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Infectious bursal disease (IBD) is characterized by immunosuppression due to the depletion of lymphocytes in the atrophied bursa of Fabricius (BF). We have sometimes encountered contradictory findings: chickens infected with the vaccine IBD virus (IBDV) strain have sometimes exhibited a highly atrophied BF, but not immunosuppression. In this study, chickens administered vaccine or wild-type strains of IBDV were later vaccinated with the B1 strain of the Newcastle disease virus (NDV). Bursal changes were examined histologically with a focus on the bursal follicle. The immunoreactivity to NDV was also evaluated with the hemagglutination inhibition test. In gross examination, we observed a few chickens with a severely atrophied BF in vaccine strain-administered groups (vaccine groups), and the level of severity was the same as that in the wild-type strain-administered group (wild-type group). However, these chickens retained humoral antibody responses to NDV and were revealed to possess a higher number of bursal follicles than those of the wild-type group. These results indicated that macroscopic evaluation dose not accurately reflect the immunoreactivity and degree of bursal damage in IBDV-administered chickens. We also found non-immunosuppressed chickens in the wild-type group. These non-immunosuppressed chickens retained a significantly higher number of normal follicles and total follicles according to our statistical analysis. Furthermore, a high correlation coefficient between the NDV-HI titer and the number of normal follicles was found in the wild-type group. These results implied that the retained number of normal follicles is important for the immunoreactivity of chickens infected with IBDV.

Chronic infection by pathogens such as hepatitis C virus induces monoclonal or oligoclonal proliferation of B cells, which produce IgM rheumatoid factor, leading to the development of mixed cryoglobulinemia (MC). Antigen-driven lymphoproliferation is essential to the onset of MC; however, the underlying mechanism is largely unknown. Herein, we show that type II MC is induced by Capillaria hepatica infection through a mechanism in which splenic B-1a cells reacting to C. hepatica-specific antigen selectively proliferate, producing IgM rheumatoid factor under co-stimulation of the specific worm antigen and IL-5. In vitro assays using B-1a cells from infected mice showed that stimulation by C. hepatica soluble fraction promoted the proliferation of B-1a cells and the secretion of IgM, which reacted with the 75-kDa antigen in the soluble fraction. The severity of MC was correlated with the increase in serum IL-5 levels in the infected mice. Furthermore, i.p. injection of the soluble worm fraction caused MC without an inflammatory response in IL-5 transgenic mice, indicating that IL-5 is critical for the development of MC. These results indicate that the selective proliferation of IgM rheumatoid factor-secreting B-1a cells is induced by co-stimulation by the specific pathogen antigen and IL-5 in the development of MC in C. hepatica-infected mice., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: The HRS/EHRA/APHRS Expert Consensus Statement for implantable cardioverter-defibrillator (ICD) in Brugada syndrome (BrS) has recently been published. However, the validity of the Class II indication for ICD in BrS patients is still unknown., Objective: The purpose of this study was to evaluate the validity of the Class II indication for ICD implantation in the Consensus Statement with a large Japanese cohort of BrS., Methods: Among 410 patients with BrS, a total of 213 consecutive BrS patients with the Class II indication for ICD implantation (mean age 53 ± 14 years, 199 men) were enrolled. Clinical outcomes were compared between patients with Class IIa (n = 66) and those with Class IIb (n = 147) indication according to the Consensus Statement., Results: The incidence of cardiac events (documented ventricular tachyarrhythmias or sudden cardiac death) during follow-up of 62 ± 34 months was significantly higher in patients with Class IIa (n = 8, 2.2% per year) than those with Class IIb indication (n = 4, 0.5% per year; P = .01)., Conclusion: We confirmed that Class IIa indication identified a group of patients with increased risk compared to Class IIb indication for ICD in the Consensus Statement of 2013. In patients with Class II indication, the combination of a history of syncope and spontaneous type 1 ECG may be an important factor in distinguishing intermediate- from low-risk patients with BrS in Japan., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

We describe a case of human Becker muscular dystrophy (BMD)-like myopathy that was characterized by the declined stainability of dystrophin at sarcolemma in a pig and the immunostaining for dystrophin on the formalin-fixed, paraffin-embedded (FFPE) tissue. The present case was found in a meat inspection center. The pig looked appeared healthy at the ante-mortem inspection. Muscular abnormalities were detected after carcass dressing as pale, discolored skeletal muscles with prominent fat infiltrations and considered so-called "fatty muscular dystrophy". Microscopic examination revealed following characteristics: diffused fat infiltration into the skeletal muscle and degeneration and regeneration of the remaining skeletal muscle fibers. Any lesions that were suspected of neurogenic atrophy, traumatic muscular degeneration, glycogen storage disease or other porcine muscular disorders were not observed. The immunostaining for dystrophin was conducted and confirmed to be applicable on FFPE porcine muscular tissues and revealed diminished stainability of dystrophin at the sarcolemma in the present case. Based on the histological observations and immunostaining results, the present case was diagnosed with BMD-like myopathy associated with dystrophin abnormality in a pig. Although the genetic properties were not clear, the present BMD-like myopathy implied the occurrence of dystrophinopathy in pigs. To the best of our knowledge, this is the first report of a natural case of myopathy associated with dystrophin abnormalities in a pig.

We classified the results of preoperative auditory brainstem response (ABR) in 121 patients with useful hearing and considered the utility of preoperative ABR as a preliminary assessment for intraoperative monitoring. Wave V was confirmed in 113 patients and was not confirmed in 8 patients. Intraoperative ABR could not detect wave V in these 8 patients. The 8 patients without wave V were classified into two groups (flat and wave I only), and the reason why wave V could not be detected may have differed between the groups. Because high-frequency hearing was impaired in flat patients, an alternative to click stimulation may be more effective. Monitoring cochlear nerve action potential (CNAP) may be useful because CNAP could be detected in 4 of 5 wave I only patients. Useful hearing was preserved after surgery in 1 patient in the flat group and 2 patients in wave I only group. Among patients with wave V, the mean interaural latency difference of wave V was 0.88 ms in Class A (n = 57) and 1.26 ms in Class B (n = 56). Because the latency of wave V is already prolonged before surgery, to estimate delay in wave V latency during surgery probably underestimates cochlear nerve damage. Recording intraoperative ABR is indispensable to avoid cochlear nerve damage and to provide information for surgical decisions. Confirming the condition of ABR before surgery helps to solve certain problems, such as choosing to monitor the interaural latency difference of wave V, CNAP, or alternative sound-evoked ABR.

We established a mass spectrometry-based quantitative method of assaying CD3ε, a component of the T-cell receptor complex. It revealed a CD3ε level of 1 mol per cell in a newly derived canine T-cell lymphoma cell line. Our results suggest that this method has sufficient sensitivity to quantify CD3ε levels in canine lymphoma cells reliably.

