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  1. Abnormal right ventricular relaxation in pulmonary hypertension

    PubMed Central

    La Gerche, Andre; Roberts, Timothy J.; Prior, David L.; MacIsaac, Andrew I.; Burns, Andrew T.

    2015-01-01

    Abstract Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure ( vs. mmHg, ) and RV end-diastolic pressure (RVEDP; vs. mmHg, ), and RV τ was significantly prolonged ( vs. ms, ). There were strong correlations between RV τ and RV minimum diastolic pressure (, ) and between RV τ and RVEDP (, ). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group ( vs. mmHg/mL, ) and a correlation between RV systolic pressure and first derivative of maximum pressure change (, ). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures. PMID:26064464

  2. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  3. Coronary arterial abnormalities in pulmonary atresia with intact ventricular septum.

    PubMed

    Calder, A L; Co, E E; Sage, M D

    1987-02-15

    The incidence and severity of abnormalities of the coronary arteries were evaluated in 35 necropsy patients with pulmonary atresia and an intact ventricular septum. Right ventricular to coronary artery fistulous connections were found in more than 60% of the cases. All patients with fistulous connections had histologic abnormalities of the coronary arteries. In 50% the lesions were mild, with medial and intimal thickening producing up to moderate luminal stenosis. In 50% there was loss of normal arterial wall structure and severe narrowing or obliteration of the arterial lumen. The coronary arterial fistulas and histologic abnormalities were prevalent in those with underdevelopment of the tricuspid valve and right ventricular cavity but were not found in patients with a normal or dilated tricuspid valve anulus. The coronary arterial abnormalities were found in more than 80% of patients with a tricuspid valve/mitral valve ratio less than 1. A single coronary artery occurred in 6 patients (17%) of this series. In 80% of those with 1 coronary artery arising from the other, the aberrantly arising coronary artery crossed anteriorly to the pulmonary artery and could be at risk in surgical attempts to reconstruct the right ventricular outflow. Aortography is recommended if the coronary arteries are not clearly delineated on ventricular cineangiocardiography.

  4. Echocardiographic assessment of abnormal left ventricular relaxation in man.

    PubMed Central

    Upton, M T; Gibson, D G; Brown, D J

    1976-01-01

    In 64 patients requiring cardiac catheterization for chest pain, echocardiograms showing anterior mitral leaflet and left ventricular cavity simultaneously were recorded. These were digitized and their first derivatives computed in order to study time relations between mitral valve and left ventricular wall movement in early distole. In 10 patients with normal left ventricular angiograms and coronary arteriograms, mitral valve opening began 1-1 +/- 9-3 ms (mean +/- SD) before the onset of outward wall movement, and reached peak opening velocity 2-0 +/- 13 ms after maximum rate of change of dimension. Virtually identical time relations were seen in 15 patients with normal left ventricular angiograms but with obstructive coronary artery disease (3-6 +/- 9-3 ms and 0-7 +/- 7-3 ms, respectively). These close relations were lost in patients with segmental abnormalities of contraction on left ventricular angiogram. In 19 such patients with normal septal motion, outward wall movement began 53 +/- 31 ms before the onset of anterior movement of the mitral valve leaflet, and this isovolumic wall movement accounted for 31 per cent of the total diastolic excursion. In 9 patients with reversed septal movement, these abnormalities were greater, 92 +/- 39 ms and 33 per cent, respectively, while in 11 patients with diffuse left ventricular involvement they were small, 5-5 +/- 13 ms and 3 per cent. Frame-by-frame digitization of cineangiograms was used to confirm these findings which appear to reflect an abnormal change in left ventricular cavity shape during isovolumic relaxation. Images PMID:973873

  5. Abnormal sexual behavior during sleep.

    PubMed

    Della Marca, Giacomo; Dittoni, Serena; Frusciante, Roberto; Colicchio, Salvatore; Losurdo, Anna; Testani, Elisa; Buccarella, Cristina; Modoni, Anna; Mazza, Salvatore; Mennuni, Gioacchino Francesco; Mariotti, Paolo; Vollono, Catello

    2009-12-01

    Automatic, uncontrolled, and unaware sexual behaviors during sleep have occasionally been described. The clinical and polysomnographic features of nocturnal sexual behavior allow it to be considered a distinct parasomnia named "sexsomnia". Recently, abnormal sexual behaviors during sleep have been evaluated in the forensic medical context because violent behaviors can be associated with this parasomnia. To describe the clinical and polysomnographic findings in three patients who referred to our sleep laboratory for sleep disorders and who reported episodes of sleep-related sexual activation. We analyzed video-polysomnographic recordings, sleep structure, sleep microstructure, and sleep-related respiratory events. The patients were three males aged 42, 32, and 46 years. All had unremarkable medical, neurological, and psychiatric histories. All underwent full-night polysomnography. Each patient presented a distinct sleep disorder: one had severe obstructive sleep apnea syndrome (OSAS), one presented clinical and polysomnographic features of non-rapid eye movement (NREM) sleep parasomnia (somnambulism), and the third presented clinical and polysomnographic features of rapid eye movement behavior disorder. In our patients, the clinical and polysomnographic findings suggest that abnormal nocturnal sexual behavior can occur in association with distinct sleep disorders, characterized by different pathophysiologic mechanisms and distinctive treatments. Abnormal sexual behaviors during sleep should be investigated with polysomnography in order to define their pathophysiology and to establish appropriate treatments.

  6. Midventricular Obstruction Caused by Abnormal Intra-Left Ventricular Septum and Papillary Muscles.

    PubMed

    Samura, Takaaki; Toda, Koichi; Saito, Shunsuke; Miyagawa, Shigeru; Yoshikawa, Yasushi; Fukushima, Satsuki; Yoshioka, Daisuke; Domae, Keitaro; Sawa, Yoshiki

    2017-09-01

    Abnormal papillary muscle is a rare cause of midventricular obstruction. In this case report, hypertrophied abnormal papillary muscles and abnormal tissue growth from the septal wall formed an intra-left ventricular septum with a small hole and resulted in severe midventricular obstruction. Radical resection of both papillary muscles and the intra-left ventricular septum was performed along with mitral valve replacement to relieve the obstruction. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Abnormal ventricular development in preterm neonates with visually normal MRIs

    NASA Astrophysics Data System (ADS)

    Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

    2015-12-01

    Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

  8. Substrate Ablation of Ventricular Tachycardia: Late Potentials, Scar Dechanneling, Local Abnormal Ventricular Activities, Core Isolation, and Homogenization.

    PubMed

    Briceño, David F; Romero, Jorge; Gianni, Carola; Mohanty, Sanghamitra; Villablanca, Pedro A; Natale, Andrea; Di Biase, Luigi

    2017-03-01

    Ventricular arrhythmias are a frequent cause of mortality in patients with ischemic cardiomyopathy and nonischemic cardiomyopathy. Scar-related reentry represents the most common arrhythmia substrate in patients with recurrent episodes of sustained ventricular tachycardia (VT). Initial mapping of scar-related VT circuits is focused on identifying arrhythmogenic tissue. The substrate-based strategies include targeting late potentials, scar dechanneling, local abnormal ventricular activities, core isolation, and homogenization of the scar. Even though substrate-based strategies for VT ablation have shown promising outcomes for patients with structural heart disease related to ischemic cardiomyopathy, the data are scarce for patients with nonischemic substrates.

  9. Cardiac sympathetic nerve abnormality predicts ventricular tachyarrhythmic events in patients without conventional risk of sudden death.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Kawamura, Mitsuharu; Asano, Taku; Tanno, Kaoru; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2008-11-01

    Patients with structural heart disease, severe left ventricular dysfunction, or history of cardiac arrest are at increased risk of sudden cardiac death. However, a useful marker for predicting sudden cardiac death is not clarified in low-risk patients without those conventional risks. We hypothesized that cardiac sympathetic nerve system (SNS) abnormality would be associated with ventricular tachyarrhythmic events in low-risk patients with ventricular tachycardia (VT). Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) scintigraphy was performed in 50 patients (mean+/-standard deviation, age 54 +/- 16 years, 52% males) with VT who did not have structural heart disease, severe left ventricular dysfunction, or history of cardiac arrest, and SNS activity was assessed from heart/mediastinal (H/M) ratio on delayed images. Over 11 years of follow-up, three patients had sudden deaths (6%) and nine patients had sustained ventricular tachyarrhythmic events (18%). SNS abnormality, defined as H/M ratio <2.8, was predictive of sudden death or ventricular tachyarrhythmic events (45% in nine of 20 patients with SNS abnormality vs 16.7% in three of 30 patients without SNS abnormality, p = 0.005). After adjustment for potential confounding variables including slight left ventricular dysfunction, SNS abnormality remained independently predictive of ventricular tachyarrhythmic events with a hazard ratio of 5.3 (95% confidence interval = 1.4 to 20.8, p = 0.016). SNS abnormality is a readily available and powerful predictor of recurrent ventricular tachyarrhythmic events in patients with VT who did not have conventional risk of sudden cardiac death. (123)I-MIBG scintigraphy can provide prognostic information of VT patients without conventional risk.

  10. Nonreentrant ventricular arrhythmias in patients with structural heart disease unrelated to abnormal myocardial substrate.

    PubMed

    Ellis, Ethan R; Shvilkin, Alexei; Josephson, Mark E

    2014-06-01

    Ventricular arrhythmias in the absence of structural heart disease are commonly referred to as "idiopathic." Patients with structural heart disease have ventricular arrhythmias with the same mechanisms and sites of origin as idiopathic ventricular arrhythmias, but the prevalence of such arrhythmias is not well defined. To identify the prevalence of nonreentrant ventricular arrhythmias unrelated to abnormal myocardial substrate in patients with structural heart disease and to compare these arrhythmias to ventricular arrhythmias in patients with structurally normal hearts. Of 249 consecutive patients referred for ablation of ventricular arrhythmias, 97 (39%) patients had nonreentrant arrhythmias unrelated to underlying structural heart disease. Fifty-five (57%) patients had structurally normal hearts, and 42 (43%) had underlying structural heart disease. Compared with patients with structurally normal hearts, patients with structural heart disease were more likely to have nonreentrant ventricular arrhythmias unrelated to underlying abnormal myocardial substrate originating from the aortic cusps and left ventricular outflow tract whereas patients without structural heart disease more often had arrhythmias originating from the right ventricular outflow tract. There was a significant increase in the average left ventricular ejection fraction after ablation in patients with structural heart disease. Nonreentrant ventricular arrhythmias unrelated to abnormal myocardial substrate are common in patients with structural heart disease, and sites of origin differ from those seen in patients with structurally normal hearts. When managing structural heart disease in patients with ventricular arrhythmias, a focus on arrhythmia mechanism, origin, and relationship to underlying myocardial substrate may have important implications for future treatment options and patient outcomes. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. Ventricular tachycardia and exercise related syncope in children with structurally normal hearts: emphasis on repolarisation abnormality.

    PubMed Central

    Noh, C. I.; Song, J. Y.; Kim, H. S.; Choi, J. Y.; Yun, Y. S.

    1995-01-01

    OBJECTIVE--To emphasize the importance of ventricular tachycardia associated with repolarisation abnormality in syncope associated with exercise. DESIGN--Retrospective analysis of data on children presenting with syncope between 1985 and 1993. PATIENTS--5 apparently normal children with recurrent exercise related syncope associated with electrocardiographically abnormal TU complexes. RESULTS--3 children were diagnosed as having an intermediate form of the long QT syndrome and catecholamine sensitive ventricular tachycardia because the abnormal TU complexes were associated with polymorphic ventricular tachycardia that was not typical of torsades de pointes. Tachycardia was induced by exercise in all patients and by isoprenaline in the one patient who was tested. One patient also had sinus node dysfunction. One child had incessant salvos of polymorphic ventricular arrhythmias and intermittent abnormal TU complexes suggestive of repolarisation abnormalities. The other had typical congenital long QT syndrome. Treatment was effective in three patients; two patients took a beta blocker alone and one took a beta blocker and low doses of amiodarone. One patient died suddenly, death being associated with sinus node dysfunction. In one patient with incessant ventricular arrhythmias treatment with a beta blocker, amiodarone, or Ic drugs was ineffective and always associated with proarrhythmia or syncope. He was not given further treatment and was asymptomatic despite having mild cardiomegaly. CONCLUSIONS--Ventricular tachycardia associated with repolarisation abnormality was an important cause of exercise related syncope in apparently normal children. TU complex abnormalities can be identified by repeated electrocardiography. beta Blockers are effective in preventing recurrent episodes. The role of amiodarone in this type of ventricular tachycardia needs further evaluation. PMID:7626354

  12. Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions.

    PubMed

    Tse, Gary; Yeo, Jie Ming

    2015-12-07

    Ventricular arrhythmias arise from disruptions in the normal orderly sequence of electrical activation and recovery of the heart. They can be categorized into disorders affecting predominantly cellular depolarization or repolarization, or those involving action potential (AP) conduction. This article briefly discusses the factors causing conduction abnormalities in the form of unidirectional conduction block and reduced conduction velocity (CV). It then examines the roles that sodium channels and gap junctions play in AP conduction. Finally, it synthesizes experimental results to illustrate molecular mechanisms of how abnormalities in these proteins contribute to such conduction abnormalities and hence ventricular arrhythmogenesis, in acquired pathologies such as acute ischaemia and heart failure, as well as inherited arrhythmic syndromes.

  13. Increase in the embedding dimension in the heart rate variability associated with left ventricular abnormalities

    NASA Astrophysics Data System (ADS)

    Andrés, D. S.; Irurzun, I. M.; Mitelman, J.; Mola, E. E.

    2006-10-01

    In the present study, the authors report evidence that the existence of premature ventricular contractions increases the embedding dimension of the cardiac dynamics. They also analyze patients with congestive heart failure, a severe clinical condition associated with abnormal left ventricular function. Results also show an increase in the embedding dimension of the heart rate variability. They used electrocardiograms collected by themselves with quality standards that make them comparable with other databases.

  14. Left ventricular false tendons and electrocardiogram repolarization abnormalities in healthy young subjects.

    PubMed

    Lazarevic, Zlatan; Ciminelli, Emanuela; Quaranta, Federico; Sperandii, Fabio; Guerra, Emanuele; Pigozzi, Fabio; Borrione, Paolo

    2016-10-26

    To describe echocardiographically left ventricular false tendon characteristics and the correlation with ventricular repolarization abnormalities in young athletes. Three hundred and sixteen healthy young athletes from different sport disciplines were evaluated from 2009 to 2011 during routine screening for agonistic sports eligibility. All subjects, as part of standard pre-participation screening medical evaluation, underwent a basal and post step test 12-lead electrocardiogram (ECG). The athletes with abnormal T-wave flattening and/or inversion were considered for an echocardiogram evaluation and an incremental maximal exercise test on a cycle ergometer. Arterial blood pressure and heart rate, during and after exercise, were also measured. Twenty-one of the 316 subjects (6.9%) showed false tendons in the left ventricle. The majority of false tendons (52.38%) were localized between the middle segments of the inferior septum and the lateral wall, 19.06% between the distal segments of the septum and the lateral wall, in 5 subjects between the middle segments of the anterior and inferior walls, and in one subject between the middle segments of the anterior septum and the posterior wall. ECG abnormalities, represented by alterations of ventricular repolarization, were found in 11 subjects (52.38%), 90% of these anomalies were T wave abnormalities from V1 to V3. These anomalies disappeared with an increasing heart rate following the three minute step test as well as during the execution of the maximal exercise. Left ventricular false tendons are frequently localized between the middle segments of the inferior septum and the lateral wall and are statistically associated with ventricular repolarization abnormalities.

  15. Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions

    PubMed Central

    Tse, Gary; Yeo, Jie Ming

    2015-01-01

    Ventricular arrhythmias arise from disruptions in the normal orderly sequence of electrical activation and recovery of the heart. They can be categorized into disorders affecting predominantly cellular depolarization or repolarization, or those involving action potential (AP) conduction. This article briefly discusses the factors causing conduction abnormalities in the form of unidirectional conduction block and reduced conduction velocity (CV). It then examines the roles that sodium channels and gap junctions play in AP conduction. Finally, it synthesizes experimental results to illustrate molecular mechanisms of how abnormalities in these proteins contribute to such conduction abnormalities and hence ventricular arrhythmogenesis, in acquired pathologies such as acute ischaemia and heart failure, as well as inherited arrhythmic syndromes. PMID:26839915

  16. Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

    SciTech Connect

    Botvinick, E.H.; Frais, M.A.; Shosa, D.W.; O'Connell, J.W.; Pacheco-Alvarez, J.A.; Scheinman, M.; Hattner, R.S.; Morady, F.; Faulkner, D.B.

    1982-08-01

    The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex and then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.

  17. Abnormal Left Ventricular Mechanics of Ventricular Ectopic Beats: Insights Into Origin and Coupling Interval in Premature Ventricular Contraction-Induced Cardiomyopathy.

    PubMed

    Potfay, Jonathan; Kaszala, Karoly; Tan, Alex Y; Sima, Adam P; Gorcsan, John; Ellenbogen, Kenneth A; Huizar, Jose F

    2015-10-01

    Left ventricular (LV) dyssynchrony caused by premature ventricular contractions (PVCs) has been proposed as a mechanism of PVC-induced cardiomyopathy. We sought to understand the impact of different PVC locations and coupling intervals (prematurity) on LV regional mechanics and global function of the PVC beat itself. Using our premature pacing algorithm, pentageminal PVCs at coupling intervals of 200 to 375 ms were delivered from the epicardial right ventricular apex, RV outflow tract, and LV free wall, as well as premature atrial contractions, from the left atrial appendage at a coupling interval of 200 ms in 7 healthy canines. LV short-axis echocardiographic images, LV stroke volume, and dP/dtmax were obtained during all ectopic beats and ventricular pacing. LV dyssynchrony was assessed by dispersion of QRS-to-peak strain (earliest-last QRS-to-peak strain) between 6 different LV segments during each of the aforementioned beats (GE, EchoPac). LV dyssynchrony was greater during long-coupled rather than short-coupled PVCs and PVCs at 375 ms compared with rapid ventricular pacing at 400 ms (P<0.0001), whereas no difference was found between PVC locations. Longer PVC coupling intervals were associated with greater stroke volume and dP/dtmax despite more pronounced dyssynchrony (P<0.001). PVCs with longer coupling intervals demonstrate more pronounced LV dyssynchrony, whereas PVC location has minimal impact. LV dyssynchrony cannot be attributed to prematurity or abnormal ventricular activation alone, but rather to a combination of both. This study suggests that late-coupled PVCs may cause a more severe cardiomyopathy if dyssynchrony is the leading mechanism responsible for PVC-induced cardiomyopathy. © 2015 American Heart Association, Inc.

  18. Clinical significance of exercise-induced ventricular tachyarrhythmias in trained athletes without cardiovascular abnormalities.

    PubMed

    Verdile, Luisa; Maron, Barry J; Pelliccia, Antonio; Spataro, Antonio; Santini, Massimo; Biffi, Alessandro

    2015-01-01

    Exercise-induced ventricular tachyarrhythmias raise clinical concern as a marker of increased risk in the presence of underlying cardiovascular disease. The aim of this study was to clarify the clinical significance of exercise-induced ventricular tachyarrhythmias in competitive athletes without evident cardiac abnormalities. Exercise electrocardiographic testing was performed in 5011 consecutive athletes without heart disease and analyzed for the occurrence of ventricular arrhythmias. Of the 5011 athletes, 367 (7.3%) showed ≥1 premature ventricular beat (PVB), including 331 (6.6%) with ≤10 PVBs and 36 (0.7%) with >10 PVBs and/or ≥1 ventricular couplets, and/or ≥1 bursts of nonsustained ventricular tachycardia. The 331 athletes with ≤10 PVBs had no restriction from competitive sports, and repeated exercise testing over 3-12 months showed spontaneous reduction of arrhythmia (from 5.2 ± 4 to 4 ± 6 PVBs; P = .002), including 83 of 331 (23%) with disappearance of PVBs. The remaining 36 athletes were disqualified from sports because of frequent and/or complex arrhythmias; 23 showed reduction of arrhythmia at 3-12 months (from 46 ± 42 to 28 ± 11 PVBs, from 8 ± 10 to 3 ± 3 couplets, and from 3.6 ± 6 to 1 ± 1 nonsustained ventricular tachycardia; P = .05) and were readmitted to competition. The other 13 athletes with persistent arrhythmias were considered for radiofrequency ablation, of whom 6 were successfully treated with abolition of arrhythmias and permitted to return to competitive sports. No events or cardiovascular disease occurred in the 367 athletes over a follow-up period of 7.4 ± 5 years. Exercise-induced ventricular tachyarrhythmias were present in a sizable minority of highly trained athletes without heart disease. These arrhythmias proved to be benign and not associated with adverse events or later development of cardiovascular disease. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  19. Abnormal eating behaviors in military women.

    PubMed

    Lauder, T D; Williams, M V; Campbell, C S; Davis, G D; Sherman, R A

    1999-09-01

    The purpose of this study was to evaluate the prevalence of abnormal eating behaviors in women on active duty in the Army. A total of 423 female soldiers from the general population on active duty volunteered to participate in this study. They completed the Eating Disorder Inventory (EDI) questionnaire. Each questionnaire was screened and any woman on active duty practicing abnormal eating behaviors (criteria set up by the authors) underwent an interview. A diagnosis, using DSM IV criteria, of one of the following was determined from the interview: 1) No eating disorder, (2) Anorexia nervosa, 3) Bulimia nervosa, 4) binge eating disorder, 5a) Eating disorder NOS, and 5b) Situational eating disorder. A situational eating disorder was defined as any abnormal eating behaviors consistent with an eating disorder NOS that was practiced intermittently and in response to external pressures associated with significant distress, such as military weigh-ins or army physical fitness testing (APFT). Of the 423 women on active duty who participated, 33.6% (N = 142) met the questionnaire screening criteria for being "at risk" for abnormal eating behaviors and underwent an interview. Of the 142 women interviewed, 33 (8%) women were diagnosed with an eating disorder. The women with eating disorders exercised, felt dissatisfied with their weight, and felt significantly more pressure about their weight than the women without eating disorders. In addition, they also had significantly greater scores on the Drive for Thinness (DT), Bulemia (B), and Body Dissatisfaction (BD) subscales, and the total EDI scores for both the 8 and 11 subscales. In the women on active duty in the Army studied, there was an 8% prevalence of eating disorders.

  20. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  1. Human fetal right ventricular ejection force under abnormal loading conditions during the second half of pregnancy.

    PubMed

    Rasanen, J; Debbs, R H; Wood, D C; Weiner, S; Weil, S R; Huhta, J C

    1997-11-01

    Our objective was to determine whether abnormal loading conditions can modify human fetal right ventricular ejection force during the second half of pregnancy. By Doppler echocardiography, we studied 73 normal fetuses between 19 and 41 weeks of gestation, 27 fetuses with hypoplastic left heart syndrome (chronic volume overload) between 18 and 38 weeks of gestation, 14 fetuses with mild to moderate constriction of the ductus arteriosus (pulsatility index (PI) between 1.0 and 1.9) and seven fetuses with severe constriction (PI < 1.0) or occlusion of the ductus arteriosus (relatively acute pressure overload) between 28 and 34 weeks of gestation. In the normal and ductal constriction/occlusion groups, blood velocity waveforms were recorded at the level of the aortic and pulmonary valves, and in the group with hypoplastic left heart syndrome at the level of the pulmonary valve. The ventricular ejection forces were calculated. In the normal group, right (RVEF; r = 0.91, p < 0.0001) and left (LVEF; r = 0.86, p < 0.0001) ventricular ejection forces increased and were equal during the second half of gestation. In the group with hypoplastic left heart syndrome the RVEF increased (r = 0.76, p < 0.0001) with advancing gestation. The RVEF (p < 0.0005) and its average weekly increase (p < 0.0001) were greater in the hypoplastic left heart syndrome group than in the normal group. In the group with mild to moderate ductal constriction, both ventricular ejection forces were similar to those of the normal group. The RVEF (p < 0.003) and its average weekly increase (p < 0.03) were lower in the group with severe ductal constriction or occlusion than in the normal group. The LVEF did not differ from that of the normal group We conclude that chronic volume overload increases and relatively acute pressure overload decreases human fetal RVEF. The right ventricular performance is modified by abnormal loading conditions.

  2. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance

    SciTech Connect

    Setaro, J.F.; Zaret, B.L.; Schulman, D.S.; Black, H.R.; Soufer, R. )

    1990-10-15

    Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second (edv/s)) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling.

  3. Abnormal propagation of calcium waves and ultrastructural remodeling in recessive catecholaminergic polymorphic ventricular tachycardia.

    PubMed

    Liu, Nian; Denegri, Marco; Dun, Wen; Boncompagni, Simona; Lodola, Francesco; Protasi, Feliciano; Napolitano, Carlo; Boyden, Penelope A; Priori, Silvia G

    2013-07-05

    The recessive form of catecholaminergic polymorphic ventricular tachycardia is caused by mutations in the cardiac calsequestrin-2 gene; this variant of catecholaminergic polymorphic ventricular tachycardia is less well characterized than the autosomal-dominant form caused by mutations in the ryanodine receptor-2 gene. We characterized the intracellular Ca²⁺ homeostasis, electrophysiological properties, and ultrastructural features of the Ca²⁺ release units in the homozygous calsequestrin 2-R33Q knock-in mouse model (R33Q) R33Q knock-in mouse model. We studied isolated R33Q and wild-type ventricular myocytes and observed properties not previously identified in a catecholaminergic polymorphic ventricular tachycardia model. As compared with wild-type cells, R33Q myocytes (1) show spontaneous Ca²⁺ waves unable to propagate as cell-wide waves; (2) show smaller Ca²⁺sparks with shortened coupling intervals, suggesting a reduced refractoriness of Ca²⁺ release events; (3) have a reduction of the area of membrane contact, of the junctions between junctional sarcoplasmic reticulum and T tubules (couplons), and of junctional sarcoplasmic reticulum volume; (4) have a propensity to develop phase 2 to 4 afterdepolarizations that can elicit triggered beats; and (5) involve viral gene transfer with wild-type cardiac calsequestrin-2 that is able to normalize structural abnormalities and to restore cell-wide calcium wave propagation. Our data show that homozygous cardiac calsequestrin-2-R33Q myocytes develop spontaneous Ca²⁺ release events with a broad range of intervals coupled to preceding beats, leading to the formation of early and delayed afterdepolarizations. They also display a major disruption of the Ca²⁺ release unit architecture that leads to fragmentation of spontaneous Ca²⁺ waves. We propose that these 2 substrates in R33Q myocytes synergize to provide a new arrhythmogenic mechanism for catecholaminergic polymorphic ventricular tachycardia.

  4. Patterns of ventricular tachyarrhythmias associated with training, deconditioning and retraining in elite athletes without cardiovascular abnormalities.

    PubMed

    Biffi, Alessandro; Maron, Barry J; Culasso, Franco; Verdile, Luisa; Fernando, Fredrick; Di Giacinto, Barbara; Di Paolo, Fernando M; Spataro, Antonio; Delise, Pietro; Pelliccia, Antonio

    2011-03-01

    Ventricular tachyarrhythmias commonly occur in trained athletes during ambulatory Holter electrocardiography and are usually associated with a benign course. Such arrhythmias have been demonstrated to be sensitive to short periods of athletic deconditioning; however, their response to retraining is not known. Twenty-four hour Holter electrocardiographic monitoring was performed at peak training and after 3 to 6 months of deconditioning and was repeated in the present study after 2, 6, and 12 months of retraining in 37 athletes with frequent and complex ventricular tachyarrhythmias and without cardiovascular abnormalities. These subjects showed partial (101 to 500 ventricular premature complexes [VPCs]/24 hours) or marked (<100 VPCs) reversibility of arrhythmias after deconditioning. Retraining initially resulted in a significant increase in arrhythmia frequency compared with deconditioning (from 280 ± 475 to 1,542 ± 2,186 VPCs; p = 0.005), couplets (0.14 ± 0.42 to 4.4 ± 8.2; p = 0.005), and nonsustained ventricular tachycardia (from 0 to 0.8 ± 1.8; p = 0.02). Subsequently, a progressive reduction was seen in the frequency of all ventricular arrhythmias during the 1 year of training to well below that at the peak training levels (VPCs 917 ± 1,630, couplets 1.8 ± 4.2, and nonsustained ventricular tachycardia 0.4 ± 1.2). Such annual arrhythmia reduction was significantly greater statistically in those athletes with marked reversibility after deconditioning than in the athletes with partial reversibility (69 ± 139 vs 1,496 ± 1,917 VPCs/24 hours, respectively; p = 0.007). No cardiac events or symptoms occurred during 1 year of follow-up. In conclusion, in elite athletes without cardiovascular disease, a resumption in intense training after deconditioning was associated with variable, but prolonged, suppression of ventricular ectopy. The absence of adverse clinical events or symptoms associated with the resumption of training supports the continued eligibility

  5. Multivariate Tensor-based Morphometry on Surfaces: Application to Mapping Ventricular Abnormalities in HIV/AIDS

    PubMed Central

    Wang, Yalin; Zhang, Jie; Gutman, Boris; Chan, Tony F.; Becker, James T.; Aizenstein, Howard J.; Lopez, Oscar L.; Tamburo, Robert J.; Toga, Arthur W.; Thompson, Paul M.

    2010-01-01

    Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics - these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain. PMID:19900560

  6. Left ventricular wall function abnormalities in patients with ankylosing spondylitis evaluated by gated myocardial perfusion scintigraphy.

    PubMed

    Yalcin, H; Guler, H; Gunay, E; Yeral, N; Turhanoglu, A; Bolaç, E; Yalcin, F

    2011-01-01

    Ankylosing spondilitis (AS) is a chronic inflammatory disease with prominent inflammation in joints and extraarticular organs. AS patients have approximately two times more risk of mortality than the normal population. One reason for this increase in mortality is increased cardiovascular risk. In this study, we have aimed to evaluate myocardial perfusion and left ventricular function using (99m)Tc-MIBI gated myocardial perfusion single photon emission computed tomography (SPECT). The study group consisted of 28 AS patients (19 men, 9 women), and mean age 39.46±10.98 years. All patients underwent (99m)Tc-MIBI gated myocardial perfusion SPECT with the same day protocol. We detected various risk factors including smoking habits in 12, family history of cardiovascular disease in 12, hypertension in 3, hyperlipidemia in 9 patients. We performed a myocardial perfusion SPECT for each patient and found normal perfusion pattern in SPECT images. Out of 28 patients, eight patients had normal perfusion but wall motion abnormalities. We detected that myocardial perfusion is preserved in the patients with AS. However, left ventricular wall motion abnormalities are seen. We concluded that ankylosing spondylitis may be associated with microvascular dysfunction and gated myocardial perfusion scintigraphy could be valuable in AS patients for the evaluation of LV function even if the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score are low and the disease duration shorter. Copyright © 2010 Elsevier España, S.L. and SEMNIM. All rights reserved.

  7. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus

    PubMed Central

    Piya, Milan K.; Shivu, Ganesh Nallur; Tahrani, Abd; Dubb, Kiran; Abozguia, Khalid; Phan, T.T.; Narendran, Parth; Pop-Busui, Rodica; Frenneaux, Michael; Stevens, Martin J.

    2011-01-01

    Left ventricular torsion is increased and cardiac energetics are reduced in uncomplicated type 1 diabetes mellitus (T1DM). Our aim was to determine the relationships of these abnormalities to cardiovascular autonomic neuropathy (CAN) in subjects with T1DM. A cross-sectional study was conducted in 20 subjects with T1DM free of known coronary heart disease attending an outpatient clinic. Cardiovascular autonomic neuropathy was assessed using heart rate variability studies and the continuous wavelet transform method. Left ventricular function was determined by speckle tracking echocardiography. Magnetic resonance spectroscopy and stress magnetic resonance imaging were used to measure cardiac energetics and myocardial perfusion reserve index, respectively. Twenty subjects (age, 35 ± 8 years; diabetes duration, 16 ± 9 years; hemoglobin A1c, 8.0% ± 1.1%) were recruited. Forty percent of the subjects exhibited definite or borderline CAN. Log peak radial strain was significantly increased in subjects with CAN compared with those without (1.56 ± 0.06 vs 1.43 ± 0.14, respectively; P = .011). Data were adjusted for log duration of diabetes, and log left ventricular torsion correlated (r = 0.593, P = .01) with log low-frequency to high-frequency ratio during the Valsalva maneuver. Log isovolumic relaxation time correlated significantly with log Valsalva ratio and log proportion of differences in consecutive RR intervals of normal beats greater than 50 milliseconds during deep breathing. However, CAN did not correlate with cardiac energetics or myocardial perfusion reserve index. Spectral analysis of low-frequency to high-frequency ratio power during the Valsalva maneuver is associated with altered left ventricular torsion in subjects with T1DM. Parasympathetic dysfunction is closely associated with diastolic deficits. Cardiovascular autonomic neuropathy is not however the principal cause of impaired cardiac energetics. The role of CAN in the development of cardiomyopathy

  8. Detection of left ventricular motion abnormality via information measures and bayesian filtering.

    PubMed

    Punithakumar, Kumaradevan; Ben Ayed, Ismail; Ross, Ian G; Islam, Ali; Chong, Jaron; Li, Shuo

    2010-07-01

    We present an original information theoretic measure of heart motion based on the Shannon's differential entropy (SDE), which allows heart wall motion abnormality detection. Based on functional images, which are subject to noise and segmentation inaccuracies, heart wall motion analysis is acknowledged as a difficult problem, and as such, incorporation of prior knowledge is crucial for improving accuracy. Given incomplete, noisy data and a dynamic model, the Kalman filter, a well-known recursive Bayesian filter, is devised in this study to the estimation of the left ventricular (LV) cavity points. However, due to similarity between the statistical information of normal and abnormal heart motions, detecting and classifying abnormality is a challenging problem, which we investigate with a global measure based on the SDE. We further derive two other possible information theoretic abnormality detection criteria, one is based on Rényi entropy and the other on Fisher information. The proposed methods analyze wall motion quantitatively by constructing distributions of the normalized radial distance estimates of the LV cavity. Using 269 x 20 segmented LV cavities of short-axis MRI obtained from 30 subjects, the experimental analysis demonstrates that the proposed SDE criterion can lead to a significant improvement over other features that are prevalent in the literature related to the LV cavity, namely, mean radial displacement and mean radial velocity.

  9. Prevalence and prognostic value of concealed structural abnormalities in patients with apparently idiopathic ventricular arrhythmias of left versus right ventricular origin: a magnetic resonance imaging study.

    PubMed

    Nucifora, Gaetano; Muser, Daniele; Masci, Pier Giorgio; Barison, Andrea; Rebellato, Luca; Piccoli, Gianluca; Daleffe, Elisabetta; Toniolo, Mauro; Zanuttini, Davide; Facchin, Domenico; Lombardi, Massimo; Proclemer, Alessandro

    2014-06-01

    Routine diagnostic work-up occasionally does not identify any abnormality among patients with monomorphic ventricular arrhythmias (VAs) of left ventricular (LV) origin. Aim of this study was to investigate the value of cardiac MRI (cMRI) for the diagnostic work-up and prognostication of these patients. Forty-six consecutive patients (65% males; mean age, 44±15 years) with monomorphic VAs of LV origin and negative routine diagnostic work-up were included. Seventy-four consecutive patients (60% males; mean age, 40±17 years) with apparently idiopathic monomorphic VAs of right ventricular origin served as control group. Both groups underwent comprehensive cMRI study and were followed-up for a median of 14 months (25th-75th percentiles, 7-37 months). The outcome event was an arrhythmic composite end point of sudden cardiac death or nonfatal episode of ventricular fibrillation or sustained ventricular tachycardia requiring external cardioversion or appropriate implantable cardioverter defibrillator therapy. The 2 groups of patients did not differ in age (P=0.14) and sex (P=0.57). No significant difference was observed between patients with VAs of LV origin and VAs of right ventricular origin about biventricular volumes and systolic function. cMRI demonstrated myocardial structural abnormalities in 19 (41%) patients with VAs of LV origin versus 4 (5%) patients with VAs of right ventricular origin (P<0.001). The outcome event occurred in 9 patients; myocardial structural abnormalities on cMRI were significantly related to the outcome event (hazard ratio, 41.6; 95% confidence interval, 5.2-225.0; P<0.001). Myocardial structural changes are detected by cMRI in a non-negligible proportion of patients with apparently idiopathic monomorphic VAs of LV origin and are associated with worse outcome. © 2014 American Heart Association, Inc.

  10. Mitral Annular Systolic Velocities Predict Left Ventricular Wall Motion Abnormality During Dobutamine Stress Echocardiography

    PubMed Central

    Sharif, Dawod; Sharif-Rasslan, Amal; Shahla, Camilia

    2011-01-01

    Background Longitudinal systolic left ventricular contraction is complementary to the radial performance and can be assessed using tissue Doppler imaging (TDI). This study was performed to evaluate the contribution of mitral annular systolic velocities using TDI after dobutamine stress echocardiography (DSE). Methods and Results Fifty subjects with suspected coronary artery disease and chest pain were examined, using DSE as usual, as well as TDI imaging of the mitral annulus at the septal, lateral, inferior, anterior, posterior regions and the proximal anteroseptal region from the apical views, before and immediately after DSE. In 24 subjects the study was normal, while wall motion abnormality was seen in 26, 9 of them only after DSE. Mitral annular systolic velocity at the 6 locations increased significantly after DSE both in normal subjects and in those with wall motion abnormality (WMA). After DSE mitral annular septal systolic velocity in normals, 19.2 ± 3.8 cm/sec, was higher than in those with WMA, 14.6 ± 2.5 cm/sec, P < 0.0003. Post-DSE mitral systolic velocity was senstive and accurate in predicting WMA. Conclusions Systolic mitral TDI velocities increase after DSE, however to a lesser extent in those with wall motion abnormality, and can differentiate them from normal subjects.

  11. Early abnormalities in left ventricular diastolic function of sodium-sensitive hypertensive patients.

    PubMed

    Musiari, L; Ceriati, R; Taliani, U; Montesi, M; Novarini, A

    1999-10-01

    The aim of this study was to evaluate whether salt-sensitivity in essential hypertension produces a significant comparative difference in diastolic function and ventricular mass when compared with sodium-resistance. Recent epidemiological data have demonstrated a positive correlation between sodium intake and arterial pressure. Furthermore, a positive correlation has been detected between sodium intake and left ventricular hypertrophy (LVH) independently of arterial pressure. Thirty-one patients who had never been treated before for uncomplicated hypertension were studied. Each subject received a 30 mmol/per day sodium diet for 14 days, supplemented with a further 190 mmol of sodium in the first study week (220 mmol for the first 7 days and 30 mmol for the second 7 days). Throughout the study compliance was assessed by measuring daily urinary sodium excretion. Sodium sensitivity of blood pressure was defined as the difference (5% or more) between blood pressure at the end of the low and high sodium intake periods. On this basis 16 patients were defined as salt-sensitive (SS) and 15 patients as salt-resistant (SR). The two groups were homogeneous for age, sex and race. Baseline mean arterial pressure (MAP) was comparable between SS (108 +/- 1.8 mm Hg) and SR (107 +/- 2.1 mm Hg, P = NS). Each patient was submitted to M-MODE and two-dimensional echocardiogram studies in order to estimate left ventricular mass using the Penn conventional formula and parameters of left ventricular diastolic function. The left ventricular mass measurement showed higher values in the SS group although this did not reach statistical significance (118.4 +/- 4.4 vs 112.0 +/- 4.2 gr/mq, P = NS). Both interventricular septal and posterior wall thickness did not demonstrate significant differences between the two groups. The salt-sensitive group showed impaired left ventricular diastolic function; in particular, the first diastolic peak representing the early maximum of diastolic filling

  12. Abnormal conduction increases risk of adverse outcomes from right ventricular pacing.

    PubMed

    Hayes, John J; Sharma, Arjun D; Love, John C; Herre, John M; Leonen, Anna O; Kudenchuk, Peter J

    2006-10-17

    The purpose of this study was to determine whether QRS duration or morphology increased the risk of adverse outcome in the DAVID (Dual Chamber and VVI Implantable Defibrillator) trial. The DAVID trial found an increased risk of the combined end point of death and new or worsening congestive heart failure (CHF) in defibrillator recipients who were paced DDDR-70 versus VVI-40. We analyzed the combined end point in patients with abnormal QRS duration (AbQRS) (> or =110 ms) compared with those with normal QRS duration (NQRS) (<110 ms). The QRS data were available for 496 of the 506 patients enrolled in the trial, including 223 patients with NQRS (45%) and 273 patients with AbQRS (55%). In patients in whom defibrillators were programmed to pace infrequently (VVI-40), having an NQRS or AbQRS was not an indicator of increased risk of adverse outcome. However, among patients in whom defibrillators were programmed in a manner that promoted more frequent ventricular pacing (DDDR-70), there was a significant adverse interaction with AbQRS; this combination was independently associated with a higher risk for developing CHF or death (p = 0.017). Although patients with AbQRS tended to have other risk factors associated with poor outcome, the interaction of QRS duration with ventricular pacing (DDDR-70) independently contributed to a worse outcome and therefore, was a marker of patients in whom such treatment may be harmful. This should not imply that right ventricular pacing in NQRS patients is safe but rather that pacing in the context of an AbQRS is probably best avoided.

  13. Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia

    SciTech Connect

    Cohn, P.F.; Brown, E.J. Jr.; Wynne, J.; Holman, B.L.; Atkins, H.L.

    1983-03-01

    Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.

  14. Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities.

    PubMed

    Swayze, V W; Andreasen, N C; Alliger, R J; Ehrhardt, J C; Yuh, W T

    1990-11-01

    Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear.

  15. Abnormal Wave Reflections and Left Ventricular Hypertrophy Late After Coarctation of the Aorta Repair

    PubMed Central

    Quail, Michael A.; Short, Rebekah; Pandya, Bejal; Steeden, Jennifer A.; Khushnood, Abbas; Taylor, Andrew M.; Segers, Patrick

    2017-01-01

    Patients with repaired coarctation of the aorta are thought to have increased afterload due to abnormalities in vessel structure and function. We have developed a novel cardiovascular magnetic resonance protocol that allows assessment of central hemodynamics, including central aortic systolic blood pressure, resistance, total arterial compliance, pulse wave velocity, and wave reflections. The main study aims were to (1) characterize group differences in central aortic systolic blood pressure and peripheral systolic blood pressure, (2) comprehensively evaluate afterload (including wave reflections) in the 2 groups, and (3) identify possible biomarkers among covariates associated with elevated left ventricular mass (LVM). Fifty adult patients with repaired coarctation and 25 age- and sex-matched controls were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal-resolution spiral phase-contrast cardiovascular magnetic resonance flow sequence. These data were used to derive central hemodynamics and to perform wave intensity analysis noninvasively. Covariates associated with LVM were assessed using multivariable linear regression analysis. There were no significant group differences (P≥0.1) in brachial systolic, mean, or diastolic BP. However central aortic systolic blood pressure was significantly higher in patients compared with controls (113 versus 107 mm Hg, P=0.002). Patients had reduced total arterial compliance, increased pulse wave velocity, and larger backward compression waves compared with controls. LVM index was significantly higher in patients than controls (72 versus 59 g/m2, P<0.0005). The magnitude of the backward compression waves was independently associated with variation in LVM (P=0.01). Using a novel, noninvasive hemodynamic assessment, we have shown abnormal conduit vessel function after coarctation of the aorta repair, including abnormal wave reflections that are associated with elevated LVM. PMID:28115510

  16. Abnormal Wave Reflections and Left Ventricular Hypertrophy Late After Coarctation of the Aorta Repair.

    PubMed

    Quail, Michael A; Short, Rebekah; Pandya, Bejal; Steeden, Jennifer A; Khushnood, Abbas; Taylor, Andrew M; Segers, Patrick; Muthurangu, Vivek

    2017-03-01

    Patients with repaired coarctation of the aorta are thought to have increased afterload due to abnormalities in vessel structure and function. We have developed a novel cardiovascular magnetic resonance protocol that allows assessment of central hemodynamics, including central aortic systolic blood pressure, resistance, total arterial compliance, pulse wave velocity, and wave reflections. The main study aims were to (1) characterize group differences in central aortic systolic blood pressure and peripheral systolic blood pressure, (2) comprehensively evaluate afterload (including wave reflections) in the 2 groups, and (3) identify possible biomarkers among covariates associated with elevated left ventricular mass (LVM). Fifty adult patients with repaired coarctation and 25 age- and sex-matched controls were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal-resolution spiral phase-contrast cardiovascular magnetic resonance flow sequence. These data were used to derive central hemodynamics and to perform wave intensity analysis noninvasively. Covariates associated with LVM were assessed using multivariable linear regression analysis. There were no significant group differences (P≥0.1) in brachial systolic, mean, or diastolic BP. However central aortic systolic blood pressure was significantly higher in patients compared with controls (113 versus 107 mm Hg, P=0.002). Patients had reduced total arterial compliance, increased pulse wave velocity, and larger backward compression waves compared with controls. LVM index was significantly higher in patients than controls (72 versus 59 g/m(2), P<0.0005). The magnitude of the backward compression waves was independently associated with variation in LVM (P=0.01). Using a novel, noninvasive hemodynamic assessment, we have shown abnormal conduit vessel function after coarctation of the aorta repair, including abnormal wave reflections that are associated with elevated LVM.

  17. Prevalence and determinants of left ventricular geometric abnormalities in hypertensive patients: A study based on the updated classification system of left ventricular geometry.

    PubMed

    Sha, Tao; Huang, Yu-Qing; Cai, An-Ping; Huang, Cheng; Zhang, Ying; Chen, Ji-Yan; Zhou, Ying-Ling; Yu, Xue-Ju; Zhou, Dan; Tang, Song-Tao; Feng, Ying-Qing; Tan, Ning

    This study was to determine whether different risk factors were associated with different type of left ventricular (LV) geometric abnormalities. This retrospective analysis included 2290 hypertensive participants without other cardiovascular disease, valve disease and with ejection fraction ≥50%. The type of LV geometric abnormality was defined on the basis of the new classification system. LV geometric abnormalities were detected in 1479 subjects (64.6%), wherein concentric LV remodeling is the most common LV geometric abnormality (40.3%). Large waist circumference (WC) and neck circumference (NC) were positively associated with concentric LV remodeling, whereas body mass index (BMI) [odds ratio (OR) 0.89, 95% CI 0.85∼0.92, P < 0.001] and systolic blood pressure (SBP) (OR 0.99, 95% CI 0.98∼0.99, P = 0.018) were inversely associated with concentric abnormalities. SBP and age were positively associated with eccentric dilated LVH, while male was inversely associated with eccentric dilated left ventricular hypertrophy (LVH). Age was the strongest risk factor for eccentric dilated LVH (OR 1.05, 95% CI 1.03∼1.07, P < 0.001). Age, NC, SBP, hyperuricemia, and alcohol use were positively associated with concentric LVH, whereas BMI (OR 0.95, 95% CI 0.90∼0.99, P = 0.033) and male (OR 0.12, 95% CI 0.07∼0.18, P < 0.001) were negatively associated with concentric LVH. The prevalence of hypertensive LV geometric abnormality in rural area of Southern China was obvious higher. Compared with eccentric LV geometric abnormalities, there were more risk factors, including large WC and NC, age, NC, SBP, hyperuricemia, alcohol use, BMI and gender, which were associated with concentric LV geometric abnormalities. Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

  18. Metabolic Abnormalities, But Not Metabolically Healthy Obesity, Are Associated with Left Ventricular Hypertrophy.

    PubMed

    Zhang, Naijin; Chen, Yintao; Guo, Xiaofan; Sun, Guozhe; Dai, Dongxue; Sun, Yingxian

    2017-03-01

    Obesity has been found to be a predictor of left ventricular hypertrophy (LVH). However, studies which divide obesity into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) to study the effect of obesity on LVH have been rare. The present study aims to make clear the effects of various obese phenotypes and metabolic abnormalities on LVH. A total of 10,804 participants were involved in this cross-sectional study. "Obesity" and "metabolically healthy" were defined as BMI ≥ 25kg/m(2) and having none of the metabolic factors respectively. It was found that metabolically unhealthy non-obesity (MUNO) (OR, 2.675; 95%CI, 1.603-4.462, P < 0.001) and MUO (OR, 9.067; 95%CI, 5.474-15.020, P<0.001) were significantly associated with LVH, while it went in reverse for MHO (OR, 1.968; 95%CI, 0.560-6.920, P=0.291), after adjustment for age, race, gender, educational status, physical activity, annual income, current smoking status, current drinking status, sleep duration and BMI. And after further adjustment for metabolic abnormalities, MUNO (OR, 0.567; 95%CI, 0.316-1.018, P=0.794) and MUO (OR, 0.632; 95%CI, 0.342-1.166, P=0.142) tended not to be associated with LVH any longer. However, among the five metabolic components of metabolic abnormalities, high blood pressure (OR, 4.358; 95%CI, 3.266-5.815, P<0.001) and high waist circumference (OR, 1.530; 95%CI, 1.139-2.054, P=0.005) were significantly associated with LVH. Metabolic abnormalities, but not MHO, were significantly associated with LVH. In addition, metabolic abnormalities were probable to mediate the connection between MUNO/MUO and LVH. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  19. Neurobiology of social behavior abnormalities in autism and Williams syndrome.

    PubMed

    Barak, Boaz; Feng, Guoping

    2016-04-26

    Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities.

  20. Neurobiology of social behavior abnormalities in autism and Williams syndrome

    PubMed Central

    Barak, B; Feng, G

    2016-01-01

    Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here, we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities. PMID:27116389

  1. Fetal Right Ventricular Prominence: Associated Postnatal Abnormalities and Coarctation Clinical Prediction Tool.

    PubMed

    Power, Alyssa; Nettel-Aguirre, Alberto; Fruitman, Deborah

    2017-07-24

    Fetal right ventricular (RV) prominence is a known indicator of possible left-sided structural heart disease with a low positive predictive value for aortic coarctation. There is a paucity of data on identifying which fetuses with RV prominence will have postnatal arch obstruction. Our study objectives were to create a clinical prediction tool for coarctation and to describe the diagnostic outcomes of our cohort with fetal RV prominence. We performed a retrospective review of patients referred with fetal RV prominence from January 2009 to October 2015. Recorded fetal echocardiographic variables included gestational age, semilunar and atrioventricular valve dimensions, left and right ventricular mid-cavitary dimensions, foramen ovale and aortic arch flow direction, and isthmal diameter. Postnatal cardiac and non-cardiac diagnoses were documented. We performed descriptive analysis for postnatal outcomes and classification tree analysis to create a clinical prediction tool. Eighty-eight patients were reviewed; 58 (66%) had abnormal postnatal echocardiograms, 45 (51%) had left-sided lesions, including 26 (30%) with coarctation, and 6 (7%) had pulmonary hypertension. Our clinical prediction tool employs gestational age, RV mid-cavitary dimension z-score, and isthmal diameter z-score to predict coarctation with 85% accuracy, 95% confidence interval [75.3, 92.4%]. Our model correctly classified 45/54 non-coarctation and 19/21 coarctation cases, with 90% sensitivity and 83% specificity. Developing an accurate prediction tool for coarctation in cases of fetal RV prominence is an important first step in improving our management of these challenging cases.

