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Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1; EC 1.1.1.146), encoded by Hsd11b1, is a key regulator of the local concentration of CORT/cortisol. Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles of Hsd11b1 in the developing mouse neocortex. Hsd11b1 was found mostly in pyramidal neurons. By retrograde tracing, we observed that some Hsd11b1-positive cells were projection neurons, indicating that at least some were excitatory. At postnatal day 0 (P0), Hsd11b1 was expressed in the deep layer of the somatosensory cortex. Then, from P3 to P8, the expression area expanded broadly; it was observed in layers 4 and 5, spanning the whole neocortex, including the primary motor cortex (M1) and the primary visual cortex (V1). The positive region gradually narrowed from P14 onwards and was ultimately limited to layer 5 of the somatosensory cortex at P26 and later. Furthermore, we administered CORT to nursing dams to increase the systemic CORT level of their pups. Here, we observed a reduced number of Hsd11b1-positive cells in the neocortex of these pups. Our observation suggests that Hsd11b1 expression in the developing neocortex is affected by systemic CORT levels. It is possible that stress on mothers influences the neocortical development of their children.

Although the volume overload of pulmonary circulation improves after atrial septal defect (ASD) closure, the increasing left ventricular preload may contribute to mitral regurgitation (MR) deterioration. We aimed to evaluate the impact of MR after transcatheter ASD closure on clinical outcomes in adults. A total of 288 consecutive patients who underwent transcatheter ASD closure were enrolled. Changes in MR were assessed at 1 month after the procedure. The end point was defined as cardiovascular events. After the procedure, MR ameliorated in 3 patients and unchanged in 253, whereas MR deteriorated in 32. During a median follow-up of 24 months, patients with MR deterioration had no cardiovascular events, and the event-free survival rate was not different between patients with MR deterioration and those with MR amelioration or no-change (p = 0.355). Even in patients with MR deterioration, the New York Heart Association functional class improved after the procedure, with no cases of worsening functional class. Multivariate logistic regression analysis showed that MR deterioration was independently related to advanced age and female gender. The degree of enlargement of mitral valve annulus diameter after the procedure was greater in patients with MR deterioration than in those with MR amelioration or no-change, and it was correlated with the degree of MR deterioration. In conclusion, MR deterioration occurs in a minority of adult patients after transcatheter ASD closure; however, it is not linked with adverse outcomes. MR deterioration may be provoked by geometric changes in mitral valve annulus, especially in women with advanced age.

Although numerous studies have shown an association between a patent foramen ovale (PFO) and cryptogenic cerebrovascular accidents (CVA), there has been no definitive control study that demonstrated the benefit of percutaneous device closure of a PFO compared to medical therapy in patients with CVA. Additionally, few clinical data exist for Japanese patients in this field. We demonstrate the initial experiences in catheter closure of a PFO as secondary prevention of CVA in Japan. Catheter closure of a PFO was attempted in 7 patients who were diagnosed with cryptogenic CVA. Mean age at the procedure was 54 ± 19 years. The presence of spontaneous interatrial right-to-left shunts was demonstrated by transesophageal contrast echocardiography without Valsalva maneuver in all of the patients. Amplatzer Cribriform device (n = 4) or Amplatzer PFO Occluder (n = 3) was used for the procedure and was successfully deployed. Device-related complications were not observed at the time of the procedure or during the follow-up period (mean period of 16 ± 9 months). Catheter closure of a PFO could be safely performed with Amplatzer Cribriform or Amplatzer PFO Occluder. This procedure may contribute to prevention of recurrent cryptogenic CVA in Japanese patients.

This study sought to evaluate the usefulness of real-time three-dimensional (3D) transesophageal echocardiography (TEE) to guide the repair of multiple atrial septal defects (ASDs). Of 212 consecutive patients with secundum ASD who were scheduled for transcatheter closure of their ASDs, 27 had multiple ASDs. These patients underwent two-dimensional (2D) transthoracic echocardiography, 2D TEE, and 3D TEE. Overall, 18 patients had two defects, and 9 patients had three or more defects. The latter group included three patients with multi-fenestrated defects. Optimal 3D images were obtained in 93 % of the patients. In patients with two defects, information on the positional relation of the defects was obtained using 2D TEE and 3D TEE in 71 and 94 % of patients, respectively (P = 0.22). The positional relations of the defects could not be evaluated with 2D TEE in patients with three or more defects, whereas it could be evaluated with 3D TEE in all of these patients (0 vs. 100 %, P = 0.008). In all patients, 3D TEE proved superior to 2D TEE for providing sufficient information (96 vs. 48 %, P = 0.002). Procedural success was obtained in 26 patients (96.3 %), without complications. Transcatheter closure of multiple ASDs under 3D TEE guidance is effective and safe. Real-time 3D TEE can provide useful information regarding complex ASD morphology. It can thus contribute to developing a successful treatment strategy, especially in patients with three or more defects.