Objectives: The aim of this study was to investigate the significance of non-type 1 anterior early repolarization (NT1-AER) combined with inferolateral early repolarization syndrome (ERS)., Background: Inferolateral ERS might be a heterogeneous entity, although it excludes type 1 Brugada syndrome (BS)., Methods: Of 84 patients with spontaneous ventricular fibrillation, 31 ERS patients were divided into 2 groups. The ERS(A)-group consisted of inferolateral ER and NT1-AER--that is, notching or slurring with J-wave ≥ 1 mm at the end of QRS to early ST segment in any of V1 to V3 leads, in which the ST-T segment did not change to a coved pattern in the standard and high costal (second and third) electrocardiographic recordings even after drug provocation tests (n = 12). The other, ERS(B)-group, showed only inferolateral ER (n = 19). Clinical characteristics and outcomes were compared between the ERS groups, 40 patients with type-1 BS (BS-group), and 13 patients with idiopathic ventricular fibrillation lacking J-wave (IVF-group)., Results: Ventricular fibrillation occurred during sleep or near sleep in 10 of 12 patients in ERS(A)-group and in 22 of 40 patients in BS-group but in 2 of 19 patients in ERS(B)-group and in 1 of 13 patients in IVF-group (ERS[A] vs. ERS[B], p < 0.0001). Ventricular fibrillation recurrence was significantly higher in ERS(A)-group (58%), particularly in patients with J waves in the high lateral lead, and BS-group (55%), compared with ERS(B)-group (11%) and IVF-group (15%) (ERS[A] vs. ERS[B], p = 0.012)., Conclusions: Inferolateral ERS comprises heterogeneous ER subtypes with and without NT1-AER. Coexistence of NT1-AER was a key predictor of poor outcome in patients with ERS., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Patients with acoustic neuroma classified in Gardner and Robertson (GR) Class II should be considered to have useful hearing, and patients classified in Class III should be considered to have not-useful hearing. Therefore, it is important for acoustic neuroma surgery to distinguish between postoperative GR Class II and Class III patients by brainstem auditory evoked potentials (BAEPs). We evaluate which BAEP parameter is the best for predicting postoperative GR Class II or III in 36 preoperative GR Class II patients with unilateral acoustic neuroma. Delay in wave V latency, reduction ratio in wave V amplitude, and interaural difference of wave V (IT5) are evaluated by a receiver-operating characteristic (ROC) curve in this study. IT5 is the best distinguishing parameter between postoperative Class II and Class III. IT5 below 1.12 millisecond (msec) should be a good marker to preserve postoperative useful hearing. Thus, comparing the latency of wave V on both sides is important, and surgeons would be able to make more informed decisions during surgery by checking IT5 on BAEPs.

Background: The aim is to evaluate the efficacy of additional radiofrequency ablation (RFCA) for spontaneous dissociated pulmonary vein activity (DPV-spike) after PV isolation (PVI) in patients with paroxysmal atrial fibrillation (AF)., Methods: One hundred fifty-two consecutive patients with paroxysmal AF referred for RFCA were enrolled. When DPV-spike was documented after PVI, we randomly assigned these patients to receive additional RFCA for DPV-spike or only PVI. We divided them into 4 groups: 87 patients without DPV-spike after PVI (No-spike group), 31 without DPV-spike after additional RFCA (Successful group), 8 with remaining DPV-spike after additional RFCA (Unsuccessful group), and 26 with DPV-spike after only PVI (Spike group). AF recurrence was evaluated among the 4 groups., Results: After PVI, DPV-spike was documented in 87 PVs (14%) from 65 patients. During 16 ± 9 months of follow-up, the incidence of the freedom from AF was significantly higher in the No-spike group than that in the Spike group and Unsuccessful group (P < 0.05), and tended to be higher in the Successful group than that in the Spike group and Unsuccessful group (P = 0.08 and 0.11, respectively). In a multivariate analysis, the remaining PV-spike after ablation was an independent predictor of AF recurrence (HR 2.44; CI 1.10-5.43, P < 0.05). No major complications including PV stenosis were observed during the follow-up., Conclusions: DPV-spike after PVI may be associated with higher electrical activity within the PVs and may be one of the risk factors for AF recurrence. Additional RFCA for DPV-spike was effective to reduce the AF recurrence after PVI., (© 2013 Wiley Periodicals, Inc.)

Introduction: The presence of early repolarization (ER) recently has been considered as a prognostic marker for sudden cardiac death in patients with idiopathic ventricular fibrillation (IVF), but there are certain numbers of IVF patients lacking ER. We aimed to clarify the clinical and electrocardiographic characteristics of the patients with IVF in the presence and absence of ER., Methods and Results: We studied 64 consecutive IVF patients from the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS) registry, which subjected with at least one episode of documented VF in the absence of structural heart diseases and excluding Brugada syndrome. We assessed clinical and electrophysiological characteristics in the IVF patients with and without ER. ER was defined as J-point elevation of >0.1 mV in either inferior or lateral leads. Twelve-lead electrocardiogram (ECG) demonstrated 24 (38%) of 64 patients with ER (ER[+] group) and the remaining 40 (62%) patients without ER (ER[-] group ). ER[+] group had a male predominance (92% for males) and ER[-] group revealed nearly equal distribution in both sexes. While no patients in ER[+] group showed intraventricular conduction disturbance (CD) with abnormal axis deviation and/or bundle branch block in ECG, 9 in ER[-] group had signs of CD (ER[-]/CD[+] subgroup). ER[-]/CD[+] subgroup had prolonged P-R interval and QRS duration compared to other patient groups., Conclusion: We found 3 distinct ECG patterns in IVF patients. In addition to the presence and absence of ER, there is a subgroup without ER demonstrating intraventricular CD, which represents a distinct clinical entity of IVF., (© 2013 Wiley Periodicals, Inc.)

Prognosis and risk factors for patients age 35years or younger with Brugada syndrome (BrS) were prospectively explored in a sub-analysis of the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS) registry. During the period from February 2002 to January 2011, 69 cases (mean age 30±6years, male=66) of the young (at or less than 35years old) BrS were enrolled in J-IVFS and the clinical course was followed for more than 1year. They were divided into 3 groups: documented ventricular fibrillation (VF) or aborted sudden cardiac death (SCD) (VF group, 12 cases), syncope without documentation of VF (Syncope group, 17 cases) and asymptomatic group (Asympt. group, 40 cases). During a mean follow-up period of 43±27months, cardiac events (VF and/or SCD) developed in 8 cases, with 5 of 12 cases in the VF (41.7%), 2 of 17 cases in the Syncope (11.8%) and 1 of 40 cases in the Asympt. group (2.5%). The VF group had a worse prognosis for cardiac events than the Syncope and Asympt. group. Multivariate analysis revealed symptoms as a risk factor for predicting cardiac events., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Although several predictors of an electrical storm (ES) are indicated in patients with idiopathic dilated cardiomyopathy (IDCM), whether the severity of the myocardial tissue damage (SMTD) evaluated by myocardial perfusion SPECT (MPS) has an association with an ES remains unclear. The purpose of this study was to elucidate the clinical significance of SMTD for the prediction of ES in IDCM patients with an ICD., Methods: Thirty-seven (27 men, mean age 58 ± 15 years) IDCM patients receiving ICD implantations for secondary prevention with preoperative MPS were enrolled in this study. The medical history, physical and laboratory findings, electrocardiograms, echocardiograms and MPS findings were evaluated. The SMTD was assessed by the summed scores of 17 segments using a 4-point system (0, normal ~3, severe defect)., Results: During a mean follow-up of 43.9 ± 30.7 months, an ES developed in 12/37 (32.4 %) patients. The SMTD score predicted an ES with a 92 % sensitivity and 56 % specificity, at a cut-off score of 10. In addition, a multivariate analysis showed that the SMTD score remained an independent predictor of an ES (HR 1.09/score 1 increase, 95 % CI 1.01-1.19, p = 0.02). The SMTD score was significantly associated with three indices of late potentials on the signal-averaged electrocardiograms, and was significantly higher in patients with positive late potentials (p = 0.0006)., Conclusion: SMTD score assessed by MPS has a strong correlation to the late potentials and higher SMTD score may increase the risk of ES among patients with IDCM and an ICD.

