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Water pollution due to plasticizers is one of the most severe environmental problems worldwide. Phthalate plasticizers can act as endocrine disruptors in vertebrates. In this study, we investigated whether the non-phthalate bis(2-ethylhexyl) sebacate (DEHS) plasticizer can act as an endocrine disruptor by evaluating changes in the expression levels of thyroid hormone-related, reproduction-related, and estrogen-responsive genes of Japanese medaka (Oryzias latipes) exposed to the plasticizer. Following the exposure, the gene expression levels of thyroid-stimulating hormone subunit beta (tshβ), deiodinase 1 (dio1), and thyroid hormone receptor alpha (trα) did not change. Meanwhile, DEHS suppressed dio2 expression, did not induce swim bladder inflation, and eventually reduced the swimming performance of Japanese medaka. These findings indicate that DEHS can potentially disrupt the thyroid hormone-related gene expression and metabolism of these fish. However, exposure to DEHS did not induce changes in the gene expression levels of kisspeptin 1 (kiss1), gonadotropin-releasing hormone (gnrh), follicle-stimulating hormone beta (fshβ), luteinizing hormone beta (lhβ), choriogenin H (chgH), and vitellogenin (vtg) in a dose-dependent manner. This is the first report providing evidence that DEHS can disrupt thyroid hormone-related metabolism in fish.

Thyroid-hormone-disrupting chemicals are increasingly attracting attention because of their potential harmful effects on animal health, including on fishes. Here, we investigated the effects of exposure to the thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil (PTU) and tetrabromobisphenol A (TBBPA) on swim bladder inflation, eye development, growth, swimming performance, and the expression of thyroid-related genes in Japanese medaka (Oryzias latipes). PTU exposure resulted in reductions in eye size, growth, and swim bladder inflation, and these effects led to poorer swimming performance. These phenotypic effects were accompanied by increased expression of the thyroid-stimulating hormone subunit beta (tshβ) paralog tshβ-like, but there were no significant changes in expression for tshβ, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trβ). For PTU exposure, we identified the key event (swim bladder inflation reduction) and an adverse outcome (swimming performance reduction). No significant effects from TBBPA exposure were seen on swim bladder inflation, eye development, growth, or swimming performance. However, expression of tshβ-like and tshβ (significantly enhanced) and trα and trβ (significantly reduced) were affected by TBBPA exposure albeit not in dose-dependent manners. There were no effects of TBBPA on the expression of dio1 and dio2. We thus show that the two thyroid-hormone-disrupting chemicals PTU and TBBPA differ in their effect profiles with comparable effects on the studied phenotypes and thyroid-related gene expression to those reported in zebrafish.

Pollution of water bodies with plasticizers is a serious environmental problem worldwide. In this study, we investigated the effects of plasticizers bis-(2-ethylhexyl) phthalate (DEHP) and bis-(2-ethylhexyl) adipate (DEHA) in Japanese medaka (Oryzias latipes). DEHP significantly increased the expression of all the genes tested: thyroid stimulating hormone beta subunit (tshβ-like), tshβ, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trβ). However, DEHA only significantly increased tshβ at 7.4 µg/L but significantly decreased dio2 expression at 25.8, 111.1, and 412.6 4 µg/L, while other genes were not significantly affected. Both chemicals reduced eye size and total body length, but did not affect embryo development, hatching time and rate, and swimming performance. DEHA alone affected swim bladder inflation and not DEHP. This is the first report that not only DEHP but also DEHA disrupt thyroid hormone activity in fish. DEHP contamination (13.2 μg/L) was detected in tap water from Kobe, Japan; thus, tap water itself may disrupt thyroid hormone activity in Japanese medaka. Importantly, the effective concentration of DEHP for thyroid hormone-related gene expression and growth was close to or lower than DEHP concentrations reported in surface water elsewhere, indicating that DEHP contamination is a serious aquatic pollution.

