Involvement of E. coli 6S RNA in Oxidative Stress Response.

6S RNA, a small non-coding RNA present in almost all bacteria, inhibits transcription via direct binding to RNA polymerase holoenzymes. The mechanism of 6S RNA action was investigated to a large extent in E. coli, however, lack of 6S RNA (ΔssrS) was demonstrated to be unfavorable but not essential for cell survival under various growth conditions. In the present study, we revealed, for the first time, a lethal phenotype of the ΔssrS strain in the presence of high concentrations of H2O2. This phenotype was rescued by complementation of the ssrS gene on a plasmid. We performed comparative qRT-PCR analyses on an enlarged set of mRNAs of genes associated with the oxidative stress response, allowing us to identify four genes known to be involved in this pathway (soxS, ahpC, sodA and tpx) that had decreased mRNA levels in the ΔssrS strain. Finally, we performed comparative proteomic analyses of the wild-type and ΔssrS strains, confirming that ΔssrS bacteria have reduced levels of the proteins AhpC and Tpx involved in H2O2 reduction. Our findings substantiate the crucial role of the riboregulator 6S RNA for bacterial coping with extreme stresses.

6S-2 RNA deletion in the undomesticated B. subtilis strain NCIB 3610 causes a biofilm derepression phenotype.

Bacterial 6S RNA regulates transcription via binding to the active site of RNA polymerase holoenzymes. 6S RNA has been identified in the majority of bacteria, in most cases encoded by a single gene. Firmicutes including Bacillus subtilis encode two 6S RNA paralogs, 6S-1 and 6S-2 RNA. Hypothesizing that the regulatory role of 6S RNAs may be particularly important under natural, constantly changing environmental conditions, we constructed 6S RNA deletion mutants of the undomesticated B. subtilis wild-type strain NCIB 3610. We observed a strong phenotype for the ∆6S-2 RNA strain that showed increased biofilm formation on solid media and the ability to form surface-attached biofilms in liquid culture. This phenotype remained undetected in derived laboratory strains (168, PY79) that are defective in biofilm formation. Quantitative RT-PCR data revealed transcriptional upregulation of biofilm marker genes such as tasA, epsA and bslA in the ∆6S-2 RNA strain, particularly during transition from exponential to stationary growth phase. Salt stress, which blocks sporulation at a very early stage, was found to override the derepressed biofilm phenotype of the ∆6S-2 RNA strain. Furthermore, the ∆6S-2 RNA strain showed retarded swarming activity and earlier spore formation. Finally, the ∆6S-1&2 RNA double deletion strain showed a prolonged lag phase of growth under oxidative, high salt and alkaline stress conditions, suggesting that the interplay of both 6S RNAs in B. subtilis optimizes and fine-tunes transcriptomic adaptations, thereby contributing to the fitness of B. subtilis under the unsteady and temporarily harsh conditions encountered in natural habitats.

MCC950 blocks enhanced interleukin-1ß production in patients with NLRP3 low penetrance variants.

OBJECTIVE: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement. METHODS: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950. Detailed clinical features were assessed and anti-IL-1 treatment response was determined. RESULTS: Peripheral blood mononuclear cells (PBMC) from patients with low penetrance NLRP3 variants displayed enhanced IL-1ß levels following inflammasome activation compared to HC. Furthermore, IL-1ß release was NLRP3-dependent as it was blocked by MCC950. The production of IL-6 and TNF-α was also increased in patients with low penetrance NLRP3 variants. Clinically, they presented with a heterogenous spectrum of neurological manifestations, while cranial nerve inflammation was the most common feature. Overall inflammasome activation did not correlate with disease severity. Eight of ten treated patients responded to anti IL-1 treatment, however a complete response was only documented in four patients. CONCLUSION: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1ß release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies.

Impact of surface condition and roughness on sediment formation: an experimental sewer system operated with real wastewater.