  2. Freud Was Right. . . about the Origins of Abnormal Behavior

    ERIC Educational Resources Information Center

    Muris, Peter

    2006-01-01

    Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

  3. Freud Was Right. . . about the Origins of Abnormal Behavior

    ERIC Educational Resources Information Center

    Muris, Peter

    2006-01-01

    Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

  4. A hemodynamics model to study the collective behavior of the ventricular-arterial system

    NASA Astrophysics Data System (ADS)

    Lin Wang, Yuh-Ying; Wang, Wei-Kung

    2013-01-01

    Applying principles from complex systems to study the efficacy of integrative therapies has become a new interest in medical research. We aimed to construct a concise model for the ventricular-arterial (VA) system and to provide a systematic method for exploring its overall behavior. The transportation of blood from the heart to the peripheral arterioles via hydraulic pressure forces was described by a multi-rank model. Parts of the VA system that have strong mutual interactions were combined into a single sub system. Sub systems of four different ranks were characterized. We then applied the multi-rank model to analyze the aortic pressure wave generated by the periodic ventricular blood ejection, the renal pressure in response to the input from the VA system, and the blood flowing from the renal artery to its arterioles. Maintaining the pressure distribution along the main arteries and in all of the organs with the lowest possible ventricular input turned out to be the first principle for the operation of an efficient VA system. By this principle, we pointed out the benefit of some arterial structures in mammals, derived specific regulation rules and deduced some fundamental concepts for healing. The justification of the biomechanics in our model that differed greatly from those in the prevailing models was given. We concluded that the oscillatory motion and the pressure pulse of the arterial system can be analyzed as steady states with resonance behaviors and suggested utilizing this model to construct integrative therapies for diseases correlated with abnormality in blood circulation.

  5. Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis.

    PubMed

    Guerra, María Montserrat; Henzi, Roberto; Ortloff, Alexander; Lichtin, Nicole; Vío, Karin; Jiménez, Antonio J; Dominguez-Pinos, María Dolores; González, César; Jara, Maria Clara; Hinostroza, Fernando; Rodríguez, Sara; Jara, Maryoris; Ortega, Eduardo; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad E; Rodríguez, Esteban M

    2015-07-01

    Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.

  6. iPSC-derived cardiomyocytes reveal abnormal TGFβ signaling in left ventricular non-compaction cardiomyopathy

    PubMed Central

    Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D.; Shukla, Praveen; Abilez, Oscar J.; Churko, Jared M.; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M.; Snyder, Michael P.; Bernstein, Daniel; Wu, Joseph C.

    2016-01-01

    Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC. PMID:27642787

  7. Subclinical left ventricular dysfunction and silent cerebrovascular disease: the Cardiovascular Abnormalities and Brain Lesions (CABL) study.

    PubMed

    Russo, Cesare; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Yoshita, Mitsuhiro; DeCarli, Charles; Wright, Clinton B; Sacco, Ralph L; Di Tullio, Marco R

    2013-09-03

    Silent brain infarcts (SBIs) and white matter hyperintensities are subclinical cerebrovascular lesions associated with incident stroke and cognitive decline. Left ventricular ejection fraction (LVEF) is a predictor of stroke in patients with heart failure, but its association with subclinical brain disease in the general population is unknown. Left ventricular global longitudinal strain (GLS) can detect subclinical cardiac dysfunction even when LVEF is normal. We investigated the relationship of LVEF and GLS with subclinical brain disease in a community-based cohort. LVEF and GLS were assessed by 2-dimensional and speckle-tracking echocardiography in 439 participants free of stroke and cardiac disease from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. SBIs and white matter hyperintensities were assessed by brain MRI. Mean age of the study population was 69±10 years, 61% were women, LVEF was 63.8±6.4%, GLS was -17.1±3.0%. SBIs were detected in 53 participants (12%), white matter hyperintensity volume was 0.63±0.86%. GLS was significantly lower in participants with SBI versus those without (-15.7±3.5% versus -17.3±2.9%, P<0.01), whereas no difference in LVEF was observed (63.3±8.6% versus 63.8±6.0%, P=0.60). In multivariate analysis, lower GLS was associated with SBI (odds ratio/unit decrease=1.18; 95% confidence interval, 1.05-1.33; P<0.01), whereas LVEF was not (odds ratio/unit increase=1.00; 95% confidence interval, 0.96-1.05; P=0.98). Lower GLS was associated with greater white matter hyperintensity volume (adjusted β=0.11, P<0.05), unlike LVEF (adjusted β=-0.04, P=0.42). Lower GLS was independently associated with subclinical brain disease in a community-based cohort without overt cardiac disease. GLS can provide additional information on cerebrovascular risk burden beyond LVEF assessment.

  8. Developmental antecedents of abnormal eating attitudes and behaviors in adolescence.

    PubMed

    Le Grange, Daniel; O'Connor, Meredith; Hughes, Elizabeth K; Macdonald, Jacqui; Little, Keriann; Olsson, Craig A

    2014-11-01

    This study capitalizes on developmental data from an Australian population-based birth cohort to identify developmental markers of abnormal eating attitudes and behaviors in adolescence. The aims were twofold: (1) to develop a comprehensive path model identifying infant and childhood developmental correlates of Abnormal Eating Attitudes and Behaviors in adolescence, and (2) to explore potential gender differences. Data were drawn from a 30-year longitudinal study that has followed the health and development of a population based cohort across 15 waves of data collection from infancy since 1983: The Australian Temperament Project. Participants in this analysis were the 1,300 youth who completed the 11th survey at 15-16 years (1998) and who completed the eating disorder inventory at this time point. Developmental correlates of Abnormal Eating Attitudes and Behaviors in mid-adolescence were temperamental persistence, early gestational age, persistent high weight, teen depression, stronger peer relationships, maternal dieting behavior, and pubertal timing. Overall, these factors accounted for 28% of the variance in Abnormal Eating Attitudes and Behaviors at 15-16 years of age. Depressive symptoms, maternal dieting behavior, and early puberty were more important factors for girls. Late puberty was a more important factor for boys. Findings address an important gap in our understanding of the etiology of Abnormal Eating Attitudes and Behaviors in adolescence and suggest multiple targets for preventive intervention. © 2014 Wiley Periodicals, Inc.

  9. Computer simulation modeling of abnormal behavior: a program approach.

    PubMed

    Reilly, K D; Freese, M R; Rowe, P B

    1984-07-01

    A need for modeling abnormal behavior on a comprehensive, systematic basis exists. Computer modeling and simulation tools offer especially good opportunities to establish such a program of studies. Issues concern deciding which modeling tools to use, how to relate models to behavioral data, what level of modeling to employ, and how to articulate theory to facilitate such modeling. Four levels or types of modeling, two qualitative and two quantitative, are identified. Their properties are examined and interrelated to include illustrative applications to the study of abnormal behavior, with an emphasis on schizophrenia.

  10. Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

    PubMed

    Nof, Eyal; Belhassen, Bernard; Arad, Michael; Bhuiyan, Zahurul A; Antzelevitch, Charles; Rosso, Raphael; Fogelman, Rami; Luria, David; El-Ani, Dalia; Mannens, Marcel M A M; Viskin, Sami; Eldar, Michael; Wilde, Arthur A M; Glikson, Michael

    2011-10-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers. The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2. Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes. M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

    PubMed

    Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

    2013-12-19

    Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.

  12. STUDYING VENTRICULAR ABNORMALITIES IN MILD COGNITIVE IMPAIRMENT WITH HYPERBOLIC RICCI FLOW AND TENSOR-BASED MORPHOMETRY

    PubMed Central

    Shi, Jie; Stonnington, Cynthia M.; Thompson, Paul M.; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C.; Reiman, Eric M.; Caselli, Richard J.; Wang, Yalin

    2014-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer’s disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. PMID:25285374

  13. Studying ventricular abnormalities in mild cognitive impairment with hyperbolic Ricci flow and tensor-based morphometry.

    PubMed

    Shi, Jie; Stonnington, Cynthia M; Thompson, Paul M; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C; Reiman, Eric M; Caselli, Richard J; Wang, Yalin

    2015-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD.

  14. Personality theory, abnormal psychology, and psychological measurement. A psychological behaviorism.

    PubMed

    Staats, A W

    1993-01-01

    Behaviorism, because it has not had a theory of personality, has been separated from the rest of psychology, unable in large part to draw from or contribute to it. Traditional psychology has not had a theory of personality that says what personality is, how it comes about, or how it functions. An antagonism has resulted that weakens rather than complements each tradition. Psychological behaviorism presents a new type of theory of personality. Derived from experimentation, it is constructed from basic theories of emotion, language, and sensory-motor behavior. It says personality is composed of learned basic behavioral repertoires (BBRs) that affect behavior. Personality measurement instruments are analyzed in terms of the BBRs, beginning the behaviorization of this field and calling for much additional research. These multilevel developments are then basic in psychological behaviorism's theory of abnormal behavior and of clinical treatment. The approach opens many new avenues of empirical and theoretical work.

  15. Clinical significance of exercise-induced left ventricular wall motion abnormality occurring at a low heart rate

    SciTech Connect

    Kimchi, A.; Rozanski, A.; Fletcher, C.; Maddahi, J.; Swan, H.J.; Berman, D.S.

    1987-10-01

    We studied the relationship between the heart rate at the time of onset of exercise-induced wall motion abnormality and the severity of coronary artery disease in 89 patients who underwent exercise equilibrium radionuclide ventriculography as part of their evaluation for coronary artery disease. Segmental wall motion was scored with a five-point system (3 = normal; -1 = dyskinesis); a decrease of one score defined the onset of wall motion abnormality. The onset of wall motion abnormality at less than or equal to 70% of maximal predicted heart rate had 100% predictive accuracy for coronary artery disease and higher sensitivity than the onset of ischemic ST segment depression at similar heart rate during exercise: 36% (25 of 69 patients with coronary disease) vs 19% (13 of 69 patients), p = 0.01. Wall motion abnormality occurring at less than or equal to 70% of maximal predicted heart rate was present in 49% of patients (23 of 47) with critical stenosis (greater than or equal to 90% luminal diameter narrowing), and in only 5% of patients (2 of 42) without such severe stenosis, p less than 0.001. The sensitivity of exercise-induced wall motion abnormality occurring at a low heart rate for the presence of severe coronary artery disease was similar to that of a deterioration in wall motion by more than two scores during exercise (49% vs 53%) or an absolute decrease of greater than or equal to 5% in exercise left ventricular ejection fraction (49% vs 45%).

  16. Left ventricular abnormal response during dynamic exercise in patients with heart failure and preserved left ventricular ejection fraction at rest.

    PubMed

    Ennezat, Pierre V; Lefetz, Yann; Maréchaux, Sylvestre; Six-Carpentier, Marie; Deklunder, Ghislaine; Montaigne, David; Bauchart, Jean Jacques; Mounier-Véhier, Claire; Jude, Brigitte; Nevière, Rémi; Bauters, Christophe; Asseman, Philippe; de Groote, Pascal; Lejemtel, Thierry H

    2008-08-01

    The mechanisms that contribute to limit functional capacity are incompletely understood in patients with preserved resting ejection fraction (HFpREF). We assessed left ventricular (LV) systolic response to dynamic exercise in patients with HFpREF and in patients with similar comorbidities to HFpREF patients but without history or evidence of heart failure. Twenty-five HFpREF patients in steady-state clinical condition without significant coronary artery disease and 25 hypertensive controls underwent exercise echocardiography. At rest, systolic pulmonary artery pressure, left atrial area, E/A and E/e' ratios were greater in patients with HFpREF than in control patients, whereas peak systolic mitral annular velocity was lower in HFpREF patients. The exercise-induced changes in LVEF, forward stroke volume, and cardiac output were significantly lower in HFpREF compared with control patients (-4 +/- 8 vs. +6 +/- 6 %, P = .001; -4 +/- 9 vs. +10 +/- 10 mL, P < .0001, and 1.6 +/- 1.2 vs. 3.5 +/- 1.8 L/min, P < .0001, respectively). Exercise-induced changes in effective arterial elastance significantly differed in HFpREF and control patients (0.5 +/- 0.6 vs. -0.2 +/- 0.5 mm Hg/mL, P < .0001). In addition, 7 of the 25 HFpREF patients developed functional mitral regurgitation during exercise and none in controls. When compared with patients with similar comorbidities but without history or evidence of heart failure, patients with HFpREF experience greater arterial stiffening and thereby a deterioration of global LV systolic performance during dynamic exercise.

  17. Abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease is associated with resting left ventricular long-axis dysfunction.

    PubMed

    Nasis, Arthur; Moir, Stuart; Meredith, Ian T; Barton, Timothy L; Nerlekar, Nitesh; Wong, Dennis T; Ko, Brian S; Cameron, James D; Mottram, Philip M

    2015-01-01

    The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE. Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function. Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal

  18. Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake

    PubMed Central

    Hayakawa, Masashi

    2013-01-01

    Simple Summary Possible electromagnetic effects on abnormal animal behavior before earthquakes. Abstract The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15–20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

  19. Clinical utility of a multigated modified anterior projection in the detection of left ventricular inferior and apical wall motion abnormalities

    SciTech Connect

    Polak, J.F.; Bianco, J.A.; Kemper, A.J.; Tow, D.E.

    1982-04-01

    Recent evidence indicates that the left anterior oblique projection (LAO) multigated radionuclide ventriculogram (RVG) underestimates presence and extent of apical and inferior left ventricular (LV) wall motion abnormalities. We investigated, prospectively, the sensitivity and specificity of a modified anterior projection (MAP), which incorporates cephalad tilting. Thirty-three consecutive patients undergoing cardiac catheterization suspected to have coronary artery disease were studied with RVG, using both the MAP and LAO views. LAO views were analyzed using the ejection fraction image (REFI), and the regional ejection fraction (REF) of the inferoapical region. The MAP studies were analyzed using stroke volume image (SVI) to evaluate apical and inferior LV regions. Results were as follows: (Formula: see text), Both intraobserver and interobserver variabilities were comparable to those of conventional angiographic studies used in detection of apical and inferior asynergy. It is concluded that the multigated MAP offers additional information about abnormalities of the LV inferior and apical regions.

  20. [Surface recording of abnormal post-QRS micropotentials. Description and frequency in ventricular tachycardias after myocardial infarction].

    PubMed

    Varenne, A; Blanc, P; Camous, J P; Grangier, L; Morand, P

    1986-10-01

    In order to study abnormal post-QRS micropotentials, so called late potentials, and to determine their frequency in post myocardial infarction ventricular tachycardia (VT), high amplification electrocardiogrammes were recorded in 180 patients classified in 3 different groups: Group A comprising 36 patients who developed sustained VT after myocardial infarction; Group B comprising 124 patients with myocardial infarction uncomplicated by VT. This group was subdivided into subgroup B1 (retrospective study of 35 patients with chronic myocardial infarction, dating on average 10 months--range 7 days to 8 years) and subgroup B2 (prospective study of 89 patients investigated on the 7th and 60th days after infarction); Group C comprising 20 young, normal control subjects. Using computer assisted high amplification electrocardiography, all patients underwent at least 3 successive recordings of the following parameters: averaging 100 cycles; sampling: 1 kHz; band pass 20-300 Hz and 80-300 Hz; gain setting 10,000 and 25,000. Late potentials usually appears, after the end of the S wave, as high frequency oscillations with an amplitude (10 to 20 microV) significantly greater than that of the background noise. Our recordings also showed: the frequent presence, especially in intraventricular blocks, of fragmentation of the end of the R wave and of the S wave or terminal potentials; the presence of an abnormal giant low frequency high amplitude wave (40 to 80 microV) in 5 patients with a large left ventricular aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Chromosomal abnormalities, meiotic behavior and fertility in domestic animals.

    PubMed

    Villagómez, D A F; Pinton, A

    2008-01-01

    Since the advent of the surface microspreading technique for synaptonemal complex analysis, increasing interest in describing the synapsis patterns of chromosome abnormalities associated with fertility of domestic animals has been noticed during the past three decades. In spite of the number of scientific reports describing the occurrence of structural chromosome abnormalities, their meiotic behavior and gametic products, little is known in domestic animal species about the functional effects of such chromosome aberrations in the germ cell line of carriers. However, some interesting facts gained from recent and previous studies on the meiotic behavior of chromosome abnormalities of domestic animals permit us to discuss, in the frame of recent knowledge emerging from mouse and human investigations, the possible mechanism implicated in the well known association between meiotic disruption and chromosome pairing failure. New cytogenetic techniques, based on molecular and immunofluorescent analyses, are allowing a better description of meiotic processes, including gamete production. The present communication reviews the knowledge of the meiotic consequences of chromosome abnormalities in domestic animals.

  2. Detecting abnormalities in left ventricular function during exercise by respiratory measurement

    SciTech Connect

    Koike, A.; Itoh, H.; Taniguchi, K.; Hiroe, M. )

    1989-12-01

    The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 {plus minus} 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 {plus minus} 11.3%, 46.5 {plus minus} 12.0%, and 37.2 {plus minus} 11.0%, respectively. Stroke volume also increased from rest (54.6 {plus minus} 17.0 ml/beat) to the point of the anaerobic threshold (65.0 {plus minus} 21.2 ml/beat) and then decreased at peak exercise (52.4 {plus minus} 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.

  3. Spent fuel behavior under abnormal thermal transients during dry storage

    SciTech Connect

    Stahl, D.; Landow, M.P.; Burian, R.J.; Pasupathi, V.

    1986-01-01

    This study was performed to determine the effects of abnormally high temperatures on spent fuel behavior. Prior to testing, calculations using the CIRFI3 code were used to determine the steady-state fuel and cask component temperatures. The TRUMP code was used to determine transient heating rates under postulated abnormal events during which convection cooling of the cask surfaces was obstructed by a debris bed covering the cask. The peak rate of temperature rise during the first 6 h was calculated to be about 15/sup 0/C/h, followed by a rate of about 1/sup 0/C/h. A Turkey Point spent fuel rod segment was heated to approx. 800/sup 0/C. The segment deformed uniformly with an average strain of 17% at failure and a local strain of 60%. Pretest characterization of the spent fuel consisted of visual examination, profilometry, eddy-current examination, gamma scanning, fission gas collection, void volume measurement, fission gas analysis, hydrogen analysis of the cladding, burnup analysis, cladding metallography, and fuel ceramography. Post-test characterization showed that the failure was a pinhole cladding breach. The results of the tests showed that spent fuel temperatures in excess of 700/sup 0/C are required to produce a cladding breach in fuel rods pressurized to 500 psing (3.45 MPa) under postulated abnormal thermal transient cask conditions. The pinhole cladding breach that developed would be too small to compromise the confinement of spent fuel particles during an abnormal event or after normal cooling conditions are restored. This behavior is similar to that found in other slow ramp tests with irradiated and nonirradiated rod sections and nonirradiated whole rods under conditions that bracketed postulated abnormal heating rates. This similarity is attributed to annealing of the irradiation-strengthened Zircaloy cladding during heating. In both cases, the failure was a benign, ductile pinhole rupture.

  4. Pentoxifylline attenuates iminodipropionitrile-induced behavioral abnormalities in rats.

    PubMed

    Al Kadasah, Saeed; Al Mutairy, Ahmad; Siddiquei, Mairaj; Khan, Haseeb Ahmad; Abdulwahid Arif, Ibrahim; Al Moutaery, Khalaf; Tariq, Mohammad

    2009-07-01

    This investigation was undertaken to study the effect of pentoxifylline (PTX) on iminodipropionitrile (IDPN)-induced behavioral abnormalities [excitation with choreiform and circling movements (ECC) syndrome] in rats. The animals were intraperitoneally injected with IDPN (100 mg/kg) daily for 7 days. PTX was administered daily 30 min before IDPN in the doses of 25, 50, and 100 mg/kg for 9 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex. The onset of ECC syndrome was observed on day 8 in the group treated with IDPN alone; all animals in this group became dyskinetic on day 10. Co-treatment with PTX dose dependently delayed the onset time and significantly reduced the incidence and severity of IDPN-induced ECC syndrome; high dose of PTX completely inhibited the abnormal behavioral signs in IDPN-treated rats. Administration of IDPN caused significant depletions in cerebral glutathione and vitamin E levels. Treatment with PTX dose dependently attenuated IDPN-induced oxidative stress in rats. The beneficial effects of PTX against IDPN toxicity may be attributed to its antioxidant and anti-inflammatory properties.

  5. Left ventricular mass-geometry and silent cerebrovascular disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) study.

    PubMed

    Nakanishi, Koki; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Tugcu, Aylin; Yoshita, Mitsuhiro; DeCarli, Charles; Wright, Clinton B; Sacco, Ralph L; Di Tullio, Marco R

    2017-03-01

    Although abnormal left ventricular geometric patterns have prognostic value for morbidity and mortality, their possible association with silent cerebrovascular disease has not been extensively evaluated. We examined 665 participants in the CABL study who underwent transthoracic echocardiography and brain magnetic resonance imaging. Participants were divided into 4 geometric patterns: normal geometry (n=397), concentric remodeling (n=89), eccentric hypertrophy (n=126), and concentric hypertrophy (n=53). Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV; expressed as log-transformed percentage of the total cranial volume). Silent brain infarcts were observed in 94 participants (14%). Mean log-WMHV was -0.97±0.93. Concentric hypertrophy carried the greatest risk for both SBI (adjusted odds ratio [OR] 3.39, P<.001) and upper quartile of log-WMHV (adjusted OR 3.35, P<.001), followed by eccentric hypertrophy (adjusted ORs 2.52 [P=.001 for SBI] and 1.96 [P=.004] for log-WMHV). Concentric remodeling was not associated with subclinical brain disease. In subgroup analyses, concentric and eccentric hypertrophies were significantly associated with SBI and WMHV in both genders and nonobese participants, but differed for SBI by age (all ages for eccentric hypertrophy, only patients ≥70years for concentric hypertrophy) and by race-ethnicity (Hispanics for eccentric hypertrophy, blacks for concentric hypertrophy; no association in whites). Left ventricular hypertrophy, with both eccentric and concentric patterns, was significantly associated with subclinical cerebrovascular disease in a multiethnic stroke-free general population. Left ventricular geometric patterns may carry different risks for silent cerebrovascular disease in different sex, age, race-ethnic, and body size subgroups. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure.

    PubMed

    Ashikaga, Hiroshi; Omens, Jeffrey H; Covell, James W

    2004-11-01

    To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 +/- 0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a significant increase in wall thickness at the final study (0.181 +/- 0.047; P < 0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.

  7. Validity of acoustic quantification colour kinesis for detection of left ventricular regional wall motion abnormalities: a transoesophageal echocardiographic study.

    PubMed

    Hartmann, T; Kolev, N; Blaicher, A; Spiss, C; Zimpfer, M

    1997-10-01

    Transoesophageal echocardiography is a sensitive monitor for intraoperative myocardial ischaemia. Colour kinesis is a new technology for echocardiographic assessment of regional wall motion based on acoustic quantification. We have examined the feasibility and accuracy of quantitative segmental analysis of colour kinesis images to provide objective evaluation of systolic regional wall motion during the perioperative period using transoesophageal echocardiography (TOE). Two-dimensional echocardiograms were obtained in the transgastric short-axis and long-axis views in 60 patients with coronary artery disease undergoing noncardiac surgery. End-systolic colour overlays superimposed on the grey scale images were obtained with colour kinesis to colour encode left ventricular endocardial motion throughout systole. These colour-encoded images were divided into segments and compared with corresponding conventional two-dimensional images. Six hundred of a potential 720 left ventricular wall segments were of sufficient resolution for grading by experts; they diagnosed wall motion abnormalities in 61 of these segments by a conventional method. In comparing the conventional TOE method with colour kinesis, there were 60 true positives, 482 true negatives, 57 false positives and 1 false negative result. This yielded a sensitivity of 98%, specificity of 89%, positive predictive value of 51% and negative predictive value of 100%. Translational and rotational movement of the heart and papillary muscle interference were common problems accounting for false positive diagnoses. We conclude that colour kinesis provides a basis for objective and on-line evaluation of left ventricular regional wall motion which is a sensitive but non-specific method. It may be a useful aid for the less experienced because it can potentially direct the anaesthetist's attention towards specific segments.

  8. Behavioral abnormalities and psychiatric symptoms in Alzheimer's disease: preliminary findings.

    PubMed

    Burns, A; Jacoby, R; Levy, R

    1990-01-01

    Behavioral abnormalities and psychiatric symptoms were assessed in 178 patients diagnosed as having Alzheimer's disease by NINCDS/ADRDA criteria. The subjects were selected from a defined catchment area and therefore were representative of a group of patients with Alzheimer's disease of varying severity. Auditory hallucinations were found in 10%, visual hallucinations in 13%, and delusions in 16%. Symptoms suggestive of depression were reported by 39% of the patients and features of depression observed in 25%. Twenty percent were aggressive, and 7% were sexually disinhibited. Nineteen percent exhibited excessive walking behavior and 10% binge eating. Nearly 50% of the sample were incontinent. Patients in the hospital were more often aggressive, incontinent, and seemingly less depressed. Patients with severe dementia displayed excessive walking behavior, were more likely to be incontinent, and reported less depressive symptoms than those with moderate or mild dementia.

  9. Shape abnormalities of subcortical and ventricular structures in mild cognitive impairment and Alzheimer's disease: detecting, quantifying, and predicting.

    PubMed

    Tang, Xiaoying; Holland, Dominic; Dale, Anders M; Younes, Laurent; Miller, Michael I

    2014-08-01

    This article assesses the feasibility of using shape information to detect and quantify the subcortical and ventricular structural changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate structural shape abnormalities in MCI and AD as compared with healthy controls (HC). Exploring the development to AD, we then divide the MCI participants into two subgroups based on longitudinal clinical information: (1) MCI patients who remained stable; (2) MCI patients who converted to AD over time. We focus on seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151 converted to AD over time, and 175 AD). The hippocampus and amygdala were further subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer exploration. For MCI and AD, prominent ventricular expansions were detected and we found that these patients had strongest hippocampal atrophy occurring at CA1 and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal ganglia structures was also detected in MCI and AD. Stronger atrophy in the amygdala and hippocampus, and greater expansion in ventricles was observed in MCI converters, relative to those MCI who remained stable. Furthermore, we performed principal component analysis on a linear shape space of each structure. A subsequent linear discriminant analysis on the principal component values of hippocampus, amygdala, and ventricle leads to correct classification of 88% HC subjects and 86% AD subjects.

  10. Assessment of left ventricular wall motion abnormalities with the use of color kinesis: a valuable visual and training aid.

    PubMed

    Lau, Y S; Puryear, J V; Gan, S C; Fowler, M B; Vagelos, R H; Popp, R L; Schnittger, I

    1997-01-01

    Accurate interpretation of left ventricular segmental wall motion by echocardiography is an important yet difficult skill to learn. Color-coded left ventricular wall motion (color kinesis) is a tool that potentially could aid in the interpretation and provide semiquantification. We studied the usefulness of color kinesis in 42 patients with a history of congestive cardiomyopathy who underwent two-dimensional echocardiograms and a color kinesis study. The expert's reading of the two-dimensional wall motion served as a reference for comparison of color kinesis studies interpreted by the expert and a cardiovascular trainee. Correlation between two-dimensional echocardiography and the expert's and trainee's color coded wall motion scores were r = 0.83 and r = 0.67, respectively. Reproducibility between reviewers and between operators was also assessed. Interobserver variability for color-coded wall motion showed a correlation of r = 0.78. Correlation between operators was also good; r = 0.84. Color kinesis is reliable and appears promising as an adjunct in the assessment of wall motion abnormalities by echocardiography. It is both a valuable visual aid, as well as a training aid for the cardiovascular trainee.

  11. Myocardial perfusion abnormality in the area of ventricular septum-free wall junction and cardiovascular events in nonobstructive hypertrophic cardiomyopathy.

    PubMed

    Kaimoto, Satoshi; Kawasaki, Tatsuya; Kuribayashi, Toshiro; Yamano, Michiyo; Miki, Shigeyuki; Kamitani, Tadaaki; Matsubara, Hiroaki

    2012-10-01

    Myocardial perfusion abnormality in the left ventricle is known to be prognostic in patients with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging and necropsy studies on HCM hearts revealed myocardial lesions predominating in the area of ventricular septum-free wall junction. We assessed perfusion abnormality in this area and correlated it with the prognosis of HCM patients. We performed exercise Tc-99m tetrofosmin myocardial scintigraphy in 55 patients with nonobstructive HCM. Perfusion abnormalities were semiquantified using a 5-point scoring system in small areas of anterior junctions of basal, mid, and apical short axis views in addition to a conventional 17-segment model. All patients were prospectively followed for sudden death, cardiovascular death and hospitalization for heart failure or stroke associated with atrial fibrillation. Cardiovascular events occurred in 10 patients during an average follow-up period of 5.7 years. Stress and rest scores from anterior junction, and conventional summed stress score were significantly higher in patients with cardiovascular events than without (all P < 0.05). Anterior junction stress score of >2 produced a sensitivity of 50% and a specificity of 98% for cardiovascular events and was an independent predictor (hazard ratio 8.33; 95% confidence interval, 1.61-43.5; P = 0.01), with rest scores producing similar values, which were higher than summed stress score of >8 (5.68; 1.23-26.3; P = 0.03). The absence of myocardial perfusion abnormality in the narrow area of anterior junction differentiated HCM patients with low-risk.

  12. Structural Brain Abnormalities and Suicidal Behavior in Borderline Personality Disorder

    PubMed Central

    Soloff, Paul H.; Pruitt, Patrick; Sharma, Mohit; Radwan, Jacqueline; White, Richard; Diwadkar, Vaibhav A.

    2012-01-01

    Background Structural brain abnormalities have been demonstrated in subjects with BPD in prefrontal and fronto-limbic regions involved in the regulation of emotion and impulsive behavior, executive cognitive function and episodic memory. Impairment in these cognitive functions is associated with increased vulnerability to suicidal behavior. We compared BPD suicide attempters and non-attempters, high and low lethality attempters to healthy controls to identify neural circuits associated with suicidal behavior in BPD. Methods Structural MRI scans were obtained on 68 BPD subjects (16 male, 52 female), defined by IPDE and DIB/R criteria, and 52 healthy controls (HC: 28 male, 24 female). Groups were compared by diagnosis, attempt status, and attempt lethality. ROIs were defined for areas reported to have structural or metabolic abnormalities in BPD, and included: mid-inf. orbitofrontal cortex, mid-sup temporal cortex, anterior cingulate, insula, hippocampus, amygdala, fusiform, lingual and parahippocampal gyri. Data were analyzed using optimized voxel-based morphometry implemented with DARTEL in SPM5, co-varied for age and gender, corrected for cluster extent (p<.001). Results Compared to HC, BPD attempters had significantly diminished gray matter concentrations in 8 of 9 ROIs, non-attempters in 5 of 9 ROIs. Within the BPD sample, attempters had diminished gray matter in Lt. insula compared to non-attempters. High lethality attempters had significant decreases in Rt. mid-sup. temporal gyrus, Rt. mid-inf. orbitofrontal gyrus, Rt. insular cortex, Lt. fusiform gyrus, Lt. lingual gyrus and Rt. parahippocampal gyrus compared to low lethality attempters. Conclusions Specific structural abnormalities discriminate BPD attempters from non-attempters and high from low lethality attempters. PMID:22336640

  13. Characteristics of intraoperative abnormal hemodynamics during resection of an intra-fourth ventricular tumor located on the dorsal medulla oblongata.

    PubMed

    Ideguchi, Makoto; Kajiwara, Koji; Yoshikawa, Koichi; Sadahiro, Hirokazu; Nomura, Sadahiro; Fujii, Masami; Suzuki, Michiyasu

    2013-01-01

    Abnormal hemodynamics during extirpation of a para-medulla oblongata (MO) tumor is common and may be associated with direct vagal stimulation of the medullary circuit. However, resection of tumors on the dorsal MO may also induce hemodynamic instability without direct vagal stimulus. The objective of this study was to examine the characteristics of hemodynamic instability unrelated to vagal stimulus during dissection of an intra-fourth ventricular tumor with attachment to the dorsal MO. A retrospective analysis was performed in 13 patients. Abnormal hemodynamics were defined as a > 20% change from the means of the intraoperative mean arterial pressure (MAP) and heart rate (HR). Relationships of intraoperative hemodynamics were evaluated with various parameters, including the volume of the MO. Six patients (46.2%) had intraoperative hypertension during separation of the tumor bulk from the dorsal MO. The maximum MAP and HR in these patients were significantly greater than those in patients with normal hemodynamics (116.0 ± 18.0 mmHg versus 85.6 ± 6.5 mmHg; 124.3 ± 22.8 bpm versus 90.5 ± 14.7 bpm). All six cases with abnormal hemodynamics showed hemodynamic fluctuation during separation of the tumor bulk from the dorsal MO. The preoperative volume of the MO in these patients was 1.11 cc less than that in patients with normal hemodynamics, but the volume after tumor resection was similar in the two groups (5.23 cc and 5.12 cc). This suggests that the MO was compressed by the conglutinate tumor bulk, with resultant fluctuation of hemodynamics. Recognition of and preparation for this phenomenon are important for surgery on a tumor located on the dorsal MO.

  14. Cortical Thickness and Behavior Abnormalities in Children Born Preterm

    PubMed Central

    Zubiaurre-Elorza, Leire; Soria-Pastor, Sara; Junque, Carme; Sala-Llonch, Roser; Segarra, Dolors; Bargallo, Nuria; Macaya, Alfons

    2012-01-01

    Aim To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. Methods We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). Results We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. Interpretation The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems. PMID:22860067

  15. Abnormal magnetization behaviors in Sm-Ni-Fe-Cu alloys

    NASA Astrophysics Data System (ADS)

    Yang, W. Y.; Zhang, Y. F.; Zhao, H.; Chen, G. F.; Zhang, Y.; Du, H. L.; Liu, S. Q.; Wang, C. S.; Han, J. Z.; Yang, Y. C.; Yang, J. B.

    2016-06-01

    The magnetization behaviors in Sm-Ni-Fe-Cu alloys at low temperatures have been investigated. It was found that the hysteresis loops show wasp-waisted character at low temperatures, which has been proved to be related to the existence of multi-phases, the Fe/Ni soft magnetic phases and the CaCu5-type hard magnetic phase. A smooth-jump behavior of the magnetization is observed at T>5 K, whereas a step-like magnetization process appears at T<5 K. The CaCu5-type phase is responsible for such abnormal magnetization behavior. The magnetic moment reversal model with thermal activation is used to explain the relation of the critical magnetic field (Hcm) to the temperature (T>5 K). The reversal of the moment direction has to cross over an energy barrier of about 6.6×10-15 erg. The step-like jumps of the magnetization below 5 K is proposed to be resulted from a sharp increase of the sample temperature under the heat released by the irreversible domain wall motion.

  16. The abnormal behavior analysis of single person on the road based on region and behavior features

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Wang, Runsheng; Chen, Yiwen

    2007-11-01

    In this paper, a method to detect whether the behavior of a single person in video sequence is abnormal is proposed. Firstly, after the pre-processing, the background model is gotten based on the Mixture Gaussian Model(GMM), at the same time the shadow is eliminated; then use the color-shape information and the Random Hough Transform (RHT) to abstract the zebra crossing and segment the background; Lastly, we use the rectangle and the centroid to judge whether the person's behavior is abnormal.

  17. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

    PubMed Central

    Chantler, Paul D.; Nussbacher, Amit; Gerstenblith, Gary; Schulman, Steven P.; Becker, Lewis C.; Ferrucci, Luigi; Fleg, Jerome L.; Najjar, Samer S.

    2011-01-01

    The coupling between arterial elastance (EA; net afterload) and left ventricular elastance (ELV; pump performance), known as EA/ELV, is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in ELV versus EA. This normal exercise-induced reduction in EA/ELV decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in EA/ELV. At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and ELV as end-systolic pressure/end-systolic volume. Resting EA/ELV did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in EA and ELV in older subjects. During peak exercise, a blunted increase in ELV in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in EA/ELV in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting EA/ELV by 31% via a reduction in EA (10%) and an increase in ELV (47%) and lowered peak exercise EA/ELV (36%) via an increase in ELV (68%) without a change in EA. Importantly, SNP attenuated the age-associated deficits in EA/ELV and ELV during exercise, and at peak exercise EA/ELV in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in EA/ELV, EA, and ELV, in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction. PMID:21378146

  18. iPSC-derived cardiomyocytes reveal abnormal TGF-β signalling in left ventricular non-compaction cardiomyopathy.

    PubMed

    Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D; Shukla, Praveen; Abilez, Oscar J; Churko, Jared M; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M; Snyder, Michael P; Bernstein, Daniel; Wu, Joseph C

    2016-10-01

    Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and this was associated with perturbed transforming growth factor beta (TGF-β) signalling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGF-β signalling. TBX20 regulates the expression of TGF-β signalling modifiers including one known to be a genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGF-β signalling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC.

  19. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    PubMed Central

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  20. Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death.

    PubMed

    Bonilla, Ingrid M; Belevych, Andriy E; Sridhar, Arun; Nishijima, Yoshinori; Ho, Hsiang-Ting; He, Quanhua; Kukielka, Monica; Terentyev, Dmitry; Terentyeva, Radmila; Liu, Bin; Long, Victor P; Györke, Sandor; Carnes, Cynthia A; Billman, George E

    2012-12-01

    The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171-H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period (n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization (P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group (P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K(+) current, which was restored by exercise training (P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training (P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.

  1. Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death

    PubMed Central

    Bonilla, Ingrid M.; Belevych, Andriy E.; Sridhar, Arun; Nishijima, Yoshinori; Ho, Hsiang-Ting; He, Quanhua; Kukielka, Monica; Terentyev, Dmitry; Terentyeva, Radmila; Liu, Bin; Long, Victor P.; Györke, Sandor; Billman, George E.

    2012-01-01

    The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171–H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period (n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization (P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group (P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K+ current, which was restored by exercise training (P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training (P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling. PMID:23042911

  2. Post-Pacing Abnormal Repolarization in Catecholaminergic Polymorphic Ventricular Tachycardia Associated with a Mutation in the Cardiac Ryanodine Receptor Gene (RyR2)

    PubMed Central

    Nof, Eyal; Belhassen, Bernard; Arad, Michael; Bhuiyan, Zahurul A.; Antzelevitch, Charles; Rosso, Raphael; Fogelman, Rami; Luria, David; Eli-Ani, Dalia; Mannens, Marcel M.A.M.; Viskin, Sami; Eldar, Michael; Wilde, Arthur A.M.; Glikson, Michael

    2011-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. Objective We present a CPVT family in which marked post-pacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of RyR2 mutation carriers. Methods The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic ECG testing with epinephrine, adenosine and flecainide. Non-invasive clinical tests were normal in 10 patients evaluated, except for both epinephrine and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in LQTS as well as RyR2. Results Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent post-pacing QT changes. Conclusions M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked post-pacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family. PMID:21699856

  3. Frequency of conduction abnormalities after transcatheter aortic valve implantation with the Medtronic-CoreValve and the effect on left ventricular ejection fraction.

    PubMed

    Tzikas, Apostolos; van Dalen, Bas M; Van Mieghem, Nicolas M; Gutierrez-Chico, Juan-Luis; Nuis, Rutger-Jan; Kauer, Floris; Schultz, Carl; Serruys, Patrick W; de Jaegere, Peter P T; Geleijnse, Marcel L

    2011-01-15

    New conduction abnormalities occur frequently after transcatheter aortic valve implantation (TAVI). The relation between new conduction disorders and left ventricular (LV) systolic function after TAVI is unknown. The purpose of the present prospective, single-center study was to investigate the effect of TAVI on LV systolic function in relation to TAVI-induced conduction abnormalities. A total of 27 patients had undergone electrocardiography and transthoracic echocardiography the day before and 6 days after TAVI with the Medtronic-CoreValve system. The LV ejection fraction (EF) was calculated using the biplane Simpson method. The systolic mitral annular velocities and longitudinal strain were measured using speckle tracking echocardiography. After TAVI, 18 patients (67%) had new conduction abnormalities; 4 (15%) had a new paced rhythm and 14 patients (52%) had new left bundle branch block. In the patients with new conduction abnormalities, the EF decreased from 47 ± 12% to 44 ± 10%. In contrast, in those without new conduction abnormalities, the EF increased from 49 ± 12% to 54% ± 12%. The change in EF was significantly different among those with and without new conduction abnormalities (p <0.05). In patients without new conduction abnormalities, an improvement was found in the systolic mitral annular velocities and longitudinal strain (p <0.05). In contrast, in patients with new conduction abnormalities, the changes were not significant. In conclusion, the induction of new conduction abnormalities after TAVI with the Medtronic-CoreValve was associated with a lack of improvement in LV systolic function. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Ventricular conduction abnormalities as predictors of long‐term survival in acute de novo and decompensated chronic heart failure

    PubMed Central

    Siirila‐Waris, Krista; Harjola, Veli‐Pekka; Marono, David; Parenica, Jiri; Kreutzinger, Philipp; Nieminen, Tuomo; Pavlusova, Marie; Tarvasmaki, Tuukka; Twerenbold, Raphael; Tolonen, Jukka; Miklik, Roman; Nieminen, Markku S.; Spinar, Jindrich; Mueller, Christian; Lassus, Johan

    2016-01-01

    Abstract Aims Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long‐term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). Methods and Results We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow‐up. Half (51.5%, n = 506) of the patients had de novo AHF. LBBB, and IVCD were more common in ADCHF than in de novo AHF: 17.2% vs. 8.7% (P < 0.001) and 20.6% vs. 13.2% (P = 0.001), respectively, and RBBB was almost equally common (6.9% and 8.1%; P = 0.5), respectively. Mortality during the follow‐up was higher in patients with RBBB (85.4%) and IVCD (73.7%) compared with patients with normal ventricular conduction (57.0%); P < 0.001 for both. The impact of RBBB on prognosis was prominent in de novo AHF (adjusted HR 1.93, 1.03–3.60; P = 0.04), and IVCD independently predicted death in ADCHF (adjusted HR 1.79, 1.28–2.52; P = 0.001). Both findings were pronounced in patients with reduced ejection fraction. LBBB showed no association with increased mortality in either of the subgroups. The main results were confirmed in a validation cohort of 1511 AHF patients with 5.9 years' mean follow‐up. Conclusions Conduction abnormalities predict long‐term survival differently in de novo AHF and ADCHF. RBBB predicts mortality in de novo AHF, and IVCD in ADCHF. LBBB has no additive predictive value in AHF requiring hospitalization. PMID:27774265

  5. Ventricular conduction abnormalities as predictors of long-term survival in acute de novo and decompensated chronic heart failure.

    PubMed

    Tolppanen, Heli; Siirila-Waris, Krista; Harjola, Veli-Pekka; Marono, David; Parenica, Jiri; Kreutzinger, Philipp; Nieminen, Tuomo; Pavlusova, Marie; Tarvasmaki, Tuukka; Twerenbold, Raphael; Tolonen, Jukka; Miklik, Roman; Nieminen, Markku S; Spinar, Jindrich; Mueller, Christian; Lassus, Johan

    2016-03-01

    Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long-term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow-up. Half (51.5%, n = 506) of the patients had de novo AHF. LBBB, and IVCD were more common in ADCHF than in de novo AHF: 17.2% vs. 8.7% (P < 0.001) and 20.6% vs. 13.2% (P = 0.001), respectively, and RBBB was almost equally common (6.9% and 8.1%; P = 0.5), respectively. Mortality during the follow-up was higher in patients with RBBB (85.4%) and IVCD (73.7%) compared with patients with normal ventricular conduction (57.0%); P < 0.001 for both. The impact of RBBB on prognosis was prominent in de novo AHF (adjusted HR 1.93, 1.03-3.60; P = 0.04), and IVCD independently predicted death in ADCHF (adjusted HR 1.79, 1.28-2.52; P = 0.001). Both findings were pronounced in patients with reduced ejection fraction. LBBB showed no association with increased mortality in either of the subgroups. The main results were confirmed in a validation cohort of 1511 AHF patients with 5.9 years' mean follow-up. Conduction abnormalities predict long-term survival differently in de novo AHF and ADCHF. RBBB predicts mortality in de novo AHF, and IVCD in ADCHF. LBBB has no additive predictive value in AHF requiring hospitalization.

  6. VASCULAR INFLAMMATION AND ABNORMAL AORTIC HISTOMORPHOMETRY IN PATIENTS FOLLOWING PULSATILE AND CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICE PLACEMENT

    PubMed Central

    Lee, Mike; Akashi, Hirokazu; Kato, Tomoko S.; Takayama, Hiroo; Wu, Christina; Xu, Katherine; Collado, Elias; Weber, Matthew P.; Kennel, Peter J.; Brunjes, Danielle L; Ji, Ruiping; Naka, Yoshifumi; George, Isaac; Mancini, Donna; Farr, Maryjane; Schulze, P. Christian

    2017-01-01

    Objective Left ventricular assist devices are increasingly used in patients with advanced heart failure as both destination therapy and bridge-to-transplantation. We aimed to analyze histomorphometric, structural and inflammatory changes following pulsatile and continuous flow left ventricular assist device placement. Method Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous flow support. Both device types showed an increased inflammatory response following left ventricular assist device placement with variable T cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusion Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous flow left ventricular assist and associated with aortic media decellularization. These findings help to explain the progressive aortic root dilation and vascular dysfunction in patients following continuous flow device placement. PMID:26899764

  7. Psychosocial correlates, outcome, and stability of abnormal adolescent eating behavior in community samples of young people.

    PubMed

    Steinhausen, Hans-Christoph; Gavez, Silvia; Winkler Metzke, Christa

    2005-03-01

    The current study investigated psychosocial correlates of abnormal adolescent eating behavior at three times during adolescence and young adulthood and its association with psychiatric diagnosis in young adulthood in a community sample. Sixty-four (10.5%) high-risk subjects (mean age 15 years) with abnormal eating behavior were identified at Time 1, another 252 (16.9%) were identified at Time 2 (mean age 16.2 years), and 164 (16.9%) were identified at Time 3 (mean age 19.7 years) and compared with three control groups matched for age and gender. Dependent measures included emotional and behavioral problems, life events, coping capacities, self-related cognition, social network, and family functions. Outcome was measured additionally by structured psychiatric interviews, and stability of abnormal eating behavior was studied in a longitudinal sample of 330 subjects. Few subjects showed more than one of five criteria of abnormal eating behavior. High-risk subjects shared a very similar pattern at all three times. They were characterized by higher scores for emotional and behavioral problems, more life events including more negative impact, less active coping, lower self-esteem, and less family cohesion. Among 10 major psychiatric disorders, only clinical eating disorders at Time 3 shared a significant association with abnormal eating disorder at the same time whereas high-risk status at Times 1 and 2 did not predict any psychiatric disorder at Time 3. Stability of abnormal eating behavior across time was very low. Stability of abnormal eating behavior across time was very low. Abnormal eating behavior in adolescence and young adulthood is clearly associated with various indicators of psychosocial maladaption. In adolescence, it does not significantly predict any psychiatric disorder including eating disorder in young adulthood and it is predominantly a transient feature. (c) 2005 by Wiley Periodicals, Inc.

  8. Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

    PubMed

    Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

    2014-04-01

    Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species.

  9. Abnormal Nocturnal Behavior due to Hypoglycemia in a Patient with Type 2 Diabetes.

    PubMed

    Yang, Kwang Ik; Kim, Hyung Ki; Baek, Jeehun; Kim, Doh-Eui; Park, Hyung Kook

    2016-04-15

    Abnormal nocturnal behavior can have many causes, including primary sleep disorder, nocturnal seizures, and underlying medical or neurological disorders. A 79-year-old woman with type 2 diabetes was admitted for evaluation of abnormal nocturnal behavior. Every night at around 04:30 she was observed displaying abnormal behavior including leg shaking, fumbling with bedclothes, crawling around the room with her eyes closed, and non-responsiveness to verbal communication. Polysomnography with 20-channel electroencephalography (EEG) was performed. EEG showed that the posterior dominant rhythm was slower than that observed in the initial EEG, with diffuse theta and delta activities intermixed, and no epileptiform activity. The serum glucose level was 35 mg/dL at that time, and both the EEG findings and clinical symptoms were resolved after an intravenous injection of 50 mL of 50% glucose. These results indicate that nocturnal hypoglycemia should be considered as one of the possible etiologies in patients presenting with abnormal nocturnal behavior.

  10. Allergies: The Key to Many Childhood Behavior Abnormalities.

    ERIC Educational Resources Information Center

    Vass, Molly; Rasmussen, Betty

    1984-01-01

    Describes the role of allergies in childhood behavior problems and discusses the role of school counselors in identifying allergic responses. Includes a list of references and resources on allergies, nutrition, support groups, and environmental care units. (JAC)

  11. Allergies: The Key to Many Childhood Behavior Abnormalities.

    ERIC Educational Resources Information Center

    Vass, Molly; Rasmussen, Betty

    1984-01-01

    Describes the role of allergies in childhood behavior problems and discusses the role of school counselors in identifying allergic responses. Includes a list of references and resources on allergies, nutrition, support groups, and environmental care units. (JAC)

  12. Behavioral and neuroanatomical abnormalities in pleiotrophin knockout mice.

    PubMed

    Krellman, Jason W; Ruiz, Henry H; Marciano, Veronica A; Mondrow, Bracha; Croll, Susan D

    2014-01-01

    Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features.

  13. The Association of Abnormal Ventricular Wall Motion and Increased Dispersion of Repolarization in Humans is Independent of the Presence of Myocardial Infarction

    PubMed Central

    Opthof, Tobias; Sutton, Peter; Coronel, Ruben; Wright, Susan; Kallis, Panny; Taggart, Peter

    2012-01-01

    Abnormal ventricular wall motion is a strong clinical predictor of sudden, arrhythmic, cardiac death. Dispersion in repolarization is a prerequisite for the initiation of re-entrant arrhythmia. We hypothesize that regionally decreased wall motion is associated with heterogeneity of repolarization. We measured local activation times, activation-recovery intervals (ARIs, surrogate for action potential duration), and repolarization times using a multielectrode grid at nine segments on the left ventricular epicardium in 23 patients undergoing coronary artery surgery. Regional wall motion was simultaneously assessed using intraoperative transesophageal echocardiography. Three groups were discriminated: (1) Patients with normal wall motion (n = 11), (2) Patients with one or more hypokinetic segments (n = 6), (3) Patients with one or more akinetic or dyskinetic segments (n = 6). The average ARI was similar in all groups (251 ± 3.7 ms, ±SEM). Dispersion of ARIs between the nine segments was significantly increased in the hypokinetic (84 ± 7.4 ms, p < 0.005) and akinetic/dyskinetic group (94 ± 3.5 ms, p < 0.0005) compared with the normal group (49 ± 5.1 ms), independent from the presence of myocardial infarction. Repolarization heterogeneity occurred primarily in the normally contracting regions of the hearts with abnormal wall motion. An almost maximal increased dispersion of repolarization was observed when there was only a single hypokinetic segment. We conclude that inhomogeneous wall motion abnormality of even moderate severity is associated with increased repolarization inhomogeneity, independent from the presence of infarction. PMID:22783201

  14. Autism-related behavioral abnormalities in synapsin knockout mice

    PubMed Central

    Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

    2013-01-01

    Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII−/− mice. SynII−/− and SynIII−/− mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI−/−, SynII−/− and SynIII−/− mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI−/− and SynII−/− mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. PMID:23280234

  15. Relation between exercise-induced left ventricular wall motion abnormalities and coronary artery disease in hypertensive patients: effects of blood pressure normalization.