This study aimed to clarify the clinical impact of transient atrial fibrillation (AF) attacks themselves and the efficacy of cardiac resynchronization therapy (CRT) in patients with intermittent AF.The benefit of CRT in patients with intermittent AF, especially the effect of the AF attacks themselves, remains unclear.Among our cohort of 269 consecutive CRT patients, we compared the percent of biventricular pacing (BIVP%) and other clinical characteristics between patients with intermittent AF and those with sinus rhythm (SR).During a median follow-up of 942 days (interquartile range: 379 to 1,464 days) a total of 22 patients, including 59% of CRT responders, developed heart failure (HF) due to a transient AF attack itself, and that accounted for 21% of all HF events. The BIVP% during the AF attacks was significantly lower than that during SR (p 0.05). When compared to the SR groups, patients with intermittent AF had a significantly higher risk of developing HF or death (hazard ratio: 2.2; 95% confidence interval: 1.3 to 3.8). However, the patients who received a BIVP% of ≥90% during AF attacks were comparable to those with SR (hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.0).A substantial number of patients developed HF due to transient AF attacks themselves even in the CRT responders, and the reason was mainly due to the loss of the BIVP%.

The advent of the subcutaneous implantable cardioverter-defibrillator (SQ-ICD) provides an alternative to transvenous and epicardial ICD therapy. Particularly germane to the young patient with congenital heart disease or inheritable arrhythmia syndromes, the SQ-ICD may be ideal for those who do not require permanent cardiac pacing. The serious complications associated with transvenous ICD systems are largely driven by the intravascular components of these devices and are avoided by this extravascular technique. Multiple clinical trials have shown that SQ-ICDs are effective in detecting and terminating ventricular arrhythmias, yet nuanced issues must be considered, especially in the context of congenital cardiovascular anomalies. This review aims to contextualize the role of this technology in contrast with traditional ICDs, and provide a logical approach to appropriate device selection.

Objectives The aim of this study was to assess sex-related differences in sporadic cases of arrhythmogenic right ventricular cardiomyopathy (ARVC). Background Previous studies have suggested male predominance in ARVC. However, the impact of sex on the heterogeneous clinical profile and prognosis of ARVC were not fully recognized. Methods The study population included 110 patients with ARVC who fulfilled the revised Task Force criteria (median age 48 years [interquartile range (IQR): 36 to 57 years]). All patients were sporadic cases without family history of ARVC. Male patients had a 3:1 predominance (75%). Ninety-seven patients (88%) were considered to have “definite” ARVC based on revised Task Force criteria. Results At the initial evaluation, there were no significant sex-related differences in age, 12-lead electrocardiogram findings, late potentials by signal-averaged electrocardiogram, left ventricular ejection fraction, or right ventricular ejection fraction. During a median follow-up of 10.0 years (IQR: 5.2 to 15.6 years), 18 patients died from cardiac causes. Kaplan-Meier analysis, considering patients’ lives since birth, revealed that male patients had a significantly higher risk of ventricular tachycardia/ventricular fibrillation than did female patients (56% vs. 90%, p = 0.02), whereas female patients had a significantly higher risk of heart failure (HF) death or heart transplantation (22% vs. 5%, p = 0.002). On multivariate Cox regression analysis, female sex was an independent risk factor for HF death or heart transplantation due to HF (hazard ratio: 6.29, 95% confidence interval: 1.29 to 40.2; p = 0.02). Conclusions Among patients with sporadic ARVC, men had a significantly higher risk of ventricular tachycardia/ventricular fibrillation, whereas women had a significantly higher risk of HF death or heart transplantation due to HF.

Objectives First, to examine the perioperative association between increased cardiac index (CI) measured using three-dimensional echocardiography (CI3D), two-dimensional echocardiography (CI2D), and FloTrac/Vigileo (CIFT) (Edwards Lifesciences, Irvine, CA) after cardiac resynchronization therapy (CRT) and decreased brain natriuretic peptide (BNP) 6 months after CRT. Second, to evaluate the accuracy and tracking ability of CI2D and CIFT. Design A prospective clinical study. Setting A cardiac surgery operating room in a single cardiovascular center. Participants Forty-five patients undergoing elective CRT lead implantation. Interventions CIFT and CI2D were determined simultaneously before and after CRT using CI3D as the reference method. Measurements and Main Results BNP was measured before CRT and 6 months after CRT. Areas under the receiver operator characteristic curves (AUCs) were calculated for each method of measurement to predict BNP decrease. AUC was largest for CI3D (AUC = 0.735, p = 0.017). Bland-Altman analysis revealed that the percentage error was 58% for CIFT and 28% for CI2D. A polar plot analysis showed that the mean angular bias was -7.26° and 0.64°, the radial limits of agreement were 70° and 29.4°, and the concordance rate was 67.7% and 93.8% for CIFT and CI2D, respectively. Conclusions CI significantly increased after CRT in patients whose BNP level decreased 6 months after CRT. However, only CI3D could predict decreases in BNP 6 months after CRT. Although CI2D was acceptable compared with CI3D, the tracking ability of CI changes was just below acceptable. CIFT has a wide limit of agreement with CI3D, with a poor tracking ability.

