High-Field High-Repetition-Rate Sources for the Coherent THz Control of Matter.

Ultrashort flashes of THz light with low photon energies of a few meV, but strong electric or magnetic field transients have recently been employed to prepare various fascinating nonequilibrium states in matter. Here we present a new class of sources based on superradiant enhancement of radiation from relativistic electron bunches in a compact electron accelerator that we believe will revolutionize experiments in this field. Our prototype source generates high-field THz pulses at unprecedented quasi-continuous-wave repetition rates up to the MHz regime. We demonstrate parameters that exceed state-of-the-art laser-based sources by more than 2 orders of magnitude. The peak fields and the repetition rates are highly scalable and once fully operational this type of sources will routinely provide 1 MV/cm electric fields and 0.3 T magnetic fields at repetition rates of few 100 kHz. We benchmark the unique properties by performing a resonant coherent THz control experiment with few 10 fs resolution.

Effect of drugs used in different type of myocardial infarction (STEMI or (NTEMI) on mortality.

We examined 416 patients with acute myocardial infarction. 249 patients had STEMI and 167 NSTEMI. 227 were men and 189 women. 142 men had STEMI and 85 men had NSTEMI. 107 women were diagnosed with STEMI and 82 with NSTEMI. 22.5% of patient with STEMI and 20.2% of patients with NSTEMI died (p = 0.58). We compared the effect of anticoagulant treatment, clopidogrel, salicylate, nitrate, beta-blocker, angiotensin-converting enzyme inhibitor, statin and trimetazidine therapy on mortality in function of the type of myocardial infarction. There were no differences between mortality of patients with STEMI and NSTEMI with respect of use of heparine, salicylate, nitrate, beta-blocker, ACE inhibitor, statin and trimetazidine. While examining the effect of clopidogrel, we observed a significantly lower mortality rate in patients with NSTEMI compared to the STEMI group (p = 0.005). These differences are due to the known variability in clopidogrel absorption and metabolism, which could be influenced by the type of myocardial infarction.

Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells.

BACKGROUND AND PURPOSE: In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts. EXPERIMENTAL APPROACH: Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts. KEY RESULTS: At concentrations ≥10 µM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC(50) value for this inhibition was 25.2 ± 2.7 µM for the transient outward K(+) current (I(to)), 72.3 ± 9.3 µM for the rapid delayed rectifier K(+) current (I(Kr)) and 82.5 ± 9.4 µM for the L-type Ca(2+) current (I(Ca) ) with Hill coefficients close to unity. The inward rectifier K(+) current (I(K1)) was not affected by rosiglitazone up to concentrations of 100 µM. Suppression of I(to), I(Kr), and I(Ca) was confirmed also under action potential voltage clamp conditions. CONCLUSIONS AND IMPLICATIONS: Alterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients.

Arterial stiffness in chronic renal failure and after renal transplantation.

Arterial stiffness is an independent cardiovascular risk factor, along with aging, hypertension, and cardiovascular disease. The augmentation index (AIx) and pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes. Arteriography was used to determine systolic and diastolic blood pressure, pulse pressure (PP), AIx, and PWV in 82 male and 64 female renal transplant recipients (mean [SD] age, 45.3 [11.2] years). Cardiovascular risk was assessed using echocardiography and ultrasonography of the carotid arteries. The left ventricular wall thickness, ejection fraction, and stenosis of the carotid arteries were also measured. Fasting serum creatinine, cystatin C, homocysteine, C-reactive protein, immunoreactive parathyroid hormone, lipid, and calcium-phosphorus concentrations were determined. The serum cystatin concentration was 2.1 (0.2) mg/L, and the homocysteine concentration, 15.2 (2.6) micromol/L. After transplantation, body mass index, fat mass, and visceral fat area increased significantly (P < .01). The AIx was increased (AIx > or =10%) in 20% of men and 37% of women, PWV was increased (>10 m/s) in 43% of men and 34% of women, and PP was pathologically high (>12 m/s) in 10% of men and 12% of women. The PWV was significantly related to age (r = 0.52) and ventricular wall thickness (r = 0.46). Pulse pressure, BMI, and systolic and diastolic blood pressure correlated positively but modestly with PWV. There was a significant relationship between AIx80 and systolic (r = 0.42) and diastolic (r = 0.39) blood pressure and PP (r = 0.33). The ejection fraction correlated negatively with PWV and AIx. There was a strong association between carotid artery stenosis, PWV, and AIx80. All patients with PWV greater than 10 m/s demonstrated carotid artery stenosis. In conclusion, arteriography is an objective, noninvasive, and convenient method for early diagnosis and follow-up of atherosclerosis.