    PubMed

    Pepi, M; Maltagliati, A; Berti, M; Muratori, M; Tavasci, E; Passaretti, B; Tamborini, G

    1997-03-01

    In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one

  16. Macro- and microscopic spectral-polarization characteristics of the structure of normal and abnormally located chordae tendianeae of left ventricular

    NASA Astrophysics Data System (ADS)

    Malyk, Yu. Yu.; Prydij, O. G.; Zymnyakov, D. A.; Alonova, M. V.; Ushakova, O. V.

    2013-12-01

    The morphological peculiarities of TS mitral valve of the heart of man in normal and abnormal spaced strings of the left ventricle and the study of their structural features depending on the location was studied. There are given the results of comparative statistics, correlation and fractal study population Mueller-matrix images (MMI) of healthy and abnormal (early forms that are not diagnosed by histological methods) BT normal and abnormally located tendon strings left ventricle of the human heart. Abnormalities in the structure of the wings, tendon strings (TS), mastoid muscle (MM) in inconsistencies elements and harmonized operation of all valve complex shown in the features of the polarization manifestations of it laser images.

  17. Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice.

    PubMed

    Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D Woodrow; Ivy, Dunbar; Perryman, M B; Garrett-Sinha, Lee Ann; Grossfeld, Paul

    2010-02-15

    Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an approximately 7 Mb 'cardiac critical region' in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease.

  18. Abnormal left ventricular vortex flow patterns in association with left ventricular apical thrombus formation in patients with anterior myocardial infarction: a quantitative analysis by contrast echocardiography.

    PubMed

    Son, Jang-Won; Park, Won-Jong; Choi, Jung-Hyun; Houle, Helene; Vannan, Mani A; Hong, Geu-Ru; Chung, Namsik

    2012-01-01

    The current study was designed to investigate the correlation between the left ventricular (LV) vortex flow pattern and LV apical thrombus formation in patients with acute anterior wall myocardial infarction (MI). Fifty-seven patients with acute anterior wall MI were enrolled in this study. Eighteen patients with apical thrombus (thrombus group) and 39 patients without apical thrombus (non-thrombus group) underwent 2-dimensional contrast echocardiography (CE). Morphology and pulsatility parameters of the LV vortex were measured using Omega flow(®) and compared between the 2 groups. In the thrombus group, the vortex was located more centrally and did not extend to the apex. In the thrombus group, quantitative vortex parameters of vortex depth (0.409±0.101 vs. 0.505±0.092, respectively; P=0.002) and relative strength (1.574±0.310 vs. 1.808±0.376, respectively, P=0.034) were significantly lower than the non-thrombus group. Following multivariate analysis, the vortex depth below 0.45 remained a significant independent parameter for formation of the LV apical thrombus (odds ratio 9.714, 95% confidence interval 1.674-56.381, P=0.011). These findings suggest that the location and pulsatility power of the LV vortex are strongly associated with the LV thrombus formation in patients with anterior MI. Therefore, LV vortex flow analysis using CE can be clinically useful for characterizing and quantifying the risk of LV apical thrombus in patients with anterior MI.

  19. Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease.

    PubMed

    Apostolova, Liana G; Di, Li Jie; Duffy, Erin L; Brook, Jenny; Elashoff, David; Tseng, Chi-Hong; Fairbanks, Lynn; Cummings, Jeffrey L

    2014-01-01

    Behavioral symptoms are common in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). We analyzed the Neuropsychiatric Inventory Questionnaire data of 3,456 MCI and 2,641 mild AD National Alzheimer's Coordinating Center database participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, Mini-Mental State Examination, functional impairment, marital status and family history on the presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with a higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed a higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI patients had more elation and agitation relative to nonamnestic MCI patients. Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had an effect on selected behaviors. © 2014 S. Karger AG, Basel.

  20. Possible relationships between trichinellosis and abnormal behavior in bears

    USGS Publications Warehouse

    Worley, David E.; Greer, Kenneth R.; Palmisciano, D.A.

    1983-01-01

    Data compiled from parasite studies of grizzly bears (Ursus arctos) and black bears (U. americanus) in the Yellowstone and Glacier National Park populations and surrounding areas of Montana and Wyoming during 1969-79 are reviewed with reference to the possible influence of infection with the muscleworm Trichinella sp. on bear behavior. In grizzly bears, the high prevalence of this parasite (61% of 254 bears infected), the elevated larval concentrations in sensitive anatomical sites such as the tongue (average, 51 larvae per gram of tissue), and the chronic nature of bear infections as indicated by the tendency for highest infection rates to occur in older age classes (> 16 yrs.), suggest a potential behavior-modifying effect might exist. However, retrospective analysis of recent human attacks by 4 grizzlies and 2 black bears in the northern Rocky Mountain region failed to demonstrate a consistent connection between erratic conduct and levels of Trichinella larvae (trichinae) in bear tissues. Clinical similarities of trichinellosis in bears and humans are hypothesized, and possible behavioral effects of ursine trichinellosis are discussed.

  1. Heterogeneous abnormalities of in-vivo left ventricular calcium influx and function in mouse models of muscular dystrophy cardiomyopathy.

    PubMed

    Greally, Elizabeth; Davison, Benjamin J; Blain, Alison; Laval, Steve; Blamire, Andrew; Straub, Volker; MacGowan, Guy A

    2013-01-16

    Manganese-enhanced cardiovascular magnetic resonance (MECMR) can non-invasively assess myocardial calcium influx, and calcium levels are known to be elevated in muscular dystrophy cardiomyopathy based on cellular studies. Left ventricular functional studies and MECMR were performed in mdx mice (model of Duchenne muscular dystrophy, 24 and 40 weeks) and Sgcd -/- mice (limb girdle muscular dystrophy 2 F, 16 and 32 weeks), compared to wild type controls (C57Bl/10, WT). Both models had left ventricular hypertrophy at the later age compared to WT, though the mdx mice had reduced stroke volumes and the Sgcd -/- mice increased heart rate and cardiac index. Especially at the younger ages, MECMR was significantly elevated in both models (both P < 0.05 versus WT). The L-type calcium channel inhibitor diltiazem (5 mg/kg i.p.) significantly reduced MECMR in the mdx mice (P < 0.01), though only with a higher dose (10 mg/kg i.p.) in the Sgcd -/- mice (P < 0.05). As the Sgcd -/- mice had increased heart rates, to determine the role of heart rate in MECMR we studied the hyperpolarization-activated cyclic nucleotide-gated channel inhibitor ZD 7288 which selectively reduces heart rate. This reduced heart rate and MECMR in all mouse groups. However, when looking at the time course of reduction of MECMR in the Sgcd -/- mice at up to 5 minutes of the manganese infusion when heart rates were matched to the WT mice, MECMR was still significantly elevated in the Sgcd -/- mice (P < 0.01) indicating that heart rate alone could not account for all the increased MECMR. Despite both mouse models exhibiting increased in-vivo calcium influx at an early stage in the development of the cardiomyopathy before left ventricular hypertrophy, there are distinct phenotypical differences between the 2 models in terms of heart rates, hemodynamics and responses to calcium channel inhibitors.

  2. Abnormal Nocturnal Behavior due to Hypoglycemia in a Patient with Type 2 Diabetes

    PubMed Central

    Yang, Kwang Ik; Kim, Hyung Ki; Baek, Jeehun; Kim, Doh-Eui; Park, Hyung Kook

    2016-01-01

    Abnormal nocturnal behavior can have many causes, including primary sleep disorder, nocturnal seizures, and underlying medical or neurological disorders. A 79-year-old woman with type 2 diabetes was admitted for evaluation of abnormal nocturnal behavior. Every night at around 04:30 she was observed displaying abnormal behavior including leg shaking, fumbling with bedclothes, crawling around the room with her eyes closed, and non-responsiveness to verbal communication. Polysomnography with 20-channel electroencephalography (EEG) was performed. EEG showed that the posterior dominant rhythm was slower than that observed in the initial EEG, with diffuse theta and delta activities intermixed, and no epileptiform activity. The serum glucose level was 35 mg/dL at that time, and both the EEG findings and clinical symptoms were resolved after an intravenous injection of 50 mL of 50% glucose. These results indicate that nocturnal hypoglycemia should be considered as one of the possible etiologies in patients presenting with abnormal nocturnal behavior. Citation: Yang KI, Kim HK, Baek J, Kim DE, Park HK. Abnormal nocturnal behavior due to hypoglycemia in a patient with type 2 diabetes. J Clin Sleep Med 2016;12(4):627–629. PMID:26943712

  3. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors

    PubMed Central

    Jacobson, Sarah L.; Bloomsmith, Mollie A.

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  4. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors.

    PubMed

    Jacobson, Sarah L; Ross, Stephen R; Bloomsmith, Mollie A

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  5. Effects of Left Ventricular Wall Motion Abnormality on Global and Regional Diastolic Function of the Left and Right Ventricles at Rest and After Stress

    PubMed Central

    Sharif, Dawod; Sharif-Rasslan, Amal; Odeh, Majed; Shahla, Camilia; Khalil, Amin; Rosenschien, Uri

    2014-01-01

    Background Diastolic dysfunction precedes systolic dysfunction in patients with coronary artery disease. The aim of the study was to evaluate the effects of left ventricular (LV) wall motion abnormality (WMA) on diastolic LV and right ventricular (RV) function at rest and after stress. Methods Fifty-nine subjects, 15 with LV-WMA (abnormal group) and 44 without (normal group), underwent dobutamine stress echocardiography (DSE) studies, in addition to evaluation of LV and RV diastolic function before and after DSE. Results Resting mitral flow parameters were similar. DSE increased peak A-wave velocities in both groups, and mitral color slope only in normal subjects. After DSE, E-wave peak velocities and mitral color slope were higher in normal subjects, P < 0.05. At rest and after DSE systolic and diastolic pulmonary vein velocities were similar in both groups; however, DSE increased these velocities only in normal subjects, P < 0.05. Regional E-wave peak velocities of LV were higher at rest in normal subjects, P < 0.05. Both LV and RV, regional peak E-wave velocities were not affected by DSE. After DSE, regional A-wave peak velocities increased in all (P < 0.01), except at the lateral region (P = 0.07). DSE increased trans-tricuspid velocities in both groups, P < 0.05. Resting A-wave velocities were higher in normal subjects, P < 0.01. Conclusions Global LV early diastolic filling parameters were not affected by LV-WMA at rest. LV-WMA blunted the response after stress. RV E-wave velocities increased after DSE, and were not affected by LV-WMA. LV-WMA reduced regional LV-E’ velocities at rest but not the reserve. A-wave velocities were not affected by WMA and increased after DSE.

  6. PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction

    PubMed Central

    Muhammad, Emad; Levitas, Aviva; Singh, Sonia R.; Braiman, Alex; Ofir, Rivka; Etzion, Sharon; Sheffield, Val C.; Etzion, Yoram; Carrier, Lucie; Parvari, Ruti

    2015-01-01

    Gene mutations, mostly segregating with a dominant mode of inheritance, are important causes of dilated cardiomyopathy (DCM), a disease characterized by enlarged ventricular dimensions, impaired cardiac function, heart failure and high risk of death. Another myocardial abnormality often linked to gene mutations is left ventricular noncompaction (LVNC) characterized by a typical diffuse spongy appearance of the left ventricle. Here, we describe a large Bedouin family presenting with a severe recessive DCM and LVNC. Homozygosity mapping and exome sequencing identified a single gene variant that segregated as expected and was neither reported in databases nor in Bedouin population controls. The PLEKHM2 cDNA2156_2157delAG variant causes the frameshift p.Lys645AlafsTer12 and/or the skipping of exon 11 that results in deletion of 30 highly conserved amino acids. PLEKHM2 is known to interact with several Rabs and with kinesin-1, affecting endosomal trafficking. Accordingly, patients' primary fibroblasts exhibited abnormal subcellular distribution of endosomes marked by Rab5, Rab7 and Rab9, as well as the Golgi apparatus. In addition, lysosomes appeared to be concentrated in the perinuclear region, and autophagy flux was impaired. Transfection of wild-type PLEKHM2 cDNA into patient's fibroblasts corrected the subcellular distribution of the lysosomes, supporting the causal effect of PLEKHM2 mutation. PLEKHM2 joins LAMP-2 and BAG3 as a disease gene altering autophagy resulting in an isolated cardiac phenotype. The association of PLEKHM2 mutation with DCM and LVNC supports the importance of autophagy for normal cardiac function. PMID:26464484

  7. Association of left ventricular structural and functional abnormalities with aortic and brachial blood pressure variability in hypertensive patients: the SAFAR study.

    PubMed

    Chi, C; Yu, S-K; Auckle, R; Argyris, A A; Nasothimiou, E; Tountas, C; Aissopou, E; Blacher, J; Safar, M E; Sfikakis, P P; Zhang, Y; Protogerou, A D

    2017-10-01

    Both brachial blood pressure (BP) level and its variability (BPV) significantly associate with left ventricular (LV) structure and function. Recent studies indicate that aortic BP is superior to brachial BP in the association with LV abnormalities. However, it remains unknown whether aortic BPV better associate with LV structural and functional abnormalities. We therefore aimed to investigate and compare aortic versus brachial BPV, in terms of the identification of LV abnormalities. Two hundred and three participants who underwent echocardiography were included in this study. Twenty-four-hour aortic and brachial ambulatory BP was measured simultaneously by a validated BP monitor (Mobil-O-Graph, Stolberg, Germany) and BPV was calculated with validated formulae. LV mass and LV diastolic dysfunction (LVDD) were evaluated by echocardiography. The prevalence of LV hypertrophy (LVH) and LVDD increased significantly with BPV indices (P⩽0.04) in trend tests. After adjustment to potential confounders, only aortic average real variability (ARV), but not brachial ARV or weighted s.d. (wSD, neither aortic nor brachial) significantly associated with LV mass index (P=0.02). Similar results were observed in logistic regression. After adjustment, only aortic ARV significantly associated with LVH (odds ratio (OR) and 95% confidence interval (CI): 2.28 (1.08, 4.82)). As for LVDD, neither the brachial nor the aortic 24-hour wSD, but the aortic and brachial ARV, associated with LVDD significantly, with OR=2.28 (95% CI: (1.03, 5.02)) and OR=2.36 (95% CI: (1.10, 5.05)), respectively. In summary, aortic BPV, especially aortic ARV, seems to be superior to brachial BPV in the association of LV structural and functional abnormalities.

  8. Positive reinforcement training moderates only high levels of abnormal behavior in singly housed rhesus macaques.

    PubMed

    Baker, Kate C; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valerie A M; Martinez, Marni

    2009-01-01

    This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals.

  9. Positive Reinforcement Training Moderates Only High Levels of Abnormal Behavior in Singly Housed Rhesus Macaques

    PubMed Central

    Baker, Kate C.; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valérie A. M.; Martinez, Marni

    2010-01-01

    This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals. PMID:20183477

  10. Neurocognitive abnormalities during comprehension of real-world goal-directed behaviors in schizophrenia.

    PubMed

    Sitnikova, Tatiana; Goff, Donald; Kuperberg, Gina R

    2009-05-01

    Origins of impaired adaptive functioning in schizophrenia remain poorly understood. Behavioral disorganization may arise from an abnormal reliance on common combinations between concepts stored in semantic memory. Avolition-apathy may be related to deficits in using goal-related requirements to flexibly plan behavior. The authors recorded event-related potentials (ERPs) in 16 patients with medicated schizophrenia and 16 healthy controls in a novel video paradigm presenting congruous or incongruous objects in real-world activities. All incongruous objects were contextually inappropriate, but the incongruous scenes varied in comprehensibility. Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) and the Brief Psychiatric Rating Scale. In patients, an N400 ERP, thought to index activity in semantic memory, was abnormally enhanced to less comprehensible incongruous scenes, and larger N400 priming was associated with disorganization severity. A P600 ERP, which may index flexible object-action integration based on goal-related requirements, was abnormally attenuated in patients, and its smaller magnitude was associated with the SANS rating of impersistence at work or school (goal-directed behavior). Thus, distinct neurocognitive abnormalities may underlie disorganization and goal-directed behavior deficits in schizophrenia.

  11. Teaching a Course in Abnormal Psychology and Behavior Intervention Skills for Nursing Home Aides.

    ERIC Educational Resources Information Center

    Glenwick, David S.; Slutzsky, Mitchel R.; Garfinkel, Eric

    2001-01-01

    Describes an 11-week course given at a nursing home to nursing home aides that focused on abnormal psychology and behavior intervention skills. Discusses the course goals, class composition, and course description. Addresses the problems and issues encountered with teaching this course to a nontraditional population in an unconventional setting.…

  12. Abnormal perilesional BOLD signal is not correlated with stroke patients’ behavior

    PubMed Central

    de Haan, Bianca; Rorden, Chris; Karnath, Hans-Otto

    2013-01-01

    Several functional magnetic resonance imaging (fMRI) studies of acute stroke have reported that patients with behavioral deficits show abnormal signal in intact regions of the damaged hemisphere close to the lesion border relative to homologous regions of the patient’s intact hemisphere (causing an interhemispheric imbalance) as well as analogous regions in healthy controls. These effects have been interpreted as demonstrating a causal relationship between the abnormal fMRI signal and the pathological behavior. Here we explore an alternative explanation: perhaps the abnormal Blood-Oxygenation Level Dependent (BOLD) fMRI signal is merely a function of distance from the acute lesion. To investigate this hypothesis, we examined three patients with an acute right hemisphere cortical stroke who did not show any overt behavioral deficits, as well as nine healthy elderly controls. We acquired fMRI data while the participants performed a simple visual orientation judgment task. In patients, we observed an abnormal interhemispheric balance consisting of lower levels of percent signal change in perilesional areas of the damaged hemisphere relative to homologous areas in neurologically healthy controls. This suggests that the physiological changes and corresponding interhemispheric imbalance detected by fMRI BOLD in acute stroke observed close to the lesion border may not necessarily reflect changes in the neural function, nor necessarily influence the individuals’ (e.g., attentional) behavior. PMID:24137123

  13. Olfaction in eating disorders and abnormal eating behavior: a systematic review.

    PubMed

    Islam, Mohammed A; Fagundo, Ana B; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M; Tinahones, Francisco J; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F; Menchón, José M; Fernandez-Aranda, Fernando

    2015-01-01

    The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

  14. Olfaction in eating disorders and abnormal eating behavior: a systematic review

    PubMed Central

    Islam, Mohammed A.; Fagundo, Ana B.; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M.; Tinahones, Francisco J.; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F.; Menchón, José M.; Fernandez-Aranda, Fernando

    2015-01-01

    The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior. PMID:26483708

  15. Teaching a Course in Abnormal Psychology and Behavior Intervention Skills for Nursing Home Aides.

    ERIC Educational Resources Information Center

    Glenwick, David S.; Slutzsky, Mitchel R.; Garfinkel, Eric

    2001-01-01

    Describes an 11-week course given at a nursing home to nursing home aides that focused on abnormal psychology and behavior intervention skills. Discusses the course goals, class composition, and course description. Addresses the problems and issues encountered with teaching this course to a nontraditional population in an unconventional setting.…

  16. Relationship between abnormal P-wave terminal force in lead V1 and left ventricular diastolic dysfunction in hypertensive patients: the LIFE study.

    PubMed

    Tanoue, Michael T; Kjeldsen, Sverre E; Devereux, Richard B; Okin, Peter M

    2017-04-01

    Abnormal P-wave terminal force in lead V1 (PTF-V1) is an ECG marker of increased left atrial (LA) volume, elevated LA filling pressures and/or LA systolic dysfunction. Because left ventricular (LV) diastolic dysfunction is one of the potential mechanisms driving LA remodelling, we hypothesized that PTF-V1 might be an additional ECG marker of diastolic dysfunction. LV diastolic function after 3 years' systematic antihypertensive treatment was examined in relation to baseline PTF-V1 in 431 hypertensive patients undergoing protocol-driven blood pressure reduction who had baseline and year-3 ECG and echocardiographic data and a preserved LV ejection fraction (EF >45%) at year-3. Abnormal diastolic function was defined by the tenth or 90th percentile values from 405 normotensive, non-obese and non-diabetic adults without overt cardiovascular disease. Abnormal PTF-V1, defined by the presence of a negative terminal P-wave in lead V1 ≥ 4000 μV·ms, was present in 167 patients (38.7%). Abnormal PTF-V1 was associated with worse year-3 mean diastolic first third filling time (0.43 ± 0.08 vs 0.40 ± 0.07 sec, p = 0.039), first half filling time (0.55 ± 0.07 vs 0.53 ± 0.07 sec, p = 0.041), mitral valve A velocity (86 ± 27 vs 76 ± 19 cm/sec, p = 0.009) and mitral valve E/A ratio (0.85 ± 0.22 vs 0.94 ± 0.27, p = 0.007) after adjusting for other potential predictors of diastolic dysfunction including race, and heart rate, systolic blood pressure and severity of ECG LVH by Cornell product criteria at baseline. In parallel multivariate logistic regression analysis, abnormal PTF-V1 was associated with significantly increased odds of abnormal mitral valve E/A ratio (OR 1.55, 95%CI 1.04-2.32 p = 0.032), and a trend toward higher odds of abnormal half filling time (OR 1.42, 95%CI 0.94-2.15, p = 0.098) at year-3 of follow-up. Abnormal P-wave terminal force in lead V1 is associated with worse diastolic

  17. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection.

    PubMed

    Li, Yu-Cheng; Liu, Ya-Min; Shen, Ji-Duo; Chen, Jun-Jie; Pei, Yang-Yi; Fang, Xiao-Yan

    2016-10-13

    Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg) by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg), fluoxetine (20 mg/kg) and pioglitazone (10 mg/kg) were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  18. [Behavioral and neurobiological abnormalities induced by social isolation as a useful animal model of schizophrenia].

    PubMed

    Lei, Ming; Luo, Lu; Ma, Shi-Qi; Zhang, Yan; Wu, Xi-Hong; Li, Liang

    2013-02-25

    Social isolation influences the development of the brain, causing dysfunctions at behavioral, cellular and molecular levels. The present paper summarizes the abnormalities induced by social isolation in behaviors, neurotransmitters and cell apoptosis. At the behavioral level, social isolation induces hyperlocomotion, abnormalities in startle reflex and prepulse inhibition (PPI), and dysfunctions in conditioned learning, reversal learning and memory. Moreover, social isolation causes changes of neurotransmitters, such as the increase of dopamine in the nucleus accumbens, the amygdala and other brain regions in the limbic system, the decrease of dopamine in medial prefrontal cortex, the decrease of 5-HT in the nucleus accumbens and the hippocampus, and changes of glutamine in the prefrontal cortex. Finally, social isolation affects cell apoptosis in different brain areas, such as the medial prefrontal cortex, amygdala, nucleus accumbens, and hippocampus. Both the changes in neurotransmitters and cell apoptosis may contribute to the behavioral dysfunctions in social isolated rats. Since schizophrenic patients have similar abnormalities in behaviors and neurotransmitters, isolation rearing can be used as a useful animal model of schizophrenia.

  19. Abnormal eating behavior in video-recorded meals in anorexia nervosa

    PubMed Central

    Gianini, Loren; Liu, Ying; Wang, Yuanjia; Attia, Evelyn; Walsh, B. Timothy; Steinglass, Joanna

    2015-01-01

    Objective Eating behavior during meals in anorexia nervosa (AN) has long been noted to be abnormal, but little research has been done carefully characterizing these behaviors. These eating behaviors have been considered pathological, but are not well understood. The current study sought to quantify ingestive and non-ingestive behaviors during a laboratory lunch meal, compare them to the behaviors of healthy controls (HC), and examine their relationships with caloric intake and anxiety during the meal. Method A standardized lunch meal was video-recorded for 26 individuals with AN and 10 HC. Duration, frequency, and latency of 16 mealtime behaviors were coded using computer software. Caloric intake, dietary energy density (DEDS), and anxiety were also measured. Results Nine mealtime behaviors were identified that distinguished AN from HC: staring at food, tearing food, nibbling/picking, dissecting food, napkin use, inappropriate utensil use, hand fidgeting, eating latency, and nibbling/picking latency. Among AN, a subset of these behaviors were related to caloric intake and anxiety. Discussion These data demonstrate that the mealtime behaviors of patients with AN and HC differ significantly, and some of these behaviors may be associated with food intake and anxiety. These mealtime behaviors may be important treatment targets to improve eating behavior in individuals with AN. PMID:26164671

  20. Abnormal eating behavior in video-recorded meals in anorexia nervosa.

    PubMed

    Gianini, Loren; Liu, Ying; Wang, Yuanjia; Attia, Evelyn; Walsh, B Timothy; Steinglass, Joanna

    2015-12-01

    Eating behavior during meals in anorexia nervosa (AN) has long been noted to be abnormal, but little research has been done carefully characterizing these behaviors. These eating behaviors have been considered pathological, but are not well understood. The current study sought to quantify ingestive and non-ingestive behaviors during a laboratory lunch meal, compare them to the behaviors of healthy controls (HC), and examine their relationships with caloric intake and anxiety during the meal. A standardized lunch meal was video-recorded for 26 individuals with AN and 10 HC. Duration, frequency, and latency of 16 mealtime behaviors were coded using computer software. Caloric intake, dietary energy density (DEDS), and anxiety were also measured. Nine mealtime behaviors were identified that distinguished AN from HC: staring at food, tearing food, nibbling/picking, dissecting food, napkin use, inappropriate utensil use, hand fidgeting, eating latency, and nibbling/picking latency. Among AN, a subset of these behaviors was related to caloric intake and anxiety. These data demonstrate that the mealtime behaviors of patients with AN and HC differ significantly, and some of these behaviors may be associated with food intake and anxiety. These mealtime behaviors may be important treatment targets to improve eating behavior in individuals with AN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. [DAILY AND ABNORMAL EATING BEHAVIORS IN A COMMUNITY SAMPLE OF CHILEAN ADULTS].

    PubMed

    Oda-Montecinos, Camila; Saldaña, Carmina; Andrés Valle, Ana

    2015-08-01

    this research aimed to characterize the daily eating behavior in a sample of Chilean adults according to their Body Mass Index (BMI) and gender and to analyze the possible links between these variables and abnormal eating behaviors. 657 participants (437 women and 220 men, age range 18-64 years) were evaluated with a battery of self-administered questionnaires. Mean BMI was 25.50 kg/m2 (women 24.96 kg/m2, men 26.58 kg/m2), being significantly higher the mean of BMI in the men group, being the BMI mean of the total sample and that of the male group in the overweight range. participants with overweight (BMI ≥ 25 kg/m2), in contrast with normal-weight group, tended to do more frequently the following behaviors: skip meals, follow a diet, eat less homemade food, eat faster and in greater quantities, in addition to do a greater number of abnormal eating behaviors of various kinds and to rate significantly higher in clinical scales that evaluated eating restraint and overeating. Men showed significantly more eating behaviors linked with overeating, and women performed more behaviors related with eating restraint and emotional eating. the results suggest that, besides "what" people eat, "how" people eat, in terms of specific behaviors, may contribute to the rapid increase of overweight in Chilean population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens.

    PubMed

    Brunberg, Emma I; Rodenburg, T Bas; Rydhmer, Lotta; Kjaer, Joergen B; Jensen, Per; Keeling, Linda J

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain-gut-microbiota axis.

  3. Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes.

    PubMed

    Xie, Ao-Ji; Liu, En-Jie; Huang, He-Zhou; Hu, Yu; Li, Ke; Lu, Youming; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2016-09-01

    Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes.

  4. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens

    PubMed Central

    Brunberg, Emma I.; Rodenburg, T. Bas; Rydhmer, Lotta; Kjaer, Joergen B.; Jensen, Per; Keeling, Linda J.

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain–gut–microbiota axis. PMID:27500137

  5. Studies of planning behavior of aircraft pilots in normal, abnormal and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of planning is presented and the results of applying the methodology within two experimental investigations of planning behavior of aircraft pilots in normal, abnormal, and emergency situations are discussed. Beyond showing that the methodology yields consistent results, these experiments also lead to concepts in terms of a dichotomy between event driven and time driven planning, subtle effects of automation on planning, and the relationship of planning to workload and flight performance.

  6. Abnormal animal behavior prior to the Vrancea (Romania) major subcrustal earthquakes

    NASA Astrophysics Data System (ADS)

    Constantin, Angela; Pantea, Aurelian

    2013-04-01

    The goal of this paper is to present some observations about abnormal animal behavior prior and during of some Romanian subcrustal earthquakes. The major Vrancea earthquakes of 4 March 1977 (Mw = 7.4, Imax = IX-X MSK), 30 August 1986 (Mw = 7.1, Io = VIII-IX MSK) and 30 May 1990 (Mw = 6.9, Io = VIII MSK), were preceded by extensive occurrences of anomalous animal behavior. These data were collected immediately after the earthquakes from the areas affected by these. Some species of animals became excited, nervous and panicked before and during the earthquakes, such as: dogs (barking and running in panic), cats, snakes, mice and rats (came into the houses and have lost their fear), birds (hens, geese, parrots), horses, fishes etc. These strange manifestations of the animals were observed on the entire territory of country, especially in the extra-Carpathian area. This unusual behavior was noticed within a few hours to days before the seismic events, but for the most of cases the time of occurrence was within two hours of the quakes. We can hope that maybe one day the abnormal animal behavior will be used as a reliable seismic precursor for the intermediate depth earthquakes.

  7. Antisocial Behavior, Psychopathic Features and Abnormalities in Reward and Punishment Processing in Youth

    PubMed Central

    Byrd, Amy L.; Loeber, Rolf; Pardini, Dustin A.

    2017-01-01

    A better understanding of what leads youth to initially engage in antisocial behavior (ASB) and more importantly persist with such behaviors into adulthood has significant implications for prevention and intervention efforts. A considerable number of studies using behavioral and neuroimaging techniques have investigated abnormalities in reward and punishment processing as potential causal mechanisms underlying ASB. However, this literature has yet to be critically evaluated, and there are no comprehensive reviews that systematically examine and synthesize these findings. The goal of the present review is twofold. The first aim is to examine the extent to which youth with ASB are characterized by abnormalities in (1) reward processing; (2) punishment processing; or (3) both reward and punishment processing. The second aim is to evaluate whether aberrant reward and/or punishment processing is specific to or most pronounced in a subgroup of antisocial youth with psychopathic features. Studies utilizing behavioral methods are first reviewed, followed by studies using functional magnetic resonance imaging. An integration of theory and research across multiple levels of analysis is presented in order to provide a more comprehensive understanding of reward and punishment processing in antisocial youth. Findings are discussed in terms of developmental and contextual considerations, proposed future directions and implications for intervention. PMID:24357109

  8. Antisocial behavior, psychopathic features and abnormalities in reward and punishment processing in youth.

    PubMed

    Byrd, Amy L; Loeber, Rolf; Pardini, Dustin A

    2014-06-01

    A better understanding of what leads youth to initially engage in antisocial behavior (ASB) and more importantly persist with such behaviors into adulthood has significant implications for prevention and intervention efforts. A considerable number of studies using behavioral and neuroimaging techniques have investigated abnormalities in reward and punishment processing as potential causal mechanisms underlying ASB. However, this literature has yet to be critically evaluated, and there are no comprehensive reviews that systematically examine and synthesize these findings. The goal of the present review is twofold. The first aim is to examine the extent to which youth with ASB are characterized by abnormalities in (1) reward processing; (2) punishment processing; or (3) both reward and punishment processing. The second aim is to evaluate whether aberrant reward and/or punishment processing is specific to or most pronounced in a subgroup of antisocial youth with psychopathic features. Studies utilizing behavioral methods are first reviewed, followed by studies using functional magnetic resonance imaging. An integration of theory and research across multiple levels of analysis is presented in order to provide a more comprehensive understanding of reward and punishment processing in antisocial youth. Findings are discussed in terms of developmental and contextual considerations, proposed future directions and implications for intervention.

  9. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice.

    PubMed

    Satomoto, Maiko; Satoh, Yasushi; Terui, Katsuo; Miyao, Hideki; Takishima, Kunio; Ito, Masataka; Imaki, Junko

    2009-03-01

    Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.

  10. Studies of planning behavior of aircraft pilots in normal, abnormal, and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of human planning behavior in complex dynamic systems is presented and applied to the study of aircraft pilot behavior in normal, abnormal and emergency situations. The method measures the depth of planning, that is the level of detail employed with respect to a specific task, according to responses to a verbal questionnaire, and compares planning depth with variables relating to time, task criticality and the probability of increased task difficulty. In two series of experiments, depth of planning was measured on a five- or ten-point scale during various phases of flight in a HFB-320 simulator under normal flight conditions, abnormal scenarios involving temporary runway closure due to snow removal or temporary CAT-III conditions due to a dense fog, and emergency scenarios involving engine shut-down or hydraulic pressure loss. Results reveal a dichotomy between event-driven and time-driven planning, different effects of automation in abnormal and emergency scenarios and a low correlation between depth of planning and workload or flight performance.

  11. Abnormal occipital event-related potentials in Parkinson's disease with concomitant REM sleep behavior disorder.

    PubMed

    Gaudreault, Pierre-Olivier; Gagnon, Jean-François; Montplaisir, Jacques; Vendette, Mélanie; Postuma, Ronald B; Gagnon, Katia; Gosselin, Nadia

    2013-02-01

    Rapid eye movement sleep behavior disorder is found in 33-46% of patients with Parkinson's disease and was shown to be associated with cognitive deficits. Our goal was to improve our understanding of the role of this sleep disorder in cerebral dysfunction occurring in Parkinson's disease using a visual cognitive task and event-related potentials. Sixteen patients with Parkinson's disease and rapid eye movement sleep behavior disorder, 15 patients with Parkinson's disease without rapid eye movement sleep behavior disorder and 16 healthy control subjects were included. The amplitude and latency of event-related potentials were compared between groups. No group differences were found for reaction times or accuracy. A Group effect was found for P2 wave amplitude; patients with rapid eye movement sleep behavior disorder had increased P2 in comparison with the control group (p < 0.05). Patients with Parkinson's disease alone were not different from the two other groups for this component. Prolonged novelty P3 latencies on Cz were associated with longer disease durations among patients with Parkinson's disease (p < 0.01). Co-morbid Parkinson's disease and rapid eye movement sleep behavior disorder were associated with abnormal visual P2 component of event-related potentials. Although patients with Parkinson's disease alone were not significantly different from patients with combined Parkinson's disease and rapid eye movement sleep behavior disorder, their P2 amplitudes were not sufficiently abnormal to differ from that of control subjects. This study confirms that rapid eye movement sleep behavior disorder accentuates cerebral dysfunctions in Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Long-Term Evaluation of Abnormal Behavior in Adult Ex-laboratory Chimpanzees (Pan troglodytes) Following Re-socialization

    PubMed Central

    Kalcher-Sommersguter, Elfriede; Franz-Schaider, Cornelia; Preuschoft, Signe; Crailsheim, Karl

    2013-01-01

    Adverse rearing conditions are considered a major factor in the development of abnormal behavior. We investigated the overall levels, the prevalence and the diversity of abnormal behavior of 18 adult former laboratory chimpanzees, who spent about 20 years single caged, over a two-year period following re-socialization. According to the onset of deprivation, the individuals were classified as early deprived (EDs, mean: 1.2 years) or late deprived (LDs, mean: 3.6 years). The results are based on 187.5 hours of scan sampling distributed over three sample periods: subsequent to re-socialization and during the first and second year of group-living. While the overall levels and the diversity of abnormal behavior remained stable over time in this study population, the amplifying effects of age at onset of deprivation became apparent as the overall levels of abnormal behavior of EDs were far above those of LDs in the first and second year of group-living, but not immediately after re-socialization. The most prevalent abnormal behaviors, including eating disorders and self-directed behaviors, however, varied in their occurrence within subjects across the periods. Most important, the significance of social companionship became obvious as the most severe forms of abnormal behavior, such as dissociative and self-injurious behaviors declined. PMID:25379228

  13. Tachycardia-dependent augmentation of "notched J waves" in a general patient population without ventricular fibrillation or cardiac arrest: not a repolarization but a depolarization abnormality?

    PubMed

    Aizawa, Yoshifusa; Sato, Masahito; Kitazawa, Hitoshi; Aizawa, Yoshiyasu; Takatsuki, Seiji; Oda, Eiji; Okabe, Masaaki; Fukuda, Keiichi

    2015-02-01

    J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood. The purpose of this study was to examine the J-wave dynamicity in a general patient population. The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals. Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality. J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

    SciTech Connect

    Brunner, H.G. ); Nelen, M.; Ropers, H.H.; van Oost, B.A. )

    1993-10-22

    Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.

  15. Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

    PubMed

    Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

    2014-03-01

    Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

  16. A survey of abnormal repetitive behaviors in North American river otters housed in zoos.

    PubMed

    Morabito, Paige; Bashaw, Meredith J

    2012-01-01

    Stereotypic behaviors, indicating poor welfare and studied in a variety of species (especially carnivores), appear related to characteristics of current and past environments. Although North American river otters (Lontra canadensis) often develop abnormal, repetitive, possibly stereotypic behaviors, no published reports describe otter housing and management or characterize how these variables relate to abnormal repetitive behavior (ARB) occurrence. The first author developed surveys to gather data on housing, individual history, management, and the prevalence of ARBs in otters housed in facilities accredited by the Association of Zoos and Aquariums. Consistent with anecdotal evidence that otters are prone to ARBs, 46% of river otters in the study exhibit them. ARBs were mostly locomotor and often preceded feeding. Exhibits where otters were fed and trained housed a greater percentage of nonhuman animals with ARBs. This study supports the Tarou, Bloomsmith, and Maple (2005) report that more hands-on management is associated with higher levels of ARBs because management efforts are only for animals with ARBs. Escape motivation, breeding season, feeding cues, and ability to forage may affect ARBs in river otters and should be investigated.

  17. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.

    PubMed

    Wang, Xiaoming; McCoy, Portia A; Rodriguiz, Ramona M; Pan, Yanzhen; Je, H Shawn; Roberts, Adam C; Kim, Caroline J; Berrios, Janet; Colvin, Jennifer S; Bousquet-Moore, Danielle; Lorenzo, Isabel; Wu, Gangyi; Weinberg, Richard J; Ehlers, Michael D; Philpot, Benjamin D; Beaudet, Arthur L; Wetsel, William C; Jiang, Yong-Hui

    2011-08-01

    SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and intellectual disability. SHANK3 also plays a key role in the chromosome 22q13.3 microdeletion syndrome (Phelan-McDermid syndrome), which includes ASD and cognitive dysfunction as major clinical features. To evaluate the role of Shank3 in vivo, we disrupted major isoforms of the gene in mice by deleting exons 4-9. Isoform-specific Shank3(e4-9) homozygous mutant mice display abnormal social behaviors, communication patterns, repetitive behaviors and learning and memory. Shank3(e4-9) male mice display more severe impairments than females in motor coordination. Shank3(e4-9) mice have reduced levels of Homer1b/c, GKAP and GluA1 at the PSD, and show attenuated activity-dependent redistribution of GluA1-containing AMPA receptors. Subtle morphological alterations in dendritic spines are also observed. Although synaptic transmission is normal in CA1 hippocampus, long-term potentiation is deficient in Shank3(e4-9) mice. We conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.

  18. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.

    PubMed

    Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W; Potter, S Steven; McKnight, Steven L

    2004-09-14

    Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis.

  19. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors

    PubMed Central

    Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W.; Potter, S. Steven; McKnight, Steven L.

    2004-01-01

    Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis. PMID:15347806

  20. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    PubMed Central

    Castelhano, Adelisandra Silva Santos; Cassane, Gustavo dos Santos Teada; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2013-01-01

    Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal SE in rodents leads to altered anxiety-related and abnormal social behaviors. PMID:23675329

  1. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

    PubMed

    Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-08-30

    We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition

    PubMed Central

    2012-01-01

    Background In the central nervous system (CNS), the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M4 muscarinic receptor knockout (M4R KO) mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI)-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M4R remain unclear. Results In this study, to further investigate precise functional roles of M4R in the CNS, M4R KO mice were subjected to a battery of behavioral tests. M4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M4R KO mice demonstrated normal startle response. M4R KO mice also displayed normal performance in the Morris water maze test. Conclusions These findings indicate that M4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia. PMID:22463818

  3. Who should report abnormal behavior at preschool age? The case of behavioral inhibition.

    PubMed

    Ballespí, Sergi; Jané, M Claustre; Riba, M Dolors

    2012-02-01

    Children who are behaviorally "inhibited"-a condition at the extreme of the behavioral inhibition dimension-experience distress in uncertain social situations. Although parents and teachers are in the best position to detect this condition, they rarely agree. This study aims to analyze the agreement between parents and teachers and to examine the relations between ratings made by parents and teachers and assessments made by clinicians and researchers. Parents, teachers and clinicians rated the behavioral inhibition of 365 preschoolers. Seventy-three randomly selected participants were observed using an adaptation of the Behavioral Inhibition Paradigm. Parent-teacher correlations on 34 items and different clusters were, on average, r = .3. The degree of convergence between observational measures and ratings by parents and teachers was moderate-low and did not improve when considering only subsamples from the ends of the distributions. Discriminant analysis suggests that both parents and teachers tend to have a moderate-low ability to detect "inhibited" children.

  4. The microbiota modulates gut physiology and behavioral abnormalities associated with autism

    PubMed Central

    Hsiao, Elaine Y.; McBride, Sara W.; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R.; McCue, Tyler; Codelli, Julian A.; Chow, Janet; Reisman, Sarah E.; Petrosino, Joseph F.; Patterson, Paul H.; Mazmanian, Sarkis K.

    2014-01-01

    SUMMARY Although autism spectrum disorder (ASD) is defined by core behavioral impairments, gastrointestinal (GI) symptoms are commonly reported. Subsets of ASD individuals display dysbiosis of the gut microbiota, and some exhibit increased intestinal permeability. Here we demonstrate GI barrier defects and microbiota alterations in a mouse model displaying features of ASD, maternal immune activation (MIA). Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition and ameliorates ASD-related defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naïve mice with a metabolite that is increased by MIA and restored by B. fragilis causes behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in ASD and identify a potential probiotic therapy for GI and behavioral symptoms of autism. PMID:24315484

  5. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia.

    PubMed

    Miyakawa, Tsuyoshi; Leiter, Lorene M; Gerber, David J; Gainetdinov, Raul R; Sotnikova, Tatyana D; Zeng, Hongkui; Caron, Marc G; Tonegawa, Susumu

    2003-07-22

    Calcineurin (CN), a calcium- and calmodulin-dependent protein phosphatase, plays a significant role in the central nervous system. Previously, we reported that forebrain-specific CN knockout mice (CN mutant mice) have impaired working memory. To further analyze the behavioral effects of CN deficiency, we subjected CN mutant mice to a comprehensive behavioral test battery. Mutant mice showed increased locomotor activity, decreased social interaction, and impairments in prepulse inhibition and latent inhibition. In addition, CN mutant mice displayed an increased response to the locomotor stimulating effects of MK-801. Collectively, the abnormalities of CN mutant mice are strikingly similar to those described for schizophrenia. We propose that alterations affecting CN signaling could comprise a contributing factor in schizophrenia pathogenesis.

  6. Environmental Enrichment Improves Behavioral Abnormalities in a Mouse Model of Angelman Syndrome.

    PubMed

    Jamal, Imran; Kumar, Vipendra; Vatsa, Naman; Singh, Brijesh Kumar; Shekhar, Shashi; Sharma, Ankit; Jana, Nihar Ranjan

    2017-09-01

    Angelman syndrome (AS) is a neurodevelopmental disorder largely caused by the loss of function of maternally inherited UBE3A. UBE3A-maternal deficient mice (AS mice) exhibit many typical features of AS including cognitive and motor deficits but the underlying mechanism of these behavioral abnormalities is poorly understood. Here, we demonstrate that rearing of AS mice in the enriched environment for prolonged period significantly improved their cognitive and motor dysfunction. Enriched environment also restored elevated serum corticosterone level and reduced anxiety-like behaviors in these mice. Biochemical analysis further revealed restoration of altered levels of brain-derived neurotrophic factor, glucocorticoid receptor, and phoshphorylated calcium/calmodulin-dependent protein kinase IIα in the hippocampus of AS mice maintained in the enriched environment. Enriched environment also significantly increased the number of parvalbumin-positive GABAergic interneuron in the hippocampus and basolateral amygdala of AS mice. These results indicate potential beneficial effect of enriched environment in the reversal of AS phenotype.

  7. An autopsy case of cortical superficial siderosis with persistent abnormal behavior.

    PubMed

    Torii, Youta; Iritani, Shuji; Fujishiro, Hiroshige; Sekiguchi, Hirotaka; Habuchi, Chikako; Umeda, Kentaro; Matsunaga, Shinji; Mimuro, Maya; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2016-12-01

    In recent years, MRI has revealed cortical superficial siderosis (cSS), which exhibits hemosiderin deposition in only the cortical surface. However, the associations between the histological findings and clinical symptoms of cSS remain unclear. We herein report an autopsy case of a 75-year-old Japanese man with cSS with persistent abnormal behavior according to cognitive impairment, hallucination and delusion. At 73 years of age, the patient presented with unusual behavior that indicated auditory hallucination and delusion. One year later, he was admitted to the hospital for malignant lymphoma. On admission, cognitive impairment was detected by a screening test. Soon after hospitalization, he presented with active delirium including visual hallucination and delusion. The patient's excited behavior was improved by the administration of a major tranquilizer. However, the abnormal behavior and cognitive impairment persisted. At 75 years of age, he died of heart failure. A neuropathological investigation revealed hemosiderin depositions in the superficial layer of the cortex in the medial and lateral frontal lobe, the lateral temporal lobe, the parietal lobe, and the medial and lateral occipital lobe. Neuritic plaques and diffuse plaques were extensively observed, which corresponded to Braak stage C and CERAD B, although NFTs were observed that corresponded to Braak stage II. Cortical amyloid angiopathy was not observed in any regions. Ischemic change of brain was also mild. Our report suggests that localized deposition of hemosiderin in the cortex might affect the manifestation of cognitive impairments and hallucination. Further clinicopathological studies are needed to clarify the clinical manifestations of patients with cSS. © 2016 Japanese Society of Neuropathology.

  8. Rare E196K mutation in the PRNP gene of a patient exhibiting behavioral abnormalities.

    PubMed

    Béjot, Yannick; Osseby, Guy-Victor; Caillier, Marie; Moreau, Thibault; Laplanche, Jean-Louis; Giroud, Maurice

    2010-04-01

    Genetic transmissible spongiform encephalopathies (TSEs) account for approximately 10-15% of overall human prion diseases worldwide, but genotype-phenotype correlations remain incomplete. Here we report the case of an 80-year-old man who developed rapidly progressive behavioral abnormalities and myoclonus following a stroke. Repeated electroencephalography (EEG) revealed a general slowing of the basic activity, as well as several episodes of triphasic waves, with neither periodic activity nor recorded seizure. 14.3.3 protein was detected in cerebral cerebrospinal fluid, and direct sequencing of the PRNP gene showed an E196K mutation associated with homozygosity for methionine at codon 129. The patient was diagnosed with probable genetic prion disease with a Creutzfeldt-Jakob disease-like phenotype. The PRNP E196K mutation has only rarely been described in the literature, and generally patients exhibited an atypical initial phenotype, mainly involving abnormal behavioral features. Further observations are needed to confirm this particular clinical pattern associated with the mutation.

  9. Abnormal behavior of supercooled liquid region in bulk-forming metallic glasses

    NASA Astrophysics Data System (ADS)

    Park, E. S.; Na, J. H.; Kim, D. H.

    2010-09-01

    A metallic glass is often viewed as an amorphous alloy exhibiting a single endothermic reaction in the supercooled liquid region (SCLR, ΔTx=Tx-Tg). Here we discuss the origin and consequences of abnormal behavior of SCLR in various bulk-forming metallic glasses (BMGs). The two-stage-like endothermic reaction in Ni-based, Cu-based, Zr-based, and Mg-based BMGs can originate from the local immiscibility of liquids, which is closely related to chemical heterogeneity in as-cast BMG. These inflections can be attributed to the overlap of the exothermic reaction for the formation and growth of clusters in SCLR. The abnormal behavior of SCLR can be modulated by controlling cooling rate as well as by tailoring alloy composition, with the consequence that the modulated local heterogeneity in these BMGs can lead to enhanced flexibility of the BMGs. This correlation assists in understanding toughening mechanism and in guiding alloy design to alleviate brittleness of BMGs.

  10. Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

    PubMed

    Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

    2016-08-01

    Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity.

  11. Regional cerebral blood flow and abnormal eating behavior in Prader-Willi syndrome.

    PubMed

    Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Fukuda, Hiroshi; Mori, Etsuro

    2013-05-01

    Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  13. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model

    PubMed Central

    Goebel-Goody, Susan M.; Wilson-Wallis, Evan D.; Royston, Sara; Tagliatela, Stephanie; Naegele, Janice R.; Lombroso, Paul J.

    2014-01-01

    Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work identified striatal-enriched protein tyrosine phosphatase (STEP) as an FMRP target mRNA. STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn, Pyk2, and subunits of NMDA and AMPA receptors. Here we demonstrate that STEP translation is dysregulated in Fmr1KO mice, resulting in elevated basal levels of STEP with a concomitant loss of mGluR-dependent STEP translation. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1KO mice. In addition to attenuating audiogenic seizures and seizure-induced c-Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1KO mice reversed characteristic social abnormalities, including approach, investigation, novelty-induced hyperactivity and anxiety. Loss of STEP also corrected select non-social anxiety-related behaviors in Fmr1KO mice, such as open arm exploration in the elevated plus maze. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores social and non-social anxiety-related behaviors in Fmr1KO mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS. PMID:22405502

  14. Scaling behavior and a Markov model for ventricular fibrillation generated by ectopic beats

    NASA Astrophysics Data System (ADS)

    Hastings, Harold; Evans, Steven; Zaharakis, Alex; Hilaire, Christian

    2006-03-01

    Sudden cardiac death is a major cause of death in the industrialized world, responsible for 300,000 deaths per year in the US. Although the cardiac electrical system normally produces one ventricular activation in response to each stimulus from the sinus node, ``spontaneous'' activations, called premature ventricular contractions (PVCs), can arise in the ventricles themselves, and propagate through the ventricles. Although usually harmless in the absence of underlying disease, PVCs can generate broken wavefronts when they meet gradients of refractoriness generated by other beats. These broken wavefronts may generate spiral waves producing ventricular tachycardia and ultimately degenerate into ventricular fibrillation (VF), causing sudden cardiac death. When does a PVC lead to ventricular fibrillation ? This is a stiff problem, involving time scales from milliseconds to many years. We overcome this problem by developing universal scaling properties and using these rules to drive a Markov process. We find two significant ``amplifiers'' and discuss consequences for variability of VF rates in human populations. We thank Elizabeth Cherry, Flavio Fenton, Anna Gelzer and James Glimm for helpful discussions.