Background: The prognostic value of a J wave and ST-segment morphology after J wave in inferolateral leads in Brugada syndrome (BS) is still unknown., Objective: To evaluate the prognostic value of a J wave and ST-segment morphology after J wave in a large Japanese cohort of BS., Methods: A total of 460 consecutive patients with BS (mean age 52±14 years, 432 men) were enrolled. The presence and location of leads showing a J wave, ST-segment morphology after J wave, and clinical outcomes were evaluated in patients with documented ventricular fibrillation (VF) (N = 84), those with syncope without documented VF (N = 109), and subjects without symptoms (N = 267)., Results: The prevalence of a J wave in the inferior and/or lateral leads was 12% (53 cases). The prevalence of a J wave among the 3 groups was not different. The incidence of cardiac events (sudden cardiac death or VF) during a mean follow-up period of 50±32 months was not different in patients with (11%) or without (8%) a J wave. Patients with a J wave in both inferior and lateral leads or with horizontal ST-segment morphology after J wave showed a higher incidence of cardiac events than those without (P = .04 and .02, respectively). Multivariate analysis revealed symptoms, QRS duration in lead V2>90 ms, and inferolateral J wave and/or horizontal ST-segment morphology after J wave were important for predicting cardiac events., Conclusion: The presence of a J wave in multiple leads and horizontal ST-segment morphology after J wave may indicate a highly arrhythmogenic substrate in patients with BS., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

This report describes a case of total anomalous pulmonary venous connection (TAPVC) in a 5-wk-old male white leghorn chicken that presented with growth retardation. This chicken was a specific-pathogen-free chicken bred in an isolator. At 5 wk of age, the chicken was euthanatized and autopsied. Macroscopically, the right ventricle and right atrium were significantly enlarged whereas the left atrium was small and blind-ending with no connection to the pulmonary veins. The pulmonary veins were connected directly to the right atrium. The above abnormality was accompanied by an ostium secundum-type atrial septal defect. No other malformations were observed. TAPVC is a very rare congenital cardiac abnormality that has not been reported in avian species to date.

Background: The slit diaphragm (SD) is a complex of podocyte-specific proteins and plays a significant role in glomerular filtration. To understand podocyte biology, it is important to determine the expression amount of the SD complex proteins. This study aimed to quantify the absolute amount of nephrin, which is believed to be a major component of SD, in podocytes and to apply that method to normal and puromycin aminonucleoside (PAN) nephrosis rats., Methods: The counting method for podocyte number in a glomerulus was developed by three-dimensional reconstruction imaging of Wilms tumor (WT-1) immunofluorescence on isolated glomeruli. Absolute amount of nephrin was quantified by mass spectrometry using the selected reaction monitoring (SRM) mode with a stable isotope-labeled peptide., Results: The number of podocytes per glomerulus was 95.5±17.6 in the control rats, 90.7±19.2 on Day 4 and 90.7±26.2 on Day 7 in PAN nephrosis rats. The amount of nephrin per glomerulus in control rats was 1.02±0.11 fmol and those in PAN nephrosis rats were reduced to 0.46±0.06 fmol and 0.35±0.04 fmol on Day 4 and Day 7. The nephrin amount per podocyte was significantly decreased association with the development of proteinuria in PAN nephrosis rats., Conclusions: This study established the absolute quantification of nephrin and determined the amount of nephrin in a podocyte of normal and PAN nephrosis rat kidneys. This highly sensitive and selective quantification method for protein is a useful tool for the analysis of SD protein in a podocyte.

Background: Use of programmed electrical stimulation (PES) for risk stratification of Brugada syndrome (BrS) is controversial., Objective: To elucidate the role of the number of extrastimuli during PES in patients with BrS., Methods: Consecutive 108 patients with type 1 electrocardiogram (104 men, mean age 46 ± 12 years; 26 with ventricular fibrillation [VF], 40 with syncope, and 42 asymptomatic) underwent PES with a maximum of 3 extrastimuli from the right ventricular apex and the right ventricular outflow tract. Ventricular arrhythmia (VA) was defined as VF or nonsustained polymorphic ventricular tachycardia >15 beats. Patients with VA induced by a single extrastimulus or double extrastimuli were assigned to group SD (Single/Double), by triple extrastimuli to group T (Triple), and the remaining patients to group N., Results: VA was induced in 81 patients (VF in 71 and polymorphic ventricular tachycardia in 10), in 4 by a single extrastimulus, in 41 by double extrastimuli, and in 36 by triple extrastimuli. During 79 ± 48 months of follow-up, 24 patients had VF events. Although the overall inducibility of VA was not associated with an increased risk of VF (log-rank P = .78), group SD had worse prognosis than did group T (P = .004). Kaplan-Meier analysis in patients without prior VF also showed that group SD had poorer outcome than did group T and group N (P = .001). Positive and negative predictive values of VA induction with up to 2 extrastimuli were, respectively, 36% and 87%, better than those with up to 3 (23% and 81%, respectively)., Conclusions: The number of extrastimuli that induced VA served as a prognostic indicator for patients with Brugada type 1 electrocardiogram. Single extrastimulus or double extrastimuli were adequate for PES of patients with BrS., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A high incidence of early repolarization (ER) pattern in the inferolateral leads has been reported in patients with idiopathic ventricular fibrillation (IVF). Brugada syndrome (BS) is characterized by J-point or ST-segment elevation in the right precordial leads and ventricular fibrillation, and some patients with BS also have ER in the inferolateral leads., Objective: To compare the clinical characteristics and effects of sodium-channel blockade on ER between IVF patients with ER (early repolarization syndrome [ERS]) and BS patients with or without ER., Methods: Fourteen patients with ERS and 21 patients with BS were included in this study. ER was defined as an elevation of at least 0.1 mV from baseline in the QRS-T junction in the inferorolateral leads. Provocative tests with sodium-channel blockers were conducted in all patients with ERS to distinguish ERS from BS., Results: In the ERS group, all patients were male and most patients experienced ventricular fibrillation during sleep or low activity (79%). ER was attenuated by sodium-channel blockers in most patients with ERS (13/14, 93%) and BS (5/5, 100%), whereas ST-segment elevation was augmented in the right precordial leads in the BS group. The rates of positive late potentials were significantly higher in the BS group (60%) than in the ERS group (7%) (P <.01)., Conclusions: Some similarities were observed between ERS and BS, including gender, arrhythmia triggers, and response of ER to sodium-channel blockers. Unlike the ST segment in the right precordial leads in BS, ER was attenuated in patients with both ERS and BS, suggesting a differential mechanism between ER in the inferolateral leads and ST elevation in the right precordial leads., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Type II mixed cryoglobulinemia is characterized by systemic vasculitis with deposition of cryoprecipitatable-immunoglobulins containing rheumatoid factor. Pathogenesis of type II mixed cryoglobulinemia has not yet been completely clarified because of the lack of an experimental animal. Here, we report an animal model of type II mixed cryoglobulinemia that is induced by experimental infection with Capillaria hepatica in ICR mice. Capillaria hepatica is a nematode that causes necrotic hepatitis in several mammals. In this study, mice experimentally infected with C. hepatica eggs developed cryoglobulinemia at 20 and 30 days post injection. Using immunological analysis, cryoglobulinemia in infected mice was classified as type II mixed cryoglobulinemia by detection of monoclonal IgM rheumatoid factor and IgA in the cryoprecipitate of serum. Using immunofluorescence, we observed an increase in the number of double-positive cells for µ heavy and κ light chains of immunoglobulin in the spleens of infected mice. Histopathologically, this model was characterized by glomerulopathy associated with intense deposition of IgM and IgA filling in capillary lumina. Ultrastructural analysis showed that glomerular deposits consisted of stacks of twisted microtubular structures. These serological and histological features resembled those of type II mixed cryoglobulinemia in human. This is the first experimental animal model of type II mixed cryoglobulinemia that will enable detailed studies on the pathogenesis of cryoglobulinemia.