The imidazole fungicide miconazole (MCZ) and the antidepressant sertraline (SER) have the potential to adversely affect aquatic organisms when they are released into the environment. To assess if they could be broken down, MCZ and SER were treated with laccase and manganese peroxidase (MnP) from lignin-degrading white-rot fungi. The MnP-dependent lipid peroxidation system with Tween 80 containing unsaturated fatty acid was effective in eliminating MCZ and SER; the MnP-Tween 80 system helped eliminate 88% of MCZ and 85% of SER after 24 h of treatment. Furthermore, this system eliminated a metabolite of SER (desmethylsertraline or DSER), and no differences between the elimination rates of DSER and SER were observed throughout the treatment period. It was also confirmed that the MnP-Tween 80 system caused a complete loss of growth inhibition by MCZ of the gram-positive bacterium Bacillus subtilis and reduced the growth inhibition by SER of the green alga Pseudokirchneriella subcapitata by 78% after 24 h of treatment. On the other hand, no appreciable elimination of MCZ and SER was obtained by treatment with laccase, MnP, or the laccase-mediator system with 1-hydroxybenzotriazole.

We report the case of a 51-year-old patient with Brugada syndrome (BrS) who experienced inappropriate shock due to T-wave oversensing (TWOS) during exercise when the optimal sensing vector was selected based on the automatic analysis by a subcutaneous implantable cardioverter-defibrillator (S-ICD). After selecting another vector during exercise testing, TWOS did not re-occur. Selection of appropriate sensing vector based on analyses under various conditions, including during exercise after S-ICD implantation, should be considered for patients with BrS.

Loss-of-function mutations in the cardiac sodium channel α-subunit gene SCN5A result in multiple inherited arrhythmic syndromes. This case report describes 2 unrelated probands carrying an identical SCN5A frameshift mutation, V1764fsX1786, who exhibited distinct clinical manifestations: progressive cardiac conduction defect (PCCD)/Brugada syndrome (patient #1) and idiopathic ventricular fibrillation (IVF) (patient #2). Using a whole-cell patch clamp technique, cells expressing V1764fsX1786 showed no observable Na+ current. Therefore, a significant phenotypic overlap was found between IVF and PCCD/Brugada syndrome in the 2 probands with the V1764fsX1786, loss-of-function frameshift mutation of the cardiac sodium channel gene SCN5A.

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).Inferolateral ERS might be a heterogeneous entity, although it excludes type 1 Brugada syndrome (BS).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).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], p0.0001). 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).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.

Background Given the exponential growth in cardiac device implantations, the need for less invasive lead extraction is increasing. The Excimer laser was approved for lead removal in Japan in 2010. The present study reports the initial experience using this novel technique to extract chronically implanted pacemaker and implantable cardioverter defibrillator (ICD) leads from Japanese patients. Methods and results We performed a retrospective study of consecutive patients undergoing lead extraction using the laser sheath at a single Japanese center. Patient and lead characteristics, indications, and outcomes were analyzed. From August 2010 to September 2012, a total of 70 leads, including 14 ICD leads, were removed using the laser sheath from 40 patients (26 male, 14 female; age 65.5 ± 18.3 [mean ± SD] years; body mass index 21.8 ± 3.5 kg/m2). The median implant duration was 87 months (range 13–328 months). Indications were infection (n = 35), venous occlusion (n = 4), and pain (n = 1). The femoral approach was used in combination with the laser technique in five cases. Complete procedural success was achieved with 68 leads (97.1%). Although the electrode tip was left behind in the remaining two leads, the desired clinical outcomes could be achieved; which were defined as clinical success. No cases resulted in failure. There were no major complications, including death and bleeding requiring open-chest surgery. Conclusions Laser sheaths appear to provide a feasible and effective means of extracting chronically implanted pacemaker and ICD leads in Japanese patients.

High levels of hydrogen sulfide are sometimes observed in the pore water of eutrophic sediments. It is important to reduce the hydrogen sulfide concentration to maintain health ecosystems as well as aquaculture activities in enclosed water bodies. The purpose of this study is to reveal the removal mechanism of hydrogen sulfide using carbonated steel slag produced through carbonation processes to alleviate alkaline impacts. Batch adsorption experiments revealed that hydrogen sulfide was adsorbed onto carbonated steel slag based on a pseudo-first-order kinetic model; its adsorption maximum was 7.5 mg g −1 . The removal mechanisms of the hydrogen sulfide included (1) the formation of pyrite, and (2) oxidation to sulfur coupled with the reduction of manganese oxide on the carbonated steel slag.