Proarrhythmic potential of antimicrobial agents.

Several antiarrhythmic and non-cardiovascular drug therapies including antimicrobial agents have been implicated as the causes for QT interval prolongation, torsades de pointes (TdP) ventricular tachycardia and sudden cardiac death. Most of the drugs that have been associated with the lengthening of the QT interval or development of TdP can also block the rapidly activating component of the delayed rectifier potassium current (IKr) in the ventricular cardiomyocytes. This article presents a review of the current literature on the QT interval prolonging effect of antimicrobials based on the results of the in vitro, in vivo studies and case reports. Our observations were derived from currently available Medline database. As we found, the most frequently QT interval prolonging antimicrobials are erythromycin, clarithromycin, fluoroquinolones, halofantrine, and pentamidine. Almost every antimicrobial-associated QT interval prolongation occurs in patients with multiple risk factors of the following: drug interactions, female gender, advanced age, structural heart disease, genetic predisposition, and electrolyte abnormalities. In conclusion, physicians should avoid prescribing antimicrobials having QT prolonging potential for patients with multiple risk factors. Recognition and appropriate treatment of TdP are also indispensable.

Effects of sex hormones on ECG parameters and expression of cardiac ion channels in dogs.

AIM: The aim of the study was to examine the effects of testosterone and oestrogen on the ECG parameters and expression of cardiac ion channels in male and female dogs, and to compare the dofetilide-induced lengthening of QTc interval in control, castrated and hormone-treated animals. METHODS: ECG records were taken from male and female anaesthetized dogs (n = 10 in each group) before castration, after castration, and following inverted hormone substitution. The animals were challenged with dofetilide at each stage of the experiment. Finally, the hearts were excised and expression of ion channels was studied using Western blot technique. RESULTS: Heart rate was decreased and PQ interval increased by deprivation of sex hormones in both genders (orchiectomy or ovarectomy), while inverted hormonal substitution restored control values. Orchiectomy significantly increased the duration of QT and QTc intervals, QTc-dispersion and the dofetilide-induced lengthening of QTc, while testosterone treatment of castrated females had opposite effects. Intraventricular conduction (QRS duration) was independent of the endocrine status of the animals. Ovarectomy or oestrogen treatment of castrated males failed to alter significantly these parameters except for QTc-dispersion. Expression of ion channel proteins responsible for mediation of I(K1) and I(to) currents (Kir2.1 and Kv4.3, respectively), was significantly higher in the testosterone-treated castrated females and normal males than in the oestrogen-treated castrated males and normal females. CONCLUSION: Repolarization of canine ventricular myocardium is significantly modified by testosterone, but not oestrogen, in both genders. This effect is likely due to augmentation of expression of K(+)-channel proteins, and thus may provide protection against arrhythmias via increasing the repolarization reserve.

Haplotype block and superblock structures of the alpha1-adrenergic receptor genes reveal echoes from the chromosomal past.

A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origins of haplotype block structure in the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome ( ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block 1 is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both ADRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data.

Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans.

The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.

QT dispersion in patients with end-stage renal failure and during hemodialysis.