Three male patients underwent lumbar peritoneal (LP) shunt for intracranial hypertension caused by intracranial Borden type 1 dural arteriovenous fistulas (D-AVFs). Endovascular treatment was performed initially, but it was ineffective in all cases. Before LP shunt, the Mariotte blind spot expanded in all cases and severe papilledema was observed in two cases. We managed the opening pressure of the shunt system in accordance with patient symptoms. Mariotte blind spot expansion and papilledema disappeared after LP shunt. Follow-up cerebral angiography revealed spontaneous closure of D-AVFs in one case and aggressive conversion in two cases. D-AVFs were completely closed by transvenous embolization. Because the angioarchitecture of the fistula frequently worsens without deterioration of the symptom after LP shunt, follow-up angiography and additional treatment are important.

An embryonal carcinoma was diagnosed in the abdominal cavity of a 55-day-old male calf. Macroscopically, a large volume of ascitic fluid was observed along with white to yellowish-white masses of various sizes densely located on the abdominal wall and the surface of abdominal organs. There was an absence of testes in the scrotum. Histologically, the tumor cells were polygonal, and the tumor was mostly composed of sheets of densely packed solid patterns with occasional papillary and tubular structures. Cell nuclei were variable in size, and cellular mitotic rate was high. Immunohistochemically, tumor cells were positive for alpha-fetoprotein, placental alkaline phosphatase, cytokeratin, and carcinoembryonic antigen. Ultrastructurally, the tumor cells had large nuclei, extensive rough endoplasmic reticulum, and small numbers of mitochondria. Microvillus-like structures and desmosomes were occasionally observed. From lectin histochemical examination, the tumor cells were positive for concanavalin A, wheat germ agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soybean agglutinin, Griffonia simplicifolia I, and Bauhinia purpurea, and negative for Ulex europaeus agglutinin I. Results of histopathological, immunohistochemical, and ultrastructural examinations of the tumor were similar to those obtained for human embryonal carcinoma., (© 2011 The Author(s))

Background: The efficacy of out-patient cardiac rehabilitation (OPCR) in patients with a low prognostic risk after acute myocardial infarction (AMI) is unclear in the recent primary intervention era., Methods and Results: A total of 637 AMI patients who participated in in-hospital cardiac rehabilitation were divided into 2 groups; low prognostic risk group (n=219; age <65 years, successful reperfusion, Killip class I, peak serum creatine kinase <6,000U/L, and left ventricular ejection fraction ≥40%) and non-low prognostic risk group (n=418). The prevalence of coronary risk factors (CRF) was compared between the 2 groups. Then, in the low-risk group, the efficacy of OPCR was compared between active OPCR participants (n=52; ≥20 sessions/3 months) and non-active participants (n=60; <6 sessions/3 months). Compared with the non-low prognostic risk group, the low prognostic risk group had a significantly higher prevalence of current smokers (72% vs. 49%, P<0.05) and patients with multiple CRF (3 or more; 49% vs. 39%, P<0.05). Among the low- risk group, active OPCR participants showed a significantly greater improvement in exercise capacity (peak VO(2), P<0.05) and maintained a better CRF profile (total cholesterol, triglyceride and blood pressure, all P<0.05) than inactive participants at 3 months., Conclusions: Low prognostic risk AMI patients have a higher prevalence of multiple CRF than non-low risk patients. Even in this low risk group, active participation in OPCR is associated with improved exercise capacity and better CRF profile.

This case report describes incessant monomorphic ventricular tachycardia (VT), not torsade de pointes, induced by intravenous amiodarone in a 48-year-old woman with dilated cardiomyopathy. VT was reproducibly triggered by short coupled premature ventricular complex (PVC) with different morphology from VT. After amiodarone infusion, the coupling interval of initiating PVC was prolonged, and moreover, the morphology of initiating PVC became the same as that of VT. Though amiodarone has become the first line drug to treat ventricular tachyarrhythmias in patients with cardiac dysfunction, it is important to be aware of its proarrhythmic effect, which may lead to an electrical storm of monomorphic VT.

Background: It remains unclear whether patients with chronic heart failure (CHF) and advanced left ventricular (LV) dysfunction on β-blocker therapy benefit from exercise training (ET)., Methods and Results: We studied 45 CHF patients with advanced LV dysfunction [ejection fraction (LVEF) < 25%] and impaired exercise tolerance [normalized peak oxygen uptake (PVO₂) < 70%] receiving a β-blocker: 33 patients participated in a cardiac rehabilitation program with ET (ET group) and 12 did not (inactive control group). Exercise capacity, LV dimension and plasma B-type natriuretic peptide (BNP) were assessed before and after a 3-month study period. At baseline, both groups had markedly reduced LVEF (ET group 18 ± 4% vs. Control group 18 ± 5%, NS) and impaired exercise capacity (normalized PVO₂ 51 ± 10% vs. 55 ± 9%, NS). Although one patient in the ET group withdrew from the program due to worsening CHF, no serious cardiac events occurred during the ET sessions. After 3 months, the ET group (n = 24) had significantly improved PVO₂ by 16 ± 15% (1,005 ± 295 to 1,167 ± 397ml/min, P < 0.001), while the PVO₂ of the control group was unchanged. LV end-diastolic dimension decreased in both groups to a similar extent, but plasma BNP was significantly decreased only in the ET group (432 to 214 pg/ml, P < 0.05)., Conclusions: The data indicate that in CHF patients with advanced LV dysfunction on β-blocker therapy, ET successfully improves exercise capacity and BNP without adversely affecting LV remodeling or causing serious cardiac complications.

A percutaneous renal biopsy was performed on a 3-year-old female Japanese domestic cat with pleural effusion, mild azotemia, hypoalbuminemia, hypercholesterolemia, and proteinuria. Glomerular lesions included mild diffuse hypercellularity and numerous capsular adhesions with segmental sclerosis/hyalinosis of glomerular tufts. Electron microscopy revealed many subendothelial dense deposits with characteristic outer protrusion of glomerular basement membrane. Diffuse and global granular deposits of IgG and C3 were detected along the capillary walls. Tubulo-interstitial changes were mild at the time of biopsy, but progression of the disease was predicted because of the many capsular adhesions of the glomerular tufts. The cat was fed a prescription diet without any other specific or symptomatic therapy after renal biopsy, and died 43 weeks after the biopsy. At necropsy, extensive tubulo-interstitial fibrosis and mononuclear cell infiltration had developed throughout the cortex and outer medulla, and most glomeruli had extensive global sclerosis or obsolescence with less prominent depositions of IgG and C3.