  15. The MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

    PubMed Central

    Oien, Derek B.; Osterhaus, Greg L.; Latif, Shaheen A.; Pinkston, Jonathan W.; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C.; Moskovitz, Jackob

    2008-01-01

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA−/−) mouse. Here we show that MsrA−/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA−/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA−/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA−/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA−/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA−/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress. PMID:18466776

  16. MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels.

    PubMed

    Oien, Derek B; Osterhaus, Greg L; Latif, Shaheen A; Pinkston, Jonathan W; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C; Moskovitz, Jackob

    2008-07-15

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA(-/-)) mouse. Here we show that MsrA(-/-) mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA(-/-) mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA(-/-) mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA(-/-) brains contained significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine were observed at 16 months of age. Moreover, striatal regions of MsrA(-/-) mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathways are impaired in MsrA(-/-) mice, which may contribute to their abnormal behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

  17. Inactivation of Ceramide Synthase 6 in Mice Results in an Altered Sphingolipid Metabolism and Behavioral Abnormalities*

    PubMed Central

    Ebel, Philipp; vom Dorp, Katharina; Petrasch-Parwez, Elisabeth; Zlomuzica, Armin; Kinugawa, Kiyoka; Mariani, Jean; Minich, David; Ginkel, Christina; Welcker, Jochen; Degen, Joachim; Eckhardt, Matthias; Dere, Ekrem; Dörmann, Peter; Willecke, Klaus

    2013-01-01

    The N-acyl chain length of ceramides is determined by the specificity of different ceramide synthases (CerS). The CerS family in mammals consists of six members with different substrate specificities and expression patterns. We have generated and characterized a mouse line harboring an enzymatically inactive ceramide synthase 6 (CerS6KO) gene and lacz reporter cDNA coding for β-galactosidase directed by the CerS6 promoter. These mice display a decrease in C16:0 containing sphingolipids. Relative to wild type tissues the amount of C16:0 containing sphingomyelin in kidney is ∼35%, whereas we find a reduction of C16:0 ceramide content in the small intestine to about 25%. The CerS6KO mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit. LacZ reporter expression in the brain reveals CerS6 expression in hippocampus, cortex, and the Purkinje cell layer of the cerebellum. Using newly developed antibodies that specifically recognize the CerS6 protein we show that the endogenous CerS6 protein is N-glycosylated and expressed in several tissues of mice, mainly kidney, small and large intestine, and brain. PMID:23760501

  18. Inactivation of ceramide synthase 6 in mice results in an altered sphingolipid metabolism and behavioral abnormalities.

    PubMed

    Ebel, Philipp; Vom Dorp, Katharina; Petrasch-Parwez, Elisabeth; Zlomuzica, Armin; Kinugawa, Kiyoka; Mariani, Jean; Minich, David; Ginkel, Christina; Welcker, Jochen; Degen, Joachim; Eckhardt, Matthias; Dere, Ekrem; Dörmann, Peter; Willecke, Klaus

    2013-07-19

    The N-acyl chain length of ceramides is determined by the specificity of different ceramide synthases (CerS). The CerS family in mammals consists of six members with different substrate specificities and expression patterns. We have generated and characterized a mouse line harboring an enzymatically inactive ceramide synthase 6 (CerS6KO) gene and lacz reporter cDNA coding for β-galactosidase directed by the CerS6 promoter. These mice display a decrease in C16:0 containing sphingolipids. Relative to wild type tissues the amount of C16:0 containing sphingomyelin in kidney is ∼35%, whereas we find a reduction of C16:0 ceramide content in the small intestine to about 25%. The CerS6KO mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit. LacZ reporter expression in the brain reveals CerS6 expression in hippocampus, cortex, and the Purkinje cell layer of the cerebellum. Using newly developed antibodies that specifically recognize the CerS6 protein we show that the endogenous CerS6 protein is N-glycosylated and expressed in several tissues of mice, mainly kidney, small and large intestine, and brain.

  19. Reproductive and behavioral abnormalities in tree swallows with high levels of PCB contamination

    SciTech Connect

    McCarty, J. |; Secord, A.; Tillitt, D.

    1995-12-31

    Tree Swallows (Tachycineta bicolor) breeding along the Hudson River forage extensively on PCB contaminated insects that emerge from the river. The authors studied the reproductive ecology and behavior of tree swallows breeding at several sites along the Hudson River. These sites vary in the severity of PCB contamination. PCB levels in both eggs and chicks were found to be among the highest ever reported in this species, with concentrations comparable to those found in aquatic organisms in the Hudson River. In 1994 reproductive success at PCB contaminated sites was significantly impaired, relative to other sites in New York. Reduced reproductive success was largely attributed to high levels of nest abandonment during incubation and reduced hatchability of eggs. Growth and development of nestlings was not significantly impaired. Abnormal nest building behavior was also noted in 1994, and this was studied in detail in 1995. Nests from contaminated areas are significantly smaller than those at a nearby reference site and at other sites in New York. The authors suggest that the reduced reproductive outputs at these sites are, in large part, a result of effects on the behavior of incubating females. The population-level implications of these patterns are unknown.

  20. Relative dipolar behavior of the equivalent T wave generator: quantitative comparison with ventricular excitation in the rabbit heart.

    PubMed

    Brody, D A; Mirvis, D M; Ideker, R E; Cox, J W; Keller, F W; Larsen, R A; Bandura, J P

    1977-03-01

    We studied the relative dipolar and nondipolar content of signal energy throughout ventricular excitation and recovery in 34 isolated, perfused rabbit hearts, suspended in an electrolyte-filled spherical chamber. Computer-processed signals were derived from 20 evenly spaced tank-surface electrodes, and a single, moving, equivalent cardiac dipole generator was optimally fitted to the recorded potentials for each 1-msec sampling interval. Superimposed, time-based plots of signal energy for the 34 preparations showed ventricular excitation to be strikingly more nondipolar than was recovery. In terms of the summed square ratio of nondipolar residual energies, overall nondipolarity of QRS exceed that of ST-T by 41%. Furthermore, the maximum instantaneous ratio during QRS was considerably greater than during the ST-T. Evaluation of paired differences, comparing nondipolar behavior throughout QRS with all of ST-T, proved highly significant (P less than .005). We also found that in contrast to the considerable mobility exhibited by the equivalent QRS dipole, the ST-T dipole locus remained nearly stationary during most of ventricular recovery. Presumably because repolarization is temporally and spatially a relatively diffuse process, it may generate electrical fields which are notably more dipolar than those caused by depolarization.

  1. Variables influencing the origins of diverse abnormal behaviors in a large sample of captive chimpanzees (Pan troglodytes).

    PubMed

    Nash, L T; Fritz, J; Alford, P A; Brent, L

    1999-01-01

    The developmental origin of abnormal behaviors is generally associated with early rearing environments that lack sufficient physical and sensory stimulation. However, other factors should also be considered. A large sample of captive chimpanzees (128 males and 140 females) was surveyed for the presence or absence of 18 abnormal behaviors. Origin variables included the subject's source (zoo, pet, performer, or laboratory), rearing (mother- or hand-reared), and sex. Animals were assessed while held at the Primate Foundation of Arizona, University of Texas M. D. Anderson Cancer Center, or White Sands Research Center. There was a confound among origin variables; more hand-reared animals than expected were from laboratories. Logistic regression tested the relationship of rearing and source, with sex as a secondary predictor variable, to each of the abnormal behaviors. There was no clear association between any abnormal behavior and source. However, for coprophagy, relative to animals from the laboratory, zoo animals tended to show a higher prevalence, while performers tended to show a lower prevalence (when rearing and sex were controlled). Rocking and self-sucking were significantly more likely in hand-reared animals. Coprophagy and depilation of self were significantly more likely in mother-reared animals. When rearing and source were statistically controlled, the only significant sex difference was a higher prevalence of coprophagy in females and a higher prevalence of rocking in males. In a second, smaller sample of 25 males and 33 females from Southwest Foundation for Biomedical Research, no significant sex association was found for coprophagy, urophagy, rocking, or self-depilation. In this second sample, coprophagy was also significantly more likely in mother-reared than hand-reared subjects. The association of some abnormal behaviors with mother-rearing suggests that some form of social learning may be involved in the origin of some of these behavior patterns

  2. Increased Metabotropic Glutamate Receptor 5 Signaling Underlies Obsessive-Compulsive Disorder-like Behavioral and Striatal Circuit Abnormalities in Mice.

    PubMed

    Ade, Kristen K; Wan, Yehong; Hamann, Harold C; O'Hare, Justin K; Guo, Weirui; Quian, Anna; Kumar, Sunil; Bhagat, Srishti; Rodriguiz, Ramona M; Wetsel, William C; Conn, P Jeffrey; Dzirasa, Kafui; Huber, Kimberly M; Calakos, Nicole

    2016-10-01

    Development of treatments for obsessive-compulsive disorder (OCD) is hampered by a lack of mechanistic understanding about this prevalent neuropsychiatric condition. Although circuit changes such as elevated frontostriatal activity are linked to OCD, the underlying molecular signaling that drives OCD-related behaviors remains largely unknown. Here, we examine the significance of type 5 metabotropic glutamate receptors (mGluR5s) for behavioral and circuit abnormalities relevant to OCD. Sapap3 knockout (KO) mice treated acutely with an mGluR5 antagonist were evaluated for OCD-relevant phenotypes of self-grooming, anxiety-like behaviors, and increased striatal activity. The role of mGluR5 in the striatal circuit abnormalities of Sapap3 KO mice was further explored using two-photon calcium imaging to monitor striatal output from the direct and indirect pathways. A contribution of constitutive signaling to increased striatal mGluR5 activity in Sapap3 KO mice was investigated using pharmacologic and biochemical approaches. Finally, sufficiency of mGluR5 to drive OCD-like behavior in wild-type mice was tested by potentiating mGluR5 with a positive allosteric modulator. Excessive mGluR5 signaling underlies OCD-like behaviors and striatal circuit abnormalities in Sapap3 KO mice. Accordingly, enhancing mGluR5 activity acutely recapitulates these behavioral phenotypes in wild-type mice. In Sapap3 KO mice, elevated mGluR5 signaling is associated with constitutively active receptors and increased and imbalanced striatal output that is acutely corrected by antagonizing striatal mGluR5. These findings demonstrate a causal role for increased mGluR5 signaling in driving striatal output abnormalities and behaviors with relevance to OCD and show the tractability of acute mGluR5 inhibition to remedy circuit and behavioral abnormalities. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Abnormal illness behavior and Internet addiction severity: The role of disease conviction, irritability, and alexithymia.

    PubMed

    Scimeca, Giuseppe; Bruno, Antonio; Crucitti, Manuela; Conti, Claudio; Quattrone, Diego; Pandolfo, Gianluca; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna

    2017-03-01

    Background and aims While the association between health anxiety and maladaptive Internet use is a well-established finding, no studies have been performed to examine the possible effect of abnormal illness behavior (AIB). AIB is a maladaptive manner of experiencing, evaluating, or acting in response to health and illness that is disproportionate to evident pathology. The aim of this study was to investigate the association between AIB and Internet addiction (IA) severity in a sample of Italian University students. The possible effect of alexithymia, anxiety, and depression was also taken into account. Methods Participants were 115 men and 163 women (mean age = 23.62 ± 4.38 years); AIB was measured via the Illness Behavior Questionnaire (IBQ), and IA severity by the Internet Addiction Test (IAT). Results The most powerful IBQ factor predicting IA severity scores was disease conviction. Irritability was the only emotional IBQ factor associated with IA severity. Nevertheless, disease conviction and alexithymia remained the only significant predictors of IAT scores when hierarchical regression analysis was executed. Discussion and conclusions Our results support previous findings showing that those characterized by health anxiety are more prone to an excessive and maladaptive use of Internet. Moreover, this study showed that irritability was the only emotional aspect of AIB predicting IA severity. This finding is consistent with the cognitive model of hypochondria, which states that cognitive factors (dysfunctional beliefs and assumptions) play a major role in the explanation of this psychopathological condition.

  4. Normal and Abnormal Development of Motor Behavior: Lessons From Experiments in Rats

    PubMed Central

    Gramsbergen, Albert

    2001-01-01

    In this essay a few relevant aspects of the neural and behavioral development of the brain in the human and in the rat are reviewed and related to the consequences of lesions in the central and peripheral nervous system at early and later age. Movements initially are generated by local circuits in the spinal cord and without the involvement of descending projections. After birth, both in humans and in rats it seems that the devlopment of postural control is the limiting factor for several motor behaviors to mature. Strong indications exist that the cerebellum is significantly involved in this control. Lesions in the CNS at early stages interfere with fundamental processes of neural development, such as the establishment of fiber connections and cell death patterns. Consequently, the functional effects are strongly dependent on the stage of development. The young and undisturbed CNS, on the other hand, has a much greater capacity than the adult nervous system for compensating abnormal reinnervation in the peripheral nervous system. Animal experiments indicated that the cerebellar cortex might play an important part in this compensation. This possibility should be investigated further as it might offer important perspectives for treatment in the human. PMID:11530886

  5. Abnormal illness behavior and Internet addiction severity: The role of disease conviction, irritability, and alexithymia

    PubMed Central

    Scimeca, Giuseppe; Bruno, Antonio; Crucitti, Manuela; Conti, Claudio; Quattrone, Diego; Pandolfo, Gianluca; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna

    2017-01-01

    Background and aims While the association between health anxiety and maladaptive Internet use is a well-established finding, no studies have been performed to examine the possible effect of abnormal illness behavior (AIB). AIB is a maladaptive manner of experiencing, evaluating, or acting in response to health and illness that is disproportionate to evident pathology. The aim of this study was to investigate the association between AIB and Internet addiction (IA) severity in a sample of Italian University students. The possible effect of alexithymia, anxiety, and depression was also taken into account. Methods Participants were 115 men and 163 women (mean age = 23.62 ± 4.38 years); AIB was measured via the Illness Behavior Questionnaire (IBQ), and IA severity by the Internet Addiction Test (IAT). Results The most powerful IBQ factor predicting IA severity scores was disease conviction. Irritability was the only emotional IBQ factor associated with IA severity. Nevertheless, disease conviction and alexithymia remained the only significant predictors of IAT scores when hierarchical regression analysis was executed. Discussion and conclusions Our results support previous findings showing that those characterized by health anxiety are more prone to an excessive and maladaptive use of Internet. Moreover, this study showed that irritability was the only emotional aspect of AIB predicting IA severity. This finding is consistent with the cognitive model of hypochondria, which states that cognitive factors (dysfunctional beliefs and assumptions) play a major role in the explanation of this psychopathological condition. PMID:28245678

  6. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish.

    PubMed

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid(A) (GABA(A)R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA(A)R agonist (muscimol, MUS; 0.1 microg/g body weight) and/or its antagonist bicuculline (BIC; 1 microg/g body weight) have corroborated a GABA(A)ergic role on motor behaviors. In particular, MUS induced moderate (p<0.05) and great (p<0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p<0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA(A)R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS+BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA(A)R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  7. [Abnormal behavior and adaptation problems in dogs and cats and their pharmacologic control].

    PubMed

    Jöchle, W

    1998-11-01

    Small animal practitioners are increasingly confronted with patients showing adaptation related problems (ARP) which are expressed as disturbed or abnormal behavior (DAB). As a result, practitioners are asked increasingly to euthanize animals which seemingly cannot be socialized. In healthy dogs and cats, three main causes for DAB can be detected: refusal of obedience because of the drive for dominance; anxiety and frustration; and geriatric DAB. Increasingly, disease conditions not readily diagnosed can cause DAB, especially hypothyroidism. Influencing and contributing factors to DAB are breed, sex, experiences as a puppy, behavior of owners, changes in the pet's environment. ARPs may also cause disturbances in the condition of skin and fur, e.g. atopic dermatitis, pruritus sine materia, lick granuloma, and of the intestinal organs (vomiting, irritated bowel syndrome) and may result in an immune deficiency. Therapeutic approaches include behavioral therapy, surgical or hormonal castration with progestins or antiandrogens, substitution with thyroxin in cases with hypothyroidism, and/or the use of psychopharmaca, most prominently of modern antidepressiva like amitriptyline; buspirone; clomipramine and fluoxetine, but also of selegiline, a mono-aminoxydase inhibitor. These compounds, among other effects, are elevating prolactin levels. This seems to allow to formulate a working hypothesis: in the canine species, prolactin is obviously a hormone enabling socialization; hence all drugs which safely cause an increase in prolactin production might be suitable to manage or control ARPs and DAB in the dog, but also in the cat. Higher levels of prolactin than those required for socialization, as seen in nursing bitches or some clinically overt cases of pseudopregnancy, may cause maternal aggression and can be controlled with prolactin inhibitors, if needed.

  8. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

    SciTech Connect

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub A}R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub A}ergic role on motor behaviors. In particular, MUS induced moderate (p < 0.05) and great (p < 0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p < 0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA{sub A}R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  9. Dopamine depletion attenuates some behavioral abnormalities in a hyperdopaminergic mouse model of bipolar disorder

    PubMed Central

    van Enkhuizen, Jordy; Geyer, Mark A.; Halberstadt, Adam L.; Zhuang, Xiaoxi; Young, Jared W.

    2014-01-01

    Background Patients with BD suffer from multifaceted symptoms, including hyperactive and psychomotor agitated behaviors. Previously, we quantified hyperactivity, increased exploration, and straighter movements of patients with BD mania in the human Behavioral Pattern Monitor (BPM). A similar BPM profile is observed in mice that are hyperdopaminergic due to reduced dopamine transporter (DAT) functioning. We hypothesized that dopamine depletion through alpha-methyl-p-tyrosine (AMPT) administration would attenuate this mania-like profile. Methods Male and female DAT wild-type (WT; n=26) and knockdown (KD; n=28) mice on a C57BL/6 background were repeatedly tested in the BPM to assess profile robustness and stability. The optimal AMPT dose was identified by treating male C57BL/6 mice (n=39) with vehicle or AMPT (10, 30, or 100 mg/kg) at 24, 20, and 4 h prior to testing in the BPM. Then, male and female DAT WT (n=40) and KD (n=37) mice were tested in the BPM after vehicle or AMPT (30 mg/kg) treatment. Results Compared to WT littermates, KD mice exhibited increased activity, exploration, straighter movement, and disorganized behavior. AMPT-treatment reduced hyperactivity and increased path organization, but potentiated specific exploration in KD mice without affecting WT mice. Limitations AMPT is not specific to dopamine and also depletes norepinephrine. Conclusions KD mice exhibit abnormal exploration in the BPM similar to patients with BD mania. AMPT-induced dopamine depletion attenuated some, but potentiated other, aspects of this mania-like profile in mice. Future studies should extend these findings into other aspects of mania to determine the suitability of AMPT as a treatment for BD mania. PMID:24287168

  10. Cardiac passive-aggressive behavior? The right ventricle in patients with a left ventricular assist device.

    PubMed

    Kimmaliardjuk, Donna May; Ruel, Marc

    2017-04-01

    Right ventricular failure (RVF) affects up to 50% of patients post-left ventricular assist device (LVAD) implantation, and carries significant morbidity and mortality. There is no widely-used long-term mechanical support option for the right ventricle, thus early identification, prevention and medical treatment of RVF is of the upmost importance. Areas covered: A PubMed search was first completed searching 'Right ventricular failure post-LVAD' which yielded 152 results, and a subsequent search was performed under 'RV mechanical support' which yielded 374 results, and was filtered to 'humans' and literature written in English, generating 219 results. We focused this research on pre-operative risk factors identified in the literature for developing RVF-post LVAD implantation, and the medical and surgical treatment options for RVF, including mechanical treatment options. Expert commentary: There is little consensus on pre-operative risk factors that reliably predict RVF post-LVAD implantation. Large prospective randomized trials would help clarify indications for specific medical and surgical therapy. We gather this knowledge in the present article and describe the main RVF remediation modalities. Surgeons and anesthesiologists should help prevent and have a low threshold for initiating supportive treatment for RVF, which may include increasingly invasive therapies up to long-term mechanical RV support.

  11. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression

    USDA-ARS?s Scientific Manuscript database

    Cellular prion protein (PrPC) is a multifunctional protein, whose exact physiological role remains elusive. Since previous studies indicated a neuroprotective function of PrPC, we investigated whether Prnp knockout mice(Prnp0/0)display age-dependent behavioral abnormalities. Matched sets of Prnp0/0 ...

  12. Comparison of right ventricular contractile abnormalities in hypertrophic cardiomyopathy versus hypertensive heart disease using two dimensional strain imaging: a cross-sectional study.

    PubMed

    Afonso, Luis; Briasoulis, Alex; Mahajan, Nitin; Kondur, Ashok; Siddiqui, Fayez; Siddiqui, Sabeeh; Alesh, Issa; Cardozo, Shaun; Kottam, Anupama

    2015-12-01

    Hypertrophic cardiomyopathy (HCM) affects the right ventricle (RV) because of the anatomically hypertrophied septum and plausibly by extension of the myopathic process to the RV. We sought to investigate RV strain in patients with left ventricular hypertrophy secondary to either HCM or hypertension (H-LVH). Our cross-sectional study included 32 patients with HCM, 21 patients with H-LVH, and 11 healthy subjects, who were evaluated with transthoracic echocardiography. Using a dedicated software package, bi-dimensional acquisitions were analyzed to measure segmental longitudinal strain in apical views. Right ventricular global longitudinal strain (GLS) was calculated by averaging septal and right free wall strains. The HCM and H-LVH groups were comparable for age and demographic characteristics. Right ventricular tricuspid annular plane systolic excursion was not significantly different between HCM and H-LVH subjects. Moreover, RV GLS, septal and lateral RV myocardial strain were significantly impaired in patients with HCM (all p < 0.001). Regional and global RV strain parameters were not significantly impaired in H-LVH compared to healthy controls An RV GLS cut-off value of >14.9% differentiated HCM and H-LVH with a 90% sensitivity and a 95% specificity (p < 0.001). RV strain parameters are impaired in patients with HCM. Assessment of two-dimensional RV strain parameters could help differentiate between HCM and H-LVH.

  13. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

    PubMed Central

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R.; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2015-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly. PMID:26693400

  14. Behavioral and Neurotransmitter Abnormalities in Mice Deficient for Parkin, DJ-1 and Superoxide Dismutase

    PubMed Central

    Hennis, Meghan R.; Seamans, Katherine W.; Marvin, Marian A.; Casey, Bradford H.; Goldberg, Matthew S.

    2013-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by loss of neurons in the substantia nigra that project to the striatum and release dopamine. The cause of PD remains uncertain, however, evidence implicates mitochondrial dysfunction and oxidative stress. Although most cases of PD are sporadic, 5-10% of cases are caused by inherited mutations. Loss-of-function mutations in Parkin and DJ-1 were the first to be linked to recessively inherited Parkinsonism. Surprisingly, mice bearing similar loss-of-function mutations in Parkin and DJ-1 do not show age-dependent loss of nigral dopaminergic neurons or depletion of dopamine in the striatum. Although the normal cellular functions of Parkin and DJ-1 are not fully understood, we hypothesized that loss-of-function mutations in Parkin and DJ-1 render cells more sensitive to mitochondrial dysfunction and oxidative stress. To test this hypothesis, we crossed mice deficient for Parkin and DJ-1 with mice deficient for the mitochondrial antioxidant protein Mn-superoxide dismutase (SOD2) or the cytosolic antioxidant protein Cu-Zn-superoxide dismutase (SOD1). Aged Parkin-/-DJ-1-/- and Mn-superoxide dismutase triple deficient mice have enhanced performance on the rotorod behavior test. Cu/Zn-superoxide dismutase triple deficient mice have elevated levels of dopamine in the striatum in the absence of nigral cell loss. Our studies demonstrate that on a Parkin/DJ-1 null background, mice that are also deficient for major antioxidant proteins do not have progressive loss of dopaminergic neurons but have behavioral and striatal dopamine abnormalities. PMID:24386432

  15. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder.

    PubMed

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2016-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.

  16. Oscillatory behavior of ventricular action potential duration in heart failure patients at respiratory rate and low frequency

    PubMed Central

    Hanson, Ben; Child, Nick; Van Duijvenboden, Stefan; Orini, Michele; Chen, Zhong; Coronel, Ruben; Rinaldi, Christopher A.; Gill, Jaspal S.; Gill, Jaswinder S.; Taggart, Peter

    2014-01-01

    Oscillations of arterial pressure occur spontaneously at a frequency of approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve activity (“Mayer waves”). This study investigated the extent to which corresponding oscillations may occur in ventricular action potential duration (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular pacing devices were studied while seated upright watching movie clips to maintain arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were obtained from unipolar electrograms recorded from the LV epicardial pacing lead during steady state RV pacing from the device. Arterial blood pressure was measured non-invasively (Finapress) and respiration monitored. Oscillations were quantified using time frequency and coherence analysis. Oscillatory behavior of ARI at the respiratory frequency was observed in all subjects. The magnitude of the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis showed a correlation with respiratory oscillation for an average of 43% of the recording time at a significance level of p < 0.05. Oscillations in systolic blood pressure in the Mayer wave frequency range were observed in all subjects for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2 ms. Coherence with Mayer waves at the p < 0.05 significance level was present for an average of 29% of the recording time. In ambulatory patients with heart failure during enhanced mental arousal, left ventricular epicardial APD (ARI) oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz). These findings may be important in understanding sympathetic activity-related arrhythmogenesis. PMID:25389408

  17. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

    2012-01-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

  18. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

    2012-10-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction.

  19. [Arrhythmogenic right ventricular dysplasia].

    PubMed

    Maia, I G; Sá, R; Bassan, R; Alves, P; Ribeiros, J C; Loyola, L H; Cruz Filho, F E; Valverde, A; Belém, L

    1991-08-01

    To evaluate the clinical findings and complementary investigation to support the diagnosis of arrhythmogenic right ventricular dysplasia. Six males with a mean age of 40 years old with episodes of sustained ventricular tachycardia with left bundle branch block pattern. All patients were submitted to a clinical investigation, EKG X rays and echocardiograms. In five patients an electrophysiologic study was performed. All patients were treated with anti-arrhythmic drugs. Palpitation was the most common complaint. T-wave inversion in leads V1-V3 was present in 4 patients. An epsilon wave was noted in 2 patients. The chest X ray was abnormal in only 1 patient. All patients had an abnormal echocardiogram, with consisted in the dilatation of the outflow tract of the RV and hypocontractility. In 2 patients aneurysm of the basal RV free wall below tricuspid valve were detected. Ventricular post-excitation waves were present in 4 patients. After a mean follow-up of 37 months, 5 patients were asymptomatic with anti-arrhythmic drugs and one in therapeutic adjustment. In patients with ventricular tachycardia with left bundle branch block pattern, the diagnosis of arrhythmogenic right ventricular dysplasia was substantiated by echocardiographic data and electrocardiographic findings such a T-wave inversion during sinus rhythm and ventricular post-excitation waves. The results obtained with anti-arrhythmic drugs in our study group, suggest that drug therapy should be the first and best approach to treat patients with this type of pathology.

  20. Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine.

    PubMed

    Uchiumi, Osamu; Kasahara, Yoshiyuki; Fukui, Asami; Hall, F Scott; Uhl, George R; Sora, Ichiro

    2013-01-01

    Dopamine transporter knockout (DAT KO) mice exhibit elevated extracellular dopamine levels in brain regions that include the striatum and the nucleus accumbens, but not the prefrontal cortex. DAT KO mice model some aspects of psychiatric disorders, including schizophrenia. Smoking is more common in patients with schizophrenia, suggesting that nicotine might ameliorate aspects of the behavioral abnormalities and/or treatment side effects seen in these individuals. We report nicotine-induced normalization of effects on locomotion and prepulse inhibition of acoustic startle (PPI) in DAT KO mice that require intact serotonin 5-HT1A systems. First, we observed that the marked hyperactivity displayed by DAT KO mice was reduced by administration of nicotine. This nicotine effect was blocked by pretreatment with the non-specific nicotinic acetylcholine (nACh) receptor antagonist mecamylamine, or the 5-HT1A antagonist WAY100635. Secondly, we examined the effects of nicotine on PPI in DAT KO mice. Treatment with nicotine significantly ameliorated the PPI deficits observed in DAT KO mice. The ameliorating action of nicotine on PPI deficits in DAT KO mice was blocked by mecamylamine, the α₇ nACh receptor antagonist methyllycaconitine or WAY100635, while the α₄β₂ nACh receptor antagonist dihydro-β-erythroidinehydrobromide (DHβE) produced only a non-significant trend toward attenuation of nicotine effects. Finally, we observed that administration of the 5-HT1A receptor agonist 8-OH-DPAT also ameliorated the deficit in PPI observed in DAT KO mice. This amelioration was antagonized by pretreatment with WAY100635. These data support the idea that nicotine might ameliorate some of the cognitive dysfunctions found in schizophrenia in a 5-HT1A-dependent fashion. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  1. Neuroprotective role of GABAB receptor modulation against streptozotocin-induced behavioral and biochemical abnormalities in rats.

    PubMed

    Kumar, Kushal; Kaur, Harmanpreet; Deshmukh, Rahul

    2017-08-15

    Stimulation as well as inhibition of GABAB (Gamma amino butyric acid) receptors has been reported to show beneficial effects in Alzheimer's disease (AD). Experimental evidences suggest that the use of GABAergic agents could influence learning and memory. The present study was designed to investigate the possible role of GABAB receptors in streptozotocin (STZ)-induced behavioral and biochemical abnormalities in rats. Herein STZ was infused (3mg/kg) bilaterally on alternate days (day 1 and day 3) to produce experimental dementia in rats. STZ-infused rats were then treated with baclofen (GABABR agonist) 5 and 10mg/kg i.p. and CGP35348 (GABABR antagonist) 25 and 50mg/kg i.p. one week following STZ infusion for 15days. Cognitive functions were assessed by using Morris water maze (MWM) and object recognition task (ORT). Levels of malondialdehyde (MDA.), reduced glutathione (GSH), andacetylcholinesterase (AChE) were determined to evaluate oxidative stress and cholinergic function. STZ-infused rats showed decreased memory retention, elevated levels of MDA, increased AChE activity, reduced GSH levels. The combination of STZ with increasing doses of Baclofen further induced a higher decrease in memory retention and increase in oxidative stress. CGP35348 restored cognitive functions and AChE activity in STZ-infused rats. The cognitive enhancement following CGP35348 may be due to its ability to restore cholinergic, serotonergic and dopaminergic function, and its antioxidant activity. Therefore, it would be safe to conclude that the pharmacological blockade of GABAB receptors would be therapeutic in the management of cognitive disorders such as Alzheimer's disease. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD.

    PubMed

    Leuzy, Antoine; Zimmer, Eduardo Rigon; Dubois, Jonathan; Pruessner, Jens; Cooperman, Cory; Soucy, Jean-Paul; Kostikov, Alexey; Schirmaccher, Esther; Désautels, René; Gauthier, Serge; Rosa-Neto, Pedro

    2016-04-01

    Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.

  3. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

    PubMed Central

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-01-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D–E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype–phenotype correlations which are still being generated for these chromosomal anomalies. PMID:26247050

  4. Effects of myocardial perfusion abnormalities on the accuracy of left ventricular volume and ejection fraction measured by thallium-201 gated single-photon emission tomography: comparison with echocardiography as the reference standard.

    PubMed

    Kurisu, Satoshi; Iwasaki, Toshitaka; Abe, Nobukazu; Tamura, Megumi; Ikenaga, Hiroki; Watanabe, Noriaki; Higaki, Tadanao; Shimonaga, Takashi; Ishibashi, Ken; Dohi, Yoshihiro; Fukuda, Yukihiro; Kihara, Yasuki

    2015-11-01

    We assessed the accuracy of left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) using quantitative gated single-photon emission computed tomography (QGS) in comparison with echocardiography as the reference standard. We also assessed the effects of total perfusion deficit (TPD) on the accuracy of QGS measurements. A total of 258 patients underwent single-photon emission computed tomography and transthoracic echocardiography within 4 weeks of each investigation for evaluating coronary artery disease. Patients were divided into four groups according to TPD scores. There were 138 patients with no/minimal TPD, 64 patients with small TPD, 35 patients with middle TPD, and 21 patients with large TPD. There were good correlations and agreements in EDV (r=0.87, 0.90, 0.71, and 0.94, respectively), ESV (r=0.92, 0.94, 0.79, and 0.94, respectively), and EF (r=0.61, 0.79, 0.61, and 0.83, respectively) between QGS and echocardiography in patients with any TPD. QGS significantly underestimated EDV and ESV in patients with no/minimal or small TPD, and significantly overestimated ESV in patients with large TPD. QGS significantly underestimated EF in patients with middle or large TPD. Our results suggest that QGS is a useful tool for assessing the left ventricular volume and function in patients with any TPD, but myocardial perfusion abnormalities should be taken into consideration when interpreting QRS measurements.

  5. Abnormal sexual behavior during sleep in temporal lobe epilepsy: a case report.

    PubMed

    Pelin, Zerrin; Yazla, Ece

    2012-06-01

    Herein, we describe a case who presented with abnormal sexual behaviour during sleep. Video-electroencephalography monitoring during sleep revealed an abnormality suggesting an epileptic basis. The patient was successfully treated with carbamazepin. The psychiatric symptoms that were thought to be related to abnormal sexual behaviours were controlled with antipsychotic treatment. Our findings strongly emphasize the fact that efforts should be spent to increase awareness of seizure activity at night, which can be misinterpreted as benign parasomnias. Such a misinterpretation may have serious consequences, such as insufficient seizure control, progressive personality changes, and cognitive impairment.

  6. [The relationship between the abnormal behavior and serum C-reactive protein in children with obstructive sleep apnea-hypopnea syndrome].

    PubMed

    Wang, Yan; Li, Yanzhong; Wang, Xin

    2009-12-01

    To explore the pathogenesis of abnormal behavior in children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The behavioral problems and C-reactive protein were measured in 40 children with OSAHS and 30 children with habitual snoring who underwent overnight Polysomnography, 40 cases of healthy children for the control group. The ratio of abnormal behavior in OSAHS and habitual snoring children was significantly higher than that of the healthy control group, while no significant difference between the two groups. The content of C-reactive protein in OSAHS children (4.24 mg/L) was significantly higher than habitual snoring (2.76 mg/L) and healthy control group (1.27 mg/L); in habitual snoring children C-reactive protein was higher than in healthy control group. The content of serum C-reactive protein in OSAHS children accompanied by abnormal behavior (4.63 mg/L) was significantly higher than that without abnormal behavior (3.23 mg/L). The content of serum C-reactive protein content in habitual snoring children accompanied by abnormal behavior (3.63 mg/L) was significantly higher than that without abnormal behavior (1.76 mg/L). OSAHS and habitual snoring children have more behavior problems. C-reactive protein levels are higher in children with OSAHS and habitual snoring, and the levels of C-reactive protein are related to the abnormal behavior in these children.

  7. Left ventricular regional contraction abnormalities by echocardiographic speckle tracking in combined right bundle branch with left anterior fascicular block compared to left bundle branch block.

    PubMed

    Leeters, Irene P M; Davis, Ashlee; Zusterzeel, Robbert; Atwater, Brett; Risum, Niels; Søgaard, Peter; Klem, Igor; Nijveldt, Robin; Wagner, Galen S; Gorgels, Anton P M; Kisslo, Joseph

    2016-01-01

    In contrast to LBBB patients less is known about patients with RBBB+LAFB regarding LV contractile abnormalities and the potential role of CRT. This study investigated whether patients with RBBB+LAFB morphology have echocardiographic mechanical strain abnormalities between the inferior and anterior LV walls, similar to abnormalities between septal and lateral walls in LBBB. Ten healthy volunteers with no-BBB, 28 LBBB and 28 RBBB+LAFB heart failure patients were included in this retrospective study. Two-dimensional regional-strains were obtained by speckle-tracking. Scar was assessed by CMR. Response on echo was defined as normal, classical, borderline or other pattern. The number of classical patterns in LBBB was significantly higher than in RBBB+LAFB and no-BBB groups (p<0.001 for both). Contrary, the RBBB+LAFB group showed a significantly higher number of borderline patterns compared to other groups (LBBB: p=0.042, no-block: p=0.012). In addition, RBBB+LAFB patients had more scar than LBBB patients (9.9% vs 3.4%, p=0.041), and the average amount of scar in each wall was also higher in RBBB+LAFB (<5% in LBBB and <16% in RBBB+LAFB). Patients with RBBB+LAFB on ECG and clinical HF demonstrate echocardiographic wall motion abnormalities between inferior and anterior LV walls, similar to abnormalities found between septal and lateral LV walls in patients with LBBB and HF. Fewer patients with RBBB+LAFB showed a classical pattern of opposing wall motion compared to LBBB. Factors that might alter strain patterns in RBBB+LAFB, including the detailed presence or absence of LV scar and coexisting block of the central fascicle, should be assessed in future studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities

    PubMed Central

    Sago, Haruhiko; Carlson, Elaine J.; Smith, Desmond J.; Kilbridge, Joshua; Rubin, Edward M.; Mobley, William C.; Epstein, Charles J.; Huang, Ting-Ting

    1998-01-01

    A mouse model for Down syndrome, Ts1Cje, has been developed. This model has made possible a step in the genetic dissection of the learning, behavioral, and neurological abnormalities associated with segmental trisomy for the region of mouse chromosome 16 homologous with the so-called “Down syndrome region” of human chromosome segment 21q22. Tests of learning in the Morris water maze and assessment of spontaneous locomotor activity reveal distinct learning and behavioral abnormalities, some of which are indicative of hippocampal dysfunction. The triplicated region in Ts1Cje, from Sod1 to Mx1, is smaller than that in Ts65Dn, another segmental trisomy 16 mouse, and the learning deficits in Ts1Cje are less severe than those in Ts65Dn. In addition, degeneration of basal forebrain cholinergic neurons, which was observed in Ts65Dn, was absent in Ts1Cje. PMID:9600952

  9. Function of a novel plakophilin-2 mutation in the abnormal expression of connexin43 in a patient with arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Wang, Pei-Ning; Wu, Shu-Lin; Zhang, Bin; Lin, Qiu-Xiong; Shan, Zhi-Xin

    2015-03-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a desmosomal disease. Desmosomes and gap junctions are important structural components of cardiac intercalated discs. The proteins plakophilin-2 (PKP-2) and connexin43 (Cx43) are components of desmosomes and gap junctions, respectively. This study was conducted to determine whether Cx43 expression is affected by the mutation of the PKP-2 gene in patients with ARVC. A novel mutation was detected in a typical patient with ARVC. The mutated gene was transfected into rat mesenchymal stem cells expressing Cx43 through a pReversied-M-29 plasmid. Cx43 expression was detected using quantitative polymerase chain reaction analysis. Cx43 expression was significantly decreased in the mutant PKP-2 group compared with that in the wild-type PKP-2 group. In conclusion, PKP-2 affected Cx43 expression at the gene transcription level in the patient with ARVC.

  10. ECG of the month. Irregular rhythm in a 25-year-old man with three prior cardiac operations. Coarse atrial fibrillation with a rapid ventricular response, left anterior fascicular block, left ventricular hypertrophy with repolarization abnormality.

    PubMed

    Glancy, D Luke; Ahmed, Jameel; Ayalloore, Siby G; LeLorier, Paul A; Diwan, Pranav M; Helmcke, Frederick R

    2013-01-01

    The patient underwent closure of an atrial septal defect at age 3, had a leaking "mitral" valve repaired at age 9, and at age 13 had a "mitral" valve replacement. He began taking warfarin sodium at that time and remained symptom-free until 10 days before his initial visit here when he presented to another hospital with dyspnea and palpitations. Treatment there consisted of lisinopril 10 mg qd, carvedilol 6.25 mg bid, aldactone 25 mg qd, furosemide 40 mg qd, digoxin 0.25 mg qd, and a continuation of warfarin sodium 7.5 mg qd. An echocardiogram showed a left ventricular ejection fraction of 20%. After diuresis, he was referred to our cardiology clinic. On his initial visit here, his heart rate was an irregular 120 beats/min, his blood pressure was 106/77 mmHg, and closing and opening snaps of a normally functioning mechanical mitral valvular prosthesis were heard. He was obese (height, 5' 9"; weight, 272 lbs). An electrocardiogram was recorded (Figure 1).

  11. ACTH acts via an anterior ventral third ventricular site to elicit grooming behavior.

    PubMed

    Dunn, A J; Hurd, R W

    1986-01-01

    Intracerebroventricular but not parenteral application of ACTH has been shown to elicit excessive grooming behavior in rats and mice. This behavior is elicited by administration of ACTH into the lateral, third, or fourth ventricles. Plugging of the cerebral aqueduct with cold cream fails to prevent grooming in response to lateral ventricle injection of ACTH. However, cold cream plugs in the third ventricle can prevent the subsequent induction of grooming behavior by lateral ventricle injection of ACTH, but only when the plugs are located in the anterior ventral third ventricle in the region of the organum vasculosum laminae terminalis (OVLT) and median eminence. These data suggest the anterior ventral third ventricle as the periventricular site of action of ACTH in eliciting excessive grooming, although it is possible that peptides taken up in this area are transported to other regions to elicit the behavioral response.

  12. Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

    PubMed

    Carter, John C; Capone, George T; Gray, Robert M; Cox, Christiane S; Kaufmann, Walter E

    2007-01-05

    The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.

  13. Calcific Aortic Valve Disease: Part 2—Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility

    PubMed Central

    2016-01-01

    In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in-parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments. PMID:27184804

  14. Instructors' Use of Trigger Warnings and Behavior Warnings in Abnormal Psychology

    ERIC Educational Resources Information Center

    Boysen, Guy A.; Wells, Anna Mae; Dawson, Kaylee J.

    2016-01-01

    College students have been increasingly demanding warnings and accommodations in relation to course topics they believe will elicit strong, negative emotions. These "trigger warnings" are highly relevant to Abnormal Psychology because of the sensitive topics covered in the course (e.g., suicide, trauma, sex). A survey of Abnormal…

  15. Instructors' Use of Trigger Warnings and Behavior Warnings in Abnormal Psychology

    ERIC Educational Resources Information Center

    Boysen, Guy A.; Wells, Anna Mae; Dawson, Kaylee J.

    2016-01-01

    College students have been increasingly demanding warnings and accommodations in relation to course topics they believe will elicit strong, negative emotions. These "trigger warnings" are highly relevant to Abnormal Psychology because of the sensitive topics covered in the course (e.g., suicide, trauma, sex). A survey of Abnormal…

  16. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

    PubMed

    Cussen, Victoria A; Mench, Joy A

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  17. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors

    PubMed Central

    Cussen, Victoria A.; Mench, Joy A.

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  18. Abnormal Central Pulsatile Hemodynamics in Adolescents With Obesity: Higher Aortic Forward Pressure Wave Amplitude Is Independently Associated With Greater Left Ventricular Mass.

    PubMed

    Pierce, Gary L; Pajaniappan, Mohanasundari; DiPietro, Amy; Darracott-Woei-A-Sack, Kathryn; Kapuku, Gaston K

    2016-11-01

    We hypothesized that increased aortic forward pressure wave amplitude (Pf), which is determined by characteristic impedance (Zc) in the proximal aorta, is the primary hemodynamic determinant of obesity-associated higher left ventricular (LV) mass in adolescents. Aortic pulsatile hemodynamics were measured noninvasively in 60 healthy adolescents (age 14-19 years; 42% male; 50% black) by sequential recordings of pulse waveforms via tonometry, brachial blood pressure, and pulsed Doppler and diameter of the LV outflow tract using 2-dimensional echocardiography. Adolescents who were overweight/obese (n=23; age 16.0±0.3 years; body mass index ≥85th percentile) had higher LV mass index, brachial and carotid systolic blood pressure and pulse pressure, normalized Zc and Pf compared with adolescents with healthy weight (n=37; 16.7±0.3 years; body mass index <85th percentile, all P<0.01). In contrast, there was no difference in mean or diastolic blood pressure, carotid-femoral pulse wave velocity, carotid augmentation index, or aortic backward wave amplitude (all P>0.05). Stepwise multiple linear regression analysis that included age, sex, race, normalized Zc, and brachial systolic blood pressure revealed that body mass index (B±SE; 0.49±0.20, P=0.02, R(2)=0.26), aortic Pf (0.22±0.07; P<0.02, R(2) change=0.11), and cardiac output (2.82±1.02, P<0.01; R(2) change=0.08) were significant correlates of LV mass index (total R(2)=0.44, P<0.01). These findings suggest that higher aortic Pf is a major hemodynamic determinant of increased LV mass in adolescents with elevated adiposity. Improper matching between aortic diameter and pulsatile flow during early systole potentially contributes to the early development of LV hypertrophy in childhood obesity.

  19. Abnormal chromosome behavior during meiosis in the allotetraploid of Carassius auratus red var. (♀)×Megalobrama amblycephala (♂).

    PubMed

    Qin, Qinbo; Wang, Yude; Wang, Juan; Dai, Jing; Liu, Yun; Liu, Shaojun

    2014-09-02

    Allopolyploids generally undergo bivalent pairing at meiosis because only homologous chromosomes pair up. On the other hand, several studies have documented abnormal chromosome behavior during mitosis and meiosis in allopolyploids plants leading to the production of gametes with complete paternal or maternal chromosomes. Polyploidy is relatively rare in animals compared with plants; thus, chromosome behavior at meiosis in the allopolyploid animals is poorly understood. Tetraploid hybrids (abbreviated as 4nRB) (4n=148, RRBB) of Carassius auratus red var. (abbreviated as RCC) (2n=100, RR) (♀)×Megalobrama amblycephala (abbreviated as BSB) (2n=48, BB) (♂) generated gametes of different size. To test the genetic composition of these gametes, the gynogenetic offspring and backcross progenies of 4nRB were produced, and their genetic composition were examined by chromosome analysis and FISH. Our results suggest that 4nRB can produce several types of gametes with different genetic compositions, including allotetraploid (RRBB), autotriploid (RRR), autodiploid (RR), and haploid (R) gametes. This study provides direct evidence of abnormal chromosome behavior during meiosis in an allotetraploid fish.

  20. Abnormal exploratory behavior in transgenic mice carrying multiple copies of the human gene for S100 beta.

    PubMed Central

    Gerlai, R; Roder, J

    1995-01-01

    S100 beta, a calcium-binding brain protein, has been implicated in brain development and hippocampal neurophysiology including long-term potentiation. Its gene maps to chromosome 21, which is duplicated in Down syndrome. S100 beta levels are elevated in both Down syndrome and Alzheimer's disease, human neurodegenerative diseases associated with mental retardation and dementia. To investigate whether or not elevated S100 beta levels can cause brain dysfunctioning in mammals, transgenic mice carrying multiple copies of the human S100 beta gene were generated. Several independent lines of transgenic mice were compared to age-matched normal control mice of identical genetic background (CD1) by measuring their exploratory behaviors in novel situations. Transgenic mice exhibited a range of defects including female specific hyperactivity, lack of habituation to novelty and reduced T-maze spontaneous alternation rate. Although the neuroanatomical or physiological substrate of these abnormalities is unknown, they are similar to the behavioral manifestations of hippocampal dysfunction. The S100 beta mouse offers one of the first opportunities to investigate the relationship between over-expression of a human chromosome 21 gene product and abnormal behavior and brain functioning. PMID:7703219

  1. HPC-1/syntaxin 1A gene knockout mice show abnormal behavior possibly related to a disruption in 5-HTergic systems.

    PubMed

    Fujiwara, Tomonori; Snada, Masumi; Kofuji, Takefumi; Yoshikawa, Takeo; Akagawa, Kimio

    2010-07-01

    HPC-1/syntaxin 1A (STX1A) is thought to regulate the exocytosis of synaptic vesicles in neurons. In recent human genetic studies, STX1A has been implicated in neuropsychological disorders. To examine whether STX1A gene ablation is responsible for abnormal neuropsychological profiles observed in human psychiatric patients, we analysed the behavioral phenotype of STX1A knockout mice. Abnormal behavior was observed in both homozygotes (STX1A(-/-)) and heterozygotes (STX1A(+/-)) in a social interaction test, a novel object exploring test and a latent inhibition (LI) test, but not in a pre-pulse inhibition test. Interestingly, attenuation of LI, which is closely related to human schizotypic symptoms, was restored by administration of the selective serotonin reuptake inhibitor, fluoxetine, but not by the dopamine reuptake inhibitor, GBR12935, or the noradrenalin reuptake inhibitor, desipramine. We also observed that LI attenuation was restored by DOI (a 5-HT(2A) receptor agonist), but not by 8-OH-DPAT (a 5-HT(1A) receptor agonist), mCPP (a 5-HT(2C) receptor agonist), SKF 38393 (a D(1) receptor agonist), quinpirole (a D(2)/D(3) receptor agonist) or haloperidol (a D(2)/D(3) receptor antagonist). Thus, attenuation of LI is mainly caused by disruption of 5-HT-ergic systems via 5-HT(2A) receptors. In addition, 5-HT release from hippocampal and hypothalamic slices was significantly reduced. Therefore, ablation of STX1A may cause disruption of 5-HT-ergic transmission and induce abnormal behavior.

  2. Lack of protracted behavioral abnormalities following intermittent or continuous chronic mild hypoxia in perinatal C57BL/6 mice.

    PubMed

    Lima-Ojeda, Juan M; Vogt, Miriam A; Richter, S Helene; Dormann, Christof; Schneider, Miriam; Gass, Peter; Inta, Dragos

    2014-08-08

    Several prospective studies indicated perinatal hypoxia as risk factor for psychiatric disorders like schizophrenia. It is thought that hypoxia prior to or during birth may contribute to alterations leading to the protracted clinical manifestation during young adulthood. However, only a small fraction of children with a history of perinatal hypoxia develop later psychotic symptoms, therefore it is not known if hypoxia alone is sufficient to trigger long-term behavioral changes. Here we exposed C57BL/6 mice from postnatal day 3-7 (P3-P7) to two established paradigms of chronic mild hypoxia (10% ambient O2), intermittent and continuous. Subsequently, mice were analysed during young adult stages using several basic behavioral tests. Previous studies demonstrated severe, but only transient, cortical damage in these paradigms; it is not clear, if these reversible morphological changes are accompanied by long-term behavioral effects. We found that neither intermittent nor continuous perinatal hypoxia induced long-term behavioral alterations. This may be due to the high regenerative capacity of the perinatal brain. Other possibilities include a potential resistance to perinatal hypoxia of the mouse strain used here or a level of hypoxia that was insufficient to trigger significant behavioral changes. Therefore, our data do not exclude a role of perinatal hypoxia as risk factor for psychiatric disorders. They rather suggest that either other, more severe hypoxic conditions like anoxia, or the presence of additional factors (as genetic risk factors) are necessary for generating long-term behavioral abnormalities.

  3. Role of social encounter-induced activation of prefrontal serotonergic systems in the abnormal behaviors of isolation-reared mice.

    PubMed

    Ago, Yukio; Araki, Ryota; Tanaka, Tatsunori; Sasaga, Asuka; Nishiyama, Saki; Takuma, Kazuhiro; Matsuda, Toshio

    2013-07-01

    Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression- and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolation-reared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolation-reared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

  4. 76 FR 22925 - Assumption Buster Workshop: Abnormal Behavior Detection Finds Malicious Actors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... card. Fraud detection algorithms (based on user behavior models) and procedures immediately set off... unusual behavior on the part of authorized users. The fraud detection algorithms use the financial... sets of values to be analyzed with well understood algorithms. For example, credit card purchases...

