The future of cardiovascular imaging and non-invasive diagnosis

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.This paper is published simultaneously in the European Heart Journal (2006;27:1750–1753) and in the European Journal of Echocardiography (2006;7:268–273).     

Congenital complete heart block associated with QT prolongation.

The coexistence of congenital complete heart block and QT prolongation represents a special type of arrhythmia. The electrophysiological and clinical characteristics of this syndrome were studied in eight patients suffering from congenital AV block and QT prolongation. Data from 22 patients suffering from congenital complete heart block only, served as a control. In the study group, the appearance of a torsade de pointes type of ventricular tachycardia could regularly be observed and the tachycardial attack could usually be provoked by ventricular extrastimuli. The corrected QT time was markedly prolonged; on ventricular stimulation, at higher pacing rates the QT interval shortened, but remained significantly higher than in the control group. Syncopal attacks--with the character of polymorphic tachycardia--appeared in each patient of the study group while occurring in only three patients from the control group. Patients were given pacemaker implants (using a higher pacing rate) and long-term administration of beta-receptor blockers. The outcome was favourable; no ventricular tachycardia or syncopal attack was observed in the follow-up period.     

Oestrogen-dependent tracing in the rat CNS after pseudorabies virus infection

This study examines the hypothesis that neuronal infectivity and the spreading of the pseudorabies virus (PRV) through the synapses in the central nervous system (CNS) are influenced by the oestrogen levels. The arcuate nucleus (ARC) and the subfornical organ (SFO) were chosen as models for analysis; the neurons in both structures possess oestrogen receptors and are mutually connected. A genetically engineered pseudorabies virus (Ba-DupLac) was used as a transneuronal tract tracer. This virus is taken up preferably by axon terminals, and transported very specifically through the synapses in a retrograde manner. Ba-DupLac was injected into the ARC of rats, followed by monitoring of the PRV-immunoreactivity (PRV-IR) in the SFO 72 h following inoculation. We found no PRV immunolabelling in the SFO of ovariectomized (OVX) rats, or in those OVX animals that received oestrogen shortly (4 h) before PRV infection (OVX + E 4 h). In contrast, in those OVX animals that received oestrogen 12 h before PRV infection (OVX + E 12 h), and also in intact control animals, PRV-IR was demonstrated in the SFO in all cases. Surprisingly, a reverse labelling was observed in the OVX rats; PRV-IR appeared in the pyriform cortex, whereas PRV-IR could not be detected in the control and OVX + E 12 h animals. As far as we are aware, this is the first study to demonstrate that transneuronal PRV labelling depends on the effects of oestrogen on certain CNS structures and connections.     

Positron emission tomography of C-11-labelled selegiline]

The combination of C-11-labelled Selegiline with PET gives the possibility of a non-invasive method for the determination of the distribution, activity and turnover of MAO-B enzyme and all the enzyme-related changes in the brain as well as for the early detection of Parkinson's disease.     

Catheter ablation for supraventricular tachycardia in children and congenital heart diseases

INTRODUCTION: Recently catheter ablation has been accepted as standard therapy for symptomatic supraventricular tachycardia in children. Nature of childhood and the variability of congenital heart diseases and congenital heart surgery distinguishes pediatric catheter ablation from the adult practice. OBJECTIVES: The aim of the present study was to summarize a single-center experience of the first 30 consecutive patients regarding the electrophysiological studies and catheter ablations, moreover to report on the national adoption of these interventions for pediatric patients in Hungary. METHODS: Between April 1996 and September 2004 catheter ablation was offered for 30 children as treatment of their supraventricular tachycardia because of failure of pharmacological therapy or parents preference. RESULTS: The mean age of the patients was 13.7 years (2.3-18.0 years) and the mean weight was 52.0 kg (12.0-81 kg). Electrophysiology study revealed 33 arrhythmogenic substrates in 30 patients, 30 of those 33 were congenital while 3 were acquired. Catheter ablation was attempted in 27 patients with acute success in 24 cases (89%). Recurrence was observed in 2 patients and the redo ablation was effective in both, although a second recurrence occurred later in one of them. There were no major complications, but two minor ones (pseudoaneurysm of arteria femoralis, transient ventricular ectopy) occurred. CONCLUSIONS: Catheter ablation is safe and effective in children with congenital heart disease. Our results are comparable with the international data.     

Facial nerve injury induces facilitation of responses in both trigeminal and facial nuclei of rat

A study was made of the effects of facial nerve transection on trigeminal stimulation- evoked field potentials in the principal trigeminal (Pr5) and facial nuclei (7) in rats. Although the transected branch of the facial nerve contains pure motoric efferents, it resulted in enhanced responses in both Pr5 and 7. These electrophysiological results suggest a functional circuitry involving the whiskers, trigeminal nerve, Pr5 and 7 and the facial nerve as efferent. The disconnection (opening) of this loop results in enhanced responsiveness of the neurons in both Pr5 and 7.     