Objectives: The goal of this study was to evaluate the prevalence and the clinical significance of ST-segment elevation during recovery from exercise testing., Background: During recovery from exercise testing, ST-segment elevation is reported in some patients with Brugada syndrome (BrS)., Methods: Treadmill exercise testing was conducted for 93 patients (91 men), 46 ± 14 years of age, with BrS (22 documented ventricular fibrillation, 35 syncope alone, and 36 asymptomatic); and for 102 healthy control subjects (97 men), 46 ± 17 years of age. Patients were routinely followed up. The clinical end point was defined as the occurrence of sudden cardiac death, ventricular fibrillation, or sustained ventricular tachyarrhythmia., Results: Augmentation of ST-segment elevation ≥0.05 mV in V(1) to V(3) leads compared with baseline was observed at early recovery (1 to 4 min at recovery) in 34 BrS patients (37% [group 1]), but was not observed in the remaining 59 BrS patients (63% [group 2]) or in the 102 control subjects. During 76 ± 38 months of follow-up, ventricular fibrillation occurred more frequently in group 1 (15 of 34, 44%) than in group 2 (10 of 59, 17%; p = 0.004). Multivariate Cox regression analysis showed that in addition to previous episodes of ventricular fibrillation (p = 0.005), augmentation of ST-segment elevation at early recovery was a significant and independent predictor for cardiac events (p = 0.007), especially among patients with history of syncope alone (6 of 12 [50%] in group 1 vs. 3 of 23 [13%] in group 2) and among asymptomatic patients (3 of 15 [20%] in group 1 vs. 0 of 21 [0%] in group 2)., Conclusions: Augmentation of ST-segment elevation during recovery from exercise testing was specific in patients with BrS, and can be a predictor of poor prognosis, especially for patients with syncope alone and for asymptomatic patients., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although a Brugada-type electrocardiogram (ECG) is occasionally detected in mass health screening examinations in apparently healthy individuals, the automatic computerized diagnostic criteria for Brugada-type ECGs have not been established., Objective: This study was performed to establish the criteria for the computerized diagnosis of Brugada-type ECGs and to evaluate their diagnostic accuracy., Methods: We examined the ECG parameters in leads V1 to V3 in patients with Brugada syndrome and cases with right bundle branch block. Based on the above parameters, we classified the ECGs into 3 types of Brugada-type ECGs, and the conditions for defining each type were explored as the diagnostic criteria. The diagnostic effectiveness of the proposed criteria was assessed using 548 ECGs from 49 cases with Brugada-type ECGs and the recordings from 192,673 cases (36,674 adults and 155,999 school children) obtained from their annual health examinations., Results: The Brugada-type ST-segment elevation in V1 to V3 was classified into 3 types, types 1, 2/3, and a suggestive Brugada ECG (type S). The automatic diagnostic criteria for each type were established by the J-point amplitude, ST-segment elevation with its amplitude and configuration, as well as the T-wave morphology in leads V1 to V3., Conclusion: The proposed criteria demonstrated a reasonable accuracy (type 1: 91.9%, type 2/3: 86.2%, type S: 76.2%) for diagnosing Brugada-type ECG in comparison to the macroscopic diagnosis by experienced observers. Moreover, the automatic criteria had a comparable detection rate (0.6% in adults, 0.16% in children) of Brugada-type ECGs to the macroscopic inspection in the health screening examinations., (Copyright © 2010. Published by Elsevier Inc.)

Background: The intervals of the driving restrictions after an implantable cardioverter defibrillator (ICD) replacement vary across the different countries around the world. However, little is known regarding the appropriate duration for driving restrictions after an ICD replacement. The aim of this study was to investigate the clinical effect of ICD replacements and to elucidate when to resume driving an automobile after an ICD replacement., Methods and Results: The study reviewed 139 consecutive patients with an ICD replacement in order to evaluate the incidence of ICD therapies before and after ICD replacements, and to assess the time-dependence of the ICD therapies after the ICD replacement. There was no significant difference in the incidence of ICD therapies delivered during durations of 3 months and 6 months before and after the ICD replacement (P=0.28, and 1.0, respectively). ICD therapies after the replacements were observed in 8.6% of the patients who were legally eligible to drive according to the Japanese guidelines at 1 year, and that was associated with a relatively low annual risk of death or injury to others., Conclusions: Implantable cardioverter defibrillator replacements did not affect the future ICD therapies under similar algorithms. The appropriate interval for driving restrictions after an ICD replacement is recommended to be a week or so, with a system integrity check performed before resumption of driving.

Background: Electrical storm (ES) is a serious problem in patients with an implantable cardioverter defibrillator (ICD). However, insufficient reports have indicated the predictors of ES in ICD patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to clarify the predictors of ES for risk stratification in DCM patients with an ICD., Methods and Results: Of 446 ICD patients, 53 DCM patients were included in this study. During a mean follow-up of 55+/-36 months, ES (> or =3 times appropriate ICD therapy within 24 h) occurred in 18/53 (34%) patients. According to multivariate Cox proportional hazard regression analysis, a duration of the terminal low amplitude signals of <40 microV (LAS40) (HR 1.4/10 ms increase, 95% confidence interval (CI) 1.1-2.1; P=0.0049) or root mean square voltage of the last 40 ms of the QRS complex (RMS40) (HR 0.88/1 microV, 95%CI 0.77-0.96; P=0.001) on the signal averaged electrocardiogram, and a history of atrial fibrillation (AF) before ICD implantation (HR 2.3, 95%CI 1.2-5.0; P=0.013) were independently associated with an increased risk of ES., Conclusions: Our data indicated that a longer LAS40, lower RMS40 and history of AF before ICD implantation could strongly predict ES, and the combination of those parameters could effectively stratify the risk of ES in DCM patients.

Background: This study evaluated the efficacy of amiodarone for avoiding inappropriate therapies by implantable cardioverter defibrillators (ICDs)., Methods and Results: A total of 232 patients with structural heart disease (58+/-13 years; 78% males) who underwent an initial ICD implantation were retrospectively investigated to compare baseline characteristics and event rates of inappropriate ICD therapy delivery between patients with oral amiodarone therapy (amiodarone group, n=116) and those without (non-amiodarone group, n=116). During a mean follow-up of 29+/-21 months, inappropriate therapies occurred less frequently in the amiodarone group than in the non-amiodarone group (12% vs 27%, P=0.0068). As a cause of inappropriate ICD therapy, only atrial fibrillation (AF) significantly differed between the groups (3% vs 12%, P=0.01). The results of multivariate logistic regression analysis showed that amiodarone therapy (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.19-0.77, P=0.0073) and no history of spontaneous AF (OR 0.27, 95%CI 0.13-0.57, P=0.0007) were independent predictors of a lower risk of inappropriate ICD therapy., Conclusions: In the present group of ICD patients with structural heart disease, inappropriate therapy delivery occurred predominantly in those with spontaneous AF and/or without amiodarone.

A 76-year-old man with a history of atrial septal defect repair underwent radiofrequency (RF) ablation of typical atrial flutter. During electrophysiological study, incessant sharp potentials were recorded, originating from the ostium of the inferior vena cava (IVC), and dissociated from atrial activity. During sinus rhythm, these potentials propagated to the atria and caused premature complexes when falling beyond the atrial refractory period. Electro-anatomical mapping revealed the presence of the earliest potential in the postero-lateral ostium of the IVC, propagating to the septal region. After RF isolation of the IVC, the patient has remained arrhythmia-free over a 5-year follow-up.

Aims: The atrioventricular (AV) septal junction includes the coronary sinus (CS) and the compact part of the AV node and its posterior extensions. It has been recognized as the target site for ablation therapy of the AV nodal reentrant tachycardia and its variant forms. Despite the clinical significance of this region, the arrangement of the musculature in the AV septal junction, including the CS, has not fully been elucidated. We tried to explore the histological muscular diversity within the AV septal junction., Methods and Results: Sixteen autopsied human hearts (seven women), mean age 59.8 years, without structural anomalies, were studied. We removed the whole AV septum, including the CS opening after the macroscopic measurements, and prepared serial sections parallel to mitral and tricuspid annuli (short-axis style) to elucidate the positional relationships between the compact AV node and the CS musculature. Out of 16 hearts, the CS musculature extended deeply into the AV septal junction in eight hearts. In the other eight hearts, the CS musculature was located above the AV septal junction. In the former group, we found that the offset of both annuli was wide (mean 3.8 +/- 1.4 vs. 2.4 +/- 1.1 mm), the distance between CS opening and membranous septum was long (mean 14.8 +/- 1.6 vs. 12.3 +/- 2.2 mm), and the CS opening level was lower and closer to the His bundle level (mean 2.8 +/- 1.9 vs. 5.8 +/- 2.9 mm) (P < 0.05)., Conclusion: The deep extension of CS musculature into the AV septal junction seems to increase the tissue non-uniformity in this area.