Regular sewer cleaning in North Rhine-Westphalia (Germany) generates annual costs of around 50 million Euros. This leads to the question of whether and to what extent sewer cleaning is necessary. To determine the effect of roughness, sewer surface condition and discharge, experiments with real wastewater were performed, using a sewer test track with acrylic glass tubes (DN 300) prepared with abrasive paper and nature stone tiles at the wastewater treatment plant (WWTP) Bochum-Ölbachtal (Ruhrverband, Germany). A logarithmic relationship between deposit height and time was found to lead to maximum deposit heights of 5 to 60 mm. Surface structure analysis by texture measuring indicated that deposits within the first 28 days after cleaning are highly influenced by the surface condition of the sewer and not necessarily by roughness. Furthermore, under dry weather conditions deposit heights are nearly stable after this time, indicating the limiting effect of sewer cleaning. Deposit formation amounted to 1.75-1.80 mm/d at a roughness of ks = 0.10 mm (fine but catchy microstructure) and 0-0.1 mm/d at ks 1.25 mm (wavy microstructure) at steady state and transient discharge within the first 28 days after sewer cleaning.

[Interventional catheter treatment of tricuspid valve regurgitation]. / Katheterinterventionelle Therapie der Trikuspidalklappeninsuffizienz.

BACKGROUND: The tricuspid valve can be considered the "forgotten" valve because in the past hardly any research has been conducted in this field and as a result only few therapeutic options existed. The prognosis of untreated tricuspid regurgitation (TR) is poor and mortality is high for patients with severe TR. Patients frequently return to medical practices and hospitals because of cardiac decompensation, with shortness of breath and leg edema. OBJECTIVE: Recent years have seen more development in catheter-based treatment options. Currently, several devices are in clinical evaluation, which are presented in this article. MATERIAL AND METHODS: A web-based literature search was carried out and information was gathered at international cardiology meetings (TCT 2016 in Washington, DGK 2017 in Mannheim, EuroPCR 2017 in Paris). RESULTS AND CONCLUSION: There are various options for interventional catheter procedures for TR, which are being investigated within the scope of clinical studies. Most aim at reducing the tricuspid annular diameter and optimizing leaflet coaptation. Because of these new therapy options patients can now be treated who were considered untreatable in the past because of the high perioperative mortality.

[Future interventional procedures for valve diseases]. / Zukünftige interventionelle Verfahren bei Herzklappenerkrankungen.

BACKGROUND: Percutaneous valve therapies represent one of the most innovative areas within interventional cardiology in the past 10 years. AIM: The aim of this work is to give an overview of current and upcoming therapeutic options. MATERIALS AND METHODS: In this manuscript, the results of a retro- and prospective literature research are summarized. RESULTS AND DISCUSSION: With the introduction of percutaneous therapies for valvular heart disease, patients who were previously considered too ill for surgery can now be treated. The percutaneous treatment of aortic or mitral valve disease has become standard therapy. Likewise, promising results have been obtained for percutaneous treatment options for pathologies of the tricuspid valve, which are still under intense investigation.

[Mitral valve interventions: Where do we stand?]. / Mitralklappeninterventionen : Wo stehen wir?

Mitral valve regurgitation (MR) with resulting heart failure is one of the most prevalent types of valvular heart disease. Currently, various approaches to catheter-based therapy of MR are already available for patients deemed to be at high-risk for surgery. Most experience has been gained with the MitraClip® system. Technological developments in the field of catheter-based treatment of MR is advancing at a rapid pace, with treatment modalities suited for patients with both primary and secondary MR. Annuloplasty is the surgical gold standard, particularly for patients with secondary MR. For catheter-based therapy of secondary MR a distinction is made between indirect and direct annuloplasty, with the latter most closely corresponding to surgical ring implantation. Catheter-based mitral valve replacement is technically feasible at present; however, experience is still limited and only few reports have been published. Technological development is markedly slower than in the field of transcatheter aortic valve replacement, predominantly owing to the far more complex structure of the mitral valve. Positive experience has already been gained with catheter-based implantation of prostheses designed for the aortic valve into degenerated mitral valve bioprostheses and failed surgical mitral annuloplasty rings (valve-in-valve and valve-in-ring implantation). Further approaches to catheter-based treatment of MR in high-risk surgical patients are expected in the future.

4D deep learning for real-time volumetric optical coherence elastography.