Interlead variability of the QT interval in surface electrocardiogram (ECG), i.e., QT dispersion, reflects regional differences in ventricular recovery time, and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT and corrected QT (QTc) interval and dispersion in chronic hemodialyzed patients. Data of 34 nondiabetic patients (male/female = 21/13; mean age, 54 +/- 15 yr) on chronic hemodialysis were studied. Polysulfone capillaries and bicarbonate dialysate containing (in mEq/L) 135 Na+, 2.0 K+, 1.5 Ca2+, and 1.0 Mg2+ were used. Simultaneous 12-lead ECG were recorded before and after hemodialysis in a standard setting. The QT intervals for each lead were measured manually on enlarged (x3) ECG by one observer using calipers. Each QT interval was corrected for patient heart rate: QTc = QT/square root of RR (in milliseconds [ms]). The average cycle intervals were 853 +/- 152 ms predialysis and 830 +/- 173 ms postdialysis; the difference was not significant. The maximal QT interval changed significantly from 449 +/- 43 to 469 +/- 41 ms (P < 0.01). The corrected maximal QT interval increased significantly from 482 +/- 42 to 519 +/- 33 ms (P < 0.01). The QT dispersion changed from 56 +/- 15 to 85 +/- 12 ms (P < 0.001) and the corrected QT interval dispersion from 62 +/- 18 to 95 +/- 17 ms (P < 0.001). During hemodialysis, the serum potassium and phosphate levels decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (mM) and from 2.3 +/- 0.5 to 1.6 +/- 0.4 (mM), respectively, whereas calcium increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (mM). It is concluded that hemodialysis increases the QT and QTc interval and QT and QTc dispersion in patients with end-stage renal failure. Thus, it may be stated that the nonhomogeneity of regional ventricular repolarization increases during hemodialysis. Measurement of QT and QTc dispersion is a simple bedside method that can be used for analyzing ventricular repolarization during hemodialysis.

[Effect of hemodialysis on QT dispersion in chronic uremia]. / A hemodialízis hatása a QT diszperzióra krónikus uraemiás betegekben.

Interlead variability of the QT interval in surface 12-lead ECG (i.e. QT dispersion) reflects regional differences in ventricular recovery time and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT dispersion in chronic hemodialyzed patients. The data of 34 patients (Male/Female = 21/13, mean age 54 +/- 15 years) on chronic hemodialysis were studied. Simultaneous 12 lead ECGs were recorded pre- and post-hemodialysis in a standard setting. The QT intervals for each lead were measured manually by one observer. Each QT interval was corrected for patient's heart rate: QTc = QT/square route of RR (sec). The maximal QT interval changed from 449 +/- 43 to 469 +/- 41 ms (p < 0.01). The maximal QTc interval increased from 482 +/- 42 to 519 +/- 33 ms (p < 0.01). The QT dispersion changed rom 56 +/- 15 to 85 +/- 12 ms (p < 0.001), and the QTc interval from 62 +/- 18 to 95 +/- 17 ms (p < 0.001). During hemodialysis the serum potassium and phosphate decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (p < 0.001), and from 2.3 +/- 0.5 to 1.6 +/- 0.4, respectively, whereas calcium level increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (p < 0.001). It can be concluded that the hemodialysis increased the inhomogeneity of regional ventricular repolarization. Measurement of QT and QTc dispersion by a cheap and simple bedside method could predict the increased myocardial inhomogeneity in dialyzed patients.

[Prevention of atrial fibrillation by atrial-based pacemaker implantation]. / A pitvari fibrilláció megelözése pitvari vagy pitvar-kamrai szekvenciális pacemaker-beültetéssel.

A large number of studies have demonstrated the long term disadvantage of single lead ventricular pacing in sick sinus syndrome. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation. The goal of the report was to study the effectiveness of single atrial and dual chamber (atrio-ventricular sequential) pacemaker treatment in the prevention of atrial fibrillation for patients with sick sinus syndrome complicated with paroxysmal atrial fibrillation. In our university hospital 16 atrial based 5 and dual chamber 11 pacemaker were implanted for treatment of patients with sick sinus syndrome (with or without AV conduction disturbances) complicated with paroxysmal atrial fibrillation. The mean age were 61 (24-78), nine males and seven females. Before or during pacemaker implantation sinus node and AV node function analysis, and echocardiography were performed. There were no surgical complications, lead and/or generator failure. All patients had routine follow-up performed at 4 weeks, 3 months, 6 months. Mean follow up was 31 +/- 8 months (range 3 to 93 months). The atrial based and dual chamber pacing were effective in 90% of our cases. In one patient the treatment had to be combined with propafenone. According to our result, the atrial based pacing may be used to reduce the incidence of atrial fibrillation with careful programming of the base atrial pacing rate, and it is associated with lower frequencies of thromboembolic complications and pacemaker syndrome.