A 41-year-old woman who had been fitted with a pacemaker 18 years prior presented for lead extraction because of device infection. First, we tried laser sheath. However, it cannot cross the binding in the innominate vein. Then we switched to the rotating mechanical sheath. Although it crunched through binding tissue, the progress halted. We removed the sheath and found pieces of calcified tissue in the sheath lumen. After removing the calcified tissue, both leads were extracted using the laser sheath, without complications. The pathological examination revealed a diagnosis of ossified thrombus. Venous thromboses associated with implanted leads can ossify with time, causing difficulties in the extraction of long-standing intravascular leads.

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.

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 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.

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.

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.

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 μg/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.

The retrograde fast pathway in typical atrioventricular nodal reentrant tachycardia (AVNRT) exhibits marked variation in its electrophysiologic properties.The purpose of this study was to characterize the retrograde fast pathway and localize the lower turnaround site of the reentrant circuit in typical AVNRT.Seventy-four patients with typical AVNRT were divided into two groups according to the response of the retrograde fast pathway to intravenous administration of adenosine triphosphate (ATP) during ventricular pacing: ATP-S [n = 47 (63.5%)] with and ATP-R without [n = 27 (36.5%)] His-atrial (H-A) block. H-A intervals were measured from the most proximal His-bundle electrogram to the earliest atrial activation during the tachycardia (HAt) and entrainment pacing from the parahisian right ventricular region (HAe). It was postulated that the HAt was the difference in conduction time between the lower common pathway (x) and retrograde fast pathway (y) (HAt = y - x), whereas HAe was the sum of the two (HAe = y + x). Hence, x = (HAe-HAt)/2. x0 suggested the presence of a lower common pathway, whereas x0 suggested the absence of a lower common pathway and lower turnaround site within the His bundle.x was significantly smaller in ATP-R than ATP-S (-6 +/- 5 vs 4 +/- 4 ms, P.05) and was0 in 23 (85%) of 27 ATP-R patients. The maximal increment in H-A interval during ventricular pacing was significantly longer in ATP-S than ATP-R (35 +/- 33 vs 2 +/- 2 ms, P.05).A concealed atriohisian tract totally bypassing the atrioventricular node constituted the retrograde fast pathway in one third of all typical AVNRT cases.

Background The electrophysiologic mechanisms of different ventriculoatrial (VA) block patterns during atrioventricular nodal reentrant tachycardia (AVNRT) are poorly understood. Objectives The purpose of this study was to characterize AVNRTs with different VA block patterns and to assess the effects of slow pathway ablation. Methods Electrophysiologic data from six AVNRT patients with different VA block patterns were reviewed. Results All AVNRTs were induced after a sudden AH "jump-up" with the earliest retrograde atrial activation at the right superoparaseptum. Different VA block patterns comprised Wenckebach His-atrial (HA) block (n = 4), 2:1 HA block (n = 1), and variable HA conduction times during fixed AVNRT cycle length (CL) (n = 1). Wenckebach HA block during AVNRT was preceded by gradual HA interval prolongation with fixed His-His (HH) interval and unchanged atrial activation sequence. AVNRT with 2:1 HA block was induced after slow pathway ablation for slow-slow AVNRT with 1:1 HA conduction, and earliest atrial activation shifted from right inferoparaseptum to superoparaseptum without change in AVNRT CL. The presence of a lower common pathway was suggested by a longer HA interval during ventricular pacing at AVNRT CL than during AVNRT (n = 5) or Wenckebach HA block during ventricular pacing at AVNRT CL (n = 1). In four patients, HA interval during ventricular pacing at AVNRT CL was unusually long (188 ± 30 ms). Ablations at the right inferoparaseptum rendered AVNRT noninducible in 5 (83%) of 6 patients. Conclusion Most AVNRTs with different VA block patterns were amenable to classic slow pathway ablation. The reentrant circuit could be contained within a functionally protected region around the AV node and posterior nodal extensions, and different VA block patterns resulted from variable conduction at tissues extrinsic to the reentrant circuit.

