photophysiological parameters: the photosynthesis of plants on both shores was high, coupled with low respiration and compensation irradiances. In contrast, morphological and habitual differences between the shores were significant: plants of the shady, northern shore had lighter, but larger leaves, and longer internodes concentrated in the apex of the plants. Thus, photophysiological variability of Potamogeton does not follow its morphological differentiation.     

Ethical regulation of biomedical research in Hungary

Hungary joined the Ovideo Treaty (a bioethical health agreement signed by EU countries in 1997), as declared by Law Nr. VI in 2002. In July 1 2002 two departmental orders were enacted: departmental order Nr. [23/2002 (V. 9.)] about the biomedical research in humans and departmental order Nr. [24/2002 (V. 9.)] about the human use and clinical trials of investigational products and the adaptation of Good Clinical Practice (GCP). Both were based on the Health Law. The departmental order on the Medical Research Council [(16/2001 (IV. 28.)] together with these two orders contains the national rules of biomedical research performed in Hungary and also the Hungarian adaptation of various, bioethical principles and directives published by EU or other internationally accepted organisations. According to these regulations from 2002 biomedical research in Hungary could be in agreement with the Oviedo Treaty. Ethical approval and supervision can be obtained from research ethical committees of three types: central, regional and local superimposed upon one another. There are three, central, ethical committees within the frames of the Medical Research Council with national responsibility: Scientific and Research Ethical Committee, Clinical Pharmacological Ethical Committee, Human Reproduction Committee. In some cases regional research ethical committees are entitled to hand out ethical approval and ethical supervision. In those research sites, where the regional research ethical committee is not existent a local committee should be organized for the local ethical control of the research investigations and experiments. This way the ethical requirements and clinical practice by the GCP can be performed in clinical research in Hungary with a special respect to the vulnerable persons possibly involved. The paper gives an overview on recent developments and major ethical principles of the Hungarian biomedical research.     

Potency and specificity of the pharmacological action of a new,antiasthmatic, topically administered soft steroid,etiprednol dicloacetate (BNP-166)

In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17alpha-dichloroacetoxy-11beta-hydroxyandrosta-1,4-diene-3-one-17beta-carboxylate), a new soft steroid, intended to use for the treatment of asthma, were investigated in an animal model of allergen sensitized and challenged Brown Norway rats using local treatment. The examinations involved the determination of the effect of the compound on the extent of allergen induced broncho-alveolar fluid and lung tissue eosinophilia, goblet cell hyperplasia and mucus production, perivascular edema formation, and airways hyperresponsiveness. The activity of etiprednol dicloacetate was compared with that of budesonide. Using in vitro methods, the soft character of etiprednol dicloacetate was investigated together with its capability to dissociate transrepressing and transactivating properties. We found that combining all the examined parameters etiprednol dicloacetate was at least equipotent with budesonide in the animal model, but in several investigated variables it surpassed the activity of budesonide. The effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of the serum, present in the assay, it was also strongly affected by the incubation time and decreased significantly when it was preincubated with human plasma. These features are characteristics of a soft drug that is quickly inactivated in the systemic circulation. In addition, it was revealed that while the transrepressing potential of etiprednol dicloacetate remained high, its transactivating activity was greatly reduced. These data indicate that the strong local effect of the compound will very likely be accompanied with a significantly reduced systemic activity predicting favorable selectivity in the pharmacological action of etiprednol dicloacetate.     

In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs

Idiosyncratic adverse drug reactions (IADRs) in humans can result in a broad range of clinically significant toxicities leading to attrition during drug development as well as postlicensing withdrawal or labeling. IADRs arise from both drug and patient related mechanisms and risk factors. Drug related risk factors, resulting from parent compound or metabolites, may involve multiple contributory mechanisms including organelle toxicity, effects related to compound disposition, and/or immune activation. In the current study, we evaluate an in vitro approach, which explored both cellular effects and covalent binding (CVB) to assess IADR risks for drug candidates using 36 drugs which caused different patterns and severities of IADRs in humans. The cellular effects were tested in an in vitro Panel of five assays which quantified (1) toxicity to THLE cells (SV40 T-antigen-immortalized human liver epithelial cells), which do not express P450s, (2) toxicity to a THLE cell line which selectively expresses P450 3A4, (3) cytotoxicity in HepG2 cells in glucose and galactose media, which is indicative of mitochondrial injury, (4) inhibition of the human bile salt export pump, BSEP, and (5) inhibition of the rat multidrug resistance associated protein 2, Mrp2. In addition, the CVB Burden was estimated by determining the CVB of radiolabeled compound to human hepatocytes and factoring in both the maximum prescribed daily dose and the fraction of metabolism leading to CVB. Combining the aggregated results from the in vitro Panel assays with the CVB Burden data discriminated, with high specificity (78%) and sensitivity (100%), between 27 drugs, which had severe or marked IADR concern, and 9 drugs, which had low IADR concern, we propose that this integrated approach has the potential to enable selection of drug candidates with reduced propensity to cause IADRs in humans.     

Determinants of bone mass in end-stage renal failure patients at the time of kidney transplantation

Abstract: Background:  Patients with chronic renal failure (CRF) are at high risk of renal osteodystrophy. Our study aimed to identify predictors of bone mass and cumulative fracture rate at the time of renal transplantation (RTx). This is important since the patients experience further substantial bone loss the first month post-transplant.
Material and methods:  Altogether 133 renal transplant patients were examined for bone mineral density (BMD) using dual-energy X-ray absorptiometry shortly after RTx.
Results:  The patients' Z -scores were significantly lower at the time of RTx compared to the reference population (p < 0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical activity (p = 0.027) were associated with high BMD. Cumulative fracture rate (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and osteopenia (p < 0.001) at the time of RTx.
Conclusion:  In a representative CRF population, BMD was reduced. Independent predictors of BMD were as for the general population, and uremia associated predictors were time on HD, previous transplantation and serum iPTH level. Fracture rate was high, and physical inactivity had the strongest association with fractures.