PURPOSE: Elasticity of soft tissue provides valuable information to physicians during treatment and diagnosis of diseases. A number of approaches have been proposed to estimate tissue stiffness from the shear wave velocity. Optical coherence elastography offers a particularly high spatial and temporal resolution. However, current approaches typically acquire data at different positions sequentially, making it slow and less practical for clinical application. METHODS: We propose a new approach for elastography estimations using a fast imaging device to acquire small image volumes at rates of 831 Hz. The resulting sequence of phase image volumes is fed into a 4D convolutional neural network which handles both spatial and temporal data processing. We evaluate the approach on a set of image data acquired for gelatin phantoms of known elasticity. RESULTS: Using the neural network, the gelatin concentration of unseen samples was predicted with a mean error of 0.65 ± 0.81 percentage points from 90 subsequent volumes of phase data only. We achieve a data acquisition and data processing time of under 12 ms and 22 ms, respectively. CONCLUSIONS: We demonstrate direct volumetric optical coherence elastography from phase image data. The approach does not rely on particular stimulation or sampling sequences and allows the estimation of elastic tissue properties of up to 40 Hz.

Northern Blot Detection of Tiny RNAs.

Successful detection of very small RNAs (tiny RNAs, ~8-15 nt in length) by northern blotting depends on tailored protocols with respect to transfer and immobilization on membranes as well as design of sensitive detection probes. For RNA crosslinking to positively charged membranes, we compared UV light with chemical RNA crosslinking by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), using either denaturing or native polyacrylamide gels. We show that northern blot detection of tiny RNAs with 5'-digoxigenin-labeled DNA/LNA mixmer probes is a highly sensitive and specific method and, in our hands, more sensitive than using a corresponding DNA/LNA mixmer probe with a 5'-32P-end-label. Furthermore, we provide a robust protocol for northern blot analysis of noncoding RNAs of intermediate size (~50-400 nt).

Ring currents in icosahedral c60.

A new formulation of the current within the London approximation allows the calculation of ring currents in topologically complex molecules. Application of this theory to C(60) demonstrates the existence of remarkable pi electron ring currents. Paramagnetic currents, in size comparable to the ones in benzene, flow within the pentagons, whereas weaker diamagnetic currents flow all around the C.(60) molecule. The overall vanishing ring-current magnetic susceptibility results from a cancellation of diamagnetic and paramagnetic contributions. The presence of ring currents significantly affects chemical shifts as measured in nuclear magnetic resonance experiments. In contrast to the magnetic susceptibility, which is a property of the molecule as a whole, chemical shifts are sensitive to the local magnetic field and the effect of ring currents does not vanish.

Covalent Group IV Atomic Clusters.

Atomic clusters containing from two to several hundred atoms offer the possibility of studying the transition from molecules to crystalline solids. The covalent group IV elements carbon, silicon, and germanium are now being examined with this long-range objective. These elements are particularly interesting because of the very different character of their crystalline solids and because they are intermediate between metals and insulators in the nature of their bonding. Small mass-selected atom cluster ions are formed by pulsed laser techniques and identified by time-of-flight methods. Laser photoexcitation is used to study the relative stability of these clusters and their modes of fragmentation. These modes for C(n)(+) clusters, which tend to fragment with a characteristic loss of a neutral C(3), are found to be different from the modes for Si(n)(+) and Ge(n)(+) clusters, which tend to fragment to "magic" clusters such as Si(4)(+), Si(6)(+) and Si(10)(+). These experimental results can be accounted for by recent theoretical calculations of the ground-state structure and stability of small silicon and carbon clusters. Several theoretical approaches give consistent results, showing that small silicon clusters are compact and different from small fragments of the bulk crystal. Calculations show that carbon clusters change from linear structures toward cyclic structures as the cluster size increases, but with significant odd-even differences.

Introducing the H2020 AQUACROSS project: Knowledge, Assessment, and Management for AQUAtic Biodiversity and Ecosystem Services aCROSS EU policies.

The AQUACROSS project was an unprecedented effort to unify policy concepts, knowledge, and management of freshwater, coastal, and marine ecosystems to support the cost-effective achievement of the targets set by the EU Biodiversity Strategy to 2020. AQUACROSS aimed to support EU efforts to enhance the resilience and stop the loss of biodiversity of aquatic ecosystems as well as to ensure the ongoing and future provision of aquatic ecosystem services. The project focused on advancing the knowledge base and application of Ecosystem-Based Management. Through elaboration of eight diverse case studies in freshwater and marine and estuarine aquatic ecosystem across Europe covering a range of environmental management problems including, eutrophication, sustainable fisheries as well as invasive alien species AQUACROSS demonstrated the application of a common framework to establish cost-effective measures and integrated Ecosystem-Based Management practices. AQUACROSS analysed the EU policy framework (i.e. goals, concepts, time frames) for aquatic ecosystems and built on knowledge stemming from different sources (i.e. WISE, BISE, Member State reporting within different policy processes, modelling) to develop innovative management tools, concepts, and business models (i.e. indicators, maps, ecosystem assessments, participatory approaches, mechanisms for promoting the delivery of ecosystem services) for aquatic ecosystems at various scales of space and time and relevant to different ecosystem types.