[Cilazapril replacing captopril in the therapy of medium-severe essential hypertension]. / Captopril kezelés felváltása cilazapril terápiával enyhe és középsúlyos essentialis hypertoniában.

Authors performed an open, crossover, multicenter study of oral cilazapril versus previous captopril treatment in mild to moderate hypertension. The treatment of the 100 outpatients on daily three or four times captopril was found ineffective, or in some cases side effects or non compliance necessitated a switch to a once daily dose of cilazapril. Reasons of ineffectivity were compliance problems in 76% of the patients during long term captopril therapy. Blood pressure decreased from 163.28 +/- 14.5/97.5 +/- 9.35 mmHg on captopril therapy to 136.67 +/- 12/83.49 +/- 7.77 mmHg at the end of a 12 week cilazapril treatment (p < 0.001). 80 patients received cilazapril monotherapy (with doses of 2.5 mg in 54 cases, 5 mg in 18 patients). 7.5 mg in 4 cases, 1 and 1.25 mg in 2 patients. In 20 patients an adjunctive diuretic was also added, while the cilazapril treatment was ineffective in 3 patients. In respect of the global evaluation and scoring of cilazapril versus captopril therapy, a clear and statistically significant improvement could be demonstrated in efficacy, tolerability and compliance after a 12 week cilazapril treatment. The 24 hour ambulatory blood pressure measurement performed in 13 patients also verified a decrease in blood pressure achieved by cilazapril therapy. Authors conclude that in case of ineffectivity of three or four times daily captopril treatment (caused most likely by non-compliance), a switch to a once daily dose drug like cilazapril is indicated.

[Tilt-table test in the diagnosis of syncope of unknown origin]. / Billenthetö ágyon fejjel fölfelé helyzetben (head up tilt table) végzett teszt alkalmazása az ismeretlen eredetü syncope diagnosztikájában.

71 patients with unexplained syncope was examined by 60 grade of head up tilt table test with or without administration of isoproterenol during 25 minutes interval. The mean age of patients was 71.44 +/- 16.40 (12-86) years. 38 (54%) were female and 33 (46%) were male. The underlying heart disease were 27 (38%) coronary artery disease, 12 (17%) arterial hypertension, 6 (8%) diabetes mellitus, 3 (4%) valvular heart disease and 14 (20%) patients had other diseases. Nine (13%) patients had no organic disease. During head up tilt table test positive reaction was found in 13 (18%) patients. Four (6%) patients were vaso-vagal syncope with classic signs, and 9 (13%) patients were vasodepressor type of syncope, without changes in the heart rate. Isoproterenol was given to 16 (23%) patients, and in 4 (6%) (2 vasodepressor and 2 mixed type of syncope) patients occurred the positive test during isoproterenol administration. Orthostatic reaction occurred during head up tilt table test in 14 (20%) patients. Normal was the result of tilt table test in 42 (59%) patients, and two (3%) patients had autonome neuropathy. The vasovagal syncope was treated by metoprolol, atenolol and disopyramid with success. The head up tilt table testing is a good, simple, useful test for evaluation of syncope patients, especially the diagnosis of vasovagal syndrome.

[Clinical cardiac electrophysiological studies in carotid sinus syndrome]. / Klinikai szív-elektrofiziológiai vizsgálatok carotis sinus syndromában szenvedö betegekben.