Objective This study evaluated the effect of echocardiographic left ventricular (LV) diastolic dysfunction on acute congestive heart failure after transcatheter atrial septal defect (ASD) closure in elderly patients. Background Although there is concern that LV diastolic dysfunction develops acute congestive heart failure after ASD closure, limited information is available regarding the influence, especially in elderly patients with severe LV diastolic dysfunction. Methods Two hundred consecutive patients older than 60 years were divided into 3 groups according to echocardiographic LV diastolic dysfunction: severe (early diastolic mitral annular velocity [e’]

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs and that specific white matter abnormalities are closely associated with MDD onset.

Background Although it has been demonstrated that cardiac remodeling and exercise capacity improve after transcatheter closure of atrial septal defect (ASD), little is known about long-term benefits in middle-aged and elderly patients with a reduction in cardiopulmonary function. Objectives To evaluate long-term extent and time course of improvements in cardiac remodeling and exercise capacity in those patients. Methods: Twenty ASD patients ≥ 40 years of age with a reduction in cardiopulmonary function (predicted peak oxygen uptake [VO2] 12 months after the procedure. Results At 1 month after the procedure, significant decreases in right ventricular (RV) end-diastolic diameter (38.2 ± 4.4 to 31.9 ± 4.4 mm; P < 0.001) and RV/left ventricular end-diastolic diameter ratio (0.95 ± 0.17 to 0.71 ± 0.13; P < 0.001) occurred, and they were maintained during the follow-up period. Normal RV size was achieved in 11 of 18 patients with RV enlargement. Predicted peak VO2 did not change at 1 month and 3 months, but it improved significantly after 6 months (53.6 ± 6.5 to 62.1 ± 12.6%; P < 0.01). Sixteen of the 20 patients showed improved predicted peak VO2. Conclusions Cardiac remodeling and exercise capacity could be improved over the long-term period after transcatheter closure of ASD in middle-aged and elderly patients with a reduction in cardiopulmonary function. There were differences in the time course of improvement between cardiac remodeling and exercise capacity in those patients. (J Interven Cardiol 2013;26:195–199)

Objectives: To evaluate the efficacy and safety of transcatheter closure of atrial septal defects (ASD) in patients over 70 years of age. Background: Transcatheter closure of ASD is an established procedure in children and young adults, but the benefits of this procedure in geriatric patients are still unclear. Methods: Between 2005 and 2010, 430 patients with ASD underwent transcatheter closure in our hospital. Among those patients, 30 consecutive patients older than 70 years of age were prospectively evaluated. Results: Mean age at procedure was 75.8 ± 3.8 years (range: 70–85 years). Mean Qp/Qs was 2.4 ± 0.7 and mean ASD diameter was 20.3 ± 6.4 mm. Nine patients (30%) had a history of hospitalization due to heart failure. ASD closure was successfully performed in 28 patients (93%) without significant complications. During the follow-up period (mean period of 19.1 ± 11.3 months), New York Heart Association (NYHA) functional class was significantly improved in 20 patients (74%). Significant improvements of plasma BNP level, resting heart rate, and systolic pulmonary artery pressure were also observed. Improvement of tricuspid regurgitation was observed in 11 of 17 patients with moderate or severe regurgitation during the follow-up period. Conversely, worsening of mitral regurgitation was observed in 10 of the 27 patients. Conclusion: Transcatheter closure of ASD in geriatric patients can be performed safely. This procedure contributes to significant improvement of symptoms and positive cardiac remodeling. Long-term follow-up is mandatory, especially for patients with mitral regurgitation. © 2012 Wiley Periodicals, Inc.