Introduction: Patients with type 1 Brugada electrocardiogram (ECG) and an episode of syncope are diagnosed as symptomatic Brugada syndrome; however, all episodes of syncope may not be due to ventricular tachyarrhythmia., Methods and Results: Forty-six patients with type 1 Brugada ECG (all males, 51 +/- 13 years, 29 spontaneous, 17 Ic-drug induced), 20 healthy control subjects (all males, 35 +/- 11 years), and 15 patients with suspected neurally mediated syncope (NMS; 9 males, 54 +/- 22 years) underwent the head-up tilt (HUT) test. During the HUT test, 12-lead ECGs were recorded in all patients, and the heart rate variability was investigated in some patients. Sixteen (35%) of 46 patients with Brugada ECG, 2 (10%) of 20 control subjects, and 10 (67%) of 15 patients with suspected NMS showed positive responses to the HUT test. Although no significant differences were observed in HUT-positive rate among Brugada patients with documented VT (7/14; 50%), syncope (5/19; 26%) and asymptomatic patients (4/13; 31%), the HUT-positive rate was significantly higher in patients with documented VT (50%) and those with VT or no symptoms (11/27, 41%) compared to that in control subjects (10%) (P < 0.05). Augmentation of ST-segment amplitude (> or =0.05 mV) in leads V1-V3 was observed in 11 (69%) of 16 HUT-positive patients with Brugada ECG during vasovagal responses, and was associated with augmentation of parasympathetic tone following sympathetic withdrawal., Conclusion: Thirty-five percent of patients with Brugada ECG showed vasovagal responses during the HUT test, suggesting that some Brugada patients have impaired balance of autonomic nervous system, which may relate to their syncopal episodes.

Two sets of PCR primers are constructed to clone the cytochrome P450 structural gene, including putative promoter and terminator structures, and its adjacent genetic loci in Campylobacter lari isolates. The putative open reading frames (ORFs) of the P450 genes from 11 C. lari isolates (n=5 for urease-negative (UN) C. lari; n=6 urease-positive thermophilic campylobacters [UPTC]) examined consisted of 1365 or 1371 bases (455 or 457 amino acid residues), differing from those of the other thermophilic campylobacters (1359 [453] for C. jejuni and C. upsaliensis; 1368 [456] for C. coli). Each of the putative ORFs from the 11 isolates examined was also shown to carry start and stop codons and ribosome binding sites. Two putative promoter structures, consisting of sequences at the -35- and -10-like regions were also identified upstream of the ORFs. A single copy of the P450 gene in the genome was identified with UN C. lari JCM2530(T) and UPTC CF89-12, based on Southern blot hybridisation analysis. In addition, when reverse transcription polymerase chain reaction (RT-PCR) analyses were carried out, the transcription of the P450 structural gene in C. lari organisms in vivo was confirmed. The transcription initiation site for the gene was also determined. High nucleotide sequence similarities (95.2-98.8%) of the full-length P450 structural gene were shown with each of the 12 C. lari isolates. The UN C. lari and UPTC organisms showed similar findings with the neighbour-joining method, based on the sequence information of the P450 structural gene.

A 74-year-old female with a diagnosis of idiopathic dilated cardiomyopathy and ventricular tachycardia died suddenly 9 years after an implantation of an implantable cardioverter-defibrillator (ICD). The destructive removal of an ICD generator and the leads by an uninformed coroner resulted in the loss of the fragile electrograms during the terminal episodes of VT/VF and caused severe charring on the surface of the ICD generator. In order to observe the conditions in which the shock deliveries occurred during the noise detection, we programmed the ICD to deliver the maximum shock energy via a programmer while keeping continuous contact between the device surface and shock lead. The maximum shock energy of 31 Joules produced significant sparks from the surface of the ICD. To avoid the loss of data from an ICD and injury to the patient, widespread notification and education through appropriate scientific societies about the functions of ICDs are highly recommended.

Background: The prognosis of patients with saddleback or noncoved type (non-type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non-type 1 ECG and those with coved (type 1) Brugada-pattern ECG., Methods and Results: A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation > or = 1 mm in leads V(1)-V(3) were divided into 2 ECG groups-type 1 (245 probands) and non-type 1 (85 probands)-and were prospectively followed for 48.7+/-15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non-type 1: 10.6%, probands with syncope; type 1: 0.6%, non-type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non-type 1: 0%). Family history of sudden cardiac death at age <45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters., Conclusions: The long-term prognosis of probands in non-type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.

We developed a cochlear nerve action potential (CNAP) monitoring technique using a microdissector and compared the results of CNAP and auditory brainstem response (ABR) monitoring. Thirty-six patients underwent vestibular schwannoma resection via the retrosigmoid approach to preserve hearing. Both CNAP with the microdissector and surface ABR were recorded during the operation. We used the microdissector as an intracranial electrode for CNAP monitoring. The CNAP waveform was classified into four types: triphasic, biphasic, positive, and flat. At the completion of the tumor resection, the triphasic waveform was observed in 11 patients and the biphasic waveform was observed in 11 patients. Hearing function was preserved in all of them, although it was preserved in only two patients with other CNAP waveform types. The prognostic value of CNAP is significantly higher than that of ABR. We found that although CNAP with a microdissector does not provide real-time monitoring, with the classification of waveforms it can be used as predictable tool for postoperative hearing more accurately than ABR.

Background: Although high defibrillation threshold (DFT) is a major and unavoidable clinical problem after implantation of an implantable cardioverter defibrillator (ICD), little is known about the cause and management of a high DFT in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to assess the predictors of a high DFT in patients with HCM., Methods and Results: Twenty-three patients with non-dilated HCM who underwent ICD implantation were included. The DFT at the time of the device implantation was measured in all patients. The patients were divided into 2 groups, a high DFT group (DFT >or=15J, n=13) and a low DFT group (DFT <15J, n=10); and their baseline characteristics were compared. The QRS duration was longer in the high than in the low DFT group (128 +/-31 vs 103 +/-12 ms, respectively; P=0.02). QRS duration, left ventricular (LV) end-systolic diameter, and LV ejection fraction were significant predictors of DFT in univariate analysis. However, in multivariate analysis, the only factor significantly associated with DFT was QRS duration (P=0.002)., Conclusions: QRS duration is the most consistent predictor of a high DFT in HCM patients undergoing ICD implantation.

A 68-year-old woman with idiopathic dilated cardiomyopathy suffered from drug-resistant monomorphic ventricular tachycardia (VT). Electrophysiological study revealed a re-entrant VT circuit located just beneath the inferior mitral valve annulus. The VT was considered to be related to the mitral valve isthmus and was abolished by radiofrequency ablation. The patient died 2 years after the ablation due to worsening of heart failure and an autopsy was performed. Pathological examination revealed ablation scar tissue on the localized myocardial bundle running parallel to the mitral valve annulus. Therefore, this bundle appeared to comprise the slow conduction area of the re-entrant VT in this case.