Nitroglycerin-induced nNOS increase in rat trigeminal nucleus caudalis is inhibited by systemic administration of lysine acetylsalicylate but not of sumatriptan

Systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor, in migraineurs triggers after several hours an attack of which the precise mechanisms are unknown. We found previously in rats that nitroglycerin (10 mg/kg s.c.) is able to increase significantly after 4 h the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurones in the cervical part of trigeminal nucleus caudalis. In the present experiments, we demonstrate that the 5-HT1B/D agonist sumatriptan (0.6 mg/kg s.c.) does not alter this phenomenon when given before NTG. By contrast, pretreatment with lysine acetylsalicylate (50 mg/kg i.m.) attenuates the NTG-induced nNOS expression in the superficial laminae of trigeminal nucleus caudalis. These findings suggest that effect of NTG on nNOS at a high dosage may involve the cycloxygenase pathway and that activation of the peripheral 5-HT1B/D receptors is not able to modify this effect. These data could help to better understand the role of NO in the pathogenesis of headaches and the action of antimigraine drugs.     

Pharmacokinetic studies of (-)-deprenyl and some of its metabolites in mouse

(-)-Deprenyl is a selective irreversible inhibitor of MAO-B. The parent compound is responsible for the enzyme inhibitory effect, but its metabolites are also playing a role in the complex pharmacological activity of the substance. In the present studies male NMRI mice were treated orally, subcutaneously, intraperitoneally and intravenously with 5 mg/kg of (-)-deprenyl. The time related changes of the plasma concentrations of the parent compound and its main metabolites (methamphetamine, desmethyl-deprenyl and amphetamine) were determined by GC/ MSD technique. The main pharmacokinetic parameters (C(max), t(max), t1/2beta, AUC(0-6), AUC(0-infinity)) have been calculated. (-)-Deprenyl is well absorbed after oral and parental treatment. The peak concentrations (C(max)) were reached at 15 min after treatment and the absorption was followed by a fast elimination (t1/2beta < or = 2h). (-)-Deprenyl has an intensive "first pass" metabolism after oral treatment; only 25% of the parent compound reaches the systemic circulation. Increased bioavailability was detected after subcutaneous (87.1%) and intraperitoneal (78.7%) administration. The main metabolic pathway of (-)-deprenyl is the N-depropargylation, leading to the formation of methamphetamine. N-demethylation of (-)-deprenyl leads to formation of desmethyl-deprenyl. Amphetamine is produced from both former metabolites. After oral treatment the plasma concentrations of methamphetamine are higher during the first 6 h than that of (-)-deprenyl, while the opposite was found after parental treatment. The results indicate, that (-)-deprenyl, a potent MAO-B inhibitor, might induce a different spectrum of activity (e.g. antidepressant), when it is administered parenterally (transdermally). The new spectrum can be due to the special pharmacokinetic behaviour of the inhibitor.     

The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence Finnish and the medium-incidence Hungarian populations

Aims/hypothesis

The rs1990760 polymorphism (Ala946Thr) of interferon induced with helicase C domain 1 (IFIH1) has been proposed to associate with type 1 diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes was investigated in two distinct white populations, the Hungarians and Finns.

Methods

The rs1990760 polymorphism was genotyped in 757/509 Hungarian/Finnish childhood-onset cases, 499/250 Hungarian/Finnish control individuals and in 529/924 Hungarian/Finnish nuclear family trios. Disease association was tested using case–control and family-based approaches. A meta-analysis of data from 9,546 cases and 11,000 controls was also performed.

Results

In the Hungarian dataset, the A allele was significantly more frequent among cases than among controls (OR 1.29, 95% CI 1.10–1.52; p?=?0.002). Combined analysis of Hungarian and Finnish datasets revealed a strong disease association (OR 1.235, 95% CI 1.083–1.408; p?=?0.002). Furthermore, the A allele was significantly overtransmitted in both family trio datasets (p?=?0.017 in Hungarians; p?=?0.007 in Finns). The A allele was increased in Hungarian vs Finnish cases (64.9% vs 60.8% in Finns; p?=?0.003). The meta-analysis yielded a significant effect for IFIH1 rs1990760 A allele on type 1 diabetes risk (OR 1.176, 95% CI 1.130–1.225; p?=?5.3?×?10^?15) with significant heterogeneity between effect sizes across the studied populations (p?=?0.023).

Conclusions/interpretation

This study represents the first independent confirmation of the association between type 1 diabetes and the IFIH1 gene in Hungarian and Finnish populations. Summarising the data published so far, a clear association between the Ala946Thr polymorphism and type 1 diabetes was detected, with an apparent difference in the contribution to disease susceptibility in different populations of European ancestry.