Interactive toxic effects between heavy metals were investigated using a sea urchin (Anthocidaris crassispina) bioassay. An effluent from an abandoned mine showed significant inhibitory effects on embryo development as well as producing specific malformations. The effects on the embryos were reproduced by synthetic polluted seawater consisting of eight metals (manganese, lead, cadmium, nickel, zinc, chromium, iron, and copper) at the concentrations detected in the mine effluent. This indicated that the heavy metals were responsible for the effects observed. Five heavy metals were ranked in decreasing order of toxicity as follows: Cu > Zn > Pb > Fe > Mn. Among these, zinc and manganese could cause malformation of the embryos. From bioassay results using 27 combinations of heavy metals, 16 combinations including zinc could produce specific malformations, such as radialized, exo-gastrulal, and spaceship Apollo-like gastrulal embryos. Zinc was one of the elements responsible for causing malformations and its effects were intensified by the presence of the other metals, such as manganese, lead, iron, and copper.

The toxicity of the polluted waters originating from a disused lead mine was evaluated using both sea urchin bioassays and heavy metal analysis. Samples from three polluted waters (a seawater and two freshwaters) were collected from the mine area and one seawater sample was taken from a non-contaminated reference site. The test waters contained higher concentrations of heavy metals such as manganese, lead, cadmium, zinc, chromium, nickel, iron, and copper than did ambient seawater. The three test waters had inhibitory effects, in a dose-dependent manner, on the first cleavage of sea urchin embryos and on pluteus formation during the development. Some malformations, such as a radialized pluteus, exo-gastrula, and spaceship Apollo-like embryos were induced by the test waters without dilution. Zinc alone also induced the same anomaly. Zinc in the test seawater was ascertained as one of the metals that caused the anomalies, but not all of the toxicity was caused by zinc. It was speculated that interactive effects, involving zinc and possibly manganese and nickel, were occurring.

Residue analyses of some antifouling herbicides (Diuron, Irgarol 1051 and the latter's degradation product M1, which is also known as GS26575), were conducted in waters collected along the coast of western Japan. In total, 142 water samples were collected from fishery harbours (99 sites), marinas (27 sites), and small ports (16 sites) around the Seto Inland Sea, the Kii Peninsula, and Lake Biwa, in August 1999. A urea-based herbicide, Diuron, was positively identified for the first time in Japanese aquatic environments. Diuron was detected in 121 samples (86%) up to a highest concentration of 3.05 microg/l, and was found in 86% of samples from fishery harbours, 89% from marinas, and 75% from ports. Four freshwater samples out of 11 collected at Lake Biwa contained Diuron. Neither Irgarol 1051 nor M1 was found in the lake waters, but both were found in many coastal waters. Irgarol 1051 was found in 84 samples (60%) at a highest concentration of 0.262 microg/l. The concentrations detected were of similar magnitude to those in our previous surveys, taken in 1997 and 1998. M1 was found in 40 samples (28%) up to a highest concentration of 0.080 microg/l. The concentrations detected were generally lower than those found in our previous surveys. The detection frequency among fishery harbours, marinas, and ports was 57-70% for Irgarol 1051 and 25-30% for M1. Ninety-five per cent of the coastal waters in which M1 was detected also contained Irgarol 1051, and 93% of the samples in which Irgarol 1051 was detected also contained Diuron. These results clearly suggest that commercial ship-bottom paints containing both Diuron and Irgarol 1051 are used extensively in the survey area.

The antifouling compound Irgarol 1051 and its degradation product M1 (also known as GS26575), along with another antifouling compound Diuron, have recently been found in Japanese coastal waters. This study was undertaken to find the origin of these chemicals and investigate their aquatic fate. Five glass plates, each coated with 1 g of antifouling paint containing Irgarol and Diuron, were submerged in 250 ml of five different test waters and the plates removed after several months. The aqueous solutions were divided into two groups: one exposed to natural sunlight, and the other kept in the dark as a control. Irgarol and Diuron were detected in all aqueous solutions, suggesting leaching from antifouling paints is the origin of these antifouling biocides found in Japanese coastal waters. Under sunlight conditions, Irgarol underwent a rapid degradation to produce M1, which remained even after Irgarol had disappeared from the system. These compounds were persistent in any aqueous solutions tested under dark conditions, indicating high stability to hydrolysis. Diuron and M1 were more persistent than Irgarol under sunlight irradiation. Since these compounds have high herbicidal activities, their ultimate impact on aquatic ecosystems is closely related to their aquatic fate.