  5. MEG premotor abnormalities in children with Asperger's syndrome: determinants of social behavior?

    PubMed

    Hauswald, Anne; Weisz, Nathan; Bentin, Shlomo; Kissler, Johanna

    2013-07-01

    Children with Asperger's syndrome show deficits in social functioning while their intellectual and language development is intact suggesting a specific dysfunction in mechanisms mediating social cognition. An action observation/execution matching system might be one such mechanism. Recent studies indeed showed that electrophysiological modulation of the "Mu-rhythm" in the 10-12Hz range is weaker when individuals with Asperger's syndrome observe actions performed by others compared to controls. However, electrophysiological studies typically fall short in revealing the neural generators of this activity. To fill this gap we assessed magnetoencephalographic Mu-modulations in Asperger's and typically developed children, while observing grasping movements. Mu-power increased at frontal and central sensors during movement observation. This modulation was stronger in typical than in Asperger children. Source localization revealed stronger sources in premotor cortex, the intraparietal lobule (IPL) and the mid-occipito-temporal gyrus (MOTG) and weaker sources in prefrontal cortex in typical participants compared to Asperger. Activity in premotor regions, IPL and MOTG correlated positively with social competence, whereas prefrontal Mu-sources correlated negatively with social competence. No correlation with intellectual ability was found at any of these sites. These findings localize abnormal Mu-activity in the brain of Asperger children providing evidence which associates motor-system abnormalities with social-function deficits.

  6. Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics

    PubMed Central

    Flanigan, Timothy J.; Xue, Yi; Rao, Shailaja Kishan; Anandh, Dhanushkodi; McDonald, Michael P.

    2014-01-01

    A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the in barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics’ avoidance of the closed arms in the plus maze. PMID:24655396

  7. Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics.

    PubMed

    Flanigan, T J; Xue, Y; Kishan Rao, S; Dhanushkodi, A; McDonald, M P

    2014-06-01

    A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics' avoidance of the closed arms in the plus maze. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. White-matter tract abnormalities and antisocial behavior: A systematic review of diffusion tensor imaging studies across development.

    PubMed

    Waller, Rebecca; Dotterer, Hailey L; Murray, Laura; Maxwell, Andrea M; Hyde, Luke W

    2017-01-01

    Antisocial behavior (AB), including aggression, violence, and theft, is thought be underpinned by abnormal functioning in networks of the brain critical to emotion processing, behavioral control, and reward-related learning. To better understand the abnormal functioning of these networks, research has begun to investigate the structural connections between brain regions implicated in AB using diffusion tensor imaging (DTI), which assesses white-matter tract microstructure. This systematic review integrates findings from 22 studies that examined the relationship between white-matter microstructure and AB across development. In contrast to a prior hypothesis that AB is associated with greater diffusivity specifically in the uncinate fasciculus, findings suggest that adult AB is associated with greater diffusivity across a range of white-matter tracts, including the uncinate fasciculus, inferior fronto-occipital fasciculus, cingulum, corticospinal tract, thalamic radiations, and corpus callosum. The pattern of findings among youth studies was inconclusive with both higher and lower diffusivity found across association, commissural, and projection and thalamic tracts.

  9. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-07-16

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer's disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency.

  10. The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake

    PubMed Central

    Godar, Sean C.; Bortolato, Marco; Castelli, M. Paola; Casti, Alberto; Casu, Angelo; Chen, Kevin; Ennas, M. Grazia; Tambaro, Simone; Shih, Jean C.

    2014-01-01

    The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-ANeo mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-ANeo mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals. PMID:24882701

  11. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1.

    PubMed

    Ribeiro, Maria J; Violante, Inês R; Bernardino, Inês; Edden, Richard A E; Castelo-Branco, Miguel

    2015-03-01

    Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and

  12. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

    PubMed

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

    2016-12-01

    The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  14. Disrupted Glutamatergic Transmission in Prefrontal Cortex Contributes to Behavioral Abnormality in an Animal Model of ADHD.

    PubMed

    Cheng, Jia; Liu, Aiyi; Shi, Michael Y; Yan, Zhen

    2017-02-08

    Spontaneously hypertensive rats (SHR) are the most widely used animal model for the study of attention deficit hyperactivity disorder (ADHD). Here we sought to reveal the neuronal circuits and molecular basis of ADHD and its potential treatment using SHR. Combined electrophysiological, biochemical, pharmacological, chemicogenetic and behavioral approaches were utilized. We found that AMPAR-mediated synaptic transmission in pyramidal neurons of prefrontal cortex (PFC) was diminished in SHR, which was correlated with the decreased surface expression of AMPAR subunits. Administration of methylphenidate (a psychostimulant drug used to treat ADHD), which blocks dopamine transporters and norepinephrine transporters, ameliorated the behavioral deficits of adolescent SHR and restored AMPAR-mediated synaptic function. Activation of PFC pyramidal neurons with a CaMKII-driven Gq-coupled DREADD (designer receptor exclusively activated by designer drug) also led to the elevation of AMPAR function and the normalization of ADHD-like behaviors in SHR. These results suggest that the disrupted function of AMPARs in PFC may underlie the behavioral deficits in adolescent SHR and enhancing PFC activity could be a treatment strategy for ADHD.Neuropsychopharmacology accepted article preview online, 08 February 2017. doi:10.1038/npp.2017.30.

  15. Ventricular tachycardia

    MedlinePlus

    ... prevented by treating heart problems and avoiding certain medicines. Alternative Names Wide-complex tachycardia; V tach; Tachycardia - ventricular Images Implantable cardioverter-defibrillator ... Ventricular arrhythmias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  16. Behavioral, Neurochemical and Neuroendocrine Effects of Abnormal Savda Munziq in the Chronic Stress Mice

    PubMed Central

    Amat, Nurmuhammat; Hoxur, Parida; Ming, Dang; Matsidik, Aynur; Kijjoa, Anake; Upur, Halmurat

    2012-01-01

    Oral administration of Abnormal Savda Munsiq (ASMq), a herbal preparation used in Traditional Uighur Medicine, was found to exert a memory-enhancing effect in the chronic stressed mice, induced by electric foot-shock. The memory improvement of the stressed mice was shown by an increase of the latency time in the step-through test and the decrease of the latency time in the Y-maze test. Treatment with ASMq was found to significantly decrease the serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and β-endorphin (β-EP) as well as the brain and serum level of norepinephrine (NE). Furthermore, ASMq was able to significantly reverse the chronic stress by decreasing the brain and serum levels of the monoamine neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT) and 3,4-dihydroxyphenylalanine (DOPAC). The results obtained from this study suggested that the memory-enhancing effect of ASMq was mediated through regulations of neurochemical and neuroendocrine systems. PMID:22919413

  17. Abnormal response to emotional stimulus in male adolescents with violent behavior in China.

    PubMed

    Qiao, Yi; Xie, Bin; Du, Xiaoxia

    2012-04-01

    The objective of the study is to explore the characteristics of emotional stimulus in adolescents with violent behavior and to identify the correlated dysfunctional regions of the brain. An event-related functional magnetic resonance imaging was obtained while the participants passively viewed pictures with neutral or negative affective valence. 15 male adolescents with violent behavior, ranging in age from 12 to 18 years old, and 16 healthy age-matched control subjects were enrolled in the study. While looking at neutral pictures, several brain regions were activated more intensely in the violent group than the control one. After digitally subtracting the control group, these areas included the bilateral amygdala, left orbital gyrus, bilateral fusiform gyrus, and left visual cortex. While passively viewing negative pictures, the right inferior frontal gyrus and the middle frontal gyrus were less activated in the violent group than the control group. Male adolescents with violent behaviors have some dysfunctions during the processing and evaluation of information from external emotional stimulus. These individuals are inclined to interpret neutral information as threatening stimulus.

  18. Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies.

    PubMed

    Titman, Penny; Pink, Elizabeth; Skucek, Emily; O'Hanlon, Katherine; Cole, Tim J; Gaspar, Jane; Xu-Bayford, Jinhua; Jones, Alison; Thrasher, Adrian J; Davies, E Graham; Veys, Paul A; Gaspar, H Bobby

    2008-11-01

    Hematopoietic stem cell transplantation (HSCT) is a highly successful treatment for severe congenital immunodeficiencies. However, some studies have suggested that children may experience cognitive difficulties after HSCT. This large-scale study assessed cognitive and behavioral function for the cohort of children treated by HSCT at one center between 1979 and 2003 to determine the frequency and severity of problems and to identify risk factors. A total of 105 patients were assessed on standardized measures of cognitive and emotional and behavioral function together with a control group of unaffected siblings. The average IQ for the cohort was 85 (95% confidence interval, 81-90), significantly lower than both the population average of 100 (P < .001) and unaffected siblings. Multivariate analysis indicated that the underlying genetic defect, diagnosis of adenosine deaminase-deficient severe combined immunodeficiency, and consanguinity were associated with worse outcome but that age at transplantation and chemotherapy conditioning were not. Children treated by HSCT for severe immunodeficiency have an increased risk of long-term cognitive difficulties and associated emotional and behavioral difficulties. The specific genetic diagnosis, consanguinity, and severe clinical course are associated with poor outcome. Long-term follow-up of these patients should include screening to identify and manage these problems more effectively.

  19. Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression.

    PubMed

    Milekic, M H; Xin, Y; O'Donnell, A; Kumar, K K; Bradley-Moore, M; Malaspina, D; Moore, H; Brunner, D; Ge, Y; Edwards, J; Paul, S; Haghighi, F G; Gingrich, J A

    2015-08-01

    Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring.

  20. Early life seizures in female rats lead to anxiety-related behavior and abnormal social behavior characterized by reduced motivation to novelty and deficit in social discrimination.

    PubMed

    Castelhano, Adelisandra Silva Santos; Ramos, Fabiane Ochai; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2015-03-01

    Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality.

  1. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease.

    PubMed

    Laforet, G A; Sapp, E; Chase, K; McIntyre, C; Boyce, F M; Campbell, M; Cadigan, B A; Warzecki, L; Tagle, D A; Reddy, P H; Cepeda, C; Calvert, C R; Jokel, E S; Klapstein, G J; Ariano, M A; Levine, M S; DiFiglia, M; Aronin, N

    2001-12-01

    Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca(2+) levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry.

  2. Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases.

    PubMed

    Gaudissard, Julie; Ginger, Melanie; Premoli, Marika; Memo, Maurizio; Frick, Andreas; Pietropaolo, Susanna

    2017-06-07

    Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the X-linked FMR1 gene, coding for the FMRP protein which is largely involved in synaptic function. FXS patients present several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and cognitive deficits. Autistic symptoms, e.g., altered social interaction and communication, are also often observed: FXS is indeed the most common monogenic cause of autism. Mouse models of FXS are therefore of great interest for research on both FXS and autistic pathologies. The Fmr1-KO2 mouse line is the most recent FXS model, widely used for brain studies; surprisingly, little is known about the face validity of this model, i.e., its FXS-like behavioral phenotype. Furthermore, no data are available for the age-related expression of the pathological phenotypes in this mouse line, a critical issue for modelling neurodevelopmental disorders. Here we performed an extensive behavioral characterization of the KO2 model at infancy, adolescent and adult ages. Hyperactivity, altered emotionality, sensory hyper-responsiveness and memory deficits were already present in KO mice at adolescence and remained evident at adulthood. Alterations in social behaviors were instead observed only in young KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic vocalizations compared to their WT littermates and as adolescents they displayed more aggressive behaviors towards a conspecific. These results strongly support the face validity of the KO2 mouse as a model for FXS, at the same time demonstrating that its ability to recapitulate social autistic-relevant phenotypes depends on early testing ages. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  3. Ameliorating effect of piperine on behavioral abnormalities and oxidative markers in sodium valproate induced autism in BALB/C mice.

    PubMed

    Pragnya, B; Kameshwari, J S L; Veeresh, B

    2014-08-15

    Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism. Piperine has been reported to have protective effect on brain. The present study aimed at evaluating effect of piperine on VPA induced neurobehavioral and biochemical alterations in BALB/c mice. Young BALB/c mice 13 days old were procured from five different litters and segregated into five groups (n=6; 3 male, 3 female) i.e., Group I served as control group, received physiological saline on PND (Post natal day) 14 & Tween 80 p.o. from PND13-40. Group II served as normal treated group and received piperine (20mg/kg p.o.) from PND 13-40 and saline s.c. on PND 14. Group III served as valproate treated group received VPA (400mg/kg s.c.) on PND 14 and Tween 80 p.o. from PND 13-40. Group IV & V served as disease treated group received VPA (400mg/kg s.c.) on PND 14 & piperine (5 & 20mg/kg p.o.) from PND 13-40 respectively. BALB/c mice pups were subjected to behavioral testing to assess motor skill development, nociceptive response, locomotion, anxiety, and cognition on various postnatal days up to PND 40. At the end of behavioral evaluation, mice were sacrificed; brain was isolated for biochemical estimations (serotonin, glutathione, MDA and nitric oxide) and histopathological examination. Our study revealed that treatment with piperine significantly improved behavioral alterations, lowered oxidative stress markers, and restored histoarchitecture of cerebellum. This ameliorating effect of piperine is attributed to its anti-oxidant activity, cognition enhancing and neuroprotective activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. 6q22.33 microdeletion in a family with intellectual disability, variable major anomalies, and behavioral abnormalities.

    PubMed

    Mackenroth, Luisa; Hackmann, Karl; Beyer, Anke; Schallner, Jens; Novotna, Barbara; Klink, Barbara; Schröck, Evelin; Di Donato, Nataliya

    2015-11-01

    Interstitial deletions on the long arm of chromosome six have been described for several regions including 6q16, 6q22.1, and 6q21q22.1, and with variable phenotypes such as intellectual disability/developmental delay, growth retardation, major and minor facial anomalies. However, an isolated microdeletion of the sub-band 6q22.33 has not been reported so far and thus, no information about the specific phenotype associated with such a copy number variant is available. Here, we define the clinical picture of an isolated 6q22.33 microdeletion based on the phenotype of six members of one family with loss of approximately 1 Mb in this region. Main clinical features include mild intellectual disability and behavioral abnormalities as well as microcephaly, heart defect, and cleft lip and palate.

  5. Delay discounting behavior and white matter microstructure abnormalities in youth with a family history of alcoholism

    PubMed Central

    Herting, Megan M.; Schwartz, Daniel; Mitchell, Suzanne H.; Nagel, Bonnie J.

    2011-01-01

    Background Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high-risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH−). Methods Thirty-three healthy youth (FH+ = 15, FH− = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging (DTI). Tract Based Spatial Statistics (Smith et al., 2006), as well as follow-up region-of-interest analyses, were performed in order to compare fractional anisotropy (FA) between FH+ and FH− youth. Results FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times on the delay discounting paradigm compared to FH− youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower reaction times on the delay discounting task. Conclusion Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing, and may act as an intrinsic risk-factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high-risk youth. PMID:20586754

  6. Abnormal resistivity behavior of Cu-Ni and Cu-Co alloys in undercooled liquid state

    NASA Astrophysics Data System (ADS)

    Guo, Fengxiang; Lu, Ting; Qin, Jingyu; Zheng, Hongliang; Tian, Xuelei

    2012-11-01

    The resistivity behavior of undercooled liquid Cu-Ni and Cu-Co alloys had been studied in the contactless method, to probe the structure transition in undercooled melts during the cooling process. Over the entire concentration range, linear behavior of resistivity with temperature was obtained in liquid and undercooled liquid Cu-Ni system. It implied that the formation of icosahedral order might not influence the electron scattering in undercooled liquid Cu-Ni alloys. Similar results were obtained in Cu-Co system in the vicinity of liquidus temperature. A turning point was obvious in temperature coefficient of resistivity for undercooled liquid Cu-Co alloys around the bimodal line, which was interpreted to be responsible for metastable liquid-liquid phase separation. During liquid phase separation process, resistivity decreased and the temperature coefficient of resistivity was larger than that of homogeneous melts. In combination with transmission electron microscopy and scanning electron microscope studies on the as-solidified microstructure, this was interpreted as the formation of egg-type structure and concentration change in Cu-rich and Co-rich phases. The mechanism controlling the separation and droplets motion was also discussed in undercooled liquid Cu-Co system.

  7. Growth retardation and abnormal maternal behavior in mice lacking testicular orphan nuclear receptor 4

    PubMed Central

    Collins, Loretta L.; Lee, Yi-Fen; Heinlein, Cynthia A.; Liu, Ning-Chun; Chen, Yei-Tsung; Shyr, Chih-Rong; Meshul, Charles K.; Uno, Hideo; Platt, Kenneth A.; Chang, Chawnshang

    2004-01-01

    Testicular orphan nuclear receptor 4 (TR4) is a member of the nuclear receptor superfamily for which a ligand has not yet been found. In vitro data obtained from various cell lines suggest that TR4 functions as a master regulator to modulate many signaling pathways, yet the in vivo physiological roles of TR4 remain unclear. Here, we report the generation of mice lacking TR4 by means of targeted gene disruption (TR4–/–). The number of TR4–/– pups generated by the mating of TR4+/– mice is well under that predicted by the normal Mendelian ratio, and TR4–/– mice demonstrate high rates of early postnatal mortality, as well as significant growth retardation. Additionally, TR4–/– females show defects in reproduction and maternal behavior, with pups of TR4–/– dams dying soon after birth with no indication of milk intake. These results provide in vivo evidence that TR4 plays important roles in growth, embryonic and early postnatal pup survival, female reproductive function, and maternal behavior. PMID:15477591

  8. Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease.

    PubMed

    Ranasinghe, Kamalini G; Gill, Jeevit S; Kothare, Hardik; Beagle, Alexander J; Mizuiri, Danielle; Honma, Susanne M; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Vossel, Keith A; Nagarajan, Srikantan S; Houde, John F

    2017-04-01

    Speakers respond automatically and rapidly to compensate for brief perturbations of pitch in their auditory feedback. The specific adjustments in vocal output require integration of brain regions involved in speech-motor-control in order to detect the sensory-feedback error and implement the motor correction. Cortical regions involved in the pitch reflex phenomenon are highly vulnerable targets of network disruption in Alzheimer's disease (AD). We examined the pitch reflex in AD patients (n = 19) compared to an age-matched control group (n = 16). We measured the degree of behavioral compensation (peak compensation) and the extent of the adaptive response (pitch-response persistence). Healthy-controls reached a peak compensation of 18.7 ± 0.8 cents, and demonstrated a sustained compensation at 8.9 ± 0.69 cents. AD patients, in contrast, demonstrated a significantly elevated peak compensation (22.4 ± 1.2 cents, p < 0.05), and a reduced sustained response (pitch-response persistence, 4.5 ± 0.88 cents, p < 0.001). The degree of increased peak compensation predicted executive dysfunction, while the degree of impaired pitch-response persistence predicted memory dysfunction, in AD patients. The current study demonstrates pitch reflex as a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration, and compromised plasticity mechanisms of memory, in AD.

  9. Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats

    PubMed Central

    Wang, Xuefei; Sugam, Jonathan A.; Carelli, Regina M.

    2016-01-01

    Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. SIGNIFICANCE STATEMENT Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence

  10. Lesch-Nyhan syndrome: The saga of metabolic abnormalities and self-injurious behavior

    PubMed Central

    Tewari, Nitesh; Mathur, Vijay Prakash; Sardana, Divesh; Bansal, Kalpana

    2017-01-01

    Summary Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder of purine metabolism caused by a mutation in Xq26.2-q26.3 (OMIM 308000.0004). The presence of the diagnostic triad, i.e. signs of self-injurious behavior (SIB) and results of pedigree analysis and novel molecular biology & genetic testing, confirms the diagnosis of LNS. With a level of hypoxanthine guanine phosphoribosyl-transferase 1 (HPRT1) enzyme activity < 2%, patients develop neurological, neurocognitive, and neuromotor symptoms along with SIB. Described here is a case of 4-year-old boy who was diagnosed with LNS. The boy displayed SIB, i.e. biting of the lips and fingers, and he had cerebral venous sinus thrombosis caused by LNS. PMID:28357186

  11. Cognitive-behavioral therapy for sleep abnormalities of chronic pain patients.

    PubMed

    Tang, Nicole K Y

    2009-12-01

    Chronic pain and insomnia often occur simultaneously, with the vast majority of chronic pain patients complaining of interrupted or poor quality sleep. The need to improve sleep in these patients is clear, given increasing evidence that sleep disturbance is associated with heightened pain sensitivity and elevated disability. This article evaluates the efficacy of pain management programs (PMPs) based on cognitive-behavioral therapy (CBT) principles and CBT for primary insomnia (CBT-I) in treating pain-related insomnia. Although PMPs effectively enhance pain management skills in patients, they do not adequately address insomnia. CBT-I has demonstrated strong efficacy in treating pain-related insomnia, but sleep improvement is not followed by pain reduction. As both CBT approaches involve strengths and limitations, a hybrid form of treatment is needed that simultaneously addresses pain and sleep.

  12. Lesch-Nyhan syndrome: The saga of metabolic abnormalities and self-injurious behavior.

    PubMed

    Tewari, Nitesh; Mathur, Vijay Prakash; Sardana, Divesh; Bansal, Kalpana

    2017-02-01

    Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder of purine metabolism caused by a mutation in Xq26.2-q26.3 (OMIM 308000.0004). The presence of the diagnostic triad, i.e. signs of self-injurious behavior (SIB) and results of pedigree analysis and novel molecular biology & genetic testing, confirms the diagnosis of LNS. With a level of hypoxanthine guanine phosphoribosyl-transferase 1 (HPRT1) enzyme activity < 2%, patients develop neurological, neurocognitive, and neuromotor symptoms along with SIB. Described here is a case of 4-year-old boy who was diagnosed with LNS. The boy displayed SIB, i.e. biting of the lips and fingers, and he had cerebral venous sinus thrombosis caused by LNS.

  13. Rats overexpressing the dopamine transporter display behavioral and neurobiological abnormalities with relevance to repetitive disorders

    PubMed Central

    Hadar, Ravit; Edemann-Callesen, Henriette; Reinel, Claudia; Wieske, Franziska; Voget, Mareike; Popova, Elena; Sohr, Reinhard; Avchalumov, Yosef; Priller, Josef; van Riesen, Christoph; Puls, Imke; Bader, Michael; Winter, Christine

    2016-01-01

    The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system. Furthermore, transgenic rats specifically exhibited behavioral and pharmaco-therapeutic profiles phenotypic of repetitive disorders. Together our findings suggest that the DAT rat model will constitute a valuable tool for further investigations into the pathological influence of DAT overexpression on neural systems relevant to neuropsychiatric disorders. PMID:27974817

  14. Targeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice.

    PubMed

    Rapanelli, Maximiliano; Frick, Luciana Romina; Xu, Meiyu; Groman, Stephanie Mary; Jindachomthong, Kantiya; Tamamaki, Nobuaki; Tanahira, Chiyoko; Taylor, Jane Rebecca; Pittenger, Christopher

    2017-08-01

    Interneuronal pathology is implicated in many neuropsychiatric disorders, including autism spectrum disorder (ASD) and Tourette syndrome (TS). Interneurons of the striatum, including the parvalbumin-expressing fast-spiking interneurons (FSIs) and the large cholinergic interneurons (CINs), are affected in patients with TS and in preclinical models of both ASD and TS. To test the causal importance of these neuronal abnormalities, we recapitulated them in vivo in developmentally normal mice using a combination transgenic-viral strategy for targeted toxin-mediated ablation. We found that conjoint ~50% depletion of FSIs and CINs in the dorsal striatum of male mice produces spontaneous stereotypy and marked deficits in social interaction. Strikingly, these behavioral effects are not seen in female mice; because ASD and TS have a marked male predominance, this observation reinforces the potential relevance of the finding to human disease. Neither of these effects is seen when only one or the other interneuronal population is depleted; ablation of both is required. Depletion of FSIs, but not of CINs, also produces anxiety-like behavior, as has been described previously. Behavioral pathology in male mice after conjoint FSI and CIN depletion is accompanied by increases in activity-dependent signaling in the dorsal striatum; these alterations were not observed after disruption of only one interneuron type or in doubly depleted female mice. These data indicate that disruption of CIN and FSI interneurons in the dorsal striatum is sufficient to produce network and behavioral changes of potential relevance to ASD, in a sexually dimorphic manner. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Abnormal Stomatal Behavior and Hormonal Imbalance in flacca, a Wilty Mutant of Tomato

    PubMed Central

    Tal, M.; Imber, D.

    1970-01-01

    The wilty tomato mutant, flacca, and the control variety, Rheinlands Ruhm, were compared with regard to the endogenous activity and concentration of auxin- and abscisic acid-like substances during ontogeny. The mutant wilts fast under water deficit because of inability to close its stomata. Symptoms characteristic of excessive auxin are evident in the developing mutant. Among these symptoms are branch and leaf epinasty, excessive rooting along the stem, and increased apical dominance. By using a leucine-incorporation assay, spray of whole plants with 2,4-dichlorophenoxyacetic acid, and wheat coleoptile bioassay, indications were found of an excess of activity and concentration of auxin-like substances in shoots of young and mature mutant plants. The wheat coleoptile bioassay also revealed a much lower amount of substances with abscisic acid-like activity in the mutant compared with the normal plant. In contrast to the appearance during ontogeny of morphological symptoms characteristic of auxin excess in the mutant, the absolute amount of auxin-like substances and their activity in incorporation of leucine decreased with age. A parallel decrease of the concentration and activity of auxin-like compounds was also found in the normal plant. The concentration of abscisic acid-like substances increased with age in both genotypes. The disagreement between the increasing morphological symptoms and the decrease of auxin-like activity and concentration is discussed, together with the possibility of a causal relationship between auxin-and abscisic acid-like activity and stomatal behavior. PMID:16657470

  16. Abnormal Stomatal Behavior and Hormonal Imbalance in flacca, a Wilty Mutant of Tomato

    PubMed Central

    Tal, M.; Imber, D.; Itai, C.

    1970-01-01

    The wilty tomato mutant, flacca, and the normal variety, Rheinlands Ruhm, were compared for kinetin-like activity in ontogeny. The mutant wilts easily because its stomata resist closure. This stomatal resistance decreases with age. The occurrence of a root factor which induces stomatal opening was inferred from grafting experiments. It was hypothesized that the excessive stomatal openings in the mutant may result from excess of kinetin-like activity in the leaf of that plant. In addition, it was suggested that the closure of stomata in the aging mutant is due to a decrease of kinetin-like activity with age. Kinetin-like activity in the leaf was determined by incorporation of labeled leucine. The concentration of cytokinins in root exudate and leaf extract was determined by the soybean callus assay. Evidence was presented of higher kinetin-like activity in the leaves of the mutant and higher cytokinin concentration in its root exudate. Cytokinin concentration in the shoot was found to be only slightly higher in the mutant than in the normal plants. Kinetin-like activity in the leaf and cytokinin concentration of root exudate decreased with age in both mutant and normal plants. Kinetin-like activity in the leaves of mutant plants, which phenocopy the normal variety as a result of continuous application of abscisic acid, was lower than in control mutant plants. The significance of these findings per se and in connection with stomatal behavior is discussed. PMID:16657469

  17. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  18. Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.

    PubMed

    Hadar, R; Bikovski, L; Soto-Montenegro, M L; Schimke, J; Maier, P; Ewing, S; Voget, M; Wieske, F; Götz, T; Desco, M; Hamani, C; Pascau, J; Weiner, I; Winter, C

    2017-04-04

    The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.52.

  19. Methylphenidate ('Ritalin') can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia.

    PubMed

    Rahman, Shibley; Robbins, Trevor W; Hodges, John R; Mehta, Mitul A; Nestor, Peter J; Clark, Luke; Sahakian, Barbara J

    2006-03-01

    The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

  20. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish

    PubMed Central

    Grone, Brian P.; Marchese, Maria; Hamling, Kyla R.; Kumar, Maneesh G.; Krasniak, Christopher S.; Sicca, Federico; Santorelli, Filippo M.; Patel, Manisha; Baraban, Scott C.

    2016-01-01

    Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing “dark-flash” visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations. PMID:26963117

  1. A gain-of-function mutation in the sodium channel gene Scn2a results in seizures and behavioral abnormalities.

    PubMed

    Kearney, J A; Plummer, N W; Smith, M R; Kapur, J; Cummins, T R; Waxman, S G; Goldin, A L; Meisler, M H

    2001-01-01

    The GAL879-881QQQ mutation in the cytoplasmic S4-S5 linker of domain 2 of the rat brain IIA sodium channel (Na(v)1.2) results in slowed inactivation and increased persistent current when expressed in Xenopus oocytes. The neuron-specific enolase promoter was used to direct in vivo expression of the mutated channel in transgenic mice. Three transgenic lines exhibited seizures, and line Q54 was characterized in detail. The seizures in these mice began at two months of age and were accompanied by behavioral arrest and stereotyped repetitive behaviors. Continuous electroencephalogram monitoring detected focal seizure activity in the hippocampus, which in some instances generalized to involve the cortex. Hippocampal CA1 neurons isolated from presymptomatic Q54 mice exhibited increased persistent sodium current which may underlie hyperexcitability in the hippocampus. During the progression of the disorder there was extensive cell loss and gliosis within the hippocampus in areas CA1, CA2, CA3 and the hilus. The lifespan of Q54 mice was shortened and only 25% of the mice survived beyond six months of age. Four independent transgenic lines expressing the wild-type sodium channel were examined and did not exhibit any abnormalities. The transgenic Q54 mice provide a genetic model that will be useful for testing the effect of pharmacological intervention on progression of seizures caused by sodium channel dysfunction. The human ortholog, SCN2A, is a candidate gene for seizure disorders mapped to chromosome 2q22-24.

  2. Oseltamivir use and severe abnormal behavior in Japanese children and adolescents with influenza: Is a self-controlled case series study applicable?

    PubMed

    Fukushima, Wakaba; Ozasa, Kotaro; Okumura, Akihisa; Mori, Masaaki; Hosoya, Mitsuaki; Nakano, Takashi; Tanabe, Takuya; Yamaguchi, Naoto; Suzuki, Hiroshi; Mori, Mitsuru; Hatayama, Hideaki; Ochiai, Hirotaka; Kondo, Kyoko; Ito, Kazuya; Ohfuji, Satoko; Nakamura, Yosikazu; Hirota, Yoshio

    2017-08-24

    Since the 1990s, self-controlled designs including self-controlled case series (SCCS) studies have been occasionally used in post-marketing evaluation of drug or vaccine safety. An SCCS study was tentatively applied to evaluate the relationship between oseltamivir use and abnormal behavior Type A (serious abnormal behavior potentially leading to an accident or harm to another person) in influenza patients. From the original prospective cohort study with approximately 10,000 Japanese children and adolescents with influenza (aged <18years), 28 subjects (mean age: 7.3years) who developed abnormal behavior Type A after the first visit to the collaborating hospitals/clinics were analyzed. We hypothesized four combination patterns of the effect period (i.e., the period that effect of oseltamivir on occurrence of abnormal behavior Type A is likely) and the control period. Mantel-Haenszel rate ratio (M-H RR) and its 95% confidence interval (CI) were calculated as the relative risk estimate. Among 28 subjects in the SCCS study, 24 subjects (86%) were administered oseltamivir and 4 subjects (14%) were not. Abnormal behavior Type A was more likely to occur in the effect period than the control period in every pattern (M-H RR: 1.90-29.1). We observed the highest estimate when the effect period was set between the initial intake of oseltamivir and Tmax (M-H RR: 29.1, 95% CI: 4.21-201). Abnormal behavior Type A was more likely to develop up to approximately 30 times during the period between the initial intake of oseltamivir and Tmax. However, this period overlapped with the early period of influenza where high fever was observed. Since useful approaches to control the influence of the natural disease course of influenza were not available in this study, we could not deny the possibility that abnormal behavior was induced by influenza itself. The SCCS study was not an optimal method to evaluate the relationship between oseltamivir use and abnormal behavior. Copyright © 2017

  3. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  4. Ventricular remodeling in global ischemia.

    PubMed

    Anversa, P; Zhang, X; Li, P; Olivetti, G; Cheng, W; Reiss, K; Sonnenblick, E H; Kajstura, J

    1995-06-01

    To determine the effects of chronic constriction of the left coronary artery on the function and structure of the heart, coronary artery narrowing was surgically induced in rats and ventricular pump performance, extent and distribution of myocardial damage, and the hypertrophic and hyperplastic response of myocytes were examined. Alterations in cardiac hemodynamics were found in all rats, but the characteristics of the physiological properties of the heart allowed a separation of the animals into two groups which exhibited left ventricular dysfunction and failure, respectively. Left ventricular hypertrophy occurred in both groups and was characterized by ventricular dilatation and wall thinning which were more severe in the failing animals. Multiple foci of myocardial damage across the wall were seen in all animals but tissue injury was more prominent in the endomyocardium and in failing rats. The anatomical and hemodynamic changes resulted in a significant increase in diastolic wall stress which paralleled the depression in ventricular performance. Myocyte cell loss and myocyte cellular hypertrophy were more severe with ventricular failure than with dysfunction. Finally, diastolic overload appeared to be coupled with activation of the DNA synthetic machinery of myocytes and nuclear mitotic division. In conclusion, a fixed lesion of the left coronary artery leads to abnormalities in cardiac dynamics with marked increases in diastolic wall stress and extensive ventricular remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia in the remaining viable tissue.

  5. Ventricular-Vascular Interaction in Heart Failure

    PubMed Central

    Borlaug, Barry A.; Kass, David A.

    2008-01-01

    Synopsis Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF). HFpEF patients tend to be older, female, and hypertensive, and characteristically display increased ventricular and arterial stiffening. In this review, we discuss the pathophysiology of abnormal ventriculoarterial stiffening and how the latter affects ventricular function, cardiovascular hemodynamics, reserve capacity, and symptoms. We conclude by exploring how novel treatment strategies targeting abnormal ventricular-arterial interaction might prove useful in the treatment of patients with HFpEF. PMID:18313622

  6. Right and left ventricular exercise performance in chronic obstructive pulmonary disease: radionuclide assessment.

    PubMed

    Matthay, R A; Berger, H J; Davies, R A; Loke, J; Mahler, D A; Gottschalk, A; Zaret, B L

    1980-08-01

    Right and left ventricular pump performance was assessed at rest and during upright bicycle exercise in 30 patients with chronic obstructive pulmonary disease and in 25 normal control subjects. Right ventricular and left ventricular ejection fractions were ascertained noninvasively using first-pass quantitative radionuclide angiocardiography. The normal ventricular response to exercise was at least a 5% absolute increase in the ejection fraction of either ventricle. In patients the predominant cardiac abnormality involved performance of the right ventricle. Right ventricular ejection fraction was abnormal at rest in eight patients. Twenty-three patients demonstrated an abnormal right ventricular response to submaximal exercise. Airway obstruction and arterial hypoxemia were significantly more severe in patients with abnormal right ventricular exercise reserve than in those with normal reserve. Abnormal left ventricular performance was infrequent either at rest (four patients) or during exercise (six patients). Thus, this radionuclide technique allows noninvasive assessment of biventricular exercise reserve in chronic obstructive pulmonary disease.

  7. Aorto-ventricular tunnel

    PubMed Central

    McKay, Roxane

    2007-01-01

    Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinutubular junction to the cavity of the left, or (less commonly) right ventricle. The exact incidence is unknown, estimates ranging from 0.5% of fetal cardiac malformations to less than 0.1% of congenitally malformed hearts in clinico-pathological series. Approximately 130 cases have been reported in the literature, about twice as many cases in males as in females. Associated defects, usually involving the proximal coronary arteries, or the aortic or pulmonary valves, are present in nearly half the cases. Occasional patients present with an asymptomatic heart murmur and cardiac enlargement, but most suffer heart failure in the first year of life. The etiology of aorto-ventricular tunnel is uncertain. It appears to result from a combination of maldevelopment of the cushions which give rise to the pulmonary and aortic roots, and abnormal separation of these structures. Echocardiography is the diagnostic investigation of choice. Antenatal diagnosis by fetal echocardiography is reliable after 18 weeks gestation. Aorto-ventricular tunnel must be distinguished from other lesions which cause rapid run-off of blood from the aorta and produce cardiac failure. Optimal management of symptomatic aorto-ventricular tunnel consists of diagnosis by echocardiography, complimented with cardiac catheterization as needed to elucidate coronary arterial origins or associated defects, and prompt surgical repair. Observation of the exceedingly rare, asymptomatic patient with a small tunnel may be justified by occasional spontaneous closure. All patients require life-long follow-up for recurrence of the tunnel, aortic valve incompetence, left ventricular function, and aneurysmal enlargement of the ascending aorta. PMID:17922908

  8. Aorto-ventricular tunnel.

    PubMed

    McKay, Roxane

    2007-10-08

    Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinutubular junction to the cavity of the left, or (less commonly) right ventricle. The exact incidence is unknown, estimates ranging from 0.5% of fetal cardiac malformations to less than 0.1% of congenitally malformed hearts in clinico-pathological series. Approximately 130 cases have been reported in the literature, about twice as many cases in males as in females. Associated defects, usually involving the proximal coronary arteries, or the aortic or pulmonary valves, are present in nearly half the cases. Occasional patients present with an asymptomatic heart murmur and cardiac enlargement, but most suffer heart failure in the first year of life. The etiology of aorto-ventricular tunnel is uncertain. It appears to result from a combination of maldevelopment of the cushions which give rise to the pulmonary and aortic roots, and abnormal separation of these structures. Echocardiography is the diagnostic investigation of choice. Antenatal diagnosis by fetal echocardiography is reliable after 18 weeks gestation. Aorto-ventricular tunnel must be distinguished from other lesions which cause rapid run-off of blood from the aorta and produce cardiac failure. Optimal management of symptomatic aorto-ventricular tunnel consists of diagnosis by echocardiography, complimented with cardiac catheterization as needed to elucidate coronary arterial origins or associated defects, and prompt surgical repair. Observation of the exceedingly rare, asymptomatic patient with a small tunnel may be justified by occasional spontaneous closure. All patients require life-long follow-up for recurrence of the tunnel, aortic valve incompetence, left ventricular function, and aneurysmal enlargement of the ascending aorta.

  9. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    SciTech Connect

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-15

    Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD). Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise. All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects and resting right ventricular ejection fraction was lower in Group 3 versus control subjects. Thus left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; lifelong volume overload may be detrimental to myocardial function.

  10. Mice lacking the serotonin transporter exhibit 5-HT(1A) receptor-mediated abnormalities in tests for anxiety-like behavior.

    PubMed

    Holmes, Andrew; Yang, Rebecca J; Lesch, Klaus-Peter; Crawley, Jacqueline N; Murphy, Dennis L

    2003-12-01

    The serotonin transporter (5-HTT) regulates serotonergic neurotransmission via clearance of extracellular serotonin. Abnormalities in 5-HTT expression or function are found in mood and anxiety disorders, and the 5-HTT is a major target for antidepressants and anxiolytics. The 5-HTT is further implicated in the pathophysiology of these disorders by evidence that genetic variation in the promoter region of the HTT (SLC6A4) is associated with individual differences in anxiety and neural responses to fear. To further evaluate the role of the 5-HTT in anxiety, we employed a mouse model in which the 5-HTT gene (htt) was constitutively inactivated. 5-HTT -/- mice were characterized for anxiety-related behaviors using a battery of tests (elevated plus maze, light<-->dark exploration test, emergence test, and open field test). Male and female 5-HTT -/- mice showed robust phenotypic abnormalities as compared to +/+ littermates, suggestive of increased anxiety-like behavior and inhibited exploratory locomotion. The selective 5-HT(1A) receptor antagonist, WAY 100635 (0.05-0.3 mg/kg), produced a significant anxiolytic-like effect in the elevated plus maze in 5-HTT -/- mice, but not +/+ controls. The present findings demonstrate abnormal behavioral phenotypes in 5-HTT null mutant mice in tests for anxiety-like and exploratory behavior, and suggest a role for the 5-HT(1A) receptor in mediating these abnormalities. 5-HTT null mutant mice provide a model to investigate the role of the 5-HTT in mood and anxiety disorders.

  11. Are There Gender-Specific Pathways from Early Adolescence Psychological Distress Symptoms toward the Development of Substance Use and Abnormal Eating Behavior?

    ERIC Educational Resources Information Center

    Beato-Fernandez, Luis; Rodriguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-01-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview,…

  12. Fragile X-like behaviors and abnormal cortical dendritic spines in cytoplasmic FMR1-interacting protein 2-mutant mice.

    PubMed

    Han, Kihoon; Chen, Hogmei; Gennarino, Vincenzo A; Richman, Ronald; Lu, Hui-Chen; Zoghbi, Huda Y

    2015-04-01

    Silencing of fragile X mental retardation 1 (FMR1) gene and loss of fragile X mental retardation protein (FMRP) cause fragile X syndrome (FXS), a genetic disorder characterized by intellectual disability and autistic behaviors. FMRP is an mRNA-binding protein regulating neuronal translation of target mRNAs. Abnormalities in actin-rich dendritic spines are major neuronal features in FXS, but the molecular mechanism and identity of FMRP targets mediating this phenotype remain largely unknown. Cytoplasmic FMR1-interacting protein 2 (Cyfip2) was identified as an interactor of FMRP, and its mRNA is a highly ranked FMRP target in mouse brain. Importantly, Cyfip2 is a component of WAVE regulatory complex, a key regulator of actin cytoskeleton, suggesting that Cyfip2 could be implicated in the dendritic spine phenotype of FXS. Here, we generated and characterized Cyfip2-mutant (Cyfip2(+/-)) mice. We found that Cyfip2(+/-) mice exhibited behavioral phenotypes similar to Fmr1-null (Fmr1(-/y)) mice, an animal model of FXS. Synaptic plasticity and dendritic spines were normal in Cyfip2(+/-) hippocampus. However, dendritic spines were altered in Cyfip2(+/-) cortex, and the dendritic spine phenotype of Fmr1(-/y) cortex was aggravated in Fmr1(-/y); Cyfip2(+/-) double-mutant mice. In addition to the spine changes at basal state, metabotropic glutamate receptor (mGluR)-induced dendritic spine regulation was impaired in both Fmr1(-/y) and Cyfip2(+/-) cortical neurons. Mechanistically, mGluR activation induced mRNA translation-dependent increase of Cyfip2 in wild-type cortical neurons, but not in Fmr1(-/y) or Cyfip2(+/-) neurons. These results suggest that misregulation of Cyfip2 function and its mGluR-induced expression contribute to the neurobehavioral phenotypes of FXS.

  13. Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-01-01

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases. PMID:25348604

  14. Lead-induced neurodegenerative events and abnormal behaviors occur via ORXRergic/GABA(A)Rergic mechanisms in a marine teleost.

    PubMed

    Zizza, Merylin; Giusi, Giuseppina; Crudo, Michele; Canonaco, Marcello; Facciolo, Rosa Maria

    2013-01-15

    The hindering effects of metals and in particular lead (Pb) are representing a growing threat to aquatic organisms such as fish. This observation derives from toxic concentrations of Pb accounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host-cleaning symbiosis. In this study, the nominal PbNO(3) concentration of 1.6 mg/L was capable of reducing feeding and resting bouts as early as 24 h of exposure while hyperactive swimming episodes were also detected. Such abnormal behaviors were tightly correlated to up-regulated orexin receptor (ORXR) mRNA expression levels in some brain areas such as the lateral thalamic nucleus (+213%) and the optic tectum (+90%) with respect to controls. Interestingly, these transcriptional effects seemed to be attenuated when Pb-exposed fish received either 100 ng/g of ORX-A (-70%) or 0.1 μg/g of γ-aminobutyric acid(A) receptor (GABA(A)R) agonist muscimol (MUS; -97%) compared to fish exposed to Pb alone. Moreover, a net neurodegenerative process of the different brain areas was reported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only. Conversely, addition of the GABA(A)R antagonist bicuculline (BIC; 1 μg/g) moderately (p<0.05) enhanced Pb-dependent behavioral and neurodegenerative actions. Overall, these first indications strongly point to altered ORXR/GABA(A)R interactions during neurotoxic events of a metal that by evoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.

    PubMed

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-03-13

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.

  16. Oseltamivir Prescription and Regulatory Actions Vis-à-Vis Abnormal Behavior Risk in Japan: Drug Utilization Study Using a Nationwide Pharmacy Database

    PubMed Central

    Urushihara, Hisashi; Doi, Yuko; Arai, Masaru; Matsunaga, Toshiyuki; Fujii, Yosuke; Iino, Naoko; Kawamura, Takashi; Kawakami, Koji

    2011-01-01

    Background In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. Methodoloy/Prinicpal Findings In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). Conclusions/Significance The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the

  17. Pattern Organization of Premature Ventricular Heartbeats

    NASA Astrophysics Data System (ADS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Ivanov, Plamen; Stanley, H. Eugene; Stanley, Gene; Goldberger, Ary L.

    2000-03-01

    Increased number of premature (abnormal) ventricular beats in a record of heartbeat intervals are known to be associated with an advanced stage of pathology (e.g. congestive heart failure). These abnormal beats usually occur in repeated bursts for relatively short periods of time. Here we ask the question if particular abnormal patterns appear throughout records of heartbeat intervals. We study the temporal organization of specific patterns of ventricular beats in long 24 hour records and their relation to different stages of disease. We analyze the statistical properties of such patterns and combination of patterns by means of crosscorrelation matrices.

  18. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  19. Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.

    PubMed

    Garner, Joseph P; Thogerson, Collette M; Dufour, Brett D; Würbel, Hanno; Murray, James D; Mench, Joy A

    2011-06-01

    The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Persistent Effects of Peer Rearing on Abnormal and Species-Appropriate Activities but Not Social Behavior in Group-Housed Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Bauer, Sharon A; Baker, Kate C

    2016-01-01

    Nursery rearing of rhesus macaques (Macaca mulatta) alters behaviors but may be necessitated by maternal rejection or death, for research protocols, or for derivation of SPF colonies. The Tulane National Primate Research Center maintains a nursery-reared colony that is free from 9 pathogens as well as a mother-reared colony free from 4 pathogens, thus affording an opportunity to assess the outcomes of differential rearing. Nursery-reared macaques had continuous contact with 2 peers and an artificial surrogate (peer rearing). Focal sampling (432 h) was collected on the behavior of 32 peer-reared and 40 mother-reared subjects (age, 1 to 10 y; immature group, younger than 4 y; adult group 4 y or older). All animals were housed outdoors in like-reared social groups of 3 to 8 macaques. Contrary to expectation, no rearing effects on affiliative or agonistic social behaviors were detected. Compared with mother-reared subjects, peer-reared macaques in both age classes had elevated levels of abnormal appetitive, abnormal self-directed, and eating behaviors and lower levels of locomoting and vigilance (highly alert to activities in surrounding environment); a trend toward reduced foraging was detected. Immature but not adult peer-reared monkeys demonstrated more enrichment-directed behavior and drinking and a trend toward more anxiety-related behavior and inactivity. No new rearing effects were detected in adults that had not been detected in immature subjects. Results suggest that modern peer-rearing practices may not result in inevitable perturbations in aggressive, rank-related, sexual, and emotional behavior. However, abnormal behaviors may be lifelong issues once they appear. PMID:27053567

  1. Relation between training-induced left ventricular hypertrophy and risk for ventricular tachyarrhythmias in elite athletes.

    PubMed

    Biffi, Alessandro; Maron, Barry J; Di Giacinto, Barbara; Porcacchia, Paolo; Verdile, Luisa; Fernando, Fredrick; Spataro, Antonio; Culasso, Francesco; Casasco, Maurizio; Pelliccia, Antonio

    2008-06-15

    The aim of this study was to analyze the relation between the magnitude of training-induced left ventricular (LV) hypertrophy and the frequency and complexity of ventricular tachyarrhythmias in a large population of elite athletes without cardiovascular abnormalities. Ventricular tachyarrhythmias are a common finding in athletes, but it is unresolved as to whether the presence or magnitude of LV hypertrophy is a determinant of these arrhythmias in athletes without cardiovascular abnormalities. From 738 athletes examined at a national center for the evaluation of elite Italian athletes, 175 consecutive elite athletes with 24-hour ambulatory (Holter) electrocardiographic recordings (but without cardiovascular abnormalities and symptoms) were selected for the study group. Echocardiographic studies were performed during periods of peak training. Athletes were arbitrarily divided into 4 groups according to the frequency and complexity of ventricular arrhythmias during Holter electrocardiographic monitoring. No statistically significant relation was evident between LV mass (or mass index) and the grade or frequency of ventricular tachyarrhythmias. In addition, a trend was noted in those athletes with the most frequent and complex ventricular ectopy toward lower calculated LV mass. In conclusion, ventricular ectopy in elite athletes is not directly related to the magnitude of physiologic LV hypertrophy. These data offer a measure of clinical reassurance regarding the benign nature of ventricular tachyarrhythmias in elite athletes and the expression of athlete's heart.

  2. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    SciTech Connect

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-02-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease.

  3. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

    PubMed Central

    Jungen, Christiane; Scherschel, Katharina; Eickholt, Christian; Kuklik, Pawel; Klatt, Niklas; Bork, Nadja; Salzbrunn, Tim; Alken, Fares; Angendohr, Stephan; Klene, Christiane; Mester, Janos; Klöcker, Nikolaj; Veldkamp, Marieke W.; Schumacher, Udo; Willems, Stephan; Nikolaev, Viacheslav O.; Meyer, Christian

    2017-01-01

    The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis. PMID:28128201

  4. PAOPA, a potent dopamine D2 receptor allosteric modulator, prevents and reverses behavioral and biochemical abnormalities in an amphetamine-sensitized preclinical animal model of schizophrenia.

    PubMed

    Beyaert, Michael G R; Daya, Ritesh P; Dyck, Bailey A; Johnson, Rodney L; Mishra, Ram K

    2013-03-01

    Allosteric modulators are emerging as new therapeutics for the treatment of psychiatric illnesses, such as schizophrenia. Conventional antipsychotic drugs are typically dopamine D2 receptor antagonists that compete with endogenous dopamine at the orthosteric site, and block excessive dopamine neurotransmission in the brain. However, they are unable to treat all symptoms of schizophrenia and often cause adverse motor and metabolic side effects. The binding profile of allosteric modulators differs, as they interact with their receptor at a novel binding site and their activity is determined by physiological signaling. In collaboration, our laboratories have synthesized and evaluated over 185 compounds for their allosteric modulatory activity at the dopamine D2 receptor. Of these compounds, PAOPA is among the most potent allosteric modulators, and has been shown to be effective in treating the MK-801 induced preclinical animal model of schizophrenia. The objective of this study was to evaluate PAOPA's ability to prevent and reverse behavioral abnormalities in an amphetamine-sensitized preclinical animal model of schizophrenia. Amphetamine sensitized rats were given PAOPA during sensitization and following sensitization to determine whether PAOPA is able to prevent and reverse behavioral abnormalities. Furthermore, changes in post-mortem dopamine levels were measured by high performance liquid chromatography in various brain regions. The results presented demonstrate that PAOPA is able to prevent and reverse behavioral and biochemical abnormalities in an amphetamine-sensitized animal model of schizophrenia. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  5. Abnormal Eu behavior at formation of H2O- and Cl-bearing fluids during degassing of granite magmas

    NASA Astrophysics Data System (ADS)

    Lukanin, Oleg

    2010-05-01

    melt. The abnormal behavior of Eu shows itself the stronger, the lower fO2and, accordingly, the more fraction of Eu2+is present in melt. The work is supported of the Geosciences Department of the Russian Academy of Science (the program 2- 2010) and RFBR (grant 08-05-00022). References [1] Reed M.J., Candela Ph.A., Piccoli Ph.M. Contrib. Mineral. Petrol. 2000. V. 140. P. 251-262. [2] Lukanin O.A., Dernov-Pegarev V.F. Vestnik Otd. Nauk Zemle RAN, No 1(25)'2007 URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2007/informbul-1_2007/term-30e.pdf [3] Drake M.J. Geochim. Cosmochim. Acta. 1975. V. 39. P. 55-64. [4] Wilke M. Behrens H. Contrib. Mineral. Petrol. 1999. V. 137. P. 102-114. [5] Lukanin O.A. Vestnik Otd. Nauk o Zemle RAN, No 1(26)'2008. URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2008/informbul-1_2008/magm-20e.pdf [6] Lukanin O.A., Dernov-Pegarev V.F. Geochemistry International, 2010 (in press)

  6. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    PubMed Central

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  7. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems.