The aim of the present study was to evaluate the impact of electrophysiological study in the diagnosis and treatment of carotid sinus syndrome. The indications for the study include (1) attempting to exclude other cardiogenic causes of syncope; block, tachyarrhythmia, (2) diagnosing a vasodepressor response in the presence of cardioinhibitory type of carotid sinus syndrome, (3) determination of the optimal pacing mode in patients who need pacemaker implantation for treatment. 51 patients, 40 male (78%) and 11 female (22%) with an average age of 62 years suffering from carotid sinus hyperaesthesia--3000 ms ventricular asystole on carotid sinus massage--were investigated with electrophysiological study. The A-H interval in 8 patients (16%), the H-V interval in 5 pts (10%) were prolonged in the His bundle electrocardiogram. In 39 patients (76%) sinoatrial block, in 12 patients (24%) A-H block was found during carotid sinus massage. Early A-H Wenckebach block occurred in 8 patients (16%). Retrograde (V-A) conduction was present in 36 patients (70%) at a frequency of 65-85 bpm, and 22 pts (43%) at a frequency of 120-180 bpm. Sinus node disease was found in 10 patients (20%) according to the sinus node recovery time and sinoatrial conduction time. In 8 patients (16%) supraventricular and in 4 patients (8%) ventricular tachyarrhythmia was induced during study. The atrial stimulation could not prevent the occurrence of A-V block during carotid sinus massage in any of the 51 patients. In 2 patients (4%) the vasodepressor reaction with ventricular stimulation was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

[Management of drug-resistant supraventricular tachycardia using AV-junction radiofrequency ablation]. / Gyógyszer rezisztens supraventricularis tachycardia kezelése az AV-junctio radiofrekvenciás ablációjával.

The closed chest His bundle ablation is a worldwide accepted therapeutic method for the treatment of drug resistant supraventricular tachycardias. In the first years high-energy DC shock was applied for achieving the needed therapeutic effect. Reducing the complications caused by the DC shock, radiofrequency energy was introduced into the clinical practice. Authors describe the first successful human application of radiofrequency ablation of AV junction in Hungary.

Ethanol-induced signal transducing mechanism associated with a transient antiviral state in human amniotic cells.

Short-term effects of ethanol on human amnion cells were investigated by studying the cellular signaling processes and the replication of vesicular stomatitis virus. Treatment of human amniotic cells with ethanol transiently triggers the breakdown of inositol phospholipids, stimulates intracellular [Ca2+]i mobilization and activates the translocation of protein kinase C. Activation of this signal transduction mechanism is associated with the development of an antiviral state, as proven by studying 3H-uridine incorporation into the RNA of vesicular stomatitis virus. Induction of the antiviral state in human amniotic cells correlates with the solubility of the alcohols in the lipid membrane of the cells.

Establishment, characterization and drug sensitivity of a new anaplastic thyroid carcinoma cell line (BHT-101).

A thyroid carcinoma cell line, BHT-101, has been established in vitro from a metastatic lymph node deposit in a female patient with a non-hormone producing anaplastic, partly thyroglobulin- and thyroxine (T4)-positive papillary thyroid cancer. The cell population is heterogeneous, containing epithelial-like and fibroblast-like cells, and has a doubling time of 24 h. The cell line is polyploid with hypertetraploid predominance and the karyotype showed trisomies, tetrasomies, pentasomies as well as many marker chromosomes. The majority of the cells are negative or weakly positive for thyroglobulin and thyroxine and estrogen and progesterone receptors are present in the cells. BHT-101 cells produce tumours when injected into immunosuppressed CBA/Ca mice. The cells are sensitive to adriamycin, methotrexate and tamoxifen but not to methimazole (Favistan). The epithelial-like clone 1 and the fibroblast-like clone 3, isolated from the parental line, differed in drug sensitivity. This new cell line is suitable for studying the biology of thyroid carcinoma and for parallel in vivo and in vitro studies of drug activity against thyroid cancer.

Incidence of rhythm disorders in hyperthyrosis with special respect of old age form.

Sinus tachycardia and atrial fibrillation are frequent features in hyperthyrosis while sinus node dysfunction is regarded as a rare complication. Bradycardia may cause diagnostic problems mainly in atypical hyperthyrosis of the old age. The authors analysed distribution and age related association of the rhythm disorders in hyperthyrosis. In case of the appearance of Sick Sinus Syndrome (SSS), parameters representing the function of sinus node were studied by electrophysiological investigations. Above the age of 50 years incidences of atrial fibrillation and SSS were significantly increased. The abnormal sinus node function proved to be reversible in a portion of the cases. In old age, in case of occurrence of the symptoms of SSS, possibility of hyperthyrosis also should be considered, especially when indication of permanent pacemaker is established.