Nowadays transcatheter closure has become the standard treatment for an atrial septal defect (ASD). Since morphologic variation of ASD is common, imaging modalities with high diagnostic ability continue to be required. Meanwhile, experts are required to visualize high-quality images with advanced imaging modalities. Echocardiography plays a pivotal role in patient selection for treatment, recently introduced 3D echocardiography is a promising modality to provide comprehensible en face images of ASD, especially in patients with a complex-shaped ASD. In addition, cardiac MRI and computed tomography can provide complementary information. Transesophageal echocardiography and intracardiac echocardiography can provide images of excellent quality for guidance of the procedure. In this review, we discuss the role of imaging for transcatheter ASD closure, focusing on echocardiography.

Coronary sinus defect is a rare type of atrial septal defect. We report two patients who had a coronary sinus atrial septal defect without persistent left superior caval vein, where the orifice of the coronary sinus was closed using the Amplatzer Septal Occluder. The procedure was successful, without any complications including conduction disturbance.

The influence of deficient rims surrounding atrial septal defects (ASDs) in patients undergoing transcatheter closure has yet to be clarified. The aim of this study was to assess the influence of a deficient surrounding rim on the procedural success and clinical outcome of transcatheter ASD closure using an Amplatzer septal occluder.A total of 474 patients (mean age, 46 ± 22 years) with ostium secundum ASDs measuring ≤40 mm in diameter who had undergone attempted transcatheter closure using Amplatzer septal occluders from September 2007 to August 2013 were assessed. A comprehensive transesophageal echocardiographic examination was done to assess the morphologic characteristics of the defects in all patients. Subjects were classified into three groups by the extent and location of rim deficiency (5 mm): patients without deficient rims (sufficient group, n = 101), patients with single deficient rims, (single group, n = 338), and patients with multiple rim deficiencies (multiple group, n = 35).There was a significant difference in the maximal defect diameter among the sufficient, single, and multiple groups (15 ± 6, 18 ± 6, and 29 ± 7 mm, respectively, P .001). Transcatheter closure was successfully accomplished in 463 patients (98%). The prevalence of procedural success differed significantly among the sufficient, single, and multiple groups (100%, 98%, and 86%, respectively, P .001). There was no significant difference in the occurrence of cardiovascular events among the three groups during a mean follow-up period of 25 ± 19 months (P = .926, log-rank test).In patients with ASDs with multiple rim deficiencies as determined by transesophageal echocardiography, successful transcatheter ASD closure using Amplatzer septal occluders is more difficult to accomplish. However, if closure is successful, rim deficiencies rarely affect intermediate-term outcomes.

Neurotrophin receptor p75 (p75NTR) knockout mice (p75(−/−) mice) provide a good animal model of progressive-onset hearing loss.1 Cell loss of the spiral ganglion neurons (SGNs) and hair cell degeneration at the basal turn of the cochlea are seen in p75(−/−) mice from 3 months of age. Furthermore, from 3 to 6 months of age, the hearing thresholds of p75(−/−) mice are gradually raised; and after 6 months of age, the mice mostly exhibit hearing loss.1 Several previous reports have indicated that electroacupuncture (EA) stimulation may improve subjective symptoms of tinnitus or hearing loss.2 ,3 However, the molecular mechanisms underlying the therapeutic effect of EA stimulation for hearing loss remain unclear. Thus, to determine whether EA stimulation is useful for the prevention of hearing loss, we used a p75(−/−) mouse model of progressive-onset hearing loss. The Ting Gong (SI19; Small Intestine 19) and the Yifeng (TE17; Triple Energiser meridian 17) are …

We assessed right ventricular (RV) geometric remodeling quantitatively in patients with chronic pulmonary hypertension (PH) secondary to left-sided heart disease using real-time 3-dimensional echocardiography by comparing segmental and total volumes to that in normal subjects. The comparison result revealed that RV geometric remodeling in the PH group mainly occurred at the basal, mid-basal, and mid-segments. Total RV end-diastolic and end-systolic volumes in the PH group were significantly larger than that in normal subjects.