  8. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

    PubMed Central

    Ryan, Nicholas P.; Catroppa, Cathy; Beare, Richard; Silk, Timothy J.; Crossley, Louise; Beauchamp, Miriam H.; Yeates, Keith Owen; Anderson, Vicki A.

    2016-01-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the ‘social brain network’ (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2–8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  9. The Electrocardiographic Manifestations of Arrhythmogenic Right Ventricular Dysplasia

    PubMed Central

    Zhang, Li; Liu, Liwen; Kowey, Peter R; Fontaine, Guy H

    2014-01-01

    The ECG is abnormal in most patients with arrhythmogenic right ventricular dysplasia (ARVD). Right ventricular parietal block, reduced QRS amplitude, epsilon wave, T wave inversion in V1-3 and ventricular tachycardia in the morphology of left bundle branch block are the characteristic changes that reflect the underlying genetic predetermined pathology and pathoelectrophysiology. Recognizing the characteristic ECG changes in ARVD will be of help in making a correct diagnosis of this rare disease. PMID:24827798

  10. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  11. Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation

    PubMed Central

    Endo, Toshihiro; Kakeyama, Masaki; Uemura, Yukari; Haijima, Asahi; Okuno, Hiroyuki; Bito, Haruhiko; Tohyama, Chiharu

    2012-01-01

    An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in mice exposed to dioxin in utero and via lactation by using our recently developed automated behavioral flexibility test and immunohistochemistry of neuronal activation markers Arc, at the 14 brain areas. Pregnant C57BL/6 mice were given orally a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of either 0, 0.6 or 3.0 µg/kg on gestation day 12.5. When the pups reached adulthood, they were group-housed in IntelliCage to assess their behavior. As a result, the offspring born to dams exposed to 0.6 µg TCDD/kg were shown to have behavioral inflexibility, compulsive repetitive behavior, and dramatically lowered competitive dominance. In these mice, immunohistochemistry of Arc exhibited the signs of hypoactivation of the medial prefrontal cortex (mPFC) and hyperactivation of the amygdala. Intriguingly, mice exposed to 3.0 µg/kg were hardly affected in both the behavioral and neuronal activation indices, indicating that the robust, non-monotonic dose-response relationship. In conclusion, this study showed for the first time that perinatal exposure to a low dose of TCDD in mice develops executive function deficits and social behavioral abnormality accompanied with the signs of imbalanced mPFC-amygdala activation. PMID:23251380

  12. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    PubMed Central

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

  13. Right ventricular outflow obstruction with intact ventricular septum in adults.

    PubMed Central

    Werner, A M; Darrell, J C; Pallegrini, R V; Woelfel, G F; Grant, K; Marrangoni, A G

    1997-01-01

    Cardiothoracic surgeons whose practice is limited to adults rarely see patients with right ventricular outflow obstruction and an intact ventricular septum. Of more than 10,000 open-heart procedures performed at our institution from 1983 to 1993 (in patients 18 to 75 years old), only 5 procedures were for correction of this problem. Both the pulmonary valve and the subvalvular area were abnormal in these 5 patients, and 4 of the 5 had subvalvular stenosis. The gradient across the right ventricular outflow tract was measured by cardiac catheterization before repair in all patients and averaged 118 mmHg. Various surgical approaches were used for repair. In the 2 patients whose pressures were measured postoperatively, the gradients were 25 mmHg and 45 mmHg, respectively. There were no operative deaths. At follow-up (range, 2 months to 5 years after surgery), all patients were in New York Heart Association functional class I and all had murmurs. Those who underwent echocardiography were found to have minimal gradients across the right ventricular outflow tract. Images PMID:9205983

  14. The α4β2 nicotinic acetylcholine receptor modulates autism-like behavioral and motor abnormalities in pentylenetetrazol-kindled mice.

    PubMed

    Takechi, Kenshi; Suemaru, Katsuya; Kiyoi, Takeshi; Tanaka, Akihiro; Araki, Hiroaki

    2016-03-15

    Epilepsy is associated with several psychiatric disorders, including cognitive impairment, autism and attention deficit/hyperactivity disorder (ADHD). However, the psychopathology of epilepsy is frequently unrecognized and untreated in patients. In the present study, we investigated the effects of ABT-418, a neuronal nicotinic acetylcholine receptor agonist, on pentylenetetrazol (PTZ)-kindled mice with behavioral and motor abnormalities. PTZ-kindled mice displayed impaired motor coordination (in the rotarod test), anxiety (in the elevated plus maze test) and social approach impairment (in the three-chamber social test) compared with control mice. ABT-418 treatment (0.05 mg/kg, intraperitoneally) alleviated these behavioral abnormalities in PTZ-kindled mice. Immunolabeling of tissue sections demonstrated that expression of the α4 nicotinic acetylcholine receptor subunit in the medial habenula was similar in control and PTZ-kindled mice. However, expression was significantly decreased in the piriform cortex in PTZ-kindled mice. In addition, we examined the expression of the synaptic adhesion molecule neuroligin 3 (NLG3). NLG3 expression in the piriform cortex was significantly higher in PTZ-kindled mice compared with control mice. Collectively, our findings suggest that ADHD-like or autistic-like behavioral abnormalities associated with epilepsy are closely related to the downregulation of the α4 nicotinic receptor and the upregulation of NLG3 in the piriform cortex. In summary, this study indicates that ABT-418 might have therapeutic potential for attentional impairment in epileptic patients with psychiatric disorders such as autism and ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Microduplications of 3p26.3p26.2 containing CRBN gene in patients with intellectual disability and behavior abnormalities.

    PubMed

    Papuc, Sorina M; Hackmann, Karl; Andrieux, Joris; Vincent-Delorme, Catherine; Budişteanu, Magdalena; Arghir, Aurora; Schrock, Evelin; Ţuţulan-Cuniţă, Andreea C; Di Donato, Nataliya

    2015-05-01

    We report on the clinical data and molecular cytogenetic findings in three unrelated patients presenting with intellectual disability and behavior abnormalities. An overlapping microduplication involving 3p26.2-26.3 was identified in these patients. All three aberrations were confirmed and proven to be parentally inherited. The sizes of the duplications were different, with a common minimal region of 423,754 bp containing two genes - TRNT1 and CRBN. Here, we hypothesize that the copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability.

  16. Postoperative normalization of left ventricular noncompaction and new echocardiographic signs in aorta to left ventricular tunnel.

    PubMed

    Malakan Rad, Elaheh; Zeinaloo, Ali Akbar

    2013-04-01

    We report postoperative normalization of left ventricular noncompaction in a neonate undergoing successful neonatal surgery for type II aorta to left ventricular tunnel (ALVT) associated with a large patent ductus arteriosus, floppy and extremely redundant anterior mitral leaflet, right coronary artery arising directly from the tunnel, and severe left ventricular noncompaction. We also described 2 novel echocardiographic findings in ALVT including "triple wavy line sign" on M-mode echocardiography which disappeared 1 month after operation and "abnormally increased left ventricular posterior wall motion" on M-mode of standard parasternal long-axis view on color tissue Doppler imaging (TDI) that also normalized postoperatively. We showed that proper definition of endocardial border is extremely important in strain and strain rate imaging in the context of left ventricular noncompaction. Preoperative longitudinal strain and strain rate were significantly decreased in comparison to radial strain and strain rate. Circumferential strain and strain rate were normal. © 2013, Wiley Periodicals, Inc.

  17. Congenital Abnormalities

    MedlinePlus

    ... while you are pregnant. Combination of Genetic and Environmental Problems Some congenital abnormalities may occur if there is a genetic tendency for the condition combined with exposure to certain environmental influences within the womb during critical stages of ...

  18. Exercise thallium testing in ventricular preexcitation

    SciTech Connect

    Archer, S.; Gornick, C.; Grund, F.; Shafer, R.; Weir, E.K.

    1987-05-01

    Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation.

  19. Anatomical Abnormalities in Autism?

    PubMed

    Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan

    2016-04-01

    Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.

  20. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  1. Genetic damage and the expression of behavioral abnormalities in the progeny of male rats exposed to ionizing radiation

    SciTech Connect

    Lowery, M.C.

    1987-01-01

    To determine the possible genetic nature of behavioral anomalies, an identifiable genetic endpoint, inherited chromosome translocations in the offspring, was selected to evaluate the relationship to behavior. Young adult male Fischer 344 rats were exposed to 50-300 rads of ionizing radiation. Two weeks following their irradiation, the males were mated with four virgin females for one week. During this time, fertilizing sperm were derived from post-meiotic spermatids, the stage of the spermatogenic cycle most sensitive to the mutagenic effects of radiation. Behavioral analyses of the resulting 390 offspring consisted of both motor reflex and motor coordination measurements as well as learning and retention parameters. Significant differences in performance were seen in several of the motor reflex measurements in progeny of males exposed to some of the higher doses of irradiation. A similar phenomenon was observed in the performance of a single learned behavior.

  2. Habitual exercise correlates with exercise performance in patients with conotruncal abnormalities.

    PubMed

    O'Byrne, Michael L; Mercer-Rosa, Laura; Ingall, Eitan; McBride, Michael G; Paridon, Stephen; Goldmuntz, Elizabeth

    2013-04-01

    Cardiopulmonary exercise testing (CPET), particularly maximal oxygen consumption (VO2max), has been used to assess the outcome for patients with palliated congenital heart disease (CHD). Small studies correlating VO2max with noninvasive imaging measures of ventricular function have led to the hypothesis that VO2max reflects cardiac performance. In other settings, physical training is associated with increased VO2max. The authors hypothesized that habitual exercise correlates with VO2max to a greater degree than ventricular function in a relatively healthy cohort of patients with palliated CHD. The habitual exercise behavior of 208 subjects with conotruncal abnormalities (tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch) at the time of previously performed, study-based CPET and cardiac magnetic resonance imaging (CMR) were retrospectively assessed via questionnaire. The association of VO2max with habitual exercise duration and CMR measures of ventricular function was tested. Of 208 subjects, 89 (43 %) completed questionnaires, and 78 % of the 89 patients had a concurrent CMR. The mean VO2max was 76 ± 21 % of that predicted. The CMR-assessed left ventricular ejection fraction was 67.6 ± 7.4 %. The hours of habitual exercise per week correlated with VO2max (p < 0.001; r (2) = 0.14). No association was found between right and left ventricular ejection fraction, cardiac index, or right ventricular end-diastolic volume and VO2max. In this study, VO2max correlated with habitual exercise to a greater degree than CMR measurements of ventricular function. These findings highlight the importance of considering the contribution of noncardiac factors when exercise data in both clinical and research settings are interpreted. The contribution of these factors to clinical outcomes deserves further study.

  3. Noninvasive assessment of left ventricular function in myotonic muscular dystrophy.

    PubMed Central

    Venco, A; Saviotti, M; Besana, D; Finardi, G; Lanzi, G

    1978-01-01

    In order to assess left ventricular function, measurements of left ventricular internal dimension and its rate of change have been made by echocardiography in 7 patients with myotonic dystrophy and the three children of one of them, who were clinically normal but had abnormal muscle biopsies. Electrocardiograms and systolic time intervals were also recorded in all. Only one patient had signs of overt heart disease and an abnormal electrocardiogram (type B WPW). Systolic time intervals were normal in all 7 patients. Five subjects had echocardiographic abnormalities, which were of minor degree except in the patient with overt heart disease who had considerable impairment of both systolic and diastolic left ventricular function. Another patient had abnormalities of both systolic and diastolic function; systolic abnormalities occurred alone in one patient and diastolic abnormalities alone in one relative. It is concluded that patients with myotonic dystrophy and no clinical signs of heart disease may have minor abnormalities of left ventricular function as shown by echocardiography. Echocardiography is more sensitive than systolic time intervals in detecting these abnormalities; both systolic and diastolic function abnormalities, alone or together, can occur. There seems to be no relation between involvement of skeletal and cardiac muscle. PMID:718766

  4. Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells

    PubMed Central

    Jia, Yun-Fang; Song, Ning-Ning; Mao, Rong-Rong; Li, Jin-Nan; Zhang, Qiong; Huang, Ying; Zhang, Lei; Han, Hui-Li; Ding, Yu-Qiang; Xu, Lin

    2014-01-01

    Dysfunction of central serotonin (5-HT) system has been proposed to be one of the underlying mechanisms for anxiety and depression, and the association of diabetes mellitus and psychiatric disorders has been noticed by the high prevalence of anxiety/depression in patients with diabetes mellitus. This promoted us to examine these behaviors in central 5-HT-deficient mice and those also suffering with diabetes mellitus. Mice lacking either 5-HT or central serotonergic neurons were generated by conditional deletion of Tph2 or Lmx1b respectively. Simultaneous depletion of both central serotonergic neurons and pancreatic islet cells was achieved by administration of diphtheria toxin (DT) in Pet1-Cre;Rosa26-DT receptor (DTR) mice. The central 5-HT-deficient mice showed reduced anxiety-like behaviors as they spent more time in and entered more often into the light box in the light/dark box test compared with controls; similar results were observed in the elevated plus maze test. However, they displayed no differences in the immobility time of the forced swimming and tail suspension tests suggesting normal depression-like behaviors in central 5-HT-deficient mice. As expected, DT-treated Pet1-Cre;Rosa26-DTR mice lacking both central serotonergic neurons and pancreatic islet endocrine cells exhibited several classic diabetic symptoms. Interestingly, they displayed increased anxiety-like behaviors but reduced immobility time in the forced swimming and tail suspension tests. Furthermore, the hippocampal neurogenesis was dramatically enhanced in these mice. These results suggest that the deficiency of central 5-HT may not be sufficient to induce anxiety/depression-like behaviors in mice, and the enhanced hippocampal neurogenesis may contribute to the altered depression-like behaviors in the 5-HT-deficient mice with diabetes. Our current investigation provides understanding the relationship between diabetes mellitus and psychiatric disorders. PMID:25294992

  5. RF-EMF exposure at 1800 MHz did not elicit DNA damage or abnormal cellular behaviors in different neurogenic cells.

    PubMed

    Su, Liling; Wei, Xiaoxia; Xu, Zhengping; Chen, Guangdi

    2017-04-01

    Despite many years of studies, the debate on genotoxic effects of radiofrequency electromagnetic fields (RF-EMF) continues. To systematically evaluate genotoxicity of RF-EMF, this study examined effects of RF-EMF on DNA damage and cellular behavior in different neurogenic cells. Neurogenic A172, U251, and SH-SY5Y cells were intermittently (5 min on/10 min off) exposed to 1800 MHz RF-EMF at an average specific absorption rate (SAR) of 4.0 W/kg for 1, 6, or 24 h. DNA damage was evaluated by quantification of γH2AX foci, an early marker of DNA double-strand breaks. Cell cycle progression, cell proliferation, and cell viability were examined by flow cytometry, hemocytometer, and cell counting kit-8 assay, respectively. Results showed that exposure to RF-EMF at an SAR of 4.0 W/kg neither significantly induced γH2AX foci formation in A172, U251, or SH-SY5Y cells, nor resulted in abnormal cell cycle progression, cell proliferation, or cell viability. Furthermore, prolonged incubation of these cells for up to 48 h after exposure did not significantly affect cellular behavior. Our data suggest that 1800 MHz RF-EMF exposure at 4.0 W/kg is unlikely to elicit DNA damage or abnormal cellular behaviors in neurogenic cells. Bioelectromagnetics. 38:175-185, 2017. © 2016 Wiley Periodicals, Inc.

  6. Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.

    PubMed

    Burgess, Alison; Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

    2014-12-01

    To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity. © RSNA, 2014.

  7. Variability in Post-Error Behavioral Adjustment Is Associated with Functional Abnormalities in the Temporal Cortex in Children with ADHD

    ERIC Educational Resources Information Center

    Spinelli, Simona; Vasa, Roma A.; Joel, Suresh; Nelson, Tess E.; Pekar, James J.; Mostofsky, Stewart H.

    2011-01-01

    Background: Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral…

  8. Neonatal exposure to sevoflurane may not cause learning and memory deficits and behavioral abnormality in the childhood of Cynomolgus monkeys.

    PubMed

    Zhou, Lisheng; Wang, Zhi; Zhou, Hui; Liu, Ting; Lu, Fudin; Wang, Shouping; Li, Jing; Peng, Shuling; Zuo, Zhiyi

    2015-06-05

    Results of animal studies have raised a significant concern that commonly used general anesthetics may induce neurotoxicity in children. It may be difficult to resolve this concern with human studies because randomizing children only for testing anesthetic toxicity may not be feasible. We randomized 6-day old male Cynomolgus monkeys to receive or not to receive sevoflurane anesthesia at surgical plane for 5 h. Sevoflurane is the most commonly used general anesthetic in children in the U.S.A. Here, we showed that sevoflurane anesthesia did not affect the behavior evaluated by holding cage method when the monkeys were 3 and 7 months old. However, there was an age-dependent decrease in the frequency of stress events and environmental exploration behavior during the test. Sevoflurane also did not affect the learning and memory of the monkeys when they were assessed from the age of 7 months. Finally, sevoflurane did not affect the expression of multiple neuron-specific proteins in the hippocampus and cerebral cortex of 10-month old monkeys after all behavioral and cognitive tests were completed. These results suggest that exposure of neonatal monkey to sevoflurane may not affect cognition, behavior and neuronal structures in childhood, indicating the safety of sevoflurane anesthesia in children.

  9. Neonatal exposure to sevoflurane may not cause learning and memory deficits and behavioral abnormality in the childhood of Cynomolgus monkeys

    PubMed Central

    Zhou, Lisheng; Wang, Zhi; Zhou, Hui; Liu, Ting; Lu, Fudin; Wang, Shouping; Li, Jing; Peng, Shuling; Zuo, Zhiyi

    2015-01-01

    Results of animal studies have raised a significant concern that commonly used general anesthetics may induce neurotoxicity in children. It may be difficult to resolve this concern with human studies because randomizing children only for testing anesthetic toxicity may not be feasible. We randomized 6-day old male Cynomolgus monkeys to receive or not to receive sevoflurane anesthesia at surgical plane for 5 h. Sevoflurane is the most commonly used general anesthetic in children in the U.S.A. Here, we showed that sevoflurane anesthesia did not affect the behavior evaluated by holding cage method when the monkeys were 3 and 7 months old. However, there was an age-dependent decrease in the frequency of stress events and environmental exploration behavior during the test. Sevoflurane also did not affect the learning and memory of the monkeys when they were assessed from the age of 7 months. Finally, sevoflurane did not affect the expression of multiple neuron-specific proteins in the hippocampus and cerebral cortex of 10-month old monkeys after all behavioral and cognitive tests were completed. These results suggest that exposure of neonatal monkey to sevoflurane may not affect cognition, behavior and neuronal structures in childhood, indicating the safety of sevoflurane anesthesia in children. PMID:26046459

  10. Variability in Post-Error Behavioral Adjustment Is Associated with Functional Abnormalities in the Temporal Cortex in Children with ADHD

    ERIC Educational Resources Information Center

    Spinelli, Simona; Vasa, Roma A.; Joel, Suresh; Nelson, Tess E.; Pekar, James J.; Mostofsky, Stewart H.

    2011-01-01

    Background: Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral…

  11. Right ventricular infarction: identification by hemodynamic measurements before and after volume loading and correlation with noninvasive techniques

    SciTech Connect

    Dell'Italia, L.J.; Starling, M.R.; Crawford, M.H.; Boros, B.L.; Chaudhuri, T.K.; O'Rourke, R.A.

    1984-11-01

    To evaluate the potential occurrence of right ventricular infarction, 53 patients with acute inferior transmural myocardial infarction were studied within 36 hours of symptoms by right heart catheterization, equilibrium radionuclide angiography and two-dimensional echocardiography. Technetium-99m pyrophosphate myocardial scintigraphy was performed 3 days after the onset of symptoms. The hemodynamic standard for right ventricular infarction was defined as both a right atrial pressure of 10 mm Hg or more and a right atrial/pulmonary artery wedge pressure ratio of 0.8 or more. Eight (15%) of the 53 patients had hemodynamic measurements at rest characteristic of right ventricular infarction, and 6 (11%) additional patients met these criteria after volume loading. Nineteen (37%) of the 51 patients who had radionuclide angiography had right ventricular dysfunction manifested by both a reduced right ventricular ejection fraction (less than 40%) and right ventricular regional wall motion abnormalities (akinesia or dyskinesia). An abnormal radionuclide angiogram was observed in 12 of 13 patients with hemodynamic measurements indicating right ventricular infarction. In 12 patients with an abnormal radionuclide angiographic study, right ventricular ejection fraction improved 6 to 12 weeks after infarction. Twenty-two (49%) of the 45 patients with adequate two-dimensional echocardiograms had a right ventricular regional wall motion abnormality. An abnormal two-dimensional echocardiogram was seen in 9 of 11 patients with hemodynamic measurements characteristic of right ventricular infarction. Technetium-99m pyrophosphate scintigraphy was positive for right ventricular infarction in 3 of 12 patients who had hemodynamic measurements indicating right ventricular infarction.

  12. [Left ventricular diastolic dysfunction. Implications for anesthesia and critical care].

    PubMed

    Meierhenrich, R; Schütz, W; Gauss, A

    2008-11-01

    Over the last two decades there has been a growing recognition that cardiac function is not solely determined by systolic but also essentially by diastolic function. Left ventricular diastolic dysfunction is characterized by an impairment of ventricular filling caused either by abnormal relaxation, an active energy consuming process or decreased compliance, which is determined by passive tissue properties of the ventricle. Doppler echocardiography, including tissue Doppler imaging, has emerged as the preferred clinical tool for the assessment of left ventricular diastolic function. Recently the importance of left ventricular diastolic function is increasingly being recognized also during the perioperative period. Newer studies have shown that after cardiopulmonary bypass there is a significant decrease in left ventricular compliance. Experimental studies have demonstrated that sepsis is associated with a decrease in both active relaxation and ventricular compliance. Initial studies are also focusing on therapeutic options for patients with isolated diastolic dysfunction.

  13. Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

    PubMed Central

    Cherry, Elizabeth M.; Fenton, Flavio H.

    2012-01-01

    Defining the cellular electrophysiological mechanisms for ventricular tachyarrhythmias is difficult, given the wide array of potential mechanisms, ranging from abnormal automaticity to various types of reentry and kk activity. The degree of difficulty is increased further by the fact that any particular mechanism may be influenced by the evolving ionic and anatomic environments associated with many forms of heart disease. Consequently, static measures of a single electrophysiological characteristic are unlikely to be useful in establishing mechanisms. Rather, the dynamics of the electrophysiological triggers and substrates that predispose to arrhythmia development need to be considered. Moreover, the dynamics need to be considered in the context of a system, one that displays certain predictable behaviors, but also one that may contain seemingly stochastic elements. It also is essential to recognize that even the predictable behaviors of this complex nonlinear system are subject to small changes in the state of the system at any given time. Here we briefly review some of the short-, medium-, and long-term alterations of the electrophysiological substrate that accompany myocardial disease and their potential impact on the initiation and maintenance of ventricular arrhythmias. We also provide examples of cases in which small changes in the electrophysiological substrate can result in rather large differences in arrhythmia outcome. These results suggest that an interrogation of cardiac electrical dynamics is required to provide a meaningful assessment of the immediate risk for arrhythmia development and for evaluating the effects of putative antiarrhythmic interventions. PMID:22467299

  14. Leukocyte abnormalities.

    PubMed

    Gabig, T G

    1980-07-01

    Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

  15. Abnormal Pre-Attentive Arousal in Young Children with Autism Spectrum Disorder Contributes to Their Atypical Auditory Behavior: An ERP Study

    PubMed Central

    Stroganova, Tatiana A.; Kozunov, Vladimir V.; Posikera, Irina N.; Galuta, Ilia A.; Gratchev, Vitaliy V.; Orekhova, Elena V.

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks (‘S1’ and ‘S2’) separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the ‘tangential’ P100 component was rightward lateralized in TD children, whereas the ‘radial’ N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD. PMID:23935931

  16. Abnormal pre-attentive arousal in young children with autism spectrum disorder contributes to their atypical auditory behavior: an ERP study.

    PubMed

    Stroganova, Tatiana A; Kozunov, Vladimir V; Posikera, Irina N; Galuta, Ilia A; Gratchev, Vitaliy V; Orekhova, Elena V

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks ('S1' and 'S2') separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the 'tangential' P100 component was rightward lateralized in TD children, whereas the 'radial' N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD.

  17. Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats⋆

    PubMed Central

    Felt, Barbara T.; Beard, John L.; Schallert, Timothy; Shao, Jie; Aldridge, J. Wayne; Connor, James R.; Georgieff, Michael K.; Lozoff, Betsy

    2006-01-01

    Background Iron deficiency anemia (IDA) has been associated with altered cognitive, motor, and social-emotional outcomes in human infants. We recently reported that rats with chronic perinatal IDA, had altered regional brain iron, monoamines, and sensorimotor skill emergence during early development. Objective To examine the long-term consequences of chronic perinatal IDA on behavior, brain iron and monoamine systems after dietary iron treatment in rats. Methods Sixty dams were randomly assigned to iron-sufficient (CN) or low-iron (EID) diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet, assessed for hematology and behavior after weaning and into adulthood and for brain measures as adults (regional brain iron, monoamines, dopamine and serotonin transporters, and dopamine receptor). Behavioral assessments included sensorimotor function, general activity, response to novelty, spatial alternation, and spatial water maze performance. Results Hematology and growth were similar for EID and CN rats by postnatal day 35. In adulthood, EID thalamic iron content was lower. Monoamines, dopamine transporter, and dopamine receptor concentrations did not differ from CN. EID serotonin transporter concentration was reduced in striatum and related regions. EID rats had persisting sensorimotor deficits (delayed vibrissae-evoked forelimb placing, longer sticker removal time, and more imperfect grooming chains), were more hesitant in novel settings, and had poorer spatial water maze performance than CN. General activity and spatial alternation were similar for EID and CN. Conclusion Rats that had chronic perinatal IDA showed behavioral impairments that suggest persistent striatal dopamine and hippocampal dysfunction despite normalization of hematology, growth and most brain measures. PMID:16713640

  18. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.

    PubMed

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-06-27

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.

  19. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

    PubMed Central

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  20. Postictal hypoperfusion/hypoxia provides the foundation for a unified theory of seizure-induced brain abnormalities and behavioral dysfunction.

    PubMed

    Farrell, Jordan S; Colangeli, Roberto; Wolff, Marshal D; Wall, Alexandra K; Phillips, Thomas J; George, Antis; Federico, Paolo; Teskey, G Campbell

    2017-09-01

    A recent article by Farrell et al. characterizes the phenomenon, mechanisms, and treatment of a local and severe hypoperfusion/hypoxia event that occurs in brain regions following a focal seizure. Given the well-established role of cerebral ischemia/hypoxia in brain damage and behavioral dysfunction in other clinical settings (e.g., stroke, cerebral vasospasm), we put forward a new theory: postictal hypoperfusion/hypoxia is responsible for the negative consequences associated with seizures. Fortunately, inhibition of two separate molecular targets, cyclooxygenase-2 (COX-2) and l-type calcium channels, can prevent the expression of postictal hypoperfusion/hypoxia. These inhibitors are important experimental tools used to separate the seizure from the resulting hypoperfusion/hypoxia and can allow researchers to address the contribution of this phenomenon to negative outcomes associated with seizures. Herein we address the implications of this postictal stroke-like event in acute behavioral dysfunction (e.g., Todd's paresis) and sudden unexpected death in epilepsy (SUDEP). Moreover, anatomic alterations such as increased blood-brain barrier permeability, glial activation, central inflammation, and neuronal loss could also be a consequence of repeated hypoperfusion/hypoxic events and, in turn, underlie chronic interictal cognitive and behavioral comorbidities (e.g., memory deficits, anxiety, depression, and psychosis) and exacerbate epileptogenesis. Thus these seemingly disparate and clinically important observations may share a common point of origin: postictal hypoperfusion/hypoxia. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. The development of behavioral and endocrine abnormalities in rats after repeated exposure to direct and indirect stress

    PubMed Central

    Daniels, Willie Mark Uren; de Klerk Uys, Joachim; van Vuuren, Petra; Stein, Daniel Joseph

    2008-01-01

    The present study compared the effects of direct and indirect stress on the behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in a two compartment box. In one compartment the direct stressed rat was subjected to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration). In the adjacent compartment, the indirect stressed rats witnessed the application of these electric foot shocks. Our data showed substantial behavioral changes in the open field test, but limited effects in the elevated plus maze. The findings suggested that single and repeated stress exposure may have different consequences, that the effects of stress exposure may develop over time and persist for an extended period, and that both direct and indirect stressed rats displayed a hyposensitive HPA axis following acute restraint stress. Overall our observations moderately indicate direct exposure to elicit behavioral changes, and both direct and indirect exposure to stress to result in aberrations within the neuroendocrine system. With additional development our stress models may be considered for studying the complex interrelationship between an external stressor, and the experience of the organism. PMID:18728793

  2. Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

    PubMed Central

    Portmann, Thomas; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L.; Zhengqui, Zhou; Miller, Michael A.; Lerch, Jason P.; Henkelman, Mark; Shamloo, Mehrdad; Malenka, Robert C.; Crawley, Jacqueline N.; Dolmetsch, Ricardo E.

    2014-01-01

    Summary A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. PMID:24794428

  3. Behavioral abnormalities and circuit defects in the basal ganglia of a mouse model of 16p11.2 deletion syndrome.

    PubMed

    Portmann, Thomas; Yang, Mu; Mao, Rong; Panagiotakos, Georgia; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L; Grueter, Brad A; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L; Zhengqui, Zhou; Miller, Michael A; Lerch, Jason P; Henkelman, R Mark; Shamloo, Mehrdad; Malenka, Robert C; Crawley, Jacqueline N; Dolmetsch, Ricardo E

    2014-05-22

    A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.

  4. MRI complements standard assessment of right ventricular function after lung transplantation.

    PubMed

    Frist, W H; Lorenz, C H; Walker, E S; Loyd, J E; Stewart, J R; Graham, T P; Pearlstein, D P; Key, S P; Merrill, W H

    1995-08-01

    Changes in right ventricular mass and ejection fraction after single-lung transplantation for pulmonary hypertension are poorly understood. To complement functional data provided by echocardiography, radionuclide ventriculography, and right heart catheterization, magnetic resonance imaging was used to assess right ventricular function in 5 single-lung transplant recipients with preoperative pulmonary hypertension and right ventricular dysfunction (right ventricular ejection fraction, 0.21 +/- 0.09). The right and left ventricular mass, ejection fraction, and mass ratio (left ventricular mass/right ventricular mass) were calculated from the magnetic resonance images. The mean pulmonary artery pressure fell from 72 +/- 18 to 21 +/- 8 mm Hg after transplantation. At 3 months after transplantation both the left ventricular and right ventricular ejection fractions approached normal values, as shown by both radionuclide ventriculography and magnetic resonance imaging, but the right ventricular mass remained abnormally high with slightly low mass ratios. By 1 year both the left ventricular and right ventricular masses had regressed to normal with near-normal mass ratios. Right ventricular performance returns to nearly normal early after transplantation, but the right ventricular mass regresses over a more prolonged time. Cine magnetic resonance imaging provides a noninvasive means of assessing changes in right ventricular function and mass after lung transplantation.

  5. [The relativity of abnormity].

    PubMed

    Nilson, Annika

    2006-01-01

    In the late 19th century and in the beginning of the 20th century, mental diseases and abnormal behavior was considered to be a great danger to culture and society. "Degeneration" was the buzzword of the time, used and misused by artists and scientists alike. At the same time, some scientists saw abnormity as the key to unlock the mysteries of the ordinary mind. Naturalistic curiosity left Pandoras box open when religion declined in Darwins wake. Two swedish scientists, the physician Bror Gadelius (1862-1938) and his friend the philosopher Axel Herrlin (1870-1937), inspired by the French psychologist Theodule Ribots (1839-1916) "psychology without a soul", denied all fixed demarcation lines between abnormity and normality. All humans are natures creatures ruled by physiological laws, not ruled by God or convention. Even ordinary morality was considered to be an utterly backward explanation and guideline for complex human behavior. Different forms of therapy, not various kinds of penalties for wicked and disturbing behavior, are the now the solution for lots of people, "normal" as well as "abnormal". Psychiatry is expanding.

  6. Hierarchical representation and machine learning from faulty jet engine behavioral examples to detect real time abnormal conditions

    NASA Technical Reports Server (NTRS)

    Gupta, U. K.; Ali, M.

    1988-01-01

    The theoretical basis and operation of LEBEX, a machine-learning system for jet-engine performance monitoring, are described. The behavior of the engine is modeled in terms of four parameters (the rotational speeds of the high- and low-speed sections and the exhaust and combustion temperatures), and parameter variations indicating malfunction are transformed into structural representations involving instances and events. LEBEX extracts descriptors from a set of training data on normal and faulty engines, represents them hierarchically in a knowledge base, and uses them to diagnose and predict faults on a real-time basis. Diagrams of the system architecture and printouts of typical results are shown.

  7. Hierarchical representation and machine learning from faulty jet engine behavioral examples to detect real time abnormal conditions

    NASA Technical Reports Server (NTRS)

    Gupta, U. K.; Ali, M.

    1988-01-01

    The theoretical basis and operation of LEBEX, a machine-learning system for jet-engine performance monitoring, are described. The behavior of the engine is modeled in terms of four parameters (the rotational speeds of the high- and low-speed sections and the exhaust and combustion temperatures), and parameter variations indicating malfunction are transformed into structural representations involving instances and events. LEBEX extracts descriptors from a set of training data on normal and faulty engines, represents them hierarchically in a knowledge base, and uses them to diagnose and predict faults on a real-time basis. Diagrams of the system architecture and printouts of typical results are shown.

  8. Sleep and Sex: What Can Go Wrong? A Review of the Literature on Sleep Related Disorders and Abnormal Sexual Behaviors and Experiences

    PubMed Central

    Schenck, Carlos H.; Arnulf, Isabelle; Mahowald, Mark W.

    2007-01-01

    Study Objectives: To formulate the first classification of sleep related disorders and abnormal sexual behaviors and experiences. Design: A computerized literature search was conducted, and other sources, such as textbooks, were searched. Results: Many categories of sleep related disorders were represented in the classification: parasomnias (confusional arousals/sleepwalking, with or without obstructive sleep apnea; REM sleep behavior disorder); sleep related seizures; Kleine-Levin syndrome (KLS); severe chronic insomnia; restless legs syndrome; narcolepsy; sleep exacerbation of persistent sexual arousal syndrome; sleep related painful erections; sleep related dissociative disorders; nocturnal psychotic disorders; miscellaneous states. Kleine-Levin syndrome (78 cases) and parasomnias (31 cases) were most frequently reported. Parasomnias and sleep related seizures had overlapping and divergent clinical features. Thirty-one cases of parasomnias (25 males; mean age, 32 years) and 7 cases of sleep related seizures (4 males; mean age, 38 years) were identified. A full range of sleep related sexual behaviors with self and/or bed partners or others were reported, including masturbation, sexual vocalizations, fondling, sexual intercourse with climax, sexual assault/rape, ictal sexual hyperarousal, ictal orgasm, and ictal automatism. Adverse physical and/or psychosocial effects from the sleepsex were present in all parasomnia and sleep related seizure cases, but pleasurable effects were reported by 5 bed partners and by 3 patients with sleep related seizures. Forensic consequences were common, occurring in 35.5% (11/31) of parasomnia cases, with most (9/11) involving minors. All parasomnias cases reported amnesia for the sleepsex, in contrast to 28.6% (2/7) of sleep related seizure cases. Polysomnography (without penile tumescence monitoring), performed in 26 of 31 parasomnia cases, documented sexual moaning from slow wave sleep in 3 cases and sexual intercourse during

  9. Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

    PubMed

    Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

    2015-09-01

    In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.

  10. Abnormal Deformation Behavior of Oxygen-Modified β-Type Ti-29Nb-13Ta-4.6Zr Alloys for Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Liu, Huihong; Niinomi, Mitsuo; Nakai, Masaaki; Cong, Xin; Cho, Ken; Boehlert, Carl J.; Khademi, Vahid

    2017-01-01

    Oxygen was added to the biomedical β-type Ti-29Nb-13Ta-4.6Zr alloy (TNTZ, mass pct) in order to improve its strength, while keeping its Young's modulus low. Conventionally, with an increase in the oxygen content, an alloy's tensile strength increases, while its tensile elongation-to-failure decreases. However, an abnormal deformation behavior has been reported in the case of oxygen-modified TNTZ alloys in that their strength increases monotonically while their elongation-to-failure initially decreases and then increases with the increase in the oxygen content. In this study, this abnormal tensile deformation behavior of oxygen-modified TNTZ alloys was investigated systematically. A series of TNTZ-(0.1, 0.3, and 0.7 mass pct)O alloy samples was prepared, treated thermomechanically, and finally solution treated; these samples are denoted as 0.1ST, 0.3ST, and 0.7ST, respectively. The main tensile deformation mechanisms in 0.1ST are a deformation-induced α″-martensitic transformation and {332}<113> mechanical twinning. The large elongation-to-failure of 0.1ST is attributable to multiple deformation mechanisms, including the deformation-induced martensitic transformation and mechanical twinning as well as dislocation glide. In both 0.3ST and 0.7ST, dislocation glide is the predominant deformation mode. 0.7ST shows more homogeneous and extensive dislocation glide along with multiple slip systems and a higher frequency of cross slip. As a result, it exhibits a higher work-hardening rate and greater resistance to local stress concentration, both of which contribute to its elongation-to-failure being greater than that of 0.3ST.

  11. Prolonged Repetitive Head Trauma Induces a Singular Chronic Traumatic Encephalopathy-Like Pathology in White Matter Despite Transient Behavioral Abnormalities.

    PubMed

    Briggs, Denise I; Angoa-Pérez, Mariana; Kuhn, Donald M

    2016-11-01

    Repetitive mild traumatic brain injury (rmTBI), resulting from insults caused by an external mechanical force that disrupts normal brain function, has been linked to the development of neurodegenerative diseases, such as chronic traumatic encephalopathy and Alzheimer disease; however, neither the severity nor frequency of head injury required to trigger adverse behavioral outcomes is well understood. In this study, the administration of 30 head impacts using two different weights to lightly anesthetized, completely unrestrained mice established a paradigm that simulates the highly repetitive nature of sports- and military-related head injury. As the number of head impacts increases, the time to recover consciousness diminishes; however, both the sensorimotor function and behavioral outcomes of impacted mice evolve during the ensuing weeks. Postmortem analyses reveal robust Alzheimer disease and chronic traumatic encephalopathy-like conditions that manifest in a singular manner throughout the white matter concomitant with evidence of chronic oligodendrogenesis. Our data suggest that latency to recover the righting reflex may be an inadequate measure of injury severity and imply that exposure to repeated head impacts may mask the severity of an underlying and developing neuropathologic condition that does not manifest itself until long after head collisions cease. In addition, our data indicate that there is a cumulative and dose-dependent effect of repetitive head impacts that induces the neurobehavioral and neuropathologic outcomes seen in humans with a history of rmTBI. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Abnormal Osmotic Avoidance Behavior in C. elegans Is Associated with Increased Hypertonic Stress Resistance and Improved Proteostasis

    PubMed Central

    Lee, Elaine C.; Kim, Heejung; Ditano, Jennifer; Manion, Dacie; King, Benjamin L.; Strange, Kevin

    2016-01-01

    Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that mutations in osm-9 and osm-12 that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons are associated with enhanced survival during hypertonic stress. Improved survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, we find that osm-9(ok1677) mutant and osm-9(RNAi) worms exhibit reductions in hypertonicity induced protein damage in non-neuronal cells suggesting that enhanced proteostasis capacity may account for improved hypertonic stress resistance in worms with defects in osmotic avoidance behavior. RNA-seq analysis revealed that genes that play roles in managing protein damage are upregulated in osm-9(ok1677) worms. Our findings are consistent with a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs. PMID:27111894

  13. Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil.

    PubMed

    Inbar, Rotem; Weiss, Ronen; Tomljenovic, Lucija; Arango, Maria-Teresa; Deri, Yael; Shaw, Christopher A; Chapman, Joab; Blank, Miri; Shoenfeld, Yehuda

    2017-02-01

    Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil + pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5 months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, p = 0.009; Gardasil, p = 0.025; Gardasil + Pt, p = 0.005). The increase in floating time was already highly significant at 4.5 months of age for the Gardasil and Gardasil + Pt group (p ≤ 0.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil + Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes.

  14. Long-term running alleviates some behavioral and molecular abnormalities in Down syndrome mouse model Ts65Dn.

    PubMed

    Kida, Elizabeth; Rabe, Ausma; Walus, Marius; Albertini, Giorgio; Golabek, Adam A

    2013-02-01

    Running may affect the mood, behavior and neurochemistry of running animals. In the present study, we investigated whether voluntary daily running, sustained over several months, might improve cognition and motor function and modify the brain levels of selected proteins (SOD1, DYRK1A, MAP2, APP and synaptophysin) in Ts65Dn mice, a mouse model for Down syndrome (DS). Ts65Dn and age-matched wild-type mice, all females, had free access to a running wheel either from the time of weaning (post-weaning cohort) or from around 7 months of age (adult cohort). Sedentary female mice were housed in similar cages, without running wheels. Behavioral testing and evaluation of motor performance showed that running improved cognitive function and motor skills in Ts65Dn mice. However, while a dramatic improvement in the locomotor functions and learning of motor skills was observed in Ts65Dn mice from both post-weaning and adult cohorts, improved object memory was seen only in Ts65Dn mice that had free access to the wheel from weaning. The total levels of APP and MAP2ab were reduced and the levels of SOD1 were increased in the runners from the post-weaning cohort, while only the levels of MAP2ab and α-cleaved C-terminal fragments of APP were reduced in the adult group in comparison with sedentary trisomic mice. Hence, our study demonstrates that Ts65Dn females benefit from sustained voluntary physical exercise, more prominently if running starts early in life, providing further support to the idea that a properly designed physical exercise program could be a valuable adjuvant to future pharmacotherapy for DS.

  15. Diacylglycerol Kinase β Knockout Mice Exhibit Attention-Deficit Behavior and an Abnormal Response on Methylphenidate-Induced Hyperactivity

    PubMed Central

    Ishisaka, Mitsue; Kakefuda, Kenichi; Oyagi, Atsushi; Ono, Yoko; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kitaichi, Kiyoyuki; Hara, Hideaki

    2012-01-01

    Background Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO) mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density), hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Methodology/Principal Findings DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.). In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p.), but showed a similar response to an N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (0.3 mg/kg, i.p.), when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK), which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. Conclusions/Significance These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum. PMID:22590645

  16. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  17. Burden and Socio-Behavioral Correlates of Uncontrolled Abnormal Glucose Metabolism in an Urban Population of India

    PubMed Central

    Mahapatra, Tanmay; Chakraborty, Kaushik; Mahapatra, Sanchita; Mahapatra, Umakanta; Pandey, Naren; Thomson, Peter L.; Musk, Arthur W.; Mitra, Ramendra N.

    2016-01-01

    Background Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM) in a representative population. Methods From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24%) were interviewed, examined [blood pressure (BP), anthropometry], tested for fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C). Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl) = 100–125 or HbA1C(%) = 5.7–6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2. Results Among participants, 28.62% [95% Confidence Interval (95%CI) = 23.19–34.06)] were overweight [body mass index(BMI) = (25–29.99)kg/meter2], 7.81% (4.58–11.03) were obese(BMI≥30kg/meter2), 20.82% (15.93–25.70) were current smokers, 12.64% (8.64–16.64) were current alcohol-drinkers and 46.32% of responders (39.16–53.47) had family history of diabetes. 17.84% (13.24–22.45) had stage-I [140≤average systolic BP (AvSBP in mm of mercury)<160 or 90≤average diastolic BP (AvDBP)<100] and 12.64% (8.64–16.64) had stage-II (AvSBP≥160 or AvDBP≥160) hypertension. Based on FPG and HbA1c, 10.41% (6.74–14.08) were diabetic and 27.88% (22.49–33.27) were pre-diabetic. Overall prevalence of diabetes was 15.61% (11.25–19.98). Among pre-diagnosed cases, 46.43% (26.74–66.12) had uncontrolled AGM. With one year increase in age [Odds Ratio(OR) = 1.05(1.03–1.07)], retired subjects [OR = 9.14(1.72–48.66)], overweight[OR = 2.78(1.37–5.64)], ex-drinkers [OR = 4

  18. Long-term recovery from hippocampal-related behavioral and biochemical abnormalities induced by noise exposure during brain development. Evaluation of auditory pathway integrity.

    PubMed

    Uran, S L; Gómez-Casati, M E; Guelman, L R

    2014-10-01

    Sound is an important part of man's contact with the environment and has served as critical means for survival throughout his evolution. As a result of exposure to noise, physiological functions such as those involving structures of the auditory and non-auditory systems might be damaged. We have previously reported that noise-exposed developing rats elicited hippocampal-related histological, biochemical and behavioral changes. However, no data about the time lapse of these changes were reported. Moreover, measurements of auditory pathway function were not performed in exposed animals. Therefore, with the present work, we aim to test the onset and the persistence of the different extra-auditory abnormalities observed in noise-exposed rats and to evaluate auditory pathway integrity. Male Wistar rats of 15 days were exposed to moderate noise levels (95-97 dB SPL, 2 h a day) during one day (acute noise exposure, ANE) or during 15 days (sub-acute noise exposure, SANE). Hippocampal biochemical determinations as well as short (ST) and long term (LT) behavioral assessments were performed. In addition, histological and functional evaluations of the auditory pathway were carried out in exposed animals. Our results show that hippocampal-related behavioral and biochemical changes (impairments in habituation, recognition and associative memories as well as distortion of anxiety-related behavior, decreases in reactive oxygen species (ROS) levels and increases in antioxidant enzymes activities) induced by noise exposure were almost completely restored by PND 90. In addition, auditory evaluation shows that increased cochlear thresholds observed in exposed rats were re-established at PND 90, although with a remarkable supra-threshold amplitude reduction. These data suggest that noise-induced hippocampal and auditory-related alterations are mostly transient and that the effects of noise on the hippocampus might be, at least in part, mediated by the damage on the auditory pathway

  19. Isolated ventricular noncompaction.

    PubMed

    Okçün Baniş; Tekin, Abdullah; Oz, Büge; Küçükoğlu, M Serdar

    2004-04-01

    Isolated ventricular noncompaction of myocardium is a rare congenital disease due to an arrest of myocardial morphogenesis during foetal development. It is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. The persistence of myocardial noncompaction is usually an associated anomaly in patients with congenital left or right ventricular outflow tract obstruction. However, isolated noncompaction of myocardium is not associated with any factors that would explain it apart from the foetal arrest of compaction of the ventricular myocardium. The disease results in systolic and diastolic ventricular dysfunction, systemic embolism and ventricular arrhythmias. We describe a case of isolated noncompaction of the ventricular myocardium in a 20-year-old man who presented initially with ventricular tachycardia.

  20. Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia

    PubMed Central

    Rahman, Shibley; Robbins, Trevor W; Hodges, John R; Mehta, Mitul A; Nestor, Peter J; Clark, Luke; Sahakian, Barbara J

    2007-01-01

    The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in ‘normalizing’ the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the ‘somatic marker’ hypothesis of impaired decision-making following orbitofrontal dysfunction. PMID:16160709

  1. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice

    PubMed Central

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life. PMID:27071011

  2. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice.

    PubMed

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life.

  3. Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction

    PubMed Central

    Carlisle, Holly J.; Luong, Tinh N.; Medina-Marino, Andrew; Schenker, Leslie; Khorosheva, Eugenia; Indersmitten, Tim; Gunapala, Keith M.; Steele, Andrew D.; O'Dell, Thomas J.; Patterson, Paul H.; Kennedy, Mary B.

    2011-01-01

    Densin is an abundant scaffold protein in the postsynaptic density (PSD) that forms a high affinity complex with αCaMKII and α-actinin. To assess the function of densin, we created a mouse line with a null mutation in the gene encoding it (LRRC7). Homozygous knockout mice display a wide variety of abnormal behaviors that are often considered endophenotypes of schizophrenia and autism spectrum disorders. At the cellular level, loss of densin results in reduced levels of α-actinin in the brain and selective reduction in the localization of mGluR5 and DISC1 in the PSD fraction; whereas, the amounts of ionotropic glutamate receptors and other prominent PSD proteins are unchanged. In addition, deletion of densin results in impairment of mGluR- and NMDA receptor-dependent forms of long-term depression (LTD), alters the early dynamics of regulation of CaMKII by NMDA-type glutamate receptors (NMDARs), and produces a change in spine morphology. These results indicate that densin influences the function of mGluRs and CaMKII at synapses, and contributes to localization of mGluR5 and DISC1 in the PSD fraction. They are consistent with the hypothesis that mutations that disrupt the organization and/or dynamics of postsynaptic signaling complexes in excitatory synapses can cause behavioral endophenotypes of mental illness. PMID:22072671

  4. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities

    PubMed Central

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-01-01

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV−/−) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV+/−) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV−/− and PV+/− mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus

  5. Vagal enhancement linking abnormal blood pressure response and subendocardial ischemia in hypertrophic cardiomyopathy.

    PubMed

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-01-01

    An abnormal blood pressure response to exercise has been reported to be associated with left ventricular subendocardial ischemia in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear. We report a case of HCM with an abnormal blood pressure response and subendocardial ischemia, in which the analysis of heart rate variability revealed exercise-induced vagal enhancement. The present case highlights the possible mechanism linking abnormal blood pressure response and left ventricular subendocardial ischemia in patients with HCM.

  6. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia.

    PubMed Central

    Blomström-Lundqvist, C; Sabel, K G; Olsson, S B

    1987-01-01

    The clinical course in 15 patients with features consistent with arrhythmogenic right ventricular dysplasia is described. At referral seven patients had abnormal physical findings, nine had abnormal electrocardiograms with non-specific right-sided abnormalities, and seven patients had increased heart size or prominent right ventricles on chest x ray. During long term follow up (mean 8.8 years, range 1.5 to 28 years) 11 patients had abnormal physical findings, 11 had electrocardiographic changes, and nine had increased heart size. Recurrent sustained right ventricular tachycardia was the most common arrhythmia (10 patients). Two patients experienced ventricular fibrillation. Seven patients suffered from over 10 episodes of ventricular tachycardia, nine required cardioversions, and 10 patients had associated serious symptoms such as syncope, severe hypotension, or cardiac arrest. Four patients required operation to correct the arrhythmia and three patients developed right heart failure. Two out of three deaths were sudden. These data suggest that in arrhythmogenic right ventricular dysplasia right ventricular abnormalities may be progressive and that the condition may affect the left ventricle. The course of the ventricular arrhythmias was highly variable and could not be predicted in individual patients. The potential for lethal ventricular arrhythmias is evident and warrants intensive diagnostic efforts to identify patients with adverse prognostic features. PMID:3676037

  7. Left ventricular noncompaction diagnosed following Graves' disease

    PubMed Central

    Habib, Habib; Hawatmeh, Amer; Rampal, Upamanyu; Shamoon, Fayez

    2016-01-01

    Isolated left ventricular noncompaction (LVNC) is a rare genetic cardiomyopathy. Clinical manifestations are variable; patients may present with heart failure symptoms, arrhythmias, and systemic thromboembolism. However, it can also be asymptomatic. When asymptomatic, LVNC can manifest later in life after the onset of another unrelated condition. We report a case of LVNC which was diagnosed following a hyperthyroid state secondary to Graves' disease. The association of LVNC with other noncardiac abnormalities including neurological, hematological, and endocrine abnormalities including hypothyroidism has been described in isolated case reports before. To the best of our knowledge, this is the first reported case of LVNC diagnosed following exacerbation in contractile dysfunction triggered by Graves' disease. PMID:27843800

  8. Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients.

    PubMed

    Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace

    2013-01-01

    Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients.

  9. Risk Factors for Asymptomatic Ventricular Dysfunction in Rheumatoid Arthritis Patients

    PubMed Central

    Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace

    2013-01-01

    Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients. PMID:24368945

  10. Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.

    PubMed

    Neutel, Dulce; Tchikviladzé, Maya; Charles, Perrine; Leu-Semenescu, Smaranda; Roze, Emmanuel; Durr, Alexandra; Arnulf, Isabelle

    2015-06-01

    Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown. To evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length. The clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype-phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video. The patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control. The nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Repetitive Model of Mild Traumatic Brain Injury Produces Cortical Abnormalities Detectable by Magnetic Resonance Diffusion Imaging (DTI/DKI), Histopathology, and Behavior.

    PubMed

    Yu, Fengshan; Shukla, Dinesh K; Armstrong, Regina C; Marion, Christina M; Radomski, Kryslaine L; Selwyn, Reed G; Dardzinski, Bernard J

    2016-12-20

    Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects of head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) in adult mice after repetitive mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay and was first characterized in the corpus callosum to demonstrate low levels of axon damage, astrogliosis, and microglial activation, without microhemorrhages. High-resolution DTI-DKI was then combined with post-imaging pathological validation along with behavioral assessments targeted for the impact regions. In the corpus callosum, only DTI fractional anisotropy at 42 days showed significant change post-injury. Conversely, cortical regions under the impact site (M1-M2, anterior cingulate) had reduced axial diffusivity (AD) at all time points with a corresponding increase in axial kurtosis (Ka) at 6 days. Post-imaging neuropathology showed microglial activation in both the corpus callosum and cortex at 42 days after r-mTBI. Increased cortical microglial activation correlated with decreased cortical AD after r-mTBI (r = -0.853; n = 5). Using Thy1-YFP-16 mice to fluorescently label neuronal cell bodies and processes revealed low levels of axon damage in the cortex after r-mTBI. Finally, r-mTBI produced social deficits consistent with the function of this anterior cingulate region of cortex. Overall, vulnerability of cortical regions is demonstrated after mild repetitive injury, with underlying differences of DTI and DKI, microglial activation, and behavioral deficits.

  12. Vagal modulation of cardiac ventricular arrhythmia.

    PubMed

    Ng, G André

    2014-02-01

    What is the topic of this review? This article addresses the relationship between vagus nerve activity and malignant ventricular arrhythmias. It focuses on the clinical association of an impaired vagal tone in cardiac disease states with high mortality from sudden cardiac death and the potential underlying mechanisms. What advances does it highlight? The article summarizes the mounting evidence that vagal innervation in the cardiac ventricle plays a key direct role in the prevention of the initiation of ventricular fibrillation. Data are presented on the role that nitric oxide plays in mediating the effects of vagal protection against ventricular fibrillation, supporting the notion that a separate non-muscarinic, nitrergic population of vagal neurons is responsible for this protection. Sudden cardiac death remains a significant unresolved clinical problem, with many of the deaths being due to malignant ventricular arrhythmias. Markers of abnormal autonomic function have been shown to be strong prognostic predictors, highlighting the important relationship between reduced vagal tone and malignant ventricular arrhythmias, such as ventricular fibrillation, in cardiac patients. Exploring the mechanisms underlying the autonomic modulation of ventricular fibrillation, my group has shown that vagus nerve stimulation protects against ventricular fibrillation in the innervated isolated heart preparation. We have provided direct evidence that nitric oxide is released in the ventricle with cervical vagus nerve stimulation and NO mediates the antifibrillatory actions of vagus nerve stimulation in the ventricle. Classical physiology teaches that vagal postganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors and, dogmatically, that there is little vagal effect in the ventricle, as innervation was believed to be sparse. Mounting evidence from many species now supports the presence of a rich vagal innervation in the ventricle. Data from my group

  13. Arrhythmogenic right ventricular disease: MR imaging vs angiography.

    PubMed

    Auffermann, W; Wichter, T; Breithardt, G; Joachimsen, K; Peters, P E

    1993-09-01

    Arrhythmogenic right ventricular disease (ARVD) is increasingly found in young adults with ventricular arrhythmias and is characterized by ventricular tachycardia originating within the right ventricle and regional or diffuse abnormalities in the contraction of the right ventricle. Until now, the gold standard for the detection of global and regional abnormalities of the right ventricular wall has been angiography combined with biopsy. The purpose of the current study was to compare MR imaging with angiography for assessing the location and extent of morphologic and functional abnormalities in patients with ARVD. Electrocardiographically gated spin-echo and cine gradient-echo MR imaging of the heart was performed in 36 consecutive patients with biopsy-proved ARVD. Patients were prospectively separated into two groups according to the results of invasive electrophysiologic tests (18 with inducible ventricular tachycardia during invasive electrophysiologic studies [ARVD 1] and 18 without inducible ventricular tachycardia [ARVD 2]) and compared with 11 control subjects. Global and regional morphology and function of the right ventricle were assessed with MR imaging, and those findings were compared with angiographic findings. Right ventricular ejection fraction was significantly lower in patients with ARVD 1 than in patients with ARVD 2 or in control subjects. Regional abnormalities of the right ventricular wall also were more pronounced in patients with ARVD 1 than in patients with ARVD 2. Signal-intensity increases corresponding to fatty replacement shown by biopsy were seen in 33% of patients with ARVD 1 and in 11% of patients with ARVD 2. Abnormal regions of the right ventricular wall seen on MR images corresponded to angiographic findings in 86% of patients. Comparison with control subjects showed that patients with ARVD 1 had a significant delay in diastolic relaxation of the right ventricle. Our results show that MR imaging can be used to assess morphologic

  14. Nuclear medical determination of left ventricular diastolic function in coronary heart disease

    SciTech Connect

    Brugger, P.; Laesser, W.K.; Kullich, W.; Stoiberer, I.; Klein, G.

    1985-06-01

    In 64 patients with coronary heart disease, the left ventricular diastolic function was determined by means of a new nuclear medical method (nuclear stethoscope). The investigations revealed an abnormal diastolic filling in 85.9% of the cases on the basis of the parameters peak filling rate and time to peak filling rate as manifestation of a disturbed ventricular function.

  15. Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid precursor protein processing and alleviate behavioral abnormalities in the APP/PS1 mouse model of Alzheimer's disease.

    PubMed

    Vepsäläinen, Saila; Koivisto, Henna; Pekkarinen, Elina; Mäkinen, Petra; Dobson, Gary; McDougall, Gordon J; Stewart, Derek; Haapasalo, Annakaisa; Karjalainen, Reijo O; Tanila, Heikki; Hiltunen, Mikko

    2013-01-01

    A growing body of epidemiological evidence suggests that fruit and vegetable juices containing various phenolic compounds can reduce the risk of Alzheimer's disease (AD). As the altered amyloid precursor protein (APP) processing leading to increased β-amyloid (Aβ) production is a key pathogenic feature of AD, we elucidated the effects of different polyphenols on neuroprotection and APP processing under different in vitro stress conditions. The effects of these compounds were also investigated in transgenic AD mice (APdE9). Free radical toxicity and apoptosis were induced in human SH-SY5Y neuroblastoma cells overexpressing APP751. Menadione-induced production of reactive oxygen species was significantly decreased upon treatment with myricetin, quercetin or anthocyanin-rich extracts in a dose-dependent manner. However, these extracts did not affect caspase-3 activation, APP processing or Aβ levels upon staurosporine-induced apoptosis. APdE9 mice fed with anthocyanin-rich bilberry or blackcurrant extracts showed decreased APP C-terminal fragment levels in the cerebral cortex as compared to APdE9 mice on the control diet. Soluble Aβ40 and Aβ42 levels were significantly decreased in bilberry-fed mice as compared to blackcurrant-fed mice. Conversely, the ratio of insoluble Aβ42/40 was significantly decreased in blackcurrant-fed mice relative to bilberry-fed mice. Both berry diets alleviated the spatial working memory deficit of aged APdE9 mice as compared to mice on the control diet. There were no changes in the expression or phosphorylation status of tau in APdE9 mice with respect to diet. These data suggest that anthocyanin-rich bilberry and blackcurrant diets favorably modulate APP processing and alleviate behavioral abnormalities in a mouse model of AD. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Computed tomography of the abnormal pericardium

    SciTech Connect

    Silverman, P.M.; Harell, G.S.; Korobkin, M.

    1983-06-01

    Computed tomographic (CT) findings in 18 patients with documented pericardial disease are reported. The pericardium appears as a thin, curvilinear, 1- to 2-mm-thick density best seen anterior to the right ventricular part of the heart. Pericardial abnormalities detected by CT include effusions, thickening, calcification, and cystic and solid masses. Computed tomography is complimentary to echocardiography in its ability to more accurately characterize pericardial effusions, masses, and pericardial thickening.

  17. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  18. Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

    PubMed

    Huang, Bao-Tao; Peng, Yong; Liu, Wei; Zhang, Chen; Huang, Fang-Yang; Wang, Peng-Ju; Zuo, Zhi-Liang; Liao, Yan-Biao; Chai, Hua; Li, Qiao; Zhao, Zhen-Gang; Luo, Xiao-Lin; Ren, Xin; Huang, Kai-Sen; Meng, Qing-Tao; Chen, Chi; Huang, De-Jia; Chen, Mao

    2015-03-01

    Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

  19. Developmental changes in ventricular diastolic function correlate with changes in ventricular myoarchitecture in normal mouse embryos.

    PubMed

    Ishiwata, Takahiro; Nakazawa, Makoto; Pu, William T; Tevosian, Sergei G; Izumo, Seigo

    2003-10-31

    Both genetic and epigenetic factors, such as abnormal hemodynamics, affect cardiac morphogenesis and the pathogenesis of congenital heart disease. Diastolic function is an important determinant of cardiac function, and tools for evaluating diastolic function in the embryo would be very valuable for assessment of cardiac performance. Using histological measurements of ventricular myoarchitecture, Doppler assessment of ventricular inflow velocities, and direct measurement of ventricular pressure, we investigated developmental changes of ventricular diastolic function in the mouse embryos from embryonic days 9.5 to 19.5. Regression analysis showed that peak velocity of A wave (an index of passive compliance) correlated with the area of trabecular myocardium in right ventricle (RV) (r2=0.92, P<0.0001) and left ventricle (LV) (r2=0.93, P<0.0001). Peak velocity of E wave (an index of active relaxation) exponentially correlated with the area of compact myocardium in RV (r2=0.98, P<0.0001) and LV (r2=0.97, P<0.0001). We used these techniques to analyze FOG-2 null embryos. FOG-2 null embryos had thin compact myocardium, higher EDP and E/A ratio, smaller -dP/dt, and diminished sucking pressure than wild-type littermates, indicating that decreased ventricular diastolic function might be the primary cause of embryonic lethality. In conclusion, during embryogenesis the development of compact myocardium tightly regulates the development of ventricular distensibility. Our study in normal mice forms the basis for future studies of embryonic cardiac function in genetically manipulated mice with abnormalities of the cardiovascular system.

  20. [Treatment of ventricular tachycardia].

    PubMed

    Iturralde Torres, P

    2001-01-01

    Evaluation and management of postinfarct ventricular tachycardia has changed dramatically in the past two decades. The introduction of the implantable cardioverter defibrillator has played a major role in this change, alternating both, the purpose of the patients evaluation and treatment options. Episodes of sustained ventricular tachycardia can occur in a variety of clinical settings; the most common of which is the patient who has suffered a myocardial infarction. In this paper, I explore the causes and effects of some of these changes and review current strategies, specially the radiofrequency catheter ablation, for the management of the patient with postinfarct ventricular tachycardia.

  1. Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

    PubMed

    Haugaa, Kristina H; Haland, Trine F; Leren, Ida S; Saberniak, Jørg; Edvardsen, Thor

    2016-07-01

    This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC.

  2. MR imaging appearance of fetal cerebral ventricular morphology.

    PubMed

    Levine, Deborah; Trop, Isabelle; Mehta, Tejas S; Barnes, Patrick D

    2002-06-01

    To elucidate further the magnetic resonance (MR) imaging appearance of fetal cerebral ventricles by comparing ultrasonographic (US) and MR images. A retrospective review of MR and US images was performed for 110 normal fetuses and 94 fetuses with central nervous system abnormalities to assess lateral ventricular morphology as having (a) a normal appearance, (b) mild, disproportionate dilatation of the occipital horns with overall preservation of ventricular morphology, (c) colpocephaly with or without normal orientation of the frontal horns, (d) abnormal orientation of the frontal horns without colpocephaly, (e) an angular appearance, (f) fused frontal horns, (g) global dilation, or (h) a distorted appearance. Ventricular morphology on US and MR images was compared and correlated with reference standard diagnoses. US and MR imaging classifications were concordant in 145 of 188 (77%) examinations. Mild disproportion of occipital horns with respect to frontal horns was seen only on MR images. This ventricular configuration was present in eight of 110 normal fetuses and in 10 of 16 fetuses with isolated mild ventriculomegaly (P <.001). An angular configuration of the lateral ventricles, which is seen in fetuses with neural tube defects (NTDs), was present on review of MR images in 11 fetuses and on US images in one fetus. The ventricles of fetuses with NTDs and angular ventricles (3-12 mm) were significantly smaller than those of fetuses with NTDs and global dilatation of the ventricles (13-25 mm; P <.05). Ventricular contours differ with differing diagnoses of central nervous system abnormalities.

  3. Ventricular Septal Defect (VSD)

    MedlinePlus

    ... specially sized mesh device to close the hole. Hybrid procedure. A hybrid procedure uses surgical and catheter-based techniques. Access ... clinicalkey.com. Accessed Sept. 15, 2014. Konetti NR. Hybrid muscular ventricular defect closure: Surgeon or physician. Indian ...

  4. Left Ventricular Hypertrophy

    MedlinePlus

    ... than are white people with similar blood pressure measurements. Sex. Women with hypertension are at higher risk ... hypertrophy than are men with similar blood pressure measurements. Left ventricular hypertrophy changes the structure and working ...

  5. [Bradykinin and ventricular function].

    PubMed

    Trochu, J N

    2002-03-01

    Kinins are vasodilator peptides implicated in many physiological and physiopathological processes such as blood pressure regulation and that of the coronary circulation and inflammatory reactions. Kinins play an essential role in ventricular function as they counteract the effects of angiotensin II during myocardial ischaemia, ventricular remodelling and severe cardiac failure, emphasising the value of treatment favouring local endogenic production of bradykinin such as ACE inhibitors, neutral endopeptidase inhibitors and antagonists of AT1 receptors of angiotensin II.

  6. Daily oral intake of theanine prevents the decline of 5-bromo-2'-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress.

    PubMed

    Takarada, Takeshi; Nakamichi, Noritaka; Kakuda, Takami; Nakazato, Ryota; Kokubo, Hiroshi; Ikeno, Shinsuke; Nakamura, Saki; Hinoi, Eiichi; Yoneda, Yukio

    2015-03-01

    Posttraumatic stress disorder is a long-lasting psychiatric disease with the consequence of hippocampal atrophy in humans exposed to severe fatal stress. We demonstrated a positive correlation between the transient decline of 5-bromo-2'-deoxyuridine (BrdU) incorporation in the hippocampal dentate gyrus (DG) and long-lasting behavioral abnormalities in mice with traumatic stress. Here, we investigated pharmacological properties of theanine on the declined BrdU incorporation and abnormal behaviors in mice with traumatic stress. Prior daily oral administration of theanine at 50-500 mg/kg for 5 days significantly prevented the decline of BrdU incorporation, while theanine significantly prevented the decline in the DG even when administered for 5 days after stress. Consecutive daily administration of theanine significantly inhibited the prolonged immobility in mice with stress in forced swimming test seen 14 days later. Although traumatic stress significantly increased spontaneous locomotor activity over 30 min even when determined 14 days later, the increased total locomotion was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress. These results suggest that theanine alleviates behavioral abnormalities together with prevention of the transient decline of BrdU incorporation in the hippocampal DG in adult mice with severe traumatic stress.

  7. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities

    PubMed Central

    Sikora, Jakub; Leddy, Jennifer; Gulinello, Maria; Walkley, Steven U.

    2016-01-01

    ABSTRACT Christianson syndrome (CS) is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI), have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO) were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal) reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs). In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably

  8. Electrophysiologic features of fetal ventricular aneurysms and diverticula

    PubMed Central

    PETERS, CARLI; WACKER-GUSSMANN, ANNETTE; STRASBURGER, JANETTE F; CUNEO, BETTINA F; GOTTEINER, NINA; GULECYUZ, MEHEMET; WAKAI, RONALD T

    2014-01-01

    Objective Congenital ventricular wall defects are very rare and include congenital ventricular aneurysms (CVAs) and diverticula (CVDs). Method We report a series of five fetuses: three with CVAs and two with CVDs referred due to fetal arrhythmia. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used. The literature in CVA and CVD is reviewed. Results Incessant premature ventricular contractions (PVC), mainly bigeminy and trigeminy were found in three fetuses with CVAs and in one with CVD, who also had ventricular couplets. The other fetus with CVD, referred because of PVCs, had only sinus tachycardia. ST elevation was noted in two. Fetal movement had a variable impact on PVC’s. Postnatal evaluation demonstrated two persistent left ventricular aneurysms and one persistent right CVD; one CVD resolved at 35 weeks gestation. Two neonates had incessant PVCs. Both arrhythmias resolved spontaneously while being treated with propranolol. Conclusion FMCG is complementary to echocardiographic imaging. In fetuses with left ventricular wall defects, additional electrophysiological diagnosis can be made by fMCG, including the complexity of ventricular ectopy, arrhythmic response to fetal movement, presence of ST-T wave abnormalities, and atrial amplitude increases. Prenatal risk factor assessment using fMCG can additionally support post-natal treatment and follow-up. PMID:25284224

  9. Arrhythmogenic right ventricular cardiomyopathy: contribution of different electrocardiographic techniques.

    PubMed

    Moreira, Davide; Delgado, Anne; Marmelo, Bruno; Correia, Emanuel; Gama, Pedro; Pipa, João; Nunes, Luís; Santos, Oliveira

    2014-04-01

    Arrhythmogenic right ventricular cardiomyopathy, also known as arrhythmogenic right ventricular dysplasia, is a condition in which myocardium is replaced by fibrous or fibrofatty tissue, predominantly in the right ventricle. It is clinically characterized by potentially lethal ventricular arrhythmias, and is a leading cause of sudden cardiac death. Its prevalence is not known exactly but is estimated at approximately 1:5000 in the adult population. Diagnosis can be on the basis of structural and functional alterations of the right ventricle, electrocardiographic abnormalities (including depolarization and repolarization alterations and ventricular arrhythmias) and family history. Diagnostic criteria facilitate the recognition and interpretation of non-specific clinical features of this disease. The authors present a case in which the diagnosis of arrhythmogenic right ventricular cardiomyopathy was prompted by the suspicion of right ventricular disease on transthoracic echocardiography. This was confirmed by detection of epsilon waves on analysis of the ECG, which generally go unnoticed but in this case were the key to the diagnosis. Their presence was also shown by non-conventional ECG techniques such as modified Fontaine ECG. The course of the disease culminated in the occurrence of ventricular tachycardia, which prompted placement of an implantable cardioverter-defibrillator.

  10. Ventricular remodeling: from bedside to molecule.

    PubMed

    Jaffe, R; Flugelman, M Y; Halon, D A; Lewis, B S

    1997-01-01

    The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.

  11. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.

    PubMed

    Goudis, Christos A; Konstantinidis, Athanasios K; Ntalas, Ioannis V; Korantzopoulos, Panagiotis

    2015-11-15

    Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed.

  12. Comparison of Left Ventricular Electromechanical Mapping and Left Ventricular Angiography

    PubMed Central

    Sarmento-Leite, Rogerio; Silva, Guilherme V.; Dohman, Hans F.R.; Rocha, Ricardo Mourilhe; Dohman, Hans J.F.; de Mattos, Nelson Durval S.G.; Carvalho, Luis Antonio; Gottschall, Carlos A.M.; Perin, Emerson C.

    2003-01-01

    We performed this prospective cohort study to correlate the findings of left ventricular angiography (LVA) and NOGA™ left ventricular electromechanical mapping (LVEM) in the evaluation of cardiac wall motion and also to establish standards for wall motion assessment by LVEM. Fifty-five patients (35 men; mean age, 60.4 ± 11.8 years) eligible for elective left cardiac catheterization underwent LVA and LVEM. Wall motion scores, LV ejection fractions (LVEF), and LV volumes derived from LVA versus LVEM data were compared and analyzed statistically. Receiver operating characteristic (ROC) curves were used to assess the accuracy of LVEM in distinguishing between normal, hypokinetic, and akinetic/dyskinetic wall motion. Mean LVEM procedure time was 37 ± 11 minutes. The LVEM and LVA findings differed for mean LVEF (55% ± 13% vs 36% ± 9%), mean end-systolic volume (56 ± 13 mL vs 36 ± 10 mL), and mean end-diastolic volume (174 ± 104 mL vs 123 ± 65 mL). Mean wall motion scores (± SD) for normokinetic, hypokinetic, and akinetic/dyskinetic segments were 13.9% ± 5.6%, 8.3% ± 5.2%, and 3.2% ± 3.1%, respectively. Cutpoints for differentiating between wall motion types were 12% and 6%. The ROC curves showed LVEM to have a 93% accuracy in differentiating between normokinetic and akinetic/dyskinetic segments and a 73% accuracy between normokinetic and hypokinetic segments. These data suggest that LVEM can differentiate between normal and abnormal cardiac wall motion, although it is more accurate at differentiating between normokinetic and akinetic/dyskinetic motion than between normokinetic and hypokinetic motion. (Tex Heart Inst J 2003;30:19–26) PMID:12638666

  13. Vulnerability to ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Janse, Michiel J.

    1998-03-01

    One of the factors that favors the development of ventricular fibrillation is an increase in the dispersion of refractoriness. Experiments will be described in which an increase in dispersion in the recovery of excitability was determined during brief episodes of enhanced sympathetic nerve activity, known to increase the risk of fibrillation. Whereas in the normal heart ventricular fibrillation can be induced by a strong electrical shock, a premature stimulus of moderate intensity only induces fibrillation in the presence of regional ischemia, which greatly increases the dispersion of refractoriness. One factor that is of importance for the transition of reentrant ventricular tachycardia to ventricular fibrillation during acute regional ischemia is the subendocardial Purkinje system. After selective destruction of the Purkinje network by lugol, reentrant tachycardias still develop in the ischemic region, but they do not degenerate into fibrillation. Finally, attempts were made to determine the minimal mass of thin ventricular myocardium required to sustain fibrillation induced by burst pacing. This was done by freezing of subendocardial and midmural layers. The rim of surviving epicardial muscle had to be larger than 20 g. Extracellular electrograms during fibrillation in both the intact and the "frozen" left ventricle were indistinguishable, but activation patterns were markedly different. In the intact ventricle epicardial activation was compatible with multiple wavelet reentry, in the "frozen" heart a single, or at most two wandering reentrant waves were seen.

  14. Left ventricular apical diseases.

    PubMed

    Cisneros, Silvia; Duarte, Ricardo; Fernandez-Perez, Gabriel C; Castellon, Daniel; Calatayud, Julia; Lecumberri, Iñigo; Larrazabal, Eneritz; Ruiz, Berta Irene

    2011-08-01

    There are many disorders that may involve the left ventricular (LV) apex; however, they are sometimes difficult to differentiate. In this setting cardiac imaging methods can provide the clue to obtaining the diagnosis. The purpose of this review is to illustrate the spectrum of diseases that most frequently affect the apex of the LV including Tako-Tsubo cardiomyopathy, LV aneurysms and pseudoaneurysms, apical diverticula, apical ventricular remodelling, apical hypertrophic cardiomyopathy, LV non-compaction, arrhythmogenic right ventricular dysplasia with LV involvement and LV false tendons, with an emphasis on the diagnostic criteria and imaging features. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13244-011-0091-6) contains supplementary material, which is available to authorized users.

  15. Ventricular Septal Defect (For Parents)

    MedlinePlus

    ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System ECG (Electrocardiogram) Anesthesia - What to Expect Tetralogy of ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Contact Us Print Resources Send to a friend ...

  16. Ventricular Septal Defect (For Parents)

    MedlinePlus

    ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System ECG (Electrocardiogram) Anesthesia - What to Expect Tetralogy of ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Contact Us Print Resources Send to a Friend ...

  17. Large right ventricular thrombus.

    PubMed

    Sousa, Carla; Almeida, Pedro; Gonçalves, Alexandra; Rodrigues, João; Rangel, Inês; Macedo, Filipe; Maciel, M Júlia

    2014-01-01

    Right ventricular thrombosis is a rare yet potentially fatal condition. It has been described in association with hypercoagulability states, autoimmune diseases and dilated cardiomyopathy. Echocardiography constitutes the election tool for diagnosis and characterization of these entities, allowing for the differentiation between the various types of thrombi. We present a case of a patient with alcoholic dilated cardiomyopathy admitted for congestive heart failure and lower respiratory infection. In the diagnostic approach, a routine echocardiography revealed a large mural right ventricular thrombus in association with severe biventricular dysfunction. The patient was proposed for anticoagulation strategy, which he refused.

  18. Parenting behaviors of African American and Caucasian families: parent and child perceptions, associations with child weight, and ability to identify abnormal weight status.

    PubMed

    Polfuss, Michele; Frenn, Marilyn

    2012-06-01

    This study examined the agreement between parent and child perceptions of parenting behaviors, the relationship of the behaviors with the child's weight status, and the ability of the parent to correctly identify weight status in 176 parent-child dyads (89 Caucasian and 87 African American). Correlational and regression analyses were used. Findings included moderate to weak correlations in child and parent assessments of parenting behaviors. Caucasian dyads had higher correlations than African American dyads. Most parents correctly identified their own and their child's weight status. Parents of overweight children used increased controlling behaviors, but the number of controlling behaviors decreased when the parent expressed concern with their child's weight.

  19. Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases.

    PubMed

    Gibson, Gary E; Starkov, Anatoly; Blass, John P; Ratan, Rajiv R; Beal, M Flint

    2010-01-01

    Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sublethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post-transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the alpha-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhances ROS production in Alzheimer's Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington's Disease (HD), a movement disorder with cognitive features distinct form AD, complex II+III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium-activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a crosslinking enzymes that can modulate transcription, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches

  20. Right ventricular dysfunction affects survival after surgical left ventricular restoration.

    PubMed

    Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

    2017-04-01

    Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was

  1. [Idiopathic ventricular tachycardia, an arrhythmia with good prognosis].

    PubMed

    Camaro, Cyril; Bos, Hans S; Smeets, Joep L R M

    2010-01-01

    Three patients, one experiencing palpitations and two complaining of chest pain in stressful situations, appeared to have monomorphic wide complex tachycardia. After excluding channelopathy, structural abnormalities and ischaemia of the heart, this arrhythmia was classified as idiopathic. Symptoms disappeared in one patient after using metoprolol, a β-adrenoceptor blocker. The other two patients were treated with radiofrequency ablation of the focus from which the tachycardias arose. Idiopathic ventricular tachycardia mostly arises from the right ventricular outflow tract. The diagnosis is made upon history taking, including family history, echocardiography, 12-lead ECG, exercise testing and 24-hour Holter monitoring. The prognosis is excellent and sudden cardiac death is rarely seen.

  2. Bidirectional ventricular tachycardia?

    PubMed

    Serra, José L; Caresani, Julian A; Bono, Julio O

    2014-01-01

    A 65-year-old woman was admitted to the hospital because of a syncopal episode with documented transient complete atrioventricular block. A DDD pacemaker was implanted. Post implantation, the patient was diagnosed with bidirectional ventricular tachycardia. Analysis of the arrhythmia and differential diagnosis is performed.

  3. Left ventricular bronchogenic cyst.

    PubMed

    Wei, Xiang; Omo, Alfred; Pan, Tiecheng; Li, Jun; Liu, Ligang; Hu, Min

    2006-04-01

    Bronchogenic cysts occurring in the left ventricle are a medical rarity. One successfully operated case is reported herein. The location of the cyst was just between the epicardium and myocardium of the inferior left ventricular wall, adjacent to the apex of the heart. Complete excision was achieved through a left anterolateral thoracotomy without extracorporeal circulation.

  4. Atlas-Based Ventricular Shape Analysis for Understanding Congenital Heart Disease.

    PubMed

    Farrar, Genevieve; Suinesiaputra, Avan; Gilbert, Kathleen; Perry, James C; Hegde, Sanjeet; Marsden, Alison; Young, Alistair A; Omens, Jeffrey H; McCulloch, Andrew D

    2016-12-01

    Congenital heart disease is associated with abnormal ventricular shape that can affect wall mechanics and may be predictive of long-term adverse outcomes. Atlas-based parametric shape analysis was used to analyze ventricular geometries of eight adolescent or adult single-ventricle CHD patients with tricuspid atresia and Fontans. These patients were compared with an "atlas" of non-congenital asymptomatic volunteers, resulting in a set of z-scores which quantify deviations from the control population distribution on a patient-by-patient basis. We examined the potential of these scores to: (1) quantify abnormalities of ventricular geometry in single ventricle physiologies relative to the normal population; (2) comprehensively quantify wall motion in CHD patients; and (3) identify possible relationships between ventricular shape and wall motion that may reflect underlying functional defects or remodeling in CHD patients. CHD ventricular geometries at end-diastole and end-systole were individually compared with statistical shape properties of an asymptomatic population from the Cardiac Atlas Project. Shape analysis-derived model properties, and myocardial wall motions between end-diastole and end-systole, were compared with physician observations of clinical functional parameters. Relationships between altered shape and altered function were evaluated via correlations between atlas-based shape and wall motion scores. Atlas-based shape analysis identified a diverse set of specific quantifiable abnormalities in ventricular geometry or myocardial wall motion in all subjects. Moreover, this initial cohort displayed significant relationships between specific shape abnormalities such as increased ventricular sphericity and functional defects in myocardial deformation, such as decreased long-axis wall motion. These findings suggest that atlas-based ventricular shape analysis may be a useful new tool in the management of patients with CHD who are at risk of impaired ventricular

  5. Ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia.

    PubMed

    Malik, Rabiya; Zilberman, Mark V; Tang, Liwen; Miller, Susan; Pandian, Natesa G

    2015-03-01

    Ectopia cordis, defined as partial or complete displacement of the heart outside of the thoracic cavity, is a rare congenital malformation. If not surgically corrected during the early years of life, ectopia cordis can prove to be a fatal abnormality. However, due to the presence of multiple intracardiac and extracardiac malformations, a corrective surgery might not always be successful. The pathology of ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia is discussed, highlighting the complexities involved in such a rare disorder. © 2014, Wiley Periodicals, Inc.

  6. Pure right ventricular infarction.

    PubMed

    Inoue, Katsuji; Matsuoka, Hiroshi; Kawakami, Hideo; Koyama, Yasushi; Nishimura, Kazuhisa; Ito, Taketoshi

    2002-02-01

    A 76-year-old man with chest pain was admitted to hospital where electrocardiography (ECG) showed ST-segment elevation in leads V1-4, indicative of acute anterior myocardial infarction. ST-segment elevation was also present in the right precordial leads V4R-6R. Emergency coronary angiography revealed that the left coronary artery was dominant and did not have significant stenosis. Aortography showed ostial occlusion of the right coronary artery (RCA). Left ventriculography showed normal function and right ventriculography showed a dilated right ventricle and severe hypokinesis of the right ventricular free wall. Conservative treatment was selected because the patient's symptoms soon ameliorated and his hemodynamics was stable. 99mTc-pyrophosphate and 201Tl dual single-photon emission computed tomography showed uptake of 99mTc-pyrophosphate in only the right ventricular free wall, but no uptake of 99mTc-pyrophosphate and no perfusion defect of 201Tl in the left ventricle. The peak creatine kinase (CK) and CK-MB were 1,381 IU/L and 127 IU/L, respectively. His natural course was favorable and the chest pain disappeared under medication. Two months after the onset, the ECG showed poor R progression in leads V1-4 indicating an old anterior infarction. Coronary angiography confirmed the ostial stenosis of the hypoplastic RCA. This was a case of pure right ventricular free wall infarction because of the occlusion of the ostium of the hypoplastic RCA, but not of the right ventricular branch. Because the electrocardiographic findings resemble those of an acute anterior infarction, it is important to consider pure right ventricular infarction in the differential diagnosis.

  7. Unknown syndrome: abnormal facies, congenital heart defects, hypothyroidism, and severe retardation.

    PubMed Central

    Young, I D; Simpson, K

    1987-01-01

    We present a female infant with (1) abnormal facies: microcephaly, blepharophimosis, small, low set, posteriorly rotated ears, bulbous nose, carp shaped mouth, micrognathia; (2) congenital heart abnormalities: large atrial and ventricular septal defects; (3) congenital hypothyroidism; (4) severe global retardation. Images PMID:3430551

  8. Outcomes of neonatal Ebstein's anomaly without right ventricular forward flow.

    PubMed

    Baek, Jae Suk; Yu, Jeong Jin; Im, Yu Mi; Yun, Tae-Jin

    2016-08-01

    In neonates with Ebstein's anomaly and absent right ventricular forward flow, pulmonary valve morphology is normal or abnormal. Although initial postnatal presentations of these 2 conditions are similar, clinical courses and therapeutic strategies for each category differ greatly. Among 29 neonates with Ebstein's anomaly without right ventricular forward flow on initial postnatal echocardiography, 16 had a normal pulmonary valve and 13 had an abnormal pulmonary valve. During the postnatal follow-up of the normal pulmonary valve group, right ventricular forward flow commenced approximately 10 days after birth (1-15 days). The ductus arteriosus was surgically ligated in 3 neonates to facilitate right ventricular forward flow. Biventricular or 1 1/2 ventricular physiology was eventually achieved in 14 patients in the normal pulmonary valve group (14/16, 88%) and 2 patients in the abnormal pulmonary valve group (2/13, 15.3%). With respect to the preoperative echocardiographic findings, the normal pulmonary valve group had a significantly larger pulmonary valve annulus (8.2 ± 1.4 mm in the normal pulmonary valve group and 6.4 ± 1.8 mm in the abnormal pulmonary valve group, P = .002) and smaller cardiothoracic ratio (0.79 ± 0.05 in the normal pulmonary valve group and 0.85 ± 0.07 in the abnormal pulmonary valve group, P = .03). Mild to moderate pulmonary regurgitation was present in all patients (16/16, 100%) in the normal pulmonary valve group, but 3 patients (3/13, 23%) in the abnormal pulmonary valve group also had pulmonary regurgitation. On logistic regression analysis, only pulmonary valve annulus size remained as an indicator of a normal pulmonary valve (P = .03). In patients with Ebstein's anomaly and absent right ventricular forward flow, large pulmonary valve annulus size indicated a normal pulmonary valve. Patients with a normal pulmonary valve showed better survival and had a higher probability of achieving biventricular hemodynamics

  9. Is There a Relationship between Restricted, Repetitive, Stereotyped Behaviors and Interests and Abnormal Sensory Response in Children with Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Gabriels, Robin L.; Agnew, John A.; Miller, Lucy Jane; Gralla, Jane; Pan, Zhaoxing; Goldson, Edward; Ledbetter, James C.; Dinkins, Juliet P.; Hooks, Elizabeth

    2008-01-01

    This study examined the relation between restricted, repetitive, and stereotyped behaviors and interests (RBs) and sensory responses in a group of 70 children and adolescents diagnosed with an autism spectrum disorder (ASD). Caregivers completed the Repetitive Behavior Scale-Revised (RBS-R) and the Sensory Profile. Controlling for IQ and age,…

  10. Is There a Relationship between Restricted, Repetitive, Stereotyped Behaviors and Interests and Abnormal Sensory Response in Children with Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Gabriels, Robin L.; Agnew, John A.; Miller, Lucy Jane; Gralla, Jane; Pan, Zhaoxing; Goldson, Edward; Ledbetter, James C.; Dinkins, Juliet P.; Hooks, Elizabeth

    2008-01-01

    This study examined the relation between restricted, repetitive, and stereotyped behaviors and interests (RBs) and sensory responses in a group of 70 children and adolescents diagnosed with an autism spectrum disorder (ASD). Caregivers completed the Repetitive Behavior Scale-Revised (RBS-R) and the Sensory Profile. Controlling for IQ and age,…

  11. [Ventricular "remodeling" after myocardial infarction].

    PubMed

    Cohen-Solal, A; Himbert, D; Guéret, P; Gourgon, R

    1991-06-01

    Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction.

  12. Abnormal Head Position

    MedlinePlus

    ... an ocular cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal ... cause permanent tightening of neck muscles that can lead to chronic neck ache or headache. An abnormal ...

  13. Skeletal limb abnormalities

    MedlinePlus

    ... medlineplus.gov/ency/article/003170.htm Skeletal limb abnormalities To use the sharing features on this page, please enable JavaScript. Skeletal limb abnormalities refers to a variety of bone structure problems ...

  14. Tooth - abnormal colors

    MedlinePlus

    ... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

  15. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  16. Arrhythmogenic right ventricular dysplasia: Atypical clinical presentation.

    PubMed

    Marçalo, José; Menezes Falcão, Luiz

    2017-03-01

    A 67-year-old man was admitted to our hospital after episodes of syncope preceded by malaise and diffuse neck and chest discomfort. No family history of cardiac disease was reported. Laboratory workup was within normal limits, including D-dimers, serum troponin I and arterial blood gases. The electrocardiogram showed sinus rhythm with T-wave inversion in leads V1 to V3. Computed tomography angiography to investigate pulmonary embolism showed no abnormal findings. Transthoracic echocardiography (TTE) displayed massive enlargement of the right ventricle with intact interatrial septum and no pulmonary hypertension. Cardiac magnetic resonance imaging (MRI) confirmed right ventricular (RV) dilatation and revealed marked hypokinesia/akinesia of the lateral wall. Exercise stress testing was negative for ischemia. According to the 2010 Task Force criteria for arrhythmogenic right ventricular dysplasia (ARVD), this patient presented two major criteria (global or regional dysfunction and structural alterations: by MRI, regional RV akinesia or dyskinesia or dyssynchronous RV contraction and RV ejection fraction ≤40%, and repolarization abnormalities: inverted T waves in right precordial leads [V1, V2, and V3]); and one minor criterion (>500 ventricular extrasystoles per 24 hours by Holter), and so a diagnosis of ARVD was made. After electrophysiologic study (EPS) the patient received an implantable cardioverter-defibrillator (ICD). This late clinical presentation of ARVD highlights the importance of TTE screening, possibly complemented by MRI. The associated risk of sudden death was assessed by EPS leading to the implantation of an ICD. Genetic association studies should be offered to the offspring of all ARVD patients. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... PROBLEMS Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... treat abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  18. Catecholaminergic polymorphic ventricular tachycardia: a rare cause of recurrent syncope

    PubMed Central

    Azevedo, Ana Isabel; Dias, Adelaide; Teixeira, Madalena; Gama Ribeiro, Vasco

    2015-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by adrenergically induced polymorphic or bidirectional ventricular tachycardia (VT). Although a rare disease, its recognition is important because of its high mortality rate when left untreated. We report an index case of a 32-year-old woman who presented with recurrent syncope. The diagnosis was confirmed by exercise-induced polymorphic ventricular premature beats and episodes of non-sustained VT, in the absence of structural heart abnormalities. She remained event free with beta-blocker therapy. CPVT is a potentially life-threatening disease and should be considered in the case of recurrent syncope, in young individuals. Diagnosis is based on clinical history and exercise testing, which is the gold standard. Therapy is mandatory in all diagnosed individuals. Exercise testing in first-degree relatives is recommended, even in the case of a mutation-negative index patient. PMID:26512332

  19. Ventricular remodeling and function: insights using murine echocardiography

    PubMed Central

    Scherrer-Crosbie, Marielle; Kurtz, Baptiste

    2009-01-01

    Summary Extracellular matrix disturbances play an important role in the development of ventricular remodeling and failure. Genetically modified mice with abnormalities in the synthesis and degradation of extracellular matrix have been generated, in particular mice with deletion or overexpression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Echocardiography is ideally suited to serially evaluate left ventricular (LV) size and function, thus defining the progression of LV remodeling and failure. This Review describes the echocardiographic parameters that may provide insights into the development of ventricular remodeling and heart failure. The application of echocardiography to study LV remodeling and function after myocardial infarction and LV pressure-overload in wild-type mice and mice deficient or overexpressing MMPs or TIMPs is then detailed. Finally, using the example of mice deficient in nitric oxide synthase 3, a cautionary example is given illustrating discrepancies between the cardiac echocardiographic phenotype and modifications of the extracellular matrix. PMID:19615377

  20. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

    PubMed Central

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  1. Left ventricular mural thrombus

    SciTech Connect

    Nixon, J.V.

    1983-08-01

    The identification of mural thrombus in patients with left ventricular aneurysm and mural thrombus probably warrants consideration of long-term anticoagulation. In patients with acute, large, anterior or anteroapical, transmural myocardial infarctions, serial noninvasive examinations are warranted to define a group of patients at high risk for the development of left ventricular aneurysm and/or mural thrombus. Anticoagulants should be considered in patients in whom mural thrombi develop as a complication of their infarction. Patients with congestive cardiomyopathy should be considered for long-term anticoagulation. These recommendations are all tempered by the realization that the use of anticoagulant therapy is not without its own risks. The decision to anticoagulate must be balanced against each individual patient's suitability for such therapy and the individual likelihood of the development of side effects.

  2. Epicardial catheter ablation of ventricular tachycardia in no entry left ventricle: mechanical aortic and mitral valves.

    PubMed

    Soejima, Kyoko; Nogami, Akihiko; Sekiguchi, Yukio; Harada, Tomoo; Satomi, Kazuhiro; Hirose, Takeshi; Ueda, Akiko; Miwa, Yousuke; Sato, Toshiaki; Nishio, Satoru; Shirai, Yasuhiro; Kowase, Shinya; Murakoshi, Nobuyuki; Kunugi, Shinobu; Murata, Hiroshige; Nitta, Takashi; Aonuma, Kazutaka; Yoshino, Hideaki

    2015-04-01

    In patients with mechanical aortic and mitral valves and left ventricular tachycardia, catheter ablation may be prevented by limited access to the left ventricle. In our series of 6 patients, 2 patients underwent direct surgical ablation and 4 underwent epicardial catheter ablation via a pericardial window. All patients had abnormal low voltage areas with fractionated or delayed isolated potentials on the apical epicardium. Most of the ventricular tachycardias were targeted by pace mapping. Sites with a good pace match or abnormal electrograms were ablated using an irrigated radiofrequency ablation catheter. A microscopic pathological evaluation of the resected tissue from 2 of the open-heart ablation patients revealed dense fibrosis on the epicardium compared with the endocardium, supporting the feasibility of an epicardial ablation for the ventricular tachycardia. Epicardial catheter ablation of ventricular tachycardia is a potentially useful therapy in patients who have mechanical aortic and mitral valves. © 2015 American Heart Association, Inc.

  3. Idiopathic fascicular ventricular tachycardia.

    PubMed

    Francis, Johnson; Venugopal, K; Khadar, S A; Sudhayakumar, N; Gupta, Anoop K

    2004-07-01

    Idiopathic fascicular ventricular tachycardia is an important cardiac arrhythmia with specific electrocardiographic features and therapeutic options. It is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal axis has also been described. Fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. Rare instances of termination with intravenous adenosine have also been noted. A presystolic or diastolic potential preceding the QRS, presumed to originate from the Purkinje fibers can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (P potential) has been used as a guide to catheter ablation. Prompt recognition of fascicular tachycardia especially in the emergency department is very important. It is one of the eminently ablatable ventricular tachycardias. Primary ablation has been reported to have a higher success, lesser procedure time and fluoroscopy time.

  4. Noninvasive Cardiac Screening in Young Athletes With Ventricular Arrhythmias

    PubMed Central

    Steriotis, Alexandros Klavdios; Nava, Andrea; Rigato, Ilaria; Mazzotti, Elisa; Daliento, Luciano; Thiene, Gaetano; Basso, Cristina; Corrado, Domenico; Bauce, Barbara

    2013-01-01

    The aim of this study was to analyze using noninvasive cardiac examinations a series of young athletes discovered to have ventricular arrhythmias (VAs) during the preparticipation screening program for competitive sports. One hundred forty-five athletes (mean age 17 ± 5 years) were evaluated. The study protocol included electrocardiography (ECG), exercise testing, 2-dimensional and Doppler echocardiography, 24-hour Holter monitoring, signal-averaged ECG, and in selected cases contrast-enhanced cardiac magnetic resonance imaging. Results of ECG were normal in most athletes (85%). VAs were initially detected prevalently during exercise testing (85%) and in the remaining cases on ECG and Holter monitoring. Premature ventricular complexes disappeared during exercise in 56% of subjects. Premature ventricular complexes during Holter monitoring averaged 4,700 per day, predominantly monomorphic (88%), single, and/or in couplets (79%). The most important echocardiographic findings were mitral valve prolapse in 29 patients (20%), congenital heart disease in 4 (3%), and right ventricular regional kinetic abnormalities in 5 (3.5%). On cardiac magnetic resonance imaging, right ventricular regional kinetic abnormalities were detected in 9 of 30 athletes and were diagnostic of arrhythmogenic right ventricular cardiomyopathy in only 1 athlete. Overall, 30% of athletes were judged to have potentially dangerous VAs. In asymptomatic athletes with prevalently normal ECG, most VAs can be identified by adding an exercise test during preparticipation screening. In conclusion, cardiac screening with noninvasive examinations remains a fundamental tool for the identification of a possible pathologic substrate and for the characterization of electrical instability. PMID:23219000

  5. Inappropriate shock therapy for nonsustained ventricular tachycardia in a dual chamber pacemaker defibrillator.

    PubMed

    Mann, D E; Kelly, P A; Reiter, M J

    1998-10-01

    We report a patient who received a CPI Ventak AV II DR ICD for ventricular tachycardia and complete heart block without an escape rhythm. During induced nonsustained ventricular tachycardia, the device, although programmed to deliver noncommitted shocks, acted like a committed device. This phenomenon is due to undocumented behavior that is likely to occur in any patient who is pacemaker dependent and has nonsustained ventricular tachycardia.

  6. Coexistence of congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LDB3 mutation: a case report.

    PubMed

    Shan, Shengshuai; He, Xiaoxiao; He, Lin; Wang, Min; Liu, Chengyun

    2017-08-19

    The coexistence of congenital left ventricular aneurysm and abnormal cardiac trabeculation with gene mutation has not been reported previously. Here, we report a case of coexisting congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LIM domain binding 3 gene mutation. A 30-year-old Asian man showed paroxysmal sinus tachycardia and Q waves in an electrocardiogram health check. There were no specific findings in physical examinations and serological tests. A coronary-computed tomography angiography check showed normal coronary artery and no coronary stenosis. Both left ventricle contrast echocardiography and cardiac magnetic resonance showed rare patterns of a combination of an apical aneurysm-like out-pouching structure with a wide connection to the left ventricle and prominent left ventricular trabecular meshwork. High-throughput sequencing examinations showed a novel mutation in the LDB3 gene (c.C793>T; p.Arg265Cys). Our finding indicates that the phenotypic expression of two heart conditions, congenital left ventricular aneurysm and prominent left ventricular trabeculation, although rare, can occur simultaneously with LDB3 gene mutation. Congenital left ventricular aneurysm and prominent left ventricular trabeculation may share the same genetic background.

  7. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. A review and update.

    PubMed

    Francés, Raúl J

    2006-06-28

    The arrhythmogenic right ventricular dysplasia/cardiomyopathy is an important cause of sudden arrhythmic death, often exertional, in young individuals and athletes. Although the aetiology remains partially unknown, genetic abnormalities have been demonstrated. Reported prevalence is 1 in 5000 individuals but it is considered there are many non-diagnosed cases. The characteristic pathologic finding is the progressive fibro-fatty replacement of the right ventricular myocardium. The clinical manifestations vary from asymptomatic patients with an episode of sudden cardiac death as first symptom to chronically symptomatic patients with recurrent palpitations and/or right or biventricular failure. Approximately a third of the patients show the characteristic Epsilon wave in the 12-lead ECG which is a useful screening test. Signal-averaged ECG frequently demonstrates late potentials. The two-dimensional echocardiography, magnetic resonance imaging, computerized tomography and right ventricular cineangiography show morphologic abnormalities in the right ventricle. Therapy is directed to prevent and/or treat malignant ventricular tachyarrhythmias with medications, implantable cardioverter defibrillator and radiofrequency ablation in selected cases.

  8. Cisapride and ventricular arrhythmia

    PubMed Central

    Hennessy, Sean; Leonard, Charles E; Newcomb, Craig; Kimmel, Stephen E; Bilker, Warren B

    2008-01-01

    AIMS We aimed to examine the association between cisapride and ventricular arrhythmia, and examine the relationship to dose and CYP3A4 inhibitors. METHODS A nested case–control study was conducted in Medicaid beneficiaries exposed to cisapride, metoclopramide or a proton pump inhibitor (PPI) from 1999 to 2000. Cases were hospitalized with a principal International Classification of Diseases-9 code indicating sudden cardiac death or ventricular arrhythmia. Controls had at least as much event-free person time following the study prescription as its matched case. RESULTS A total of 145 cases and 7250 controls were identified. The unadjusted rate ratio for cisapride vs. PPIs was 1.49 (95% confidence interval 0.96, 2.25). The adjusted odds ratio (OR) for cisapride vs. PPIs was 2.10 (1.34, 3.28). Excluding persons in managed care, the adjusted OR for cisapride was 2.92 (1.55, 5.49). In the initial prescription period, the adjusted OR for cisapride vs. PPIs was 7.85 (1.95, 31.60). Non-arrhythmogenic CYP3A4 inhibitors were not associated with an increased risk in users of cisapride or PPI inhibitors. The OR for potentially arrhythmogenic CYP3A4 inhibitors was 3.79 (1.76, 8.15) in cisapride users and 3.47 (2.06, 5.83) in PPI users. CONCLUSIONS Cisapride was associated with a doubling to tripling of the risk of hospitalization for ventricular arrhythmia, and a nearly eightfold risk in the initial prescription period. Although use of potentially arrhythmogenic CYP3A4 inhibitors was associated with an increased risk, this appears to be due to a direct effect of the drugs themselves rather than an interaction with cisapride. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Case reports have linked cisapride to ventricular arrhythmia and sudden cardiac death. However, two prior epidemiological studies have failed to show an association between cisapride and serious arrhythmia. WHAT THIS STUDY ADDS Overall, cisapride was associated with a doubling to tripling of the risk of

  9. Ventricular hypertrophy in cardiomyopathy.

    PubMed

    Oakley, C

    1971-01-01

    Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some

  10. Premature Ventricular Contractions (PVCs)

    MedlinePlus

    ... abnormal rhythms. Common types of portable ECGs include: Holter monitor. This portable device is carried in your ... rhythm at the time of your symptoms. A Holter monitor or event recorder can help identify the ...

  11. Ablation of idiopathic ventricular tachycardia.

    PubMed

    Schreiber, Doreen; Kottkamp, Hans

    2010-09-01

    Idiopathic ventricular arrhythmias occur in patients without structural heart disease. They can arise from a variety of specific areas within both ventricles and in the supravalvular regions of the great arteries. Two main groups need to be differentiated: arrhythmias from the outflow tract (OT) region and idiopathic left ventricular, so-called fascicular, tachycardias (ILVTs). OT tachycardia typically originates in the right ventricular OT, but may also occur in the left ventricular OT, particularly in the sinuses of Valsalva or the anterior epicardium or the great cardiac vein. Activation mapping or pace mapping for the OT regions and mapping of diastolic potentials in ILVTs are the mapping techniques that are typically used. The ablation of idiopathic ventricular arrhythmias is highly successful, associated with only rare complications. Newly recognized entities of idiopathic ventricular tachycardias are those originating in the papillary muscles and in the atrioventricular annular regions.

  12. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes

    PubMed Central

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano

    2016-01-01

    Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211

  13. The relationship between ventricular-vascular uncoupling during exercise and impaired left ventricular longitudinal functional reserve in hypertensive patients.

    PubMed

    Shim, Chi Young; Park, Sungha; Choi, Eui-Young; Hong, Geu-Ru; Choi, Donghoon; Jang, Yangsoo; Chung, Namsik

    2013-01-01

    Uncoupling between heart and vessel may be accompanied by left ventricular (LV) dysfunction during exercise. We investigated the association between ventricular-vascular uncoupling during exercise and impaired LV longitudinal functional reserve in hypertensive subjects. Supine bicycle exercise echocardiography (25-watt, 3-minute increments) was performed in 216 hypertensive patients (106 male; mean age, 58 ± 9 years). Arterial elastance (Ea), end-systolic ventricular elastance (Ees), and ventricular-vascular interaction (VVI) index (Ea/Ees) were calculated at rest and at each stage of exercise. The patients were divided into three groups according to the tertile value of VVI ratio. The VVI ratio was defined as the ratio of VVI index at 50 W exercise over VVI index at rest; normal VVI response (n = 72); borderline VVI response (n = 72); and abnormal VVI response (n = 72). There were no significant differences in conventional echo parameters, mitral inflow velocities, mitral annular early diastolic (E') velocity, and mitral annular systolic velocity (S') at rest among the three groups. However, E' velocities and S' velocities at 25 W and 50 W were significantly lower in patients with abnormal VVI response compared with those in the other groups (P = .010 at 25 W, P = .008 at 50 W in E' velocity; P = .022 at 25 W, P = .043 at 50 W in S' velocity). Longitudinal diastolic functional reserve index from rest to 50 W was significantly lower in patients with abnormal VVI response compared with the other groups. Ventricular-vascular uncoupling during exercise was related to impaired LV longitudinal functional reserve in hypertensive patients.

  14. Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation.

    PubMed Central

    Emori, T; Ohe, T; Shimomura, K

    1993-01-01

    A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms. PMID:8489870

  15. Totally tubular: the mystery behind function and origin of the brain ventricular system.

    PubMed

    Lowery, Laura Anne; Sive, Hazel

    2009-04-01

    A unique feature of the vertebrate brain is the ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system.

  16. Cardiovascular Abnormalities in Sickle Cell Disease

    PubMed Central

    Gladwin, Mark T.; Sachdev, Vandana

    2013-01-01

    Sickle cell disease is characterized by recurrent episodes of ischemia-reperfusion injury to multiple vital organ systems and a chronic hemolytic anemia, both contributing to progressive organ dysfunction. The introduction of treatments that induce protective fetal hemoglobin and reduce infectious complications has greatly prolonged survival. However, with increased longevity, cardiovascular complications are increasingly evident, with the notable development of a progressive proliferative systemic vasculopathy, pulmonary hypertension (PH) and left ventricular diastolic dysfunction. Pulmonary hypertension is reported in autopsy studies and numerous clinical studies have shown that increased pulmonary pressures are an important risk marker for mortality in these patients. In epidemiological studies, the development of PH is associated with intravascular hemolysis, cutaneous leg ulceration, renal insufficiency, iron overload and liver dysfunction. Chronic anemia in sickle cell disease results in cardiac chamber dilation and a compensatory increase in left ventricular mass. This is often accompanied by left ventricular diastolic dysfunction which has also been a strong independent predictor of mortality patients with sickle cell disease. Both PH and diastolic dysfunction are associated with marked abnormalities in exercise capacity in these patients. Sudden death is an increasingly recognized problem and further cardiac investigations are necessary to recognize and treat high-risk patients. PMID:22440212

  17. Abnormal behavior of threshold voltage shift in bias-stressed a-Si:H thin film transistor under extremely high intensity illumination.

    PubMed

    Han, Sang Youn; Park, Kyung Tea; Kim, Cheolkyu; Jeon, Sanghyun; Yang, Sung-Hoon; Kong, Hyang-Shik

    2015-07-22

    We report on the unusual behavior of threshold voltage turnaround in a hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) when biased under extremely high intensity illumination. The threshold voltage shift changes from negative to positive gate bias direction after ∼30 min of bias stress even when the negative gate bias stress is applied under high intensity illumination (>400 000 Cd/cm(2)), which has not been observed in low intensity (∼6000 Cd/cm(2)). This behavior is more pronounced in a low work function gate metal structure (Al: 4.1-4.3 eV), compared to the high work function of Cu (4.5-5.1 eV). Also this is mainly observed in shorter wavelength of high photon energy illumination. However, this behavior is effectively prohibited by embedding the high energy band gap (∼8.6 eV) of SiOx in the gate insulator layer. These imply that this behavior could be originated from the injection of electrons from gate electrode, transported and trapped in the electron trap sites of the SiNx/a-Si:H interface, which causes the shift of threshold voltage toward positive gate bias direction. The results reported here can be applicable to the large-sized outdoor displays which are usually exposed to the extremely high intensity illumination.

  18. Ventricular arrhythmias in congestive heart failure: clinical significance and management.

    PubMed Central

    Khoshnevis, G R; Massumi, A

    1999-01-01

    The benefit of defibrillator therapy has been well established for patients with LV dysfunction (ejection fraction less than 35%), coronary artery disease, NSVT, and inducible and nonsuppressible ventricular tachycardia. Implantable cardioverter-defibrillator therapy is also indicated for all CHF patients in NYHA functional classes I, II, and III who present with aborted sudden cardiac death, or ventricular fibrillation, or hemodynamically unstable ventricular tachycardia--and also in patients with syncope with no documented ventricular tachycardia but with inducible ventricular tachycardia at electrophysiology study. The ongoing MADIT II trial was designed to evaluate the benefit of prophylactic ICD implantation in these patients (ejection fraction less than 30%, coronary artery disease, and NSVT) without prior risk stratification by PES. The CABG Patch trial concluded that prophylactic placement of an ICD during coronary artery bypass grafting in patients with low ejection fraction and abnormal SAECG is not justifiable. Except for the indications described above, ICD implantation has not been proved to be beneficial as primary or secondary therapy. Until more data are available, patients should be encouraged to enroll in the ongoing clinical trials. PMID:10217470

  19. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    SciTech Connect

    Tal, A.; Leiberman, A.; Margulis, G.; Sofer, S.

    1988-01-01

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present.

  20. Effects of early or late prenatal immune activation in mice on behavioral and neuroanatomical abnormalities relevant to schizophrenia in the adulthood.

    PubMed

    da Silveira, Vivian T; Medeiros, Daniel de Castro; Ropke, Jivago; Guidine, Patricia A; Rezende, Gustavo H; Moraes, Marcio Flavio D; Mendes, Eduardo Mazoni A M; Macedo, Danielle; Moreira, Fabricio A; de Oliveira, Antonio Carlos P

    2017-05-01

    Maternal immune activation (MIA) during pregnancy in rodents increases the risk of the offspring to develop schizophrenia-related behaviors, suggesting a relationship between the immune system and the brain development. Here we tested the hypothesis that MIA induced by the viral mimetic polyinosinic-polycytidylic acid (poly I:C) in early or late gestation of mice leads to behavioral and neuroanatomical disorders in the adulthood. On gestational days (GDs) 9 or 17 pregnant dams were treated with poly I:C or saline via intravenous route and the offspring behaviors were measured during adulthood. Considering the progressive structural neuroanatomical alterations in the brain of individuals with schizophrenia, we used magnetic resonance imaging (MRI) to perform brain morphometric analysis of the offspring aged one year. MIA on GD9 or GD17 led to increased basal locomotor activity, enhanced motor responses to ketamine, a psychotomimetic drug, and reduced time spent in the center of the arena, suggesting an increased anxiety-like behavior. In addition, MIA on GD17 reduced glucose preference in the offspring. None of the treatments altered the relative volume of the lateral ventricles. However, a decrease in brain volume, especially for posterior structures, was observed for one-year-old animals treated with poly I:C compared with control groups. Thus, activation of the maternal immune system at different GDs lead to neuroanatomical and behavioral alterations possibly related to the positive and negative symptoms of schizophrenia. These results provide insights on neuroimmunonological and neurodevelopmental aspects of certain psychopathologies, such as schizophrenia. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. Autoshaping of abnormal children.

    PubMed

    Deckner, C W; Wilcox, L M; Maisto, S A; Blanton, R L

    1980-09-01

    Three experimentally naive abnormal children were exposed to a terminal operant contingency, i.e., reinforcement was delivered only if the children pressed a panel during intervals when it was lighted. Despite the absence of both successive approximation and manual shaping, it was found that each child began to respond discriminatively within a small number of trials. These data replicated previous animal studies concerned with the phenomena of autoshaping and signal-controlled responding. It was also found, however, that one type of autoshaping, the classical conditioning procedure, had a powerful suppressive effect on the discriminative responding. An experimental analysis that consisted procedure, had a powerful suppressive effect on discriminative responding. An experimental analysis that consisted of intrasubject reversal an multiple baseline designs established the internal validity of the findings. The finding of rapid acquisition of signal-controlled responding obtained with the initial procedure is suggessted to have practical significance. The disruptive effects of the classical form of autoshaping are discussed in terms of negative behavioral contrast.

  2. Exercise-induced ventricular tachycardia in association with a myocardial bridge.

    PubMed

    Feld, H; Guadanino, V; Hollander, G; Greengart, A; Lichstein, E; Shani, J

    1991-05-01

    Sustained ventricular tachycardia induced by exercise is uncommon. This is a report of a patient who has a positive exercise test at a high level of exercise. The electrocardiogram has classic ischemic ST depressions. Following the appearance of these ST depressions, the patient developed ventricular tachycardia at a rapid rate. Workup that included an echocardiogram and cardiac catheterization revealed myocardial bridging of the left anterior descending artery as the only structural abnormality. Electrophysiologic studies revealed the patient to have ventricular tachycardia only with isoproterenol (Isuprel) infusion.

  3. Childhood behavioral characteristics and adult brain morphology in schizophrenia.

    PubMed

    Walker, E F; Lewine, R R; Neumann, C

    1996-11-15

    It is well established that many schizophrenia patients manifest behavioral dysfunction long before the onset of clinical symptoms of illness. Some show signs of motor and socioemotional deficit as early as infancy. The present study examines the relations among childhood neuromotor, affective and behavior characteristics, and the association of these factors with adult brain morphology (MRI) in schizophrenia patients. Data on neuromotor functions and negative affect were obtained from coding of childhood films. Parents of patients provided information about six dimensions of childhood behavior problems. Analyses of data from patients and healthy siblings revealed that childhood neuromotor abnormalities and negative affect were associated with some of the behavioral dimensions. Among the patients, early childhood neuromotor deficits and negative affect were linked with greater ventricular enlargement in adulthood. The ratings of the behavior problem dimensions showed a complex relation with adult brain morphology, suggesting that externalized problems are linked with more abnormalities (smaller brain volume and larger ventricles), whereas internalized problems are associated with less abnormality. The findings are discussed in light of their implications for the developmental origins of brain abnormalities in schizophrenia.

  4. Isolated Left Ventricular Apical Hypoplasia with Right Ventricular Outflow Tract Obstruction: A Rare Combination.

    PubMed

    Zhao, Yonghui; Zhang, Jiaying; Zhang, Jing

    2015-09-01

    Isolated left ventricular (LV) apical hypoplasia is a unusual and recently recognized congenital cardiac anomaly. A 19-year-old man was found to have an abnormal ECG and cardiac murmur identified during a routine health check since joining work. His ECG revealed normal sinus rhythm, right-axis deviation, poor R wave progression, and T wave abnormalities. On physical examination, a 2/6~3/6 systolic murmur was heard at the second intercostal space along the left sternal border. Subsequent echocardiography and cardiac magnetic resonance imaging confirmed the LV apical hypoplasia. Of note, we first found that LV apical hypoplasia was accompanied by RV outflow tract obstruction due to exaggerated rightward bulging of the basal-anterior septum during systole. A close follow-up was performed for the development of heart failure, pulmonary hypertension, and potentially tachyarrhythmia.

  5. [Language disorders in children with morphologic abnormalities of the hippocampus].

    PubMed

    Agostini, G; Mancini, J; Chabrol, B; Villeneuve, N; Milh, M; George, F; Maurel, B; Girard, N

    2010-07-01

    Morphologic abnormalities of the hippocampal formations (MAHF) are more frequently observed in magnetic resonance imaging (MRI). We wished to specify the types of disorders associated with these malformations based on a retrospective case series by studying the language of the children presenting these abnormalities. From the data of all the MRIs taken in the neuroradiology ward of our center over 16 months in patients under 18 years of age, we retrospectively selected the children with an MAHF, isolated or associated with other malformations. The MAHFs were defined and described according to criteria of shape or orientation defects of the hippocampal formations. We studied the files of the patients with isolated MAHF again. Those whose clinical presentation was compatible with language assessment were tested in a prospective approach. Out of 2208 MRIs from 1 January 2007 to 30 April 2008, 96 (4.3%) showed an MAHF, including 61 (64%) boys and 35 (36%) girls, aged from 2 months to 17 years. Eighty-two (85%) had associated abnormalities, mainly including cerebral atrophy, corpus callosum agenesis or defect, and abnormal ventricular frontal horns. Fourteen (15%) had an isolated MAHF: 2 on the left hemisphere, 2 on the right hemisphere, and 10 on both. Of these 14, 9 were compatible with language assessment. From the test results, we divided these children into 2 groups, depending on the type and severity of the impairment. Four had very serious language disorders as part of mental retardation or autistic disorders; 4 others had language disorders predominantly in expression and phonology, with weak to pathological visual memory. This study showed no potential relation between the lateralization of MAHF and language disorders, nor between the existence of epilepsy and the severity of the language disorders. Of these 14 children, 9 had behavior and autism spectrum disorders and 7 were epileptic. Even though language disorders are often part of a larger deficiency

  6. Acquired and congenital coronary artery abnormalities.

    PubMed

    Young, Ming-Lon; McLeary, Michael; Chan, Kak-Chen

    2017-01-01

    Sudden unexpected cardiac deaths in approximately 20% of young athletes are due to acquired or congenital coronary artery abnormalities. Kawasaki disease is the leading cause for acquired coronary artery abnormalities, which can cause late coronary artery sequelae including aneurysms, stenosis, and thrombosis, leading to myocardial ischaemia and ventricular fibrillation. Patients with anomalous left coronary artery from the pulmonary artery can develop adequate collateral circulation from the right coronary artery in the newborn period, which remains asymptomatic only to manifest in adulthood with myocardial ischaemia, ventricular arrhythmias, and sudden death. Anomalous origin of coronary artery from the opposite sinus occurs in 0.7% of the young general population aged between 11 and 15 years. If the anomalous coronary artery courses between the pulmonary artery and the aorta, sudden cardiac death may occur during or shortly after vigorous exercise, especially in patients where the anomalous left coronary artery originates from the right sinus of Valsalva. Symptomatic patients with evidence of ischaemia should have surgical correction. No treatment is needed for asymptomatic patients with an anomalous right coronary artery from the left sinus of Valsalva. At present, there is no consensus regarding how to manage asymptomatic patients with anomalous left coronary artery from the right sinus of Valsalva and interarterial course. Myocardial bridging is commonly observed in cardiac catheterisation and it rarely causes exercise-induced coronary syndrome or cardiac death. In symptomatic patients, refractory or β-blocker treatment and surgical un-bridging may be considered.

  7. Effect of licofelone--a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats.

    PubMed

    Kumar, Ashok; Sharma, Sorabh; Prashar, Ashwani; Deshmukh, Rahul

    2015-03-01

    The present study was designed to investigate the effect of licofelone-a dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitor in intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficit and biochemical abnormalities in rats. ICV-STZ is a widely used model of sporadic Alzheimer's disease. In this study, STZ was administered intracerebroventricular (i.c.v.)-bilaterally 3 mg/kg in rats. The STZ-injected rats were treated with different doses of licofelone (2.5, 5, and 10 mg/kg, p.o.) for 21 days. Cognitive functions were assessed by using Morris water maze and passive avoidance task. Levels of malondialdehyde (MDA), nitrite, reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were determined to check oxidative stress and cholinergic function. Cytokine levels (IL-1β and TNF-α) were also determined as markers of neuroinflammation. Administration of STZ caused a significant increase in AChE activity and cognitive dysfunction. Increased oxidative stress and the proinflammatory cytokine levels were also observed following STZ administration in rats. Licofelone treatment attenuated STZ-induced cholinergic hypofunction and cognitive deficit in rats. In addition, licofelone attenuated STZ-induced oxidative stress and elevated cytokine levels. The cognitive enhancement following licofelone administration in STZ rats may be due to its ability to restore cholinergic functions or its antioxidant activity. These observed results suggest the therapeutic potential of dual COX/5-LOX inhibitors in neurodegenerative disorders associated with oxidative stress and cognitive impairment.

  8. [Repetitive monomorphic ventricular tachycardia].

    PubMed

    Maia, I G; Cruz Filho, F; Costa, A M; Boghossian, S H; Fagundes, M; Ribeiro, J C; Sá, R; Alves, P A

    1994-01-01

    To evaluate retrospectively clinical features of repetitive monomorphic ventricular tachycardia (RMVT). Files of 11 patients with RMVT were analyzed (9 females, mean-age 37 +/- 17 years). All patients were submitted to clinical evaluation, ECG, Holter monitoring stress test, high-resolution ECG and echocardiogram; they were treated with antiarrhythmic drugs. Patients were in NYHA class I or II, 9 asymptomatics and 2 with palpitations. The ECG was normal in all of them. Cardiac memory was observed in 3. A left bundle branch block with inferior axis deviation in the frontal plane was present during RMVT in all patients (right ventricular outflow tract focus). Holter monitoring revealed mean of 12031 +/- 8345 isolated PVC/24h; 2892 +/- 234 ventricular couplets/24h and 1367 +/- 890 VTs/24h (mainly nonsustained). In 6 patients RMVT was suppressed during maximal exercise treadmill. High-resolution ECG was negative in all group. Five patients had a normal echocardiogram while 5 showed mitral valve prolapse. One patient developed tachycardiomyopathy. The arrhythmia was controlled with 320mg of oral sotalol in 3 of 4 that used this drug and with 120mg oral propranolol in one of 6 that used this drug. Drug resistance was present in the others. The mean follow-up period was 38 +/- 16 months. The results demonstrate that RMVT is a benign form of VT with no detectable anatomic substract by the currently used methods. It is probably induced by nonreentrant mechanism and frequently drug resistance is observed. Among the antiarrhythmic drugs commonly used, sotalol showed to be the most effective.

  9. Effects of ventricular insertion sites on rotational motion of left ventricular segments studied by cardiac MR

    PubMed Central

    Robson, M D; Rider, O J; Pegg, T J; Dasanu, C A; Jung, B A; Clarke, K; Holloway, C J

    2013-01-01

    Objective: Obtaining new details for rotational motion of left ventricular (LV) segments using velocity encoding cardiac MR and correlating the regional motion patterns to LV insertion sites. Methods: Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Peak rotational velocities and circumferential velocity curves were obtained for 16 ventricular segments. Results: Reduced peak clockwise velocities of anteroseptal segments (i.e. Segments 2 and 8) and peak counterclockwise velocities of inferoseptal segments (i.e. Segments 3 and 9) were the most prominent findings. The observations can be attributed to the LV insertion sites into the right ventricle, limiting the clockwise rotation of anteroseptal LV segments and the counterclockwise rotation of inferoseptal segments as viewed from the apex. Relatively lower clockwise velocities of Segment 5 and counterclockwise velocities of Segment 6 were also noted, suggesting a cardiac fixation point between these two segments, which is in close proximity to the lateral LV wall. Conclusion: Apart from showing different rotational patterns of LV base, mid ventricle and apex, the study showed significant differences in the rotational velocities of individual LV segments. Correlating regional wall motion with known orientation of myocardial aggregates has also provided new insights into the mechanisms of LV rotational motions during a cardiac cycle. Advances in knowledge: LV insertion into the right ventricle limits the clockwise rotation of anteroseptal LV segments and the counterclockwise rotation of inferoseptal segments adjacent to the ventricular insertion sites. The pattern should be differentiated from wall motion abnormalities in cardiac pathology. PMID:24133098

  10. Ventricular fibrillation and defibrillation

    PubMed Central

    Jones, P; Lodé, N

    2007-01-01

    Cardiac arrest in children is not often due to a disturbance in rhythm that is amenable to electrical defibrillation, contrary to the situation in adults. When a shockable rhythm is present, defibrillation using an external electric shock applied at an early stage after pre‐oxygenation and chest compressions is of proven efficacy. Success at conversion of ventricular fibrillation is dependent on the delay before delivering the shock and defibrillation efficiency, which is itself a function of thoracic impedance, energy dose and waveform. PMID:17895341

  11. Giant left ventricular pseudoaneurysm.

    PubMed

    Prakash, Sumi; Garg, Nadish; Xie, Gong-Yuan; Dellsperger, Kevin C

    2010-01-01

    Left ventricular (LV) pseudoaneurysm (PS) is an uncommon, often fatal complication associated with myocardial infarction, cardiothoracic surgery, trauma, and, rarely, infective endocarditis. A 28-year-old man with prior history of bioprosthetic mitral valve replacement presented with congestive heart failure and bacteremia with Abiotrophia granulitica. Transesophageal echocardiogram showed bioprosthesis dysfunction, large vegetations, mitral regurgitation, and probable PS. Cardiac and chest CT confirmed a PS communicating with the left ventricle Patient had pulseless electrical activity and died. Autopsy showed a giant PS with layered thrombus and pseudo-endothelialized cavity. Our case highlights the importance of multimodality imaging as an important tool in management of PS.

  12. Omega-3 Fatty Acid Deficient Male Rats Exhibit Abnormal Behavioral Activation in the Forced Swim Test Following Chronic Fluoxetine Treatment: Association with Altered 5-HT1A and Alpha2A Adrenergic Receptor Expression

    PubMed Central

    Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K.

    2014-01-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n=34) or without (DEF, n=30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n=14) and DEF (n=12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (−26%, p=0.0001) and DEF+FLX (−32%, p=0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF+FLX rats exhibited significantly greater climbing behavior compared with CON+FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF+FLX rats exhibited significant elevations in climbing behavior. DEF+FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON+FLX rats. DEF+FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats. PMID:24360505

  13. Deficiency in EP4 Receptor-Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease.

    PubMed

    Fujikawa, Risako; Higuchi, Sei; Nakatsuji, Masato; Yasui, Mika; Ikedo, Taichi; Nagata, Manabu; Hayashi, Kosuke; Yokode, Masayuki; Minami, Manabu

    2017-08-01

    Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor-associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20(+/-) onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20(+/-)EPRAP(+/+) and J20(+/-)EPRAP(-/-) mice. EPRAP deficiency reversed the reduced anxiety of J20(+/-) mice but did not affect hyperactivity. No differences in spatial memory were observed between J20(+/-)EPRAP(+/+) and J20(+/-)EPRAP(-/-) mice. In comparison with J20(+/-)EPRAP(+/+), J20(+/-)EPRAP(-/-) mice exhibited less microglial accumulation and reductions in the Cd68 and tumor necrosis factor-α mRNAs in the prefrontal cortex and hippocampus. No significant differences were found between the two types of mice in the amount of amyloid-β 40 or 42 in the cortex and hippocampus. J20(+/-)EPRAP(-/-) mice reversed the reduced anxiety-like behavior and had reduced microglial activation compared with J20(+/-)EPRAP(+/+) mice. Further research is required to identify the role of EPRAP in AD, but our results indicate that EPRAP may be related to behavioral and psychological symptoms of dementia and inflammation in patients with AD. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Cerebral ventricular volume during hyponatraemia.

    PubMed Central

    Decaux, G; Szyper, M; Grivegnée, A

    1983-01-01

    In order to determine if the neurologic manifestations in chronic hyponatraemia result partly from brain oedema, we measured the cerebral ventricular volume before and after correction of hyponatraemia in eight patients with central nervous system manifestations. Only the three patients with seizures showed a clear change in the ventricular size and probably had brain oedema. PMID:6101182

  15. Right ventricular metastasis of leiomyosarcoma.

    PubMed

    Dencker, Magnus; Valind, Sven; Stagmo, Martin

    2009-05-05

    Metastatic presentation of leiomyosarcoma in the heart is very rare. We present transthoracic echocardiography and combined PET/CT images of a case with a large right ventricular metastasis of leiomyosarcoma. The patient was placed on cytostatic drugs for palliative purposes, but passed away one month later because of an untreatable ventricular tackycardia.

  16. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  17. [Fascicular ventricular tachycardia].

    PubMed

    Chiarandà, G; Di Guardo, G; Gulizia, M; Lazzaro, A; Regolo, T

    2001-11-01

    Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site.

  18. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  19. Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency–Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus123

    PubMed Central

    Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

    2016-01-01

    Background: Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. Objectives: We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring’s hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Methods: Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Results: Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Conclusions: Fetal-neonatal iron deficiency

  20. Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency-Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus.

    PubMed

    Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

    2016-03-01

    Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring's hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Fetal-neonatal iron deficiency reprograms molecular networks associated with the

  1. Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia

    PubMed Central

    Weng, Ching-Hui; Chung, Fa-Po; Chen, Yao-Chang; Lin, Shien-Fong; Huang, Po-Hsun; Kuo, Terry B. J.; Hsu, Wei-Hsuan; Su, Wen-Cheng; Sung, Yen-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Yeh, Hung-I; Chen, Yi-Jen; Hong, Yi-Ren; Chen, Shih-Ann; Hu, Yu-Feng

    2016-01-01

    Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage. PMID:27966586

  2. Abnormal rubbing and keratectasia.

    PubMed

    McMonnies, Charles W

    2007-11-01

    Hypotheses for the varied pathogenesis of the different forms of keratoconus have been outlined. Against this background, the possibility that abnormal rubbing causes or contributes to the development or progression of some forms of keratoconus has been examined. Circumstantial evidence that shows an association between abnormal rubbing and keratoconus is reviewed, and a wide range of different forms of abnormal rubbing is described. Also examined is evidence of several processes whereby the cornea appears to be, or could be, adversely affected by mechanical trauma caused by rubbing. Conditions that may increase susceptibility to mechanical rubbing trauma have been discussed. Evidence of a role for inflammatory mediators in the pathogenesis of keratoconus appears to void the description of keratoconus as a noninflammatory condition. When vigorous knuckle-rubbing forces are located on the normal peripheral cornea, the thinner or weakened cone apex may be exposed to high intraocular pressure distending forces that may tend to promote ectasia. It appears reasonable to conclude that abnormal rubbing is a cause of some types of keratoconus, not because all abnormal rubbing, or only abnormal rubbing, leads to the development of some types of keratoconus, but because abnormal rubbing may increase the likelihood of the development of some forms of keratoconus. Abnormal rubbing habits may commence or continue after routine contact lens wear is established. Any associated rubbing or contact lens trauma may contribute to the progression of keratoconus. The abnormal rubbing-ectasia association in keratoconus may extend to other forms of keratectasia, including that seen after laser in situ keratomileusis, for which a contributory abnormal rubbing hypothesis may be appropriate.

  3. Structural abnormalities of corpus callosum and cortical axonal tracts accompanied by decreased anxiety-like behavior and lowered sociability in spock3- mutant mice.

    PubMed

    Yamamoto, Ayako; Uchiyama, Koji; Nara, Tomoka; Nishimura, Naomichi; Hayasaka, Michiko; Hanaoka, Kazunori; Yamamoto, Tatsuro

    2014-01-01

    Spock3/Testican-3 is a nervous system-expressed heparan sulfate proteoglycan belonging to a subgroup of the BM-40/SPARC/osteonectin family, the role of which in brain development is unclear. Because Spock1, a member of the Spock family, inhibits their attachment to substrates and the neurite outgrowth of cultured neuronal cells, Spock3 is also thought to be similarly involved in the neuronal development. In the present study, we established a Spock3-mutant mouse harboring a deletion extending from the presumptive upstream regulatory region to exon 4 of the Spock3 locus and performed histological and behavioral studies on these mutant mice. In wild-type (WT) mice, all Spock members were clearly expressed during brain development. In adults, intense Spock1 and Spock2 expressions were observed throughout the entire brain; whereas, Spock3 expression was no longer visible except in the thalamic nuclei. Thus, Spock3 expression is mostly confined to the developmental stage of the brain. In adult mutant mice, the cells of all cortical layers were swollen. The corpus callosum was narrowed around the central region along the rostral-caudal axis and many small spaces were observed without myelin sheaths throughout the entire corpus callosum. In addition, the cortical input and output fibers did not form into thick bundled fibers as well as the WT counterparts did. Moreover, a subpopulation of corticospinal axonal fibers penetrated into the dorsal striatum with moderately altered orientations. Consistent with these modifications of brain structures, the mutant mice exhibited decreased anxiety-like behavior and lowered sociability. Together, these results demonstrate that Spock3 plays an important role in the formation or maintenance of major neuronal structures in the brain.

  4. A Case of Incontinentia Pigmenti Associated with Multiorgan Abnormalities

    PubMed Central

    Chung, Woon-Kyong; Lee, Deok-Woo; Chang, Sung-Eun; Lee, Mi-Woo; Choi, Jee-Ho

    2009-01-01

    Incontinentia pigmenti is a systemic disorder affecting the skin, teeth, eyes, nervous tissue, hair, nails, musculoskeletal system, and heart. We describe an 11-month-old girl with incontinentia pigmenti associated with a ventricular septal defect, left hemiatrophy, hemangiomas, an abnormal labial frenum, and spastic cerebral palsy manifested as left hemiplegia and developmental delay. We believe this patient illustrates that incontinentia pigmenti is a systemic disorder necessitating a multidisciplinary approach to management. PMID:20548858

  5. [Clinical value of cardiovascular magnetic resonance imaging in the diagnostic work-up of patients with suspected arrhythmogenic right ventricular dysplasia].

    PubMed

    Sánchez-Rubio, Juan; Carreras, Francesc; Pujadas, Sandra; Leta, Rubén; Guillaumet, Eva; Grande, Carlos; Viñolas, Xavier; Pons-Lladó, Guillem

    2005-09-01

    To analyze retrospectively the usefulness of cardiovascular magnetic resonance imaging in the assessment of patients with clinically suspected arrhythmogenic right ventricular dysplasia. We reviewed retrospectively findings from 46 consecutive patients (mean age, 42+/-19 years; 25 male) who were referred for investigation to rule out right ventricular dysplasia. Abnormal findings were classified according to the general diagnostic criteria established by the European Society of Cardiology. Evaluable images were available for all patients. Abnormal right ventricular findings were reported in 24 patients (52%), but only 5 were given a definite diagnosis of right ventricular dysplasia. Fatty infiltration was observed in 9 patients; it was an isolated finding in 6 but was associated with right ventricular contractile dysfunction in 3. These latter patients belonged to the group with confirmed dysplasia. None of the 22 patients (48%) with normal findings on magnetic resonance imaging was given a diagnosis of dysplasia. Cardiovascular magnetic resonance imaging enabled the right ventricle to be assessed in all patients. In those with clinically suspected dysplasia, normal findings ruled out the diagnosis. However, only 21% of those with abnormal findings on magnetic resonance imaging were finally given a confirmed diagnosis of dysplasia. Fatty infiltration of the right ventricular wall does not imply dysplasia unless it is associated with other abnormalities in right ventricular morphology or contractility. Cardiovascular magnetic resonance imaging is useful in the work-up of patients with clinically suspected arrhythmogenic right ventricular dysplasia.

  6. Congenital Left Ventricular Diverticulum Complicated by Ventricular Fibrillation.

    PubMed

    Yamasaki, Manabu; Kawamatsu, Naoto; Yoshino, Kunihiko; Abe, Kohei; Misumi, Hiroyasu

    2017-09-01

    Congenital left ventricular diverticulum (CLVD) is a rare congenital anomaly and may be associated with fatal adverse events. A previously healthy 20-year-old man collapsed as a result of sudden ventricular fibrillation (VF). Despite intractable VF, he had return of spontaneous circulation with cardiopulmonary resuscitation and subsequent introduction of venoarterial extracorporeal membrane oxygenation (ECMO). After ECMO was discontinued, cardiac magnetic resonance imaging revealed CLVD at the posterolateral wall of the left ventricle. Given the risk of recurrent VF and left ventricular rupture, he underwent surgical repair for CLVD and implantation of a subcutaneous implantable cardioverter defibrillator. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Symbolic dynamics of ventricular tachycardia and ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Chen, Jie

    2010-05-01

    In this paper, the symbolic dynamics analysis was used to analyze the complexity of normal heartbeat signal (NSR), Ventricular tachycardia (VT) and ventricular fibrillation (VF) signals. By calculating the information entropy value of symbolic sequences, the complexities were quantified. Based on different information entropy values, NSR, VT and VF signals were distinguished with satisfactory results. The study showed that a sudden drop of symbolic sequence’s entropy value indicated that the patients most likely entered the episode of ventricular tachycardia and this was a crucial episode for the clinical treatment of patients. It had important clinical significance for the automatic diagnosis.

  8. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

    PubMed

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J C; Van Leeuwen, Fred W; Dantuma, Nico P; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-03-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin.

  9. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    PubMed Central

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J. C.; Van Leeuwen, Fred W.; Dantuma, Nico P.; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin. PMID:25343989

  10. Disrupted mGluR5-Homer scaffolds mediate abnormal mGluR5 signaling, circuit function and behavior in a mouse model of Fragile X Syndrome

    PubMed Central

    Ronesi, Jennifer A.; Collins, Katie A.; Hays, Seth A.; Tsai, Nien-Pei; Guo, Weirui; Birnbaum, Shari G.; Hu, Jia-Hua; Worley, Paul F.; Gibson, Jay R.; Huber, Kimberly M.

    2012-01-01

    Enhanced mGluR5 function is causally associated with the pathophysiology of Fragile X Syndrome (FXS), a leading inherited cause of intellectual disability and autism. Here we provide evidence that altered mGluR5-Homer scaffolds contribute to mGluR5 dysfunction and phenotypes in the FXS mouse model, Fmr1 KO. In Fmr1 KO mice mGluR5 is less associated with long Homer isoforms, but more associated with the short Homer1a. Genetic deletion of Homer1a restores mGluR5- long Homer scaffolds and corrects multiple phenotypes in Fmr1 KO mice including altered mGluR5 signaling, neocortical circuit dysfunction, and behavior. Acute, peptide-mediated disruption of mGluR5-Homer scaffolds in wildtype mice mimics many Fmr1 KO phenotypes. In contrast, Homer1a deletion does not rescue altered mGluR-dependent long-term synaptic depression or translational control of FMRP target mRNAs. Our findings reveal novel functions for mGluR5-Homer interactions in the brain and delineate distinct mechanisms of mGluR5 dysfunction in a mouse model of cognitive dysfunction and autism. PMID:22267161

  11. On the abnormal "forced hydration" behavior of P(MEA-co-OEGA) aqueous solutions during phase transition from infrared spectroscopic insights.

    PubMed

    Hou, Lei; Wu, Peiyi

    2016-06-21

    Turbidity, DLS and FTIR measurements in combination with the perturbation correlation moving window (PCMW) technique and 2D correlation spectroscopy (2Dcos) analysis have been utilized to investigate the LCST-type transition of a oligo ethylene glycol acrylate-based copolymer (POEGA) in aqueous solutions in this work. As demonstrated in turbidity and DLS curves, the macroscopic phase separation was sharp and slightly concentration dependent. Moreover, individual chemical groups along polymer chains also display abrupt changes in temperature-variable IR spectra. However, according to conventional IR analysis, the C-H groups present obvious dehydration, whereas C[double bond, length as m-dash]O and C-O-C groups exhibit anomalous "forced hydration" during the steep phase transition. From these analyses together with the PCMW and 2Dcos results, it has been confirmed that the hydrophobic interaction among polymer chains drove the chain collapse and dominated the phase transition. In addition, the unexpected enhanced hydration behavior of C[double bond, length as m-dash]O and C-O-C groups was induced by forced hydrogen bonding between polar groups along polymer chains and entrapped water molecules in the aggregates, which originated from the special chemical structure of POEGA.

  12. Epicardial ventricular tachycardia.

    PubMed

    Garan, Hasan

    2013-12-01

    In ventricular tachycardia (VT) arising in the myocardial tissue, the site of origin may be the endocardium, mid-myocardium or epicardium. The incidence of epicardial origin varies with the underlying heart disease, and is probably not more than 20% in ischemic heart disease and higher in non-ischemic cardiomyopathies. Percutaneous subxiphoid access to the pericardial space has enabled a non-surgical approach to catheter mapping and ablation of epicardial VT. Several algorithms are available for electrocardiographic recognition of epicardial origin. Idiopathic epicardial VTs are rare but may be curable by catheter ablation. The electrophysiologic principles guiding the mapping and ablation of epicardial VTs are similar to those used for endocardial VTs, but the biophysics of energy delivery may be different. Complications of the epicardial approach are also different from those of endocardial ablation, and specific precautions have to be taken to protect the coronary arteries and phrenic nerves and to avoid pericardial tamponade.

  13. [Late potentials and ventricular arrhythmia].

    PubMed

    Adamec, R; Zimmermann, M

    1986-04-01

    When electrodes are placed at the surface of the thorax, high-amplification electrocardiography (HA-ECG) combined with signal summation as a function of time provides a non-invasive method for detecting electric potentials occurring after the QRS complex of the clinical electrocardiogram. These potentials are called late, and can probably be likened to the "divided" or "fragmented" potentials recorded directly on the heart or in its ventricles near zones of ischemia, infarction or aneurysm. The prevalence of late potentials of ventricular activation (LPVA) and their association with the occurrence of ventricular arrhythmias seems well established, notably in the presence of ventricular aneurysm and anamnesis of severe ventricular arrhythmia. Some studies have shown that detection of LPVAs is of value in identifying heart patients at risk of ventricular arrhythmia or sudden death. Heart disease aside, the presence of LPVAs has been demonstrated in arrhythmogenic right ventricular dysplasia and reported in Fallot's tetralogy after complete correction. A standardization of recordings and a more precise definition of LPVAs are necessary before HA-ECG can become a routine clinical method. Further, the possibility of "beat by beat" recordings with "spatial" summation will allow detection of LPVAs which vary with time and in nature and hence provide a better understanding of the genesis of ventricular arrhythmias.

  14. Familial pericentric inversion of chromosome 18: behavioral abnormalities in patients heterozygous for either the dup(18p)/del(18q) or dup(18q)/del(18p) recombinant chromosome.

    PubMed

    Vermeulen, Stefan J; Speleman, Frank; Vanransbeeck, Leen; Verspeet, Jasmien; Menten, Björn; Verschraegen-Spae, Marie-Rose; Wilde, Philippe De; Messiaen, Ludwine; Michaelis, Ron C; Leroy, Jules G

    2005-01-01

    We describe a family in which the largest hitherto reported pericentric inversion of chromosome 18, inv(18)(p11.22q23), segregates. Individuals heterozygous for the nonrecombinant inversion were unaffected. However, those heterozygous for either the dup(18p)/del(18q) or dup(18q) /del(18p) recombinant exhibited mild learning difficulty, personality disorders and deficient social behavior in the absence of mental retardation. Of the three family members tested, the behavioral abnormalities were more prominent in the two individuals with the dup(18p)/del(18q) recombinant than in the one with the dup(18q)/del(18p) recombinant. Genetic counseling issues for this family, in particular for the affected, include the enhanced probability of reduced fertility as well as the recurrence risk of the parental inversion equaling 1/2 in surviving offspring. This observation kindles the interest in determining the frequency of subtelomeric rearrangements in individuals with learning difficulty and deficiency in social interaction, phenotypic features often considered to be of multifactorial causation.

  15. Abnormal menstrual periods (image)

    MedlinePlus

    ... have a variety of causes, such as endometrial hyperplasia, endometrial polyps, uterine fibroids, and abnormal thyroid or ... endometrium becomes unusually thick it is called endometrial hyperplasia. Hyperplasia may cause profuse or extended menstrual bleeding.

  16. Abnormal haemoglobins: detection & characterization

    PubMed Central

    Wajcman, Henri; Moradkhani, Kamran

    2011-01-01

    Haemoglobin (Hb) abnormalities though quite frequent, are generally detected in populations during surveys and programmes run for prevention of Hb disorders. Several methods are now available for detection of Hb abnormalities. In this review, the following are discussed: (i) the methods used for characterization of haemoglobin disorders; (ii) the problems linked to diagnosis of thalassaemic trait; (iii) the strategy for detection of common Hb variants; and (iv) the difficulties in identification of rare variants. The differences between developing and industrialized countries for the strategies employed in the diagnosis of abnormal haemoglobins are considered. We mention the limits and pitfalls for each approach and the necessity to characterize the abnormalities using at least two different methods. The recommended strategy is to use a combination of cation-exchange high performance chromatography (CE-HPLC), capillary electrophoresis (CE) and when possible isoelectric focusing (IEF). Difficult cases may demand further investigations requiring specialized protein and/or molecular biology techniques. PMID:22089618

  17. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  18. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  19. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  20. Muscle tone abnormalities.

    PubMed

    Habel, M

    1997-01-01

    Rehabilitation nurses frequently encounter clients with neurological disorders that adversely affect muscle tone. By understanding the physiological etiology of abnormal muscle tone, individual practitioners can design nursing interventions for various care settings that appropriately protect clients from injury and that can help clients and caregivers learn effective techniques for managing muscle tone problems. This article explains muscle tone abnormalities in detail and offers insight into how rehabilitation nurses can play a key role in managing clients' alterations in muscle tone.

  1. Right ventricular centripetal plication: an aggressive right ventricular exclusion technique.

    PubMed

    Sugiura, Junya; Murayama, Hiroomi; Okada, Noritaka

    2017-01-01

    In patients with a functional single ventricle such as neonatal Ebstein's anomaly or pulmonary atresia with intact ventricular septum, the right ventricle can compress the left ventricle and decrease its performance due to the volume or pressure overload of the right ventricle. We have performed right ventricular centripetal plication from the inside to exclude the right ventricle and to minimize the adverse effect on the left ventricle and the results have been satisfactory.

  2. Effects of isometric handgrip and dynamic exercise on left-ventricular function

    SciTech Connect

    Peter, C.A.; Jones, R.H.

    1980-12-01

    Radionuclide angiocardiography was used to assess cardiac function during isometric handgrip and bicycle exercise in ten normal volunteers and in 20 patients with documented coronary artery disease. Handgrip stress evoked a small increase in cardiac output that resulted from a concomitant increase i heart rate and no change in left-left-ventricular function. The most reliable criterion for diagnosis of coronary artery disease by handgrip was development of a new wall-motion abnormality. However, abnormal wall motion was observed in only 45% of patients with coronary artery disease and in one of the ten normal subjects. In normal subjects, left ventricular function during bicycle exercise was characterized by an increase in left-ventricular ejection fraction with little change in cardiac volumes. The failure to increase left-ventricular ejection fraction by at least 0.05 identified 19 of 20 patients with coronary artery disease with no false positives. Therefore, bicycle exercise evokes a more dramatic cardiovascular response than handgrip stress and is the preferable stress modality for inducing abnormalities of left-ventricular function for detection of coronary artery disease.

  3. Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

    NASA Technical Reports Server (NTRS)

    Makikallio, T. H.; Koistinen, J.; Jordaens, L.; Tulppo, M. P.; Wood, N.; Golosarsky, B.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

    1999-01-01

    The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

  4. Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

    NASA Technical Reports Server (NTRS)

    Makikallio, T. H.; Koistinen, J.; Jordaens, L.; Tulppo, M. P.; Wood, N.; Golosarsky, B.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

    1999-01-01

    The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

  5. Diabetes, gender, and left ventricular structure in African-Americans: the atherosclerosis risk in communities study

    PubMed Central

    Foppa, Murilo; Duncan, Bruce B; Arnett, Donna K; Benjamin, Emelia J; Liebson, Philip R; Manolio, Teri A; Skelton, Thomas N

    2006-01-01

    Background Cardiovascular risk associated with diabetes may be partially attributed to left ventricular structural abnormalities. However, the relations between left ventricular structure and diabetes have not been extensively studied in African-Americans. Methods We studied 514 male and 965 female African-Americans 51 to 70 years old, in whom echocardiographic left ventricular mass measurements were collected for the ARIC Study. In these, we investigated the independent association of diabetes with left ventricular structural abnormalities. Results Diabetes, hypertension and obesity prevalences were 22%, 57% and 45%, respectively. Unindexed left ventricular mass was higher with diabetes in both men (238.3 ± 79.4 g vs. 213.7 ± 58.6 g; p < 0.001) and women (206.4 ± 61.5 g vs. 176.9 ± 50.1 g; p < 0.001), respectively. Prevalence of height-indexed left ventricular hypertrophy was higher in women while increased relative wall thickness was similar in men and women. Those with diabetes had higher prevalences of height-indexed left ventricular hypertrophy (52% vs. 32%; p < 0.001), and of increased relative wall thickness (73% vs. 64%; p = 0.002). Gender-adjusted associations of diabetes with left ventricular hypertrophy (OR = 2.29 95%CI:1.79–2.94) were attenuated after multiple adjustments in logistic regression (OR = 1.50 95%CI:1.12–2.00). Diabetes was associated with higher left ventricle diameter (OR = 2.13 95%CI:1.28–3.53) only in men and with higher wall thickness (OR = 1.89 95%CI:1.34–2.66) only in women. Attenuations in diabetes associations were frequently seen after adjustment for obesity indices. Conclusion In African-Americans, diabetes is associated with left ventricular hypertrophy and, with different patterns of left ventricular structural abnormalities between genders. Attenuation seen in adjusted associations suggests that the higher frequency of structural abnormalities seen in diabetes may be due to factors other than hyperglycemia. PMID

  6. [Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

    PubMed

    Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B

    2009-01-01

    The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI < 2.06 mg/g - RWT > 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT < 0.71; and concentric LVH, LVMI > 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.

  7. Right Ventricular Myocardial Ischemia with Arrhythmia in an Asphyxiated Newborn

    PubMed Central

    Solevåg, Anne Lee; Schmölzer, Georg M.; Cheung, Po-Yin

    2016-01-01

    Background Infant and neonatal myocardial infarction (MI) has been described in association with congenital heart disease, coronary artery abnormalities, myocarditis, and tumors. MI in the perinatal period in a structurally normal heart and with ventricular arrhythmia as a presenting feature has not been thoroughly described. Published case reports describe treatment methods extrapolated from adult MI. However, due to the rare occurrence, the most appropriate acute treatment for both MI and ventricular arrhythmia in newborn infants remains unknown. Case A male term infant with perinatal asphyxia and need for extensive cardiopulmonary resuscitation at birth had ventricular tachyarrhythmia and ST-elevations on electrocardiogram. Four hours after birth, he died from cardiogenic failure. A thrombus at the right coronary artery was found on autopsy. Conclusion MI in the perinatal period in a structurally normal heart is very rare and mortality is high. Although acute treatments extrapolated from adult MI has been described to result in favorable outcomes in newborn infants, guidelines are lacking on how to manage acute MI and associated ventricular arrhythmia. PMID:27280062

  8. Normal and abnormal lid function.

    PubMed

    Rucker, Janet C

    2011-01-01

    This chapter on lid function is comprised of two primary sections, the first on normal eyelid anatomy, neurological innervation, and physiology, and the second on abnormal eyelid function in disease states. The eyelids serve several important ocular functions, the primary objectives of which are protection of the anterior globe from injury and maintenance of the ocular tear film. Typical eyelid behaviors to perform these functions include blinking (voluntary, spontaneous, or reflexive), voluntary eye closure (gentle or forced), partial lid lowering during squinting, normal lid retraction during emotional states such as surprise or fear (startle reflex), and coordination of lid movements with vertical eye movements for maximal eye protection. Detailed description of the neurological innervation patterns and neurophysiology of each of these lid behaviors is provided. Abnormal lid function is divided by conditions resulting in excessive lid closure (cerebral ptosis, apraxia of lid opening, blepharospasm, oculomotor palsy, Horner's syndrome, myasthenia gravis, and mechanical) and those resulting in excessive lid opening (midbrain lid retraction, facial nerve palsy, and lid retraction due to orbital disease).

  9. Catheter Ablation for Ventricular Arrhythmias

    PubMed Central

    Nof, Eyal; Stevenson, William G; John, Roy M

    2013-01-01

    Catheter ablation has emerged as an important and effective treatment option for many recurrent ventricular arrhythmias. The approach to ablation and the risks and outcomes are largely determined by the nature of the severity and type of underlying heart disease. In patients with structural heart disease, catheter ablation can effectively reduce ventricular tachycardia (VT) episodes and implantable cardioverter defibrillator (ICD) shocks. For VT and symptomatic premature ventricular beats that occur in the absence of structural heart disease, catheter ablation is often effective as the sole therapy. Advances in catheter technology, imaging and mapping techniques have improved success rates for ablation. This review discusses current approaches to mapping and ablation for ventricular arrhythmias. PMID:26835040

  10. [Repetitive monomorphic ventricular tachycardia (Gallavardin type): clinical and electrophysiological characteristics in 20 patients].

    PubMed

    Hoffmann, E; Reithmann, C; Neuser, H; Nimmermann, P; Remp, T; Steinbeck, G

    1998-05-01

    Repetitive monomorphic ventricular tachycardia (RMVT) is defined by the presence of numerous monomorphic isolated, premature ventricular complexes, couplets, and runs of unsustained ventricular tachycardia having the same morphology in patients without structural heart disease. Patients with RMVT mostly demonstrate the typical left bundle branch block morphology with normal or rightward axis during tachycardia. At our institution, 20 patients with RMVT have been systematically studied: a syncope had occurred in 35% of our patients, in three cases a syncope was the first manifestation of the RMVT. Of our RMVT patients, 25% developed sustained episodes (> 3 min) of ventricular tachycardia as documented by Holter ECG. The salvos of ventricular tachycardia are generally short in RMVT. This behavior and the typical exercise dependence differentiates RMVT from paroxysmal sustained idiopathic ventricular tachycardia. Exercise testing is mandatory for correct diagnosis of RMVