bluuebunny/crossref_metadata_2025 huggingface dataset:
Both allergen‐specific CD4 and CD8 Type 2 T cells decreased in asthmatic children with immunotherapy
Authors: Fu Chi‐Ling , Ye Yi‐Ling , Lee Yueh‐Lun , Chiang Bor‐Luen
Published: August 2003

Allergen‐specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen‐specific T cells in the non‐atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro, stimulated with crude mite extract to enrich the mite‐specific T‐cell population. After 14 days, the enriched mite‐specific T cells were stimulated with phorbol‐12‐myristate‐13‐acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN‐γ, IL‐4 in CD4+ and CD8+ T lymphocytes. The data here demonstrated that the levels of mite‐specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL‐4 expressing CD4+ and CD8+ T cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p < 0.05). In contrast, the frequency of IFN‐γ expressing CD4+ and CD8+ T cells did not significantly differ between untreated and SIT‐treated groups. All these data suggested that decreased Type 2 CD4+ and CD8+ T cells might be closely correlated with the regulatory mechanisms of immunotherapy.
Predictive features for persistence of atopic dermatitis in children
Authors: Pajno Giovanni B. , Peroni Diego G. , Barberio Giovanni , Pietrobelli Angelo , Boner Attilio L.
Published: August 2003

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy‐one AD children (age range 14–158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD– group), while in 33 AD persisted (AD+ group). At enrollment, AD+ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD+ children developed more respiratory symptoms in comparison to AD– children (p < 0.001). None of the AD– children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders.
Preferences of mature male brown trout and Atlantic salmon parr for orifice and weir fish pass entrances matched for peak velocities and turbulence
Authors: Guiny E. , Armstrong J. D. , Ervine D. A.
Published: August 2003

Abstract –  Mature male brown trout and Atlantic salmon parr were offered a choice of two fish pass entrances: a weir and an orifice. Peak velocities and turbulence were closely matched between the pass entrances. There was very strong selection for the orifice among both salmon (20 of 20) and trout (19 of 20). Combined with data in the literature, these results add to the impression that the main behavioural characteristics of salmonid fish migrating upstream through fish passes may largely be independent of size and life stage.
Efficiency of a nature‐like bypass channel for sea trout (Salmo trutta) ascending a small Danish stream studied by PIT telemetry
Authors: Aarestrup K. , Lucas M. C. , Hansen J. A.
Published: August 2003

Abstract – Upstream passage of adult sea trout (Salmo trutta) in a nature‐like bypass channel was investigated in the Tirsbæk brook, Denmark, in autumn and winter 1999/2000. Sea trout were caught by electrofishing up‐ and downstream of the weir at which the bypass was situated. Fish were tagged with passive integrated transponder (PIT) tags and released downstream of the weir. Automatic PIT‐tag logging stations were positioned downstream, in the lower part, and at the upstream exit of the bypass to investigate the passage success of the fish. The bypass was neither size‐ nor sex‐selective in the size ranges investigated. The majority (68%) of fish approached the bypass at night. Over 90% of tagged upstream‐searching fish located and entered the bypass channel, but only about half of them passed through. The inefficiency is suggested to be because of a combination of the length of the bypass channel and inadequate flow in the bypass channel.
Taking Possession: Biogenesis of theSalmonella‐Containing Vacuole
Authors: Knodler Leigh A. , Steele‐Mortimer Olivia
Published: August 2003

The Gram‐negative pathogenSalmonella entericacan survive and replicate within a variety of mammalian cells. Regardless of the cell type, internalized bacteria survive and replicate within theSalmonella‐containing vacuole, the biogenesis of which is dependent on bacterially encoded virulence factors. In particular, Type III secretion systems translocate bacterial effector proteins into the eukaryotic cell where they can specifically interact with a variety of targets.Salmonellahas two distinct Type III secretion systems that are believed to have completely different functions. The SPI2 system is induced intracellularly and is required for intracellular survival in macrophages; it plays no role in invasion but is categorized as being required forSalmonella‐containing vacuole biogenesis. In contrast, the SPI1 Type III secretion system is induced extracellularly and is essential for invasion of nonphagocytic cells. Its role in post‐invasion processes has not been well studied. Recent studies indicate thatSalmonella‐containing vacuole biogenesis may be more dependent on SPI1 than previously believed. Other non‐SPI2 virulence factors and the host cell itself may play critical roles in determining the intracellular environment of this facultative intracellular pathogen. In this review we discuss the recent advances in determining the mechanisms by whichSalmonellaregulateSalmonella‐containing vacuole biogenesis and the implications of these findings.
Intra‐oesophageal distribution and perception of acid reflux in patients with non‐erosive gastro‐oesophageal reflux disease
Authors: Cicala M. , Emerenziani S. , Caviglia R. , Guarino M. P. L. , Vavassori P. , Ribolsi M. , Carotti S. , Petitti T. , Pallone F.
Published: September 2003

Background: The majority of patients with gastro‐oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non‐erosive gastro‐oesophageal reflux disease are less responsive than patients with oesophagitis to acid‐suppressive therapy.

Aim: To assess the role of acid reflux in gastro‐oesophageal reflux disease symptoms.

Methods: The spatio‐temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non‐erosive gastro‐oesophageal reflux disease and 20 patients with erosive oesophagitis.

Results: Compared with healthy controls, all patients showed a higher intra‐oesophageal proximal spread of acid, which was prominent in patients with non‐erosive gastro‐oesophageal reflux disease (> 50% of events lasting for 1–2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6–12.5), being maximal in patients with non‐erosive gastro‐oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2–22.3).

Conclusions: Patients with non‐erosive gastro‐oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short‐lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non‐erosive gastro‐oesophageal reflux disease presenting with a normal pH‐metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid‐suppressive treatment.
Acceptance of disability and sense of coherence in individuals with Ehlers–Danlos syndrome
Authors: Berglund Britta , Mattiasson Anne‐Cathrine , Nordström Gun
Published: August 2003

• Ehlers–Danlos syndrome (EDS) is a relatively rare, inherited connective tissue disorder and skin hyperextensibility, joint hypermobility, chronic joint and limb pain, blood vessel and tissue fragility are frequent symptoms.

• The aims of this study were to describe the degree to which individuals with EDS accept and cope with perceived limitations related to the syndrome, and to determine the relationships between acceptance of disability (AD), sense of coherence (SOC), functional health status and background data.

• Four questionnaires were mailed: the AD scale Modified (ADM), the SOC Scale, the Sickness Impact Profile (SIP) and a background form. The respondents with EDS were recruited through the EDS National Association in Sweden and the response rate was 74% (69 females and eight males).

• The Ethical Committee at Huddinge University Hospital (ref. no. 152/95) approved the study.

• This study has shown that the level of AD and SOC in individuals with EDS is similar to other patient groups, e.g. individuals with ostomy and with diabetes. Further, the SOC was in concordance with that of the general population. Those working full‐time accepted their disability to a greater degree than those on sick leave or disability pension. A multiple regression analysis showed that a greater AD was associated with a higher level of SOC and a better functional health status. The SOC and SIP together accounted for 50% of the variance in the ADM.

• For health promotion in nursing practice it is important to have insight into the problem areas which may influence the overall life situation for an individual with EDS. A key issue for nurses is to identify individuals with low acceptance of their disease and/or low SOC in order to support these persons' adaptation process. Future research on EDS may be directed towards projects focusing on the development and implementation of models to strengthen the level of AD and SOC in this group.
Advanced nursing practitioners in primary care settings: an exploration of the developing roles
Authors: Carnwell Ros , Daly William M.
Published: August 2003

• Recent health care policies have resulted in patients having access to an integrated system of care that is quick and reliable. In concert with these changes, opportunities for professional development in nursing have increased, together with a reduction in the numbers of doctors. Advanced Nurse Practitioners (ANPs) have, therefore, developed to meet the complex demands of health care systems.

• This paper reports on a study that aimed to explore the current role of ANPs in primary care in the West Midlands region of the UK and how ANPs within three different nursing disciplines in primary care developed their roles over time.

• The study utilized a qualitative exploratory design incorporating a longitudinal element. Twenty‐one ANPs were interviewed during phase one, 15 of whom were interviewed again during phase two, approximately 15 months later. Their managers (where appropriate) were also interviewed during phase one.

• The findings reveal that the nature and focus of practice varies between disciplines. At the extreme practice end of the practice‐strategic continuum, Practice Nurse ANPs’ expertise lies in their advanced practical assessment and diagnosis of individual patients, with little opportunity for strategic development. Health Visitor and District Nurse ANPs operate at the strategic end of the practice‐strategic continuum, but operate differently at this level. Health Visitors, being community and public health focused are involved in multi‐agency work, practice development and policy formulation. District Nurses work with individual patients/carers and the nursing team, thus their involvement in strategic developments tends to focus at the patient care level, such as protocol and practice developments, although their work also involves work in all three other domains. Overall, the findings reveal a unique role for all three with a potential career pathway for ANPs to become Nurse Consultants in the future.
Male sterility in transgenic tobacco plants induced by tapetum‐specific deacetylation of the externally applied non‐toxic compound N‐acetyl‐l‐phosphinothricin
Authors: Kriete G. , Niehaus K. , Perlick A.M. , Pühler A. , Broer I.
Published: August 2003

A system for the inducible destruction of plant tissues based on the deacetylation of the non‐toxic compound N‐acetyl‐l‐phosphinothricin (N‐ac‐Pt) has been developed. The argE gene product of Escherichia coli, representing a N‐acetyl‐l‐ornithine deacetylase was identified to remove the acetyl‐group from N‐ac‐Pt giving the cytotoxic compound l‐phosphinothricin (Pt, glufosinate). Transgenic Nicotiana tabacum plants constitutively expressing the argE gene were constructed. No effect of the bacterial N‐acetyl‐l‐ornithine deacetylase on plant growth and reproduction could be traced. However, application of N‐ac‐Pt on leaves of the transgenic plants led to the formation of necrotic areas due to the release of Pt. Additionally, due to the uptake of the N‐ac‐Pt by roots, transgenic shoots grown on medium containing N‐ac‐Pt bleached within 6–7 days and finally died. Untransformed controls showed no reaction to high amounts of N‐ac‐Pt applied, either under sterile or under unsterile conditions.

In order to construct inducible male‐sterile plants, the argE coding region was fused to a DNA fragment carrying sequences homologous to the tobacco TA29 promoter, known to function exclusively in the tapetum. Owing to the tapetum‐specific expression of the chimeric gene the application of N‐ac‐Pt led to empty anthers resulting in male‐sterile plants. The sanity of the female reproductive part of the male‐sterile flowers could be demonstrated by cross‐pollination. Without N‐ac‐Pt treatment the plants turned out to be completely fertile making fertility restoration in the F1 generation superflous. The system presented is easy to handle and might be applicable to a wide range of crop plants.
Different mechanisms influencing permeation of PDGF‐AA and PDGF‐BB across the blood–brain barrier
Authors: Kastin Abba J. , Akerstrom Victoria , Hackler Laszlo , Pan Weihong
Published: September 2003

Platelet‐derived growth factor (PDGF) exerts neurotrophic and neuromodulatory effects on the CNS. To determine the permeability of the blood–brain barrier (BBB) to PDGF, we examined the blood‐to‐brain influx of radioactively labeled PDGF isoforms (PDGF‐AA and PDGF‐BB) by multiple‐time regression analysis after intravenous (i.v.) injection and by in‐situ perfusion, and also determined the physicochemical characteristics which affect their permeation across the BBB, including lipophilicity (measured by octanol:buffer partition coefficient), hydrogen bonding (measured by differences in octanol : buffer and isooctane : buffer partition coefficients), serum protein binding (measured by capillary electrophoresis), and stability of PDGF in blood 10 min after i.v. injection (measured by HPLC). After i.v. bolus injection, neither 125I‐PDGF‐AA nor 125I‐PDGF‐BB crossed the BBB, their influx rates being similar to that of the vascular marker 99mTc‐albumin. 125I‐PDGF‐AA degraded significantly faster in blood than 125I‐PDGF‐BB. PDGF‐BB, however, was completely bound to a large protein in serum whereas PDGF‐AA showed no binding. Thus, degradation might explain the poor blood‐to‐brain influx of PDGF‐AA, whereas protein binding could explain the poor influx of circulating PDGF‐BB. Despite their lack of permeation in the intact mouse, both 125I‐PDGF‐AA and 125I‐PDGF‐BB entered the brain by perfusion in blood‐free buffer, and the significantly faster rate of 125I‐PDGF‐AA than 125I‐PDGF‐BB may be explained by the lower hydrogen bonding potential of 125I‐PDGF‐AA. Thus, the lack of significant distribution of PDGF from blood to brain is not because of the intrinsic barrier function of the BBB but probably because of degradation and protein binding. Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent.
Altered distribution of mitochondria impairs calcium homeostasis in rat hippocampal neurons in culture
Authors: Wang Guang Jian , Jackson Joshua G. , Thayer Stanley A.
Published: September 2003

The specificity of Ca2+ signals is conferred in part by limiting changes in cytosolic Ca2+ to subcellular domains. Mitochondria play a major role in regulating Ca2+ in neurons and may participate in its spatial localization. We examined the effects of changes in the distribution of mitochondria on NMDA‐induced Ca2+ increases. Hippocampal cultures were treated with the microtubule‐destabilizing agent vinblastine, which caused the mitochondria to aggregate and migrate towards one side of the neuron. This treatment did not appear to decrease the energy status of mitochondria, as indicated by a normal membrane potential and pH gradient across the inner membrane. Moreover, electron microscopy showed that vinblastine treatment altered the distribution but not the ultrastructure of mitochondria. NMDA (200 µm, 1 min) evoked a greater increase in cytosolic Ca2+ in vinblastine‐treated cells than in untreated cells. This increase did not result from impaired Ca2+ efflux, enhanced Ca2+ influx, opening of the mitochondrial permeability transition pore or altered function of endoplasmic reticulum Ca2+ stores. Ca2+ uptake into mitochondria was reduced by 53% in vinblastine‐treated cells, as reported by mitochondrially targeted aequorin. Thus, the distribution of mitochondria maintained by microtubules is critical for buffering Ca2+ influx. A subset of mitochondria close to a Ca2+ source may preferentially regulate Ca2+ microdomains, set the threshold for Ca2+‐induced toxicity and participate in local ATP production.
Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein
Authors: Hoshino Masataka , Tagawa Kazuhiko , Okuda Tomohiro , Murata Miho , Oyanagi Kiyomitsu , Arai Nobutaka , Mizutani Toshio , Kanazawa Ichiro , Wanker Erich E. , Okazawa Hitoshi
Published: September 2003

Perturbation of histone acetyl‐transferase (HAT) activity is implicated in the pathology of polyglutamine diseases, and suppression of the counteracting histone deacetylase (HDAC) proteins has been proposed as a therapeutic candidate for these intractable disorders. Meanwhile, it is not known whether mutant polyglutamine disease protein affects the HDAC activity in declining neurons, though the answer is essential for application of anti‐HDAC drugs for polyglutamine diseases. Here, we show the effect of mutant huntingtin (htt) protein on the expression and activity of HDAC proteins in rat primary cortical neurons as well as in human Huntington's disease (HD) brains. Our findings indicate that expression and activity of HDAC proteins are not repressed by mutant htt protein. Furthermore, expression of normal and mutant htt protein slightly increased HDAC activity although the effects of normal and mutant htt were not remarkably different. In human HD cerebral cortex, HDAC5 immunoreactivity was increased in the nucleus of striatal and cortical neurons, suggesting accelerated nuclear import of this class II HDAC. Meanwhile, western blot and immunohistochemical analyses showed no remarkable change in the expression of class I HDAC proteins such as HDAC1 and HDCA8. Collectively, retained activity in affected neurons supports application of anti‐HDAC drugs to the therapy of HD.
Inclusion formation in Huntington's disease R6/2 mouse muscle cultures
Authors: Orth M. , Cooper J. M. , Bates G. P. , Schapira A. H. V.
Published: September 2003

Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the number of glutamine repeats in the N‐terminal region of the huntingtin protein. Nuclear and cytoplasmic aggregates of the N‐terminal portion of huntingtin have been found in the brains of HD patients and the brains and non‐neuronal tissues of the R6/2 HD transgenic mouse. We have cultured myoblasts and myotubes from transgenic R6/2 mice and littermate controls to investigate the formation of these inclusions in post mitotic cells. Huntingtin immunoreactivity was intense in differentiating, desmin positive myoblasts and myotubes from both control and R6/2 mice suggesting that it may play a role in myotube differentiation. Following differentiation huntingtin and ubiquitin positive aggregates were observed in R6/2 but not control cultures. After 3 weeks in differentiation medium cytoplasmic huntingtin and ubiquitin immunoreactive aggregates were observed in non‐myotube cells, while nuclear huntingtin aggregates were seen in a proportion of myotubes after 6 weeks. Growth in the absence of serum resulted in a marked increase in the number of R6/2 myotubes containing nuclear inclusions after 6 weeks demonstrating that environmental factors influenced huntingtin aggregate formation in these cells. Consequently, cultured myotubes from R6/2 mice may be a useful post mitotic cell culture model to study both the biochemical consequences of huntingtin aggregates and the factors that may influence aggregate formation.
Pronounced Effect of Procainamide on Clockwise Right Atrial Isthmus Conduction Compared with Counterclockwise Conduction: Possible Mechanism of the Greater Incidence of Common Atrial Flutter During Antiarrhythmic Therapy
Authors: MORITA NORISHIGE , KOBAYASHI YOSHINORI , IWASAKI YU‐KI , HAYASHI MEISO , ATARASHI HIROTSUGU , KATOH TAKAO , TAKANO TERUO
Published: August 2003

Bidirectional Conduction Property of Low RA Isthmus.
Introduction: It has been shown that the induction rates of common and reversed common atrial flutter are comparable during baseline control study, whereas the rate is significantly greater for common flutter than reversed common flutter during administration of antiarrhythmic agents. The mechanism of this discrepancy is not known.

Methods and Results: The study consisted of 15 patients (group 1) with clinically documented common atrial flutter either with (n = 10) or without (n = 5) Class I antiarrhythmic therapy, and 15 patients with paroxysmal supraventricular tachycardia (group 2). Bidirectional conduction velocity and minimal pacing cycle length of 1:1 conduction during incremental pacing from both the low lateral right atrium and coronary sinus were assessed. The response of these variables to procainamide was analyzed in correlation with the induction rate of each type of flutter during the pacing protocol. Conduction velocity in the clockwise (CW) direction was significantly slower for all pacing cycle lengths than conduction velocity in the counterclockwise (CCW) direction in group 1 but was similar in group 2. Minimal pacing cycle length of 1:1 conduction did not differ between CW and CCW conduction in either group. However, in group 1, minimal pacing cycle length of 1:1 conduction of CW conduction was prolonged to a greater degree after procainamide than that of CCW conduction. There also was a significant increase in the induction rate of common flutter. This preferential effect of procainamide on CW conduction was not observed in group 2.

Conclusion: CW conduction over the isthmus is preferentially influenced by procainamide compared with CCW conduction, which may explain the greater incidence and induction probability of common flutter during antiarrhythmic therapy.
Electrical Restitution and Cardiac Fibrillation
Authors: WEISS JAMES N. , CHEN PENG‐SHENG , QU ZHILIN , KARAGUEUZIAN HRAYR S. , LIN SHIN‐FONG , GARFINKEL ALAN
Published: August 2003

Restitution and Fibrillation. Combined experimental and theoretical work has shown that restitution properties of the cardiac action potential duration and conduction velocity contribute to breakup of reentrant wavefronts during cardiac fibrillation independent of preexisting electrophysiologic heterogeneities in the tissue. Developing therapies that favorably alter these cardiac electrical restitution properties are a promising new approach to preventing fibrillation.
Prognostic Significance of Nonsustained Ventricular Tachycardia After Revascularization
Authors: MITTAL SUNEET , LOMNITZ DAVID J. , MIRCHANDANI SUNIL , STEIN KENNETH M. , MARKOWITZ STEVEN M. , SLOTWINER DAVID J. , IWAI SEI , DAS MITHILESH K. , LERMAN BRUCE B.
Published: August 2003

Ventricular Tachycardia After Revascularization.
Introduction: Two randomized trials (Multicenter Automatic Defibrillator Implantation Trial [MADIT] and Multicenter Unsustained Tachycardia Trial [MUSTT]) suggest that implantable cardioverter defibrillator (ICD) placement is associated with improved survival in patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia (VT) who also have inducible sustained VT. However, neither study directly addresses the management of such patients who develop nonsustained VT early after revascularization.