This paper considers how the operating performance of JASDAQ companies is affected by the ownership structure pre- and post-IPOs. We document that operating performance varies according to managerial ownership in addition to the age and size of the firm. Our results on JASDAQ contrast with evidence from Cai and Wei [Pacific-Basin Finance Journal 5 (1997) 389], who analyze the operating performance of companies newly listed on the Tokyo Stock Exchange (TSE). They indicate the post-IPO deterioration in operating performance cannot be attributed to the reduced managerial ownership.

A simple, rapid toxicity test was developed using the suspension-cultured fish cell line CHSE-sp derived from chinook salmon Oncorhynchus tshawytscha embryos in order to assess the toxicity of new marine antifouling compounds. The compounds tested were copper pyrithione, Diuron, Irgarol 1051, KH101, Sea-Nine 211, and zinc pyrithione, all of which have been nominated in Japan as possible replacements for organotin compounds. The in vitro acute toxicity (24-h EC 50 ) of the six compounds to these fish cells was evaluated using the dye Alamar Blue™ to determine cell viability, and then correlated with the results of in vivo chronic toxicities (28-day LC 50 ) to juvenile rainbow trout Oncorhynchus mykiss . The suspension-cultured fish cells were found to be suitable for the screening of such chemicals before performing an in vivo test. The toxicities of the test compounds obtained from both tests, shown in decreasing order, were as follows: copper pyrithione > zinc pyrithione > KH101 ⩾ Sea-Nine 211 > Diuron > Irgarol 1051. The herbicides Diuron and Irgarol 1051 showed the least toxicity, while the pyrithiones had the greatest toxicity.

This research examines initial public offering (IPO) underpricing in Japan between 1980 and 1998. Consistent with prior research, we find no evidence that underwriter reputation influences the level of mispricing. Keiretsu-affiliated firms are more fully priced, though healthy firms and healthy keiretsu-affiliated firms are significantly more underpriced, than are other firms. The mispricing of healthy firms occurs prior to implementation of the discriminatory price auction system and is consistent with a high demand for these IPO firms. Reduced mispricing of keiretsu firms during the post-auction period is consistent with the notion that they have more stable earnings than other firms.

Residue analyses and ecotoxicity assessment were conducted on the new antifouling compound Irgarol 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) and its degradation product M1 (2-methylthio-4-tert-butylamino-6-amino-s-triazine) in order to delineate the environmental fate and impact of Irgarol 1051 on the aquatic ecosystem. For the first time, the Irgarol degradation product (M1) was positively identified in environmental samples. During the 1998 Irgarol survey, concentrations of M1 (up to 1870 ng/l) were generally higher than those of Irgarol in the coastal waters of the Seto Inland Sea in Japan, suggesting a greater environmental persistence for M1 than for the parent compound Irgarol 1051 in the aquatic ecosystem. Ecotoxicity testing revealed that Irgarol 1051 and M1 were moderately toxic to a marine bacterium and the four crustaceans tested, but were highly toxic to some algae and higher plants. In the root elongation inhibition bioassay, M1 showed a phytotoxicity at least 10 times greater than that of Irgarol and six other triazine herbicides (terbutryn, terbutylazine, terbumeton, simetryn, atrazine and simazine). These results strongly suggest that both Irgarol 1051 and its persistent degradation product M1 may potentially affect and/or damage the primary producer community in aquatic ecosystems. To safeguard the aquatic ecosystem from the damaging impact of micro contaminants, it is recommended that, besides monitoring for the target parent compound, major degradation products should also be included in environmental surveys. Otherwise, there is a risk of underestimating the ultimate impact of a particular toxicant on the environment.

The phytotoxicity of the new antifouling compound Irgarol 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) and its degradation product M1 (2-methylthio-4-tert-butylamino-6-amino-s-triazine) was assessed by a battery of bioassays with marine and freshwater species. Both compounds at low concentrations affected aquatic plant species such as the red macroalga Porphyra yezoensis conchospores, the brown macroalga Eisenia bicyclis gametophytes, the freshwater green microalga Closterium ehrenbergii, the floating macrophytes Lemna gibba G3 and Lemna minor 1769. The toxicity of Irgarol 1051 was higher than that of M1 for all the aquatic plant species tested, but M1 showed a higher toxicity to root elongation of a terrestrial plant. The NOEC (0.3 μg / l ) of Irgarol to the brown seaweed was identical to the maximum concentration (0.296 μg / l ) detected in Japanese coastal waters, and the maximum concentration of M1 (1.87 μg / l ) detected amounted to only 20% of the NOEC value. The bioassay results suggest the possibility that both Irgarol 1051 and M1 may influence the primary producer community in the aquatic environment.