Intracellular and nuclear binding of [3H]dihydrotestosterone in cultured genital skin fibroblasts of patients with severe hypospadias.

Androgens stimulate the development and growth of the male external genitalia. Because hypospadias is the most common congenital defect of the male urethra and because in most cases the cause of this malformation is unknown, we examined the hypothesis that the etiology of the severe forms of this disorder, which is frequently associated with other genital anomalies, might be explained by receptor abnormalities. Intracellular and nuclear binding of androgens were determined in cultured genital skin fibroblasts from 10 males who underwent circumcision for phimosis (controls A), 2 patients with 5 alpha-reductase deficiency (controls B), and 11 patients with severe forms of hypospadias of unknown etiology. Genital skin fibroblast monolayers were incubated for 60 min at 37 degrees C with varying concentrations of [3H]-dihydrotestosterone ([3H]DHT), and specific binding in whole cells and nuclei was measured. Maximum binding (Bmax) in the whole cell assay averaged 0.88 +/- 0.15 fmol . microgram DNA-1 (mean +/- SD) in the control group (controls A, 0.89 +/- 0.16 fmol . microgram DNA-1; controls B, 0.85 fmol . microgram DNA-1) and 0.7 +/- 0.25 fmol . microgram DNA-1 in the patients with hypospadias. In the latter group, Bmax in six patients was below the minimum values determined in the controls. Maximum specific nuclear binding in the control groups averaged 43% (range, 30-55%) of the corresponding intracellular binding. In contrast, nuclear binding in strains from patients with hypospadias was lower (range, 0-12% of whole cell Bmax). In particular, no high affinity saturable nuclear [3H]DHT binding could be measured in 6 of the 11 patients. We interpret these data to suggest that defective intracellular and/or nuclear binding might be the cause of defective genital development in some patients with severe hypospadias.

Diffusion tensor imaging-based fractional anisotropy quantification in the corticospinal tract of patients with amyotrophic lateral sclerosis using a probabilistic mixture model.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), fiber degeneration within the corticospinal tract (CST) can be quantified by diffusion tensor imaging (DTI) as an indirect marker of upper motor neuron involvement. A new method of measuring quantitative DTI parameters using a probabilistic mixture model for fiber tissue and background in the corticospinal tract of patients with ALS is evaluated. MATERIALS AND METHODS: Axial echo-planar imaging (EPI) DTI datasets (6 gradient directions, 10 repetitions) were acquired for 10 patients and 20 healthy control subjects. The diffusion tensor was visualized in a multiplanar viewer using a unique color coding method. Pure fiber tissue inside a region is separated from background and mixture voxels using a probabilistic mixture model. This allows for a reduction of errors as a result of partial volume effects and measurement variability. RESULTS: Fractional anisotropy (FA) was measured within the CST at levels ranging from internal capsule to pons. Mean coefficients of variation of intrarater, scan-rescan, and inter-rater reproducibility were 2.4%, 3.0%, and 5.7%, respectively. Optimal measurement positions along the CST with respect to minimum variability and maximum difference between patients and healthy subjects were identified in the caudal half of the internal capsule. Moreover, a negative correlation between the age-corrected FA and the disease duration but not the ALS Severity scale score was found. CONCLUSION: The new software for fiber integrity quantification is suited to assess FA in the corticospinal tract with high reproducibility. Thus, this tool can be useful in future studies for monitoring disease status and potential treatment efficiency.

Detection and Compensation of Periodic Motion in Magnetic Particle Imaging.