Methods and Results: We evaluated 109 consecutive patients who underwent electrophysiologic testing to evaluate nonsustained VT, which occurred 5 ± 4 days following revascularization. Sustained monomorphic VT was inducible in 46 (42%) patients; these patients received an ICD. The remaining 63 (58%) noninducible patients received neither antiarrhythmic drug therapy nor an ICD. During 27 ± 12 months of follow‐up, 15 (33%) of 45 patients with an implanted ICD received at least one appropriate therapy from the device and 26 (24%) of the 109 study patients died. The 1‐ and 2‐year freedom from ventricular tachycardia/fibrillation or sudden death in noninducible patients (97% and 93%) was significantly greater than that of inducible patients (84% and 71%; P = 0.001). However, no difference was observed in total mortality.

Conclusion: Patients with nonsustained VT during the early postrevascularization period who have inducible VT have a high incidence of arrhythmic events. Although this study was not designed to assess the impact of ICD placement on the total mortality of inducible patients, the finding that one third of these patients received appropriate ICD therapy suggests that the device may have a protective effect in these patients.
Permanent Left Atrial Tachycardia: Radiofrequency Catheter Ablation Through the Coronary Sinus
Authors: PAVIN DOMINIQUE , BOULMIER DOMINIQUE , DAUBERT JEAN‐CLAUDE , MABO PHILIPPE
Published: August 2003

Ablation of Atrial Tachycardia Through the CS. The case of a 13‐year‐old child with an unusually localized “focal” permanent atrial tachycardia is reported. Electrophysiologic study showed that the earliest atrial activation occurred in the distal coronary sinus and preceded the atrial depolarization recorded along the endocardial side of the lateral part of the mitral annulus. Distal coronary sinus mapping revealed a fragmented, polyphasic atrial electrogram. Radiofrequency current delivery to the site permanently stopped the tachycardia.
Long‐Term Follow‐Up After Radiofrequency Catheter Ablation of Ventricular Tachycardia: A Successful Approach?
Authors: VAN DER BURG ALIDA E. BORGER , DE GROOT NATASJA M.S. , VAN ERVEN LIESELOT , BOOTSMA MARIANNE , VAN DER WALL ERNST E. , SCHALIJ MARTIN J.
Published: August 2003

RF Catheter Ablation of VT.
Introduction: Radiofrequency ablation (RFCA) of ventricular tachycardia (VT) is a potential curative treatment modality. We evaluated the results of RFCA in patients with VT.

Methods and Results: One hundred fifty‐one consecutive patients (122 men and 29 women; age 57 ± 16 years) with drug‐refractory VT were treated. Underlying heart disease was ischemic heart disease in 89 (59%), arrhythmogenic right ventricular cardiomyopathy (ARVC) in 32 (21%), and idiopathic VT in 30 (20%; left ventricle in 9 [30%]; right ventricle in 21 [70%]). Ablation was performed using standard ablation techniques. Three hundred six different VTs were treated (cycle length 334 ± 87 msec, 2.0 ± 1.4 VTs per patient). Procedural success (noninducibility of VT after RFCA) was achieved in 126 (83%) patients (70 ischemic heart disease [79%]; 28 ARVC [88%]; 27 idiopathic VT [93%]). Procedure‐related complications (< 48 hours) occurred in 11 (7%) patients: death 3 (2.0%), cerebrovascular accident 2 (1.3%), complete heart block 4 (2.6%), and pericardial effusion 3 (2.0%). Thirty‐three (22%) patients received an implantable cardioverter defibrillator (because of hemodynamic unstable VT, failure of the procedure, or aborted sudden death). During follow‐up (34 ± 11 months), VT recurrences occurred in 38 (26%) patients (recurrence rate: 19% in successfully ablated patients and 64% in nonsuccessfully ablated patients; P < 0.001). During follow‐up, 12 (8%) patients died (heart failure 8, unknown cause 1, noncardiac cause 3).

Conclusion: RFCA of VT can be performed with a high degree of success (83%). The long‐term outcome of successfully ablated patients is promising, with a 75% relative risk reduction compared with nonsuccessfully ablated patients. During follow‐up, only one patient died suddenly, supporting a selective ICD placement approach in patients with hemodynamically stable VT.
Receptor‐Operated Ca2+‐Permeable Nonselective Cation Channels in Vascular Smooth Muscle: A Physiologic Perspective
Authors: LARGE WILLIAM A.
Published: August 2003

Nonselective Cation Channels in Vascular Myocytes. This article summarizes the literature on receptor‐operated Ca2+‐permeable nonselective cation channels in vascular smooth muscle cells. One of these conductances, the P2X1 receptor, is a classic ligand‐gated channel, but others are likely to be mediated via G‐protein‐coupled receptors. The most studied receptor‐operated channel in vascular myocytes is the norepinephrine‐evoked nonselective cation channel in rabbit portal vein myocytes. The data regarding the transduction mechanisms and biophysical properties of whole‐cell and single‐channel currents in this preparation are described. The channels have a conductance of 20 to 25 pS and complex kinetic behavior with at least two open and two closed states. These channels are activated by norepinephrine and acetylcholine via G‐protein‐coupled receptors linked to phospholipase C and by diacylglycerol (DAG). The action of DAG occurs by a mechanism independent of protein kinase C, but other kinases may mediate the responses to norepinephrine and DAG. In addition, activation of tyrosine kinases leads to opening of this channel. Other vasoconstrictors, such as endothelin, vasopressin, serotonin, and angiotensin II, open Ca2+‐permeable nonselective cation channels, but there may be differences between these conductances and the norepinephrine‐evoked channels. A homologue of the transient receptor potential protein (TRPC6) is an essential component of the norepinephrine‐activated channel in rabbit portal vein, and it is likely that this family of proteins plays an important role in mediating Ca2+ influx in vascular smooth muscle.
Beta‐Adrenergic Stimulation of Pig Myocytes with Decreased Cytosolic Free Magnesium Prolongs the Action Potential and Enhances Triggered Activity
Authors: WEI SHAO‐KUI , HANLON STEPHEN U. , HAIGNEY MARK C.P.
Published: August 2003

Beta‐Adrenergic Stimulation and Repolarization.
Introduction: Heart failure results in chronic beta‐adrenergic stimulation, repolarization lability, and arrhythmias associated with early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs). Having described a significant reduction in intracellular free magnesium ([Mg2+]i) in experimental heart failure, we asked whether a reduction in [Mg2+]i would delay repolarization or facilitate EADs and/or DADs.

Methods and Results: Left ventricular myocytes were isolated from Yorkshire swine. Cytosolic free [Mg2+] was set at 0.12 mM (LoMg) or 1.2 mM (HiMg) through pipette dialysis. Action potentials (AP), Ca current (ICa), and sodium/calcium exchange current (INCX) were measured in the presence or absence of isoproterenol (2 μM) at 37°C. Under basal conditions (0.1‐Hz stimulation, 2 mM external [Ca2+]), reducing [Mg2+]i had no effect on AP duration and ICa but did significantly enhance INCX. In contrast, during superfusion with isoproterenol, reduced [Mg2+]i caused a significant increase in AP duration at both 50% and 90% repolarization (APD50 and APD90) compared with HiMg (P < 0.05). LoMg cells manifested a high incidence of triggered activities, including spontaneous AP, EADs, and DADs (83.3% in LoMg, n = 12 vs 38.3% in HiMg, n = 13; P < 0.05). ICa and INCX were significantly increased in LoMg cells compared with HiMg cells (P < 0.05).

Conclusion: Decreased cytosolic free magnesium prolongs AP duration and increases the incidence of triggered activity during beta‐adrenergic stimulation. These effects may be due to increased ICa and INCX in the presence of reduced intracellular [Mg2+]. A magnesium‐dependent increase in triggered activity coupled with delayed repolarization during beta‐adrenergic stimulation could contribute to the arrhythmogenic substrate in heart failure.
Complete Elimination of Incessant Polymorphic Ventricular Tachycardia in an Infant with MIDAS Syndrome: Use of Endocardial Mapping and Radiofrequency Catheter Ablation
Authors: PAUL THOMAS , LAOHAKUNAKORN PREECHA , LONG BLAKE , SAUL J. PHILIP
Published: August 2003

Catheter Ablation of Polymorphic VT. Experience with radiofrequency catheter ablation of ventricular tachycardia (VT) in pediatric patients is limited. A 5‐month‐old white female infant (body weight 5.5 kg) with MIDAS syndrome who suffered from incessant polymorphic VT (ventricular rates 250 to 300 beats/min) and was unresponsive to medical treatment resulting in significantly depressed left ventricular (LV) function underwent a total of four catheter ablation procedures during a 5‐month period. Each of the procedures reduced the number of morphologies and the rate of the tachycardia, but VT returned after each of the first three procedures, despite concomitant medical therapy. Activation mapping and pace mapping were used to identify the anatomic substrates, which were found at different locations at the LV septum and LV free wall. All forms of VT finally were ablated successfully. There were no significant complications. After the fourth procedure, the patient was in continuous sinus rhythm. Follow‐up examination 29 months after the last procedure while the child was not taking any medication showed normal sinus rhythm and normal LV function. This report demonstrates the usefulness and safety of radiofrequency catheter ablation in an infant with polymorphic VT who was unresponsive to medical therapy.
Prevention of Ventricular Fibrillation by Cilostazol, an Oral Phosphodiesterase Inhibitor, in a Patient with Brugada Syndrome
Authors: TSUCHIYA TAKESHI , ASHIKAGA KEIICHI , HONDA TOSHIHIRO , ARITA MAKOTO
Published: August 2003