Irgarol 1051, (2-methylthio-4- tert -butylamino-6-cyclopropylamino- s -triazine), is a newly developed herbicidal additive for use in copper-based antifouling paints. It is intended as replacement for the highly toxic antifouling agent tributyltin, which has been regulated internationally. Currently, there is no information in the open literature on its environmental occurrence outside Europe. A two-year survey was conducted in 1996–1997 to investigate the occurrence of Irgarol 1051 in Canadian and Japanese aquatic environments. Six large trade ports (Vancouver, Toronto, Montreal, Halifax, Mizushima and Kobe), 73 marinas and 13 fishery harbors were surveyed. Irgarol 1051 was not detected in the Canadian aquatic environment, but was positively identified in the enclosed coastal waters of the Seto Inland Sea in Japan. Among the six trade ports surveyed, only the Mizushima Port had low levels of Irgarol 1051, up to 19.5 ng/L. Approximately 27% of the marinas surveyed in the Seto Inland Sea were found to have been contaminated by Irgarol 1051, ranging in concentration between 12.5 and 264.2 ng/L. Irgarol 1051 was found more frequently in fishery harbors than in marinas, indicating that besides marinas and trade ports, fishery harbors can also be a significant source of contamination for the aquatic environment. Survey for Irgarol 1051 in the fishery harbors has not been reported before, and it is suggested that fishery harbors, in addition to ports and marinas, should be included in the survey list during the Irgarol 1051 monitoring study. Irgarol 1051 has been reported to be highly toxic to nontarget marine algae with the observable growth inhibition at a concentration as low as 50 ng/L, which is well within the ambient concentration levels found in some localities of the Seto Inland Sea.

The effect of agricultural land run-off on the water quality of Lake Kojima, Japan, was investigated using a short-term bioassay-guided chemical analysis. Water samples were collected for 1 year starting from June 1995 to June 1996. Toxicity of the dissolved and adsorbed extracts in the water samples was evaluated using the Daphnia immobilization test and the concentrations of pesticides and putative toxic substance in the extracts were determined by high performance liquid chromatography. Most of the dissolved extracts caused immobilization of the test Daphnia magna at low concentrations during the period of paddy pesticide application. Some extracts were found to contain pesticides such as dymron, mefenacet and flutolanil, but their concentrations were too low to have a toxic effect on the daphnia. An unknown toxic compound, Peak C, was isolated from some river water samples, but it produced only a relatively weak toxicity to Daphnia. To better understand the impact of agricultural run-off on a receiving water body, the relationship between the observed toxicity and the concentrations of pesticides and Peak C in the water samples was studied both temporally and spatially.

Irgarol 1051, 2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine, is a newly developed herbicidal additive for use in copper-based antifouling paints. It is intended to replace the antifouling agent tributyltin, which has been regulated internationally due to its severe impact on the aquatic ecosystem. However, there is no information in the open literature on the abiotic degradation of Irgarol, a fact that hinders the assessment of its ultimate impact on the environment. This study showed that mercuric chloride was capable of rapidly catalyzing the hydrolysis of Irgarol 1051 in distilled water and buffer solutions. The degradation appeared to follow the reaction of a catalyzed hydrolysis and was not significantly affected by the pH tested (5 to 9). All other 5 heavy metal salts tested (AgNO3, CdCl2, CuSO4, PbCl2 and ZnCl2) had practically no catalytic property on Irgarol hydrolysis, implying the involvement of a specific activity for Hg2+ in this reaction. The mechanism for the catalyzed hydrolysis may be the formation of bidentate chelation through nitrogen (No. 5) on the ring and the nitrogen on the cyclopropylamino side chain in Irgarol 1051 with the Hg2+ ion. The resulting four-member chelate complex would weaken the cyclopropyl-amino bond considerably, thus facilitating the hydrolysis reaction. Ultraviolet spectroscopy of the reaction mixtures and the identification of Irgarol hydrolysis product M1 (2-methylthio-4-tert-butylamino-6-amino-s-triazine) by GC-MS and LC-MS provided the basis for the proposed mechanism on the HgCl2-catalyzed hydrolysis of Irgarol 1051. M1 appeared to be more stable than the parent compound Irgarol 1051, thus implying its possible accumulation in the environment. One practical aspect of this work is that HgCl2 should not be used in preserving water samples in Irgarol 1051 monitoring programs.