Balloon angioplasty of a bifurcation lesion is associated with lower rates of success and higher rates of complications than such treatment of lesions of most other morphologies. To date, the best device or procedure for bifurcation lesions has not been determined. The aim of this study was to compare the immediate and 3-month follow-up outcome of cutting balloon angioplasty (CBA) versus conventional balloon angioplasty (PTCA) for the treatment of bifurcation lesions. We treated 87 consecutive bifurcation lesions with CBA (n = 50) or PTCA (n = 37). Paired angiograms were analyzed by quantitative angiography, and angiographic follow-up was achieved for 93% of the lesions. The procedural success was 92% in the CBA group and 76% in the PTCA group (P < 0.05). Major in-hospital complications occurred in two lesions in the CBA group and six in the PTCA group (P = 0.05). The incidence of bail-out stenting in the CBA group was lower than in the conventional PTCA (8% vs 24%, P < 0.05). At the 3-month follow-up, the restenosis rate was 40% in the CBA group versus 67% in the PTCA group (P < 0.05). Clinical events during follow-up did not differ between the two groups. In conclusion, in comparison with PTCA, procedural success was greater and the restenosis rate lower with CBA. The results of this study support the use of the cutting balloon as optimal treatment for bifurcation lesions. (J Interven Cardiol 2004;17:1–7)

Platypnea-orthodeoxia is a rare condition characterized by dyspnea and oxygen desaturation induced by the upright position and relieved by recumbency. The most common cause of this syndrome is right-to-left shunt through interatrial communications such as patent foramen ovale (PFO) or atrial septal defect (ASD). In addition, this syndrome can be caused by other extracardiac components, including pulmonary emphysema, pericardial disease, and prominent Eustachian valve. We experienced 3 cases of this syndrome, including 1 patient with PFO and 2 patients with ASD. Computer tomography imaging revealed aortic elongation and compression of the right atrium by ascending aorta in all of 3 patients. Transcatheter closure of PFO or ASD was successfully performed in all patients, including immediate improvements of symptoms and oxygen saturation without any complications.

Impaired exercise capacity has been found in patients with diastolic dysfunction with preserved systolic function. Although conventional transthoracic echocardiography (TTE) provides useful clinical information about systolic and diastolic cardiac function, its capability to evaluate exercise capacity has been controversial. The inertia force of late systolic aortic flow is known to have a tight relationship with left ventricular (LV) performance during the period from near end-systole to isovolumic relaxation. The inertia force and the time constant of LV pressure decay during isovolumic relaxation can be estimated noninvasively using the second peak (W(2)) of wave intensity (WI), which is measured with an echo-Doppler system. We sought to determine whether W(2) is associated with exercise capacity in patients with chronic heart failure with normal ejection fraction (HFNEF) and to compare its ability to predict exercise capacity with parameters obtained by conventional TTE including tissue Doppler imaging. Sixteen consecutive patients with chronic HFNEF were enrolled in this study. Wave intensity was obtained with a color Doppler system for measurement of blood velocity combined with an echo-tracking system for detecting changes in vessel diameter. Concerning conventional TTE, we measured LV ejection fraction (EF), peak velocities of early (E) and late (A) mitral inflow using pulse-wave Doppler, and early (Ea) and late (Aa) diastolic velocities using tissue Doppler imaging. Left ventricular EF, E/A ratio, Ea, and E/Ea ratio did not correlate with exercise capacity, whereas W(2) significantly correlated with peak VO(2) (r = 0.54, p = 0.03), VE/VCO(2) slope (r = -0.53, p = 0.03), and ΔVO(2)/ΔWR (r = 0.56, p = 0.02). W(2) was associated with exercise capacity in patients with chronic HFNEF. In conclusion, W(2) is considered to be clinically more useful than conventional TTE indices for evaluating exercise capacity in patients with chronic HFNEF.

A recent study has shown that cryptogenic stroke can occur even in patients with small or insignificant atrial septal defects (ASD). However, clinical experience in this field is still limited in Japan, also the efficacy and safety of catheter closure of such defects have not been identified. To evaluate the efficacy and safety of catheter closure of interatrial communication in patients with cryptogenic stroke, 13 patients who were diagnosed with cerebrovascular events due to cryptogenic embolism were included in this study. Mean age at procedure was 43 ± 15 (range 17–68) years. In all patients, the presence of spontaneous or provoked interatrial right-to-left shunts was demonstrated by transesophageal contrast echocardiography. Mean defect size evaluated by the balloon sizing technique was 9.2 ± 2.8 mm, and mean size of the Amplatzer Septal Occluder deployed was 9.5 ± 2.8 mm. Devices were successfully deployed in all patients, though one device migrated into the descending aorta was retrieved by a snare catheter. Complete closure was detected by transesophageal contrast echocardiography at 12 months after the procedure was in 11 (85%) of the 13 patients. During the follow-up period (30.1 ± 9.4 months), no recurrent thromboembolic event was observed. Catheter closure of interatrial right-to-left communications can be safely performed. This procedure may contribute to reduction or prevention of recurrent neurological events in this patient population.

Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

Atrial fibrillation (AF) often occurs in Brugada syndrome (BrS), and BrS patients with spontaneous AF often experience ventricular fibrillation (VF) attacks. Atrial vulnerability providing a substrate for AF is known to be enhanced in BrS, but there are no data on atrial structural attributes.The objective of this study was to assess atrial electrophysiological and structural characteristics in BrS and their relationships with gene mutations.We studied 57 patients with BrS. Intra-atrial conduction time (CT) was defined as the interval from the stimulus at the high right atrium to atrial deflection at the distal portion of the coronary sinus. Left atrial volume index (LAVI) was measured by the modified Simpson method at left ventricular end-systole using echocardiography. SCN5A mutations were analyzed in all patients.In patients with documented VF, spontaneous AF frequently occurred and prolonged CT and increased LAVI were observed compared with those in patients without VF (all P.05; LAVI: 22 +/- 5 vs. 32 +/- 7 ml/m(2)). Even among patients without AF, CT and LAVI were still increased in patients with VF (all P.05; LAVI: 22 +/- 5 vs. 29 +/- 5 ml/m(2)). The presence of SCN5A mutation was associated with prolonged CT (P.05) and increased LAVI (P.01), but not with arrhythmic episodes.Both atrial vulnerability and structural remodeling are enhanced in high-risk patients with BrS, even in those without AF. These morphological characteristics suggest that BrS is a form of genetic myocardial disease.

Objectives: The aim of this study is to evaluate the feasibility and efficacy of device closure of atrial septal defect (ASD) in elderly patients with permanent atrial fibrillation. Background: Little is known about the feasibility of device closure of ASD in those patients. Methods: Nine consecutive patients (mean age 68.1 years) with permanent atrial fibrillation (>1 year persistent) underwent catheter closure using the Amplatzer septal occluder. Transthoracic echocardiography and plasma B-type natriuretic peptide (BNP) level were assessed before and at 24 hours; and 1, 3, and >6 months after the closure. Before the procedure, appropriate dose of warfarin was used in all, diuretics was used in 8/9. Same amount of medications were continued after the procedure. Results: ASD could be closed in all (mean device size 27.3 mm) without hemodynamic and thromboembolic complications. New York Heart Association (NYHA) functional classification was significantly improved in all patients after device closure. No hemodynamic and thromboembolic complications were observed during the follow-up period (mean 10.6 months). Although permanent atrial fibrillation did not change in all after the procedure, resting heart rate decreased from 76.2 ± 16.0 to 68.3 ± 13.2 beats/min (P = 0.015). There was statistically significant improvement in right ventricular/left ventricular diameter ratio (1.08 ± 0.16 to 0.73 ± 0.10, P = 0.008) and plasma BNP level (183.7 ± 90.5 to 94.6 ± 47.4 pg/mL, P = 0.008) after >6 months device closure. Conclusions: Even in the patients complicated with permanent fibrillation, transcatheter closure of ASD can contribute to symptomatic improvement as well as cardiac geometric remodeling. © 2009 Wiley-Liss, Inc.

Background: Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. WI can be defined at any site in the circulatory system and provide a great deal of information. However, the clinical usefulness of the second peak of WI, which is related to the ability of the left ventricle to activity stop aortic blood flow, has not been fully reported. In previous study, the magnitude of W2 was related to the inertia force of late systolic aortic flow. Also, the higher augmented inertia force, which was calculated with cardiac catheterization, was associated with greater exercise capacity. Then, we hypothesize that WI is correlated to exercise capacity. In this study, we investigated whether WI and the echocardiographic parameters would be correlated with exercise capacity. Methods: A total of 24 patients of heart disease were enrolled. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. As echocardiographic parameters, we analyzed ejection fraction (EF), the early (E) and late (A) diastolic mitral velocities, and early (Ea) and late (Aa) diastolic velocities measured using Tissue Doppler imaging. We evaluated exercise capacity (peak VO2, VE/VCO2, and AT). We used Pearson’s correlation analysis for statistics. Results: EF, the E/A ratio, and the E/Ea ratio were not correlated to exercise capacity. However, the second peak of WI was significant correlated to the peak VO2 (r=0.50, p