Cilostazol and Brugada Syndrome. We report the case of 67‐year‐old man with Brugada syndrome, in whom daily episodes of ventricular fibrillation (VF) occurred every early morning for 4 days. The episodes of VF were completely prevented by an oral administration of cilostazol, a phosphodiesterase inhibitor. This effect was confirmed by the on‐and‐off challenge test, in which discontinuation of the drug resulted in recurrence of VF and resumption of the drug again prevented VF. This effect may be related to the suppression of Ito secondary to the increase in heart rate and/or to an increase in Ca2+ current (ICa) due to an elevation of intracellular cyclic AMP concentration via inhibition of phosphodiesterase activity. This drug might have an anti‐VF potential in patients with Brugada syndrome.
Usefulness of Paced Activation Sequence Mapping in Catheter Ablation of Accessory Pathways
Authors: PÉREZ‐CASTELLANO NICASIO , ALMENDRAL JESÚS , VILLACASTÍN JULIÁN , ARENAL ANGEL , GONZÁLEZ SERGIO , MORENO JAVIER , ORTIZ MERCEDES , TORRECILLA ESTEBAN , MACAYA CARLOS
Published: August 2003

Pace Mapping for Accessory Pathways.
Introduction: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time‐consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs.

Methods and Results: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia ≤5 msec (P < 0.001), a local AV ratio ≥1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria.

Conclusion: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs.
Prognostic Significance of Nonsustained Ventricular Tachycardia Identified Postoperatively After Coronary Artery Bypass Surgery in Patients with Left Ventricular Dysfunction
Authors: PIRES LUIS A. , HAFLEY GAIL E. , LEE KERRY L. , FISHER JOHN D. , JOSEPHSON MARK E. , PRYSTOWSKY ERIC N. , BUXTON ALFRED E.
Published: August 2003

Post‐CABG Nonsustained VT.
Introduction: Nonsustained ventricular tachycardia (NSVT) occurs frequently in the postoperative period (≤30 days) after coronary artery bypass graft (CABG) surgery, a setting where many factors may play a role in its genesis. The prognosis of NSVT in this setting in patients with left ventricular (LV) dysfunction is unknown. This study was designed to assess its significance.

Methods and Results: We compared the outcome of untreated patients enrolled in the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD), LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age 67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66 years, 85% males). Sustained monomorphic ventricular tachycardia was induced in 27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT, respectively. The 2‐ and 5‐year rates of arrhythmic events were 6% and 16%, respectively, in postoperative patients versus 15% and 29% in nonpostoperative patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2‐ and 5‐year overall mortality rates were 15% and 36%, respectively, for postoperative patients versus 24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P = 0.027). Patients whose NSVT was identified early (<10 days) versus late (10–30 days) after CABG had significantly lower 2‐ (13% vs 23%) and 5‐year (30% vs 52%) mortality rates (unadjusted P = 0.024, adjusted P = 0.018).

Conclusion: In this population of patients with CAD and LV dysfunction, the occurrence of postoperative NSVT, especially within 10 days after CABG, portends a far better outcome than when it occurs in nonpostoperative settings. This suggests that in a such setting, NSVT represents a less specific risk factor for future events and should be considered when assigning risk and treatment of similar patients.
Catheter Tip Cooling During Radiofrequency Ablation of Intra‐Atrial Reentry: Effects on Power, Temperature, and Impedance
Authors: BLAUFOX ANDREW D. , NUMAN MOHAMED T. , LAOHAKUNAKORN PREECHA , KNICK BARBARA , PAUL THOMAS , SAUL J. PHILIP
Published: August 2003

Catheter Tip Cooling.
Introduction: Cooling the catheter tip either passively with increased tip size or actively during radiofrequency catheter ablation (RFCA) has been shown in canine thigh preparations to create larger lesions than standard catheter tips, yielding a theoretical advantage for improving the outcome of RFCA for intra‐atrial reentrant tachycardia (IART).

Methods and Results: The pediatric RFCA database at the Medical University of South Carolina was reviewed for RFCA of IART in patients with structural heart disease. From a total of 31 patients who underwent procedures during the study period, 8 patients in whom ablation with conventional ablation techniques failed and who went on to passive cooling with an 8‐mm tip catheter or active cooling with an internally cooled‐tip catheter were studied. Power delivery was greater but temperature and impedance were lower during cooled ablation than during conventional ablation. Passive cooling was associated with higher power than active cooling. These changes in RF biophysical characteristics were associated with successful elimination of 11 of 13 IART circuits in 7 of 8 patients.

Conclusion: Cooling during RF ablation of atrial tachycardia clearly yielded greater power delivery in vivo and was associated with success.
Increased Intermittency and Decreased Nonstationarity of Heart Rates During the Daytime in Patients with Neurocardiogenic Syncope
Authors: YUM MYUNG‐KUL , KIM JUNE SOO
Published: August 2003

Intermittency and Nonstationarity in Syncope.
Introduction: During head‐up tilt (HUT) test, patients with neurocardiogenic syncope show a sudden severe decrease in heart rate at the beginning of their induced syncopal attacks (termed intermittency). They also exhibit slow and progressive increases in their mean heart rates long before the induced syncopal attacks (termed nonstationarity). The aim of this study was to test our hypothesis that during daily activity, although not as prominently as during HUT test, patients show different degrees of intermittency and nonstationarity compared to healthy persons.