Postmortem examination of a meerkat which had been captive for eight years in zoo, revealed multinodular white masses filling the thoracic cavity with systemic metastasis. Microscopically, the neoplastic cells were polygonal to spindle-shaped and had eosinophilic cytoplasm often with variable numbers of small lipid droplets. Immunohistochemically, the neoplastic cells were intensely positive for vimentin and occasionally weakly positive for S-100. Ultrastructurally, several lipid droplets without limiting membranes were observed in the cytoplasm. Based on the findings above, the tumor was diagnosed as a pleomorphic liposarcoma arising from the thoracic cavity. To date, neoplasms have seldom been reported in Herpestidae animals. To the authors' knowledge, this is the first reported case of liposarcoma in a meerkat.

Background: Intra-atrial reentrant tachyarrhythmia (IART) after surgical repair for congenital heart diseases (CHD) has not been noninvasively characterized., Methods and Results: The 28 patients after surgery for CHD and 14 patients without surgery were investigated by 87-lead body surface mapping (BSM), 12-lead electrocardiogram (ECG), 20-lead signal averaged ECG (SAECG) and endocardial electroanatomical mapping (CARTO) during clockwise (CW: n=9) or counterclockwise (CCW: n=5) incisional atrial tachycardia (Incision-AT), CCW (n=23) or CW (n=4) cavotricuspid isthmus-dependent atrial flutter (CTI-AFL), and double-loop reentry (n=4). On the BSM, the isopotential map pattern and its locus of the minimum potential could differentiate the reentrant circuits, and the activation map revealed the reentrant circuits, which were highly coincident with those obtained from CARTO. On the 12-lead ECG, negative-positive polarity in the inferior leads or a discordant pattern in the precordial leads was observed in all cases of CTI-AFL, but 3/14 Incision-AT, positive polarity in lead V(1) was observed in all cases of CCW, but none of CW CTI-AFL, positive polarity in lead I was observed in all cases of CW, but none of CCW Incision-AT., Conclusions: Flutter-wave isopotential map and its activation sequence from the BSM predict reentrant circuits of IART after surgery for CHD. Flutter-wave polarity on the 12-lead ECG could differentiate these reentrant patterns.

Background: It is well-known that the incidence of ventricular tachyarrhythmias is the highest in winter and during the daytime in patients with structural heart disease. However, little is known about the seasonal and circadian distributions of ventricular fibrillation (VF) in patients with Brugada syndrome., Objective: The aim of this study was to investigate seasonal and circadian distributions of VF in patients with Brugada syndrome., Methods: We analyzed the data of appropriate shock episodes for VF recorded by an implantable cardioverter-defibrillator (ICD) in patients with Brugada syndrome., Results: Among 62 consecutive Brugada syndrome patients with an ICD (48 +/- 14 years, 58 males), 19 patients had at least one episode of an appropriate ICD shock due to VF during a mean follow-up of 70 +/- 36 months, and 98 episodes were evaluated as isolated VF. There was a significant peak between March and June (P = .03). As for the circadian variation, significantly more VF occurred from midnight to 6:00 (P <.0001). Electrical storms of VF occurred in seven patients. The seasonal and circadian variations of electrical storms were similar to those of the isolated VF episodes., Conclusions: In patients with Brugada syndrome, there was a significant seasonal peak from spring to early summer and a significant circadian peak from midnight to early morning in terms of the occurrences of VF.

Introduction: The objective of this study was to determine the extent to which substance P (SP) increases proinflammatory cytokine production and osteoclast formation of human dental pulp fibroblasts (HDPF) in patients with severe orthodontically induced inflammatory root resorption (OIIRR)., Methods: HDPF were obtained from 5 patients with severe apical root resorption after orthodontic treatment. The levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were determined after 24 hours by using ELISA kits. Furthermore, culture supernatants were added to cultured human osteoclasts, and osteoclast formation was observed after tartrate-resistant acid phosphatase (TRAP) staining and the formation of resorption cavities., Results: Stimulation with SP increased the levels of IL-1beta, IL-6, and TNF-alpha, in a time- and concentration-dependent manner, although the increase was greater in the severe root resorption (SRR) group than in the nonresorption (NR) group (P < 0.001, 3-way repeated measures ANOVA). As for osteoclast formation, the numbers of TRAP-positive multinucleate cells and resorptive pits were significantly increased in the SRR group compared with the NR group (P < 0.001, 2-way repeated measures ANOVA)., Conclusions: These results suggest that HDPF stimulated with SP might be deeply involved in the progress of inflammation in pulp tissue and the incidence of SRR during orthodontic treatment.

This case report describes a patient with an intravascular infection of a pacemaker system with Stenotrophomonas maltophilia, which occurred 17 years after the implantation. The patient was treated with appropriate antibiotics and debridement of the infectious tissue in the pocket, and the entire pacemaker system was removed by open heart surgery. She was discharged from our center after a 6-week course of antibiotics and implantation of a new pacemaker., ((c) 2007 S. Karger AG, Basel)

Background: Although an electrophysiologic study (EPS) and Holter-monitoring are often helpful in evaluating the efficacy of antiarrhythmic drugs in patients with ventricular tachyarrhythmias (ventricular tachycardia/fibrillation (VT/VF)), the efficacy of EPS- or Holter-guided oral amiodarone therapy in Japanese patients is still unclear., Methods and Results: EPS was performed 1 month after starting amiodarone, and Holter-monitoring was recorded before and 1 month after amiodarone in 188 patients with sustained VT/VF because of structural heart diseases. In spite of the judgment of EPS (n=89) or Holter (n=75), all patients continued amiodarone. Patients were followed up to 3 years and the primary endpoint was VT/VF recurrence and secondary endpoint was death by all cause. Kaplan-Meier estimated the risk of VT/VF recurrence was significantly smaller with EPS-guided amiodarone (p<0.01) but not with Holter-guided amiodarone. Multivariate Cox hazard analysis revealed that EPS-guided amiodarone was an independent factor suppressing the recurrence of VT/VF (p<0.05, 95% confidence interval =0.15 to 0.96). In the subgroup analysis, EPS-guided amiodarone was effective in patients with relatively well-preserved left ventricular ejection fraction (LVEF > or =0.30) but not in patients with lower LVEF (LVEF <0.30)., Conclusion: EPS-guided amiodarone was useful for preventing recurrence of VT/VF in patients with a relatively well-preserved LVEF, but not always beneficial in patients with a lower LVEF.

Background: Neither the clinical characteristics nor risk stratification in Brugada syndrome have been clearly determined. We compared the clinical and ECG characteristics of symptomatic and asymptomatic patients with Brugada syndrome to identify new markers for high-risk patients., Methods: A total of 188 consecutive individuals with Brugada syndrome (mean age 53 +/- 14 years, 178 males) were enrolled in the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS). Clinical and ECG characteristics were evaluated in three groups of patients: Ventricular fibrillation (VF) group: patients with documented VF (N = 33); Syncope (Sy) group: patients with syncope without documented VF (N = 57); and asymptomatic (As) group: subjects without symptoms (N = 98). Their prognostic parameters were evaluated over a 3-year follow-up period., Results: (1) Clinical characteristics: incidence of past history of atrial fibrillation (AF) was significantly higher in the VF and Sy groups than in the AS group (P = 0.04). (2) On 12-lead ECG, r-J interval in lead V2 and QRS duration in lead V6 were longest in the VF group (P = 0.001, 0.002, respectively). (3) Clinical follow-up: during a mean follow-up period of 37 +/- 16 months, incidences of cardiac events (sudden death and/or VF) were higher in the symptomatic (VF/Sy) groups than in the As group (P < 0.0001). The r-J interval in lead V2 >/= 90 ms and QRS duration in lead V6 >/= 90 ms were found to be possible predictors of recurrence of cardiac events in symptomatic patients., Conclusions: Prolonged QRS duration in precordial leads was prominent in symptomatic patients. This ECG marker may be useful for distinguishing high- from low-risk patients with Brugada syndrome.