Objectives: To evaluate acute cardiac remodeling after transcatheter closure of atrial septal defect (ASD) in adult patients. Background: In adult patients with ASD, longer periods of cardiac adaptation should be expected after the procedure due to long-standing RV volume overload and subsequent changes in the pulmonary vasculature. There are limited reports about this remodeling in adult patients. Methods: We prospectively enrolled 17 adults (mean age 58.4 ± 17.3 years) who underwent successful transcatheter closure of their ASDs from August 2005 to July 2006. We performed routine transthoracic echocardiographic studies, including LV and RV myocardial performance indices, or Tei indices, and plasma brain natriuretic peptide (BNP) sampling before closure of the ASD, and 1 day, 1 month, and 3 months after closure. Results: We found (1) LV end diastolic diameter increased, and RVEDD decreased markedly after the closure; (2) differences existed in LV and RV adaptation. While LV Tei index improved soon after the procedure, RV Tei index worsened until 1 month after the procedure, then recovered by the 3 month follow-up visit; and (3) BNP elevated 1 day after closure of the ASD and declined by the 1-month follow-up visit. Conclusion: “Shrinkage” of the RV and “expansion” of the LV occurred soon after the procedure, even in elderly patients. Device closure of ASDs caused rapid improvement of LV function, but RV function underwent transient deterioration, probably due to delayed changes in RV ventricular mass in the face of acute volume reduction in this aged cohort. © 2007 Wiley-Liss, Inc.

Objective We sought to evaluate improvement of flow capacity in a left internal thoracic artery graft by means of pressure measurement. Methods Eighteen patients who received a left internal thoracic artery graft to the left anterior descending coronary artery were studied. Angiography and pressure measurement at the proximal and distal portions of the left internal thoracic artery graft during maximal hyperemia with a pressure guide wire were performed at 1 month (early study) and 6 months (late study) after surgical intervention. Results There are no significant differences between the early and late studies in resting mean aortic pressure, left ventricular end-diastolic pressure, left ventricular ejection fraction, and percentage diameter stenosis of the recipient left anterior descending coronary artery. There was no stenosis in the anastomosis site of the left internal thoracic artery graft and the distal left anterior descending coronary artery, as determined by means of angiography, in the early and late studies. The mean diameter of the distal left internal thoracic artery graft was significantly increased in the late study (1.6 ± 0.2 vs. 1.8 ± 0.2 mm, P = .011). There was a significant difference between the early and late studies in the pressure gradient through the graft (15 ± 4 vs 13 ± 3 mm Hg, P = .036). The ratio of distal to proximal pressure within the left internal thoracic artery graft in the late study was significantly increased from that in the early study (0.80 ± 0.04 to 0.84 ± 0.03, P = .0003). Conclusions The pressure ratio within the left internal thoracic artery graft became higher as the left internal thoracic artery graft adapted itself to the myocardial circulation. This finding might relate to decreasing the resistance of the left internal thoracic artery graft.

Brain natriuretic peptide (BNP) level has been used as a marker of left ventricular (LV) systolic dysfunction (LVSD), even though some patients with atherosclerosis have a high BNP level irrespective of LV function. In this study, we investigate whether augmentation index (AI), which is an index of wave reflection, is involved in increasing BNP level in hypertensive patients without LVSD. Sixty treated hypertensive patients were enrolled in this study. Radial AI (r-AI) was measured in all patients. The patients were classified into tertiles on the basis of r-AI to identify the characteristics of the patients with a high r-AI. BNP level was significantly higher in the patients classified into the highest tertile of r-AI. In echocardiography, e', which is index of left ventricular (LV) diastolic function, decreased and LV mass index (LVMI) increased gradually with r-AI, whereas there was no difference in LV ejection fraction (LVEF). r-AI significantly correlated with LVMI (r=0.35, p

The neurotrophin receptor p75 (p75NTR) is expressed in the developmental stage of the cochlea. However, the role of the p75NTR in the inner ear remains to be established. In this study, we conducted electrophysiological and morphological analyses of the auditory function of mice carrying a mutation in the p75 gene at different longitudinal stages. The mice carrying a mutation in the p75 gene showed an age-related progressive hearing loss. At 1 month, there was no obvious morphological change in the cochlea of the mice carrying a mutation in the p75 gene compared to wild-type mice, except for a slight loss of spiral ganglion neurons (SGNs). Auditory function was not significantly different between both genotypes from 1 to up to 4 months of age. The mice carrying a mutation in the p75 gene started to show progressive hearing loss at 4 months, when both SGN degeneration and hair cell (HC) loss were observed at the basal turn. These results suggest that the neurotrophin receptor p75 may play a significant role in the maintenance of cochlear function, and that mice carrying a mutation in the p75 gene could be a good animal model of early onset progressive hearing loss.