The temporal resolution of the tomographic imaging method magnetic particle imaging (MPI) is remarkably high. The spatial resolution is degraded for measured voltage signal with low signal-to-noise ratio, because the regularization in the image reconstruction step needs to be increased for system-matrix approaches and for deconvolution steps in x -space approaches. To improve the signal-to-noise ratio, blockwise averaging of the signal over time can be advantageous. However, since block-wise averaging decreases the temporal resolution, it prevents resolving the motion. In this paper, a framework for averaging motion-corrupted MPI raw data is proposed. The motion is considered to be periodic as it is the case for respiration and/or the heartbeat. The same state of motion is thus reached repeatedly in a time series exceeding the repetition time of the motion and can be used for averaging. As the motion process and the acquisition process are, in general, not synchronized, averaging of the captured MPI raw data corresponding to the same state of motion requires to shift the starting point of the individual frames. For high-frequency motion, a higher frame rate is potentially required. To address this issue, a binning method for using only parts of complete frames from a motion cycle is proposed that further reduces the motion artifacts in the final images. The frequency of motion is derived directly from the MPI raw data signal without the need to capture an additional navigator signal. Using a motion phantom, it is shown that the proposed method is capable of averaging experimental data with reduced motion artifacts. The methods are further validated on in-vivo data from mouse experiments to compensate the heartbeat.

Entry routes of malignant lymphoma into the brain and eyes in a mouse model.

We have recently developed a novel mouse model for studying the infiltration of malignant lymphoma to the eye and brain. After i.p. inoculation of variant S49 mouse lymphoma cells into young mice (optimum: day 7 postnatal), specific homing of these cells (named Rev-2-T-6) to the brain and eyes took place. This model offers an opportunity to study the routes of infiltration to these sites and spread thereof, as well as the molecular mechanisms that govern this metastasis. By applying a time course histopathological analysis, we demonstrate that infiltration of the brain and eyes can be visualized as early as days 9 and 14 after inoculation, respectively. The lymphoma cells enter the brain preferentially through the choroid plexus and cranial nerves. Infiltration of the rostral part occurs before the caudal part of the brain. Once within the brain, the cells spread within it as well as migrate along the optic nerve sheath into the eyes, where they continue to migrate along the choroid, ciliary body, iris, and into the anterior chamber of the eye. The orbit is also infiltrated by the lymphoma cells. However, this occurs independent of the brain-optic nerve-intraocular route.

Determination of 5-AMP in the presence of excess 3'(2')-AMP with the aid of antibodies raised against n6-carboxymethyl-5'-AMP conjugates. Use for the quantitation of pyridine nucleotides and of protein-bound ADP-ribose.

5'-AMP antigens were synthesized by conjugation of N6-carboxymethyl-5'-AMP (Cm65'-AMP) to native or methylated serum albumin. Injection of the antigens resulted in antibodies with high affinity and specificity for 5'-AMP in all animals, thus allowing discrimination against 3'(2')-AMP even when present at 10(4)-10(5) times higher concentrations. This specificity was comparable to that of anti 5'-AMP antibodies raised against Cm65'-AMP serum albumin antigens formed in situ from Cm6ADP-ribose serum albumin conjugates by intracellular or pericellular phosphodiesterases. The hapten in the Cm65'-AMP-methylated serum albumin conjugate appeared to be bound almost exclusively via the N6-position. Due to the free exposure of the 5'-phosphate group in this antigen, the resulting antibodies discriminated 5'-AMP derivatives substituted at the phosphate group more efficiently than derivatives with modifications in the adenine ring. It also led to the concomitant formation of adenosine-specific antibodies due presumably to dephosphorylation of the antigen by phosphatases present in the recipient animals. The conjugates formed from Cm65'-AMP and native serum albumin, which appeared to be linked to a large extent via carboxyl groups of the protein and hydroxyl groups of the ribose, recognized modifications in the adenine ring much better than substitutions at the phosphate group. However, in spite of these relatively small differences in specificity, all three types of antibodies could be used successfully to quantitate by radioimmunoassay protein-bound ADP-ribose in adult rat liver and NAD+-NADH in Ehrlich ascites tumor cells as shown by the excellent agreement of the values obtained with the three antisera.

Balloon-protected carotid artery stenting: relationship of periprocedural neurological complications with the size of particulate debris.

BACKGROUND: Carotid artery stenting (CAS) has been advocated as an alternative to endarterectomy. To prevent cerebral atheroembolism during CAS, distal balloon occlusion of the target artery increasingly is employed during the procedure. A correlation of the size of captured particles with the incidence of periprocedural neurological complications (PNCs) has not been attempted. METHODS AND RESULTS: In a 4-center, phase-1 trial, 54 patients (46 men; age, 69+/-8 years) underwent 58 CAS procedures using the PercuSurge GuardWire system for distal protection. Aspirated debris was sent for histological/cytological analysis. Stent placement was successful in all cases. Mean balloon occlusion time was 10.4+/-4.0 minutes (range, 3.0 to 22.0 minutes). Three patients (5.2%) experienced PNCs: 1 prolonged reversible ischemic neurological deficit that resolved in /=10 000 micrometer(2)) were found in 48 aspirates (83%). The median number of particles, their maximum diameter, and their maximum area were all significantly higher in the aspirates obtained during procedures associated with PNCs than in aspirates obtained during procedures not associated with PNCs. However, pronounced overlap in the distributions (PNCs versus no PNCs) of the number and maximum diameter of particles precluded any predictive inferences. In contrast, a maximum particle area >800 000 micrometer(2) (>0.8 mm(2)) was associated with a 60% chance of having a PNC. CONCLUSIONS: Despite balloon protection, PNCs occurred in 5.2% of patients who underwent CAS procedures. The maximum area of aspirated particles seems to be an indicator of increased risk for PNCs.

Modification of the substrate for maintenance of idiopathic human atrial fibrillation: efficacy of radiofrequency ablation using nonfluoroscopic catheter guidance.

BACKGROUND: Catheter ablative techniques to modify the substrate to maintain atrial fibrillation (AF) require the creation of continuous radiofrequency current-induced ablation lines. This study was designed to assess the efficacy and safety of nonfluoroscopic mapping in this setting. METHODS AND RESULTS: A total of 45 consecutive patients with idiopathic AF were studied. The first 13 underwent ablation confined to the left atrium by creating a circular line isolating the pulmonary vein ostia and a second line connecting the former with the mitral annulus. Subsequently, 12 of these patients underwent a procedure confined to the right atrium (RA), where attempts were made to create an isthmus line between the inferior vena cava and the tricuspid annulus, an anterior line connecting the tricuspid annulus with the superior vena cava, and an intercaval line between the ostia of the inferior and superior venae cavae. In the last 32 patients, only the RA approach was performed. Technical difficulties prevented the creation of the intended left atrial line pattern: all patients experienced recurrences. A 100% recurrence rate was also observed after subsequent RA ablation, despite creation of a complete line pattern in 4 of 12 patients. Of the final 32 patients, AF recurred in 94%; a complete ablation line pattern had been achieved in 18 patients (56%), 16 of whom had recurrences. CONCLUSIONS: The electroanatomically-guided creation of extended radiofrequency current lesions is technically feasible only in the RA. However, procedural success in the RA does not suppress recurrences of AF in the majority of patients.

Catheter ablation from right atrium of anteroseptal accessory pathways using radiofrequency current.

Catheter ablation with radiofrequency current has recently been introduced as a therapeutic regimen for symptomatic patients with the Wolff-Parkinson-White syndrome or atrioventricular (AV) tachycardia mediated by a retrogradely conducting (concealed) accessory AV pathway. These pathways may be located, although infrequently, in the anteroseptal region of the heart in close proximity to the AV node-His bundle conduction system. Any attempt to interrupt an anteroseptal accessory pathway therefore is subject to the potential complication of inadvertent impairment of normal AV conduction. This study was conducted to establish whether abolition of anteroseptal accessory pathways by radiofrequency current aimed at the atrial as opposed to the ventricular insertion of the pathway can be achieved with preservation of AV node-His bundle conduction. Twelve patients (mean age 37 +/- 13 years; 10 with Wolff-Parkinson-White syndrome, 2 with a concealed accessory pathway) were studied. In the majority of patients, radiofrequency current (500 kHz; mean energy 577 +/- 207 J) was applied through a steerable catheter with a long tip electrode placed in the anterior septal space at the atrial aspect of the tricuspid anulus, with the intention to destroy the atrial insertion of the accessory pathway. All pathways were successfully ablated. The AV node or His bundle conduction was not impaired in any patient. Right bundle branch block was induced in two patients (17%). There were no complications related to the procedure. It is concluded that catheter ablation from the right atrium using radiofrequency current provides effective and safe interruption of anteroseptal accessory pathways with good preservation of the normal conduction system.