Neural stem/progenitor cells (NPCs) reside in the subventricular zone (SVZ) and dentate gyrus in the adult mammalian brain. It has been reported that endogenous NPCs are activated after brain insults such as ischemic stroke. We investigated whether proliferation and migration of endogenous NPCs are increased after a collagenase-induced small intracerebral hemorrhage (ICH) near the internal capsule in rats. Bromodeoxyuridin (BrdU) administration for 14 days after ICH (post-labeling) resulted in an increase in the number of BrdU-positive cells as shown in both ipsilateral and contralateral SVZs. BrdU treatment given for 2 days before ICH to label endogenous NPCs (pre-labeling), caused more BrdU-positive cells to be detected in the ipsilateral dorsal striatum (dSTR) compared to those in the contralateral dSTR 14 days after ICH. BrdU- and doublecortin (Dcx)-positive cells were found in the ipsilateral STR. An increase in the number of Dcx-positive migrating immature neurons was found in the dSTR and peri-hemorrhage area 14 days after ICH, and a cluster of Dcx-positive cells was found in the STR around the lesion 28 days after ICH. Matrix metalloproteinase-2 (MMP-2) was strongly expressed in wide area of the injured brain, particularly around the lesion 14 and 28 days after ICH. Dcx- and MMP-2-positive cells were detected in the ipsilateral STR near the lesion. These data suggest that collagenase-induced ICH enhances the proliferation of endogenous NPCs and the migration of newly born neuroblasts toward the hemorrhage area.

To investigate changes of electrocardiographic parameters with aging and their relation to the presence of SCN5A mutation in probands with Brugada syndrome (BS), we measured several electrocardiographic parameters prospectively during long-term follow-up (10 +/- 5 years) in 8 BS probands with SCN5A mutation (SCN5A-positive group, all men; age 46 +/- 10 years) and 36 BS probands without SCN5A mutation (SCN5A-negative group, all men; age 46 +/- 13 years). Throughout the follow-up period, depolarization parameters, such as P-wave (lead II), QRS (leads II, V(2), V(5)), S-wave durations (leads II, V(5)), and PQ interval (leads II) were all significantly longer and S-wave amplitude (II, V(5)) was significantly deeper in the SCN5A-positive group than in the SCN5A-negative group. The SCN5A-positive group showed a significantly longer corrected QT interval (lead V(2)) and higher ST amplitude (lead V(2)) than those in the SCN5A-negative group. The depolarization parameters increased with aging during the follow-up period in both groups; however, the PQ interval (lead II) and QRS duration (lead V(2)) were prolonged more prominently and the QRS axis deviated more to the left with aging in the SCN5A-positive group than in the SCN5A-negative group. In conclusion, conduction slowing was more marked and more progressively accentuated in Brugada probands with SCN5A mutation than in those without SCN5A mutation.

Objective: The effects of 2:1 AV block (AVB) on AV nodal reentrant tachycardia (AVNRT) remain to be elucidated. This study was performed to localize the site of 2:1 AVB and elucidate the effects of 2:1 AVB on typical AVNRT., Methods: The His bundle (HB) electrograms during typical AVNRT with 2:1 AV block were reviewed in 24 patients. It was hypothesized that if 2:1 AVB at the HB or below changed tachycardia cycle length (TCL), the lower turnaround point of the reentrant circuit (RC) might be located within the HB and parts of the HB might be involved in the RC., Results: A HB potential was absent in blocked beats during 2:1 AVB in four patients (supra-Hisian block), and the maximal amplitude of the HB potential in blocked beats was the same as that in conducted beats in four patients (infra-Hisian block), and was significantly smaller than that in conducted beats (0.1 +/- 0.1 versus 0.5 +/- 0.2 mV, P < 0.05) in 16 patients (intra-Hisian block). Eight patients (33%) with intra-Hisian block had a nearly identical prolongation of the H-A and A-A intervals in blocked beats (12 +/- 3 and 13 +/- 2 ms, respectively) with unchanged A-H intervals, while the remaining 16 patients (67%) exhibited invariable A-A and/or H-A intervals., Conclusion: The site of 2:1 AVB during typical AVNRT was estimated to be at the HB or below in 83% of the cases. Two-to-one intra-Hisian block transiently prolonged TCL, possibly indicating involvement of the proximal HB in the RC in one-third of typical the AVNRT cases with 2:1 AVB.

Background: Exercise training (ET) is an emerging therapy for chronic heart failure, but the baseline patient characteristics for predicting cardiac events (CEs) during the course of ET remain unknown., Methods and Results: Of the 111 stable heart failure patients who participated in a 3-month ET program, 6 withdrew from the program for cardiac reasons and 9 had transient interruptions in the program because of CEs. The baseline clinical characteristics of these 15 patients (CE group) and the remaining 96 patients (No-CE group) were compared. Compared with the No-CE group, the CE group had a significantly higher prevalence of pacemaker/implantable cardioverter-defibrillators, larger left ventricular end-diastolic diameter (LVEDDs), lower peak oxygen uptake, greater ventilation drive, and higher plasma brain natriuretic peptide concentration at baseline. Multivariate logistic regression analysis showed that a larger LVEDD was a significant predictor of the occurrence of a transient interruption to or permanent withdrawal from the ET program because of CEs. Receiver operating characteristic curve analysis demonstrated that an LVEDD > or = 65 mm had a sensitivity of 93% and specificity of 48% in predicting CEs., Conclusions: Patients with a large LVEDD (> or = 65 mm) at baseline should be monitored carefully during the course of an ET program.

Background: Some patients with Brugada syndrome experience an electrical storm of ventricular fibrillation (VF)., Objective: The purpose of this study was to investigate the clinical, laboratory, electrocardiographic, and electrophysiologic characteristics, acute and subsequent chronic treatment, and follow-up data of patients with Brugada syndrome associated with electrical storm of VF., Methods: Sixty-seven patients with Brugada syndrome (65 men and 2 women, age 46 +/- 14 years) were divided into three groups: 7 patients with a history of electrical storm of VF (group I), 39 symptomatic patients with documented VF and/or syncope (group II), and 21 asymptomatic patients (group III). Electrical storm was defined as three or more episodes of VF per day recorded by the memory of an implantable cardioverter-defibrillator., Results: No significant differences were observed among the three groups with regard to clinical (age at diagnosis, familial history of sudden cardiac death), laboratory (SCN5A mutation and serum potassium level), electrocardiographic and electrophysiologic characteristics, and follow-up duration after diagnosis. However, arrhythmic events during follow-up after diagnosis and number of arrhythmic events per patient were significantly higher in group I compared with groups II and III. Isoproterenol infusion (0.003 +/- 0.003 microg/kg/min for 24 +/- 13 days) completely suppressed electrical storm of VF in all five patients treated and was successfully replaced with oral medications, including denopamine, quinidine, isoproterenol, cilostazol, and bepridil alone or in combination., Conclusion: No specifically clinical, laboratory, electrocardiographic, and electrophysiologic characteristics were recognized in patients with Brugada syndrome associated with electrical storm of VF. Isoproterenol infusion was effective as an acute treatment in suppressing electrical storm of VF and was successfully replaced with chronic oral medications.