Irgarol 1051, 2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine, is a newly developed herbicidal additive for use in copper-based antifouling paints. It is intended to replace the antifouling agent tributyltin, which has been regulated internationally due to its severe impact on the aquatic ecosystem. However, there is no information in the open literature on the persistence and degradation of Irgarol, a fact that hinders the assessment of its ultimate impact on the environment. This study showed that the white rot fungus Phanerochaete chrysosporium was capable of biotransforming Irgarol 1051. It appears that the metabolism of Irgarol by the fungus proceeds mainly via partial N-dealkylation. Metabolic dealkylation occurs at the cyclopropylamino group resulting in metabolite M1, which has tentatively been identified as 2-methylthio-4-tert-butylamino-6-amino-s-triazine. M1 appeared to be a stable and/or terminal metabolite. No evidence of the heterocyclic ring cleavage of Irgarol 1051 was observed, thus implying a possibility of its degradation product(s) accumulating in the environment.

Antioxidant activity of an extract from Eucalyptus rostrata was the highest among 16 Eucalyptus species tested. From the leaves of Eucalyptus rostrata nine active compounds were isolated: 1,2,6-tri- O -galloyl-β- d -glucose and tellimagrandin 1 as tannins; spiraeoside, hyperoside, isoquercitrin, and myricetin 3- O -α- l -arabinopyranoside as flavonol glycosides; quercetin 3- O -α-arabinopyranoside-2″-gallate, kaempferol 3- O -α-arabinopyranoside-2″-gallate, quercetin 4′- O -β- d -glucopyranoside-6″-gallate as acylated flavonol glycosides. Antioxidant activity of the tannins and acylated flavonol glycosides, all with galloyl groups, was much higher than that of a synthetic antioxidant. Two of the compounds, spiraeoside and quercetin 4′-glucosylgallate, showed high superoxide dismutase activity.

From the leaves of Eucalyptus rostrata, two new acylated flavonol glycosides were isolated together with quercetin 3-O-α-arabinopyranoside-2″-gallate and quercetin 4′-O-β- d -glucopyranoside. The structures of the new compounds were identified as quercetin 4′-O-β- d -glucopyranoside-6″-gallate and kaempferol 3-O-α-arabinopyranoside-2″-gallate.

Patients with neurological illnesses often require prolonged enteral or parenteral nutrition. The complications of this type of feeding may be unfamiliar to neurosurgeous and neurologists, however, these complications may be an important source of ongoing morbidity. We present a case of severe anemia due to copper deficiency in a patient requiring enteral nutrition after SAH. The anemia resolved with copper supplements. A high index of suspicion is needed to recognise and treat complications of enteral nutrition.

handling alteration associated with HF importantly contribute to the proarrhyth- mic consequence. HF decreases K + -currents including transient outward current and the slow delayed rectifier current, apparently by transcriptional down-regulation of their component subunits. The K + -channel remodeling may not greatly prolong QT or APD but may result in exaggerated responses upon IKr blockade, exposing reduced repolarization reserve. L-type Ca 2+ channels and sarcoplasmic reticulum Ca 2+ -release channels are hyperphosphorylated by calmodulin kinase II (CaMKII), which are key components of arrhythmogenic afterdepolarization formation in HF. IKr blockade may aggravate these functional abnormalities because APD prolongation itself causes an increased activity of CaMKII. From these mechanistic points of view, precautions to use of class III agents in HF patients should be necessary. Whether K + -channel blockade in the ionically remodeled failing hearts is antiarrhythmic remains to be determined.

SESSION 27: NONINVASIVE EVALUATION I: Refinement of Risk Stratification Friday, May 6, 2005 8:15 a.m.–9:45 a.m.

P4-33 CLINICAL CHARACTERISTICS AND ATTENDANCE PATTERN OF SYNCOPE AT EMERGENCY DEPARTMENTS IN SPAIN. A PROSPECTIVE ANALYSIS (THE GESINUR STUDY) Angel Moya, Alfonso Martin, Roberto Garcia-Civera, Carmen Del Arco, Gonzalo Baron, Pedro Laguna and Jesus Martinez-Alday. Hospital Vall D Hebron, Barcelona, Spain, Hospital de Mostoles, Madrid, Spain, Hospital Clinico Valencia, Spain, Hospital La Princesa, Madrid, Spain, Hospital Virgen del Rocio, Sevilla, Spain, Hospital Puerta de Hierro, Madrid, Spain and C. H. Donostia, San Sebastian, Spain.