Method and Results: Thirty patients with a positive HUT test and 30 healthy controls without a history of syncope were studied. The RR intervals of their 24‐hour ambulatory ECGs were analyzed. To quantify the intermittency (C1) and nonstationarity (H1) behavior, multifractal analysis was performed using Mexican hat and Haar wavelet function, respectively. In the syncope group, C1 and H1 were significantly higher at 6 A.M.–6 P.M. and lower at 6 A.M.–midnight, respectively. However, the values were not different at midnight–6 A.M. The significant night‐day circadian change shown in the control group was lost in C1 and diminished in H1.

Conclusion: Patients with neurocardiogenic syncope show increased intermittency and decreased nonstationarity of heart rates in the daytime during daily activity, and abnormal night‐day circadian changes of the intermittency and nonstationarity. These findings may be useful in the early identification of patients with neurocardiogenic syncope and in the investigation of abnormalities in heart rate regulating mechanisms.
Heart Transplantation as Last Resort Against Brugada Syndrome
Authors: AYERZA MÁXIMO RIVERO , DE ZUTTER MARC , GOETHALS MARC , WELLENS FRANCIS , GEELEN PETER , BRUGADA PEDRO
Published: August 2003

Heart Transplantation for Brugada Syndrome. We report the first case, to the best of our knowledge, of a patient with Brugada syndrome who required heart transplantation to control multiple “electrical storms.”
Unidirectional Conduction Block at Cavotricuspid Isthmus Created by Radiofrequency Catheter Ablation in Patients With Typical Atrial Flutter
Authors: MATSUSHITA TAKEHIKO , CHUN SUNG , LIEM L. BING , FRIDAY KAREN J. , SUNG RUEY J.
Published: August 2003

Unidirectional Block at Cavotricuspid Isthmus.
Introduction: Although unidirectional conduction block at the cavotricuspid isthmus can be created by radiofrequency ablation for atrial flutter, its underlying mechanism has not been elucidated.

Methods and Results: Twenty‐seven patients (22 men and 5 women; mean age 59 ± 11 years) who met the following criteria were studied: (1) bidirectional isthmus conduction demonstrable at baseline; (2) at least one linear lesion attempted on the cavotricuspid isthmus with radiofrequency catheter ablation; and (3) conduction times at anterolateral and posteromedial portions of the isthmus measured for both clockwise and counterclockwise directions before the ablation procedure. Unidirectional conduction block was observed before achieving bidirectional block in 9 patients (group I); the remaining 18 patients did not exhibit unidirectional conduction block (group II). All unidirectional conduction blocks were demonstrated in the counterclockwise direction. Anterolateral isthmus conduction time in group I was significantly longer than that in group II in both directions. However, there were no significant differences in posteromedial isthmus conduction time between groups I and II in either direction. Anterolateral isthmus conduction time was significantly longer than posteromedial conduction time in group I but not in group II.

Conclusion: There were significant differences in conduction properties at the cavotricuspid isthmus between patients who developed unidirectional conduction block and those who did not. Our results support the notion that anisotropy contributes to the genesis of unidirectional conduction block at the cavotricuspid isthmus during the radiofrequency ablation procedure.
Effect of Shock‐Induced Changes in Transmembrane Potential on Reentrant Waves and Outcome During Cardioversion of Isolated Rabbit Hearts
Authors: EVANS FREDERICK G. , IDEKER RAYMOND E. , GRAY RICHARD A.
Published: August 2003

Shock Effects on Reentry.
Introduction: Although numerous theories exist for the mechanisms of defibrillation, experimental data directly relating these mechanisms to the termination of reentry in whole hearts are lacking.

Methods and Results: Using video imaging technology, we recorded ~5,000 optical action potentials simultaneously from the anterior and posterior ventricular epicardium of rabbit hearts during cardioversion of stable reentrant arrhythmias. Monophasic shocks at three strengths for each polarity were delivered between electrodes inside the right ventricle (RV) and above the left atrium. Cardioversion efficacy at the three strengths was 21%, 42%, and 92% for RV+ shocks, which primarily depolarized the epicardium, and 10%, 15%, and 33% for RV– shocks, which primarily hyperpolarized the epicardium. The mechanism of cardioversion for RV+ shocks was elimination of excitable gaps and reentry via excitation ahead of wavefronts and action potential prolongation at wavetails, both of which increased with shock strength. Partial elimination of these gaps resulted in resetting of preshock reentry and/or induction of new reentry. RV– shocks cardioverted primarily via deexcitation, which terminated reentry by creating new postshock wavefronts via break excitation that rapidly activated excitable gaps. Outcome was dependent on the preshock state for both polarities at strengths near the 50% success level. Before successful shocks, more epicardium was recovered, resulting in more excitation and longer postshock depolarization (RV+ shocks) and faster postshock elimination of excitable gaps (RV– shocks).

Conclusion: These findings provide a direct mechanistic link between shock‐induced changes in Vm and the effect of polarity, strength, and timing on cardioversion efficacy.