A 25-year-old male was admitted to hospital with a 3-day history of worsening faintness. The electrocardiogram showed complete atrioventricular block. Echocardiography showed generalized hypokinesis and prominent trabeculations ranged from the apex to the mid-ventricular lateral wall of the left ventricle as well. Furthermore, trabeculations in the left ventricle were seen in his sister and brother. Thus, isolated ventricular noncompaction (IVNC) was diagnosed and a permanent pacemaker was implanted. Common clinical symptoms of IVNC are heart failure, ventricular arrhythmias, and embolic events. This is the first reported adult case of IVNC disclosed by the presence of complete atrioventricular block.

A 36-year-old Japanese man was hospitalized with coughing and exertional dyspnea (NYHA class I). He was diagnosed as having congestive heart failure, and was treated with diuretics and a beta-adrenergic blocking agent. He responded well to the treatment and his symptoms completely disappeared within a few days. Based on his clinical, laboratory, and molecular genetic findings, he was diagnosed as having X-linked dilated cardiomyopathy (XLDCM). He was found to have a large deletion in the dystrophin gene, involving exons 45-55. This is the first report on a Japanese XLDCM patient with a mutation in the central hot-spot region of this gene.

A 29-year-old man was hospitalized because of dyspnea and palpitation. Electrocardiography demonstrated normal sinus rhythm and borderline right atrial enlargement. Twodimensional transthoracic echocardiography (2D-TTE) revealed a normal left ventricular systolic function. There was a paradoxical septal motion consistent with right ventricular volume overload (Fig. 1a). Although the right ventricle was mildly dilated, its systolic function was preserved. 2D-TTE revealed a large atrium without distinct interatrial septum (Fig. 1b). Left-to-right shunt flow was not detected clearly through the defect on color-flow Doppler imaging. Real-time three-dimensional echocardiography (RT3D-TTE) visualized a large defect of interatrial septum clearly (Fig. 2). The patient was referred for surgery. Only a tiny vestige of the interatrial septum could be confirmed with the naked eye, and the two atrioventricular valves were normal. The patch closure was performed successfully using a fresh autologous pericardial patch. Atrial septal defect (ASD) is a common congenital heart disease presenting in adulthood. Our patient showed a large secundum ASD like single atrium. It is sometimes difficult to distinguish a large secundum ASD from a single atrium. Levy et al. recommended that the term ‘‘single atrium’’ should be used to denote a condition comprising: (1) complete absence of the interatrial septum, (2) absence of malformation of the atrioventricular valves, and (3) absence of interventricular communication [1]. In our case, the morphological diagnosis was supposed to be a large secundum type atrial septal defect, because a small part of the interatrial septum was found. In this case, RT3D-TTE enhanced the understanding of the anatomy and spatial relationship between the defect and its adjacent structure. Previous study has shown the usefulness of RT3D-TTE for patient selection for surgical or transcatheter closure of atrial septal defects. It has been reported that RT3D-TTE allows accurate determination of the ASD location, ASD size, and surrounding tissue of the interatrial septum [2, 3]. Although our patient demonstrated a large part to be missing from the interatrial septum, RT3D-TTE could clearly visualize a large defect of the interatrial septum. RT3D-TTE provided additional, clinically relevant qualitative information for the evaluation of this patient with a large defect of the interatrial septum. N. Watanabe Y. Tanabe Division of Medical Support, Okayama University Hospital, Okayama, Japan

Transcatheter closure of atrial septal defects (ASDs) has become an accepted and reliable procedure. Although various complications have been recognized, tear of the atrial septal rim is a rare complication. We report a case of atrial septal rim tear that was diagnosed during the procedure by real-time three-dimensional transesophageal echocardiography (TEE). The device was successfully implanted 3 months after the initial intervention. RT3D TEE is more useful for displaying the entire shape of the defect and its spatial relationship (RT3D) with its neighboring structures compared with conventional two-dimensional echocardiography. By using both two-dimensional and RT3D TEE images, especially in cases with complicated ASD morphology, both the echocardiologist and interventionalist gain valuable information on the morphology of the ASD before and during the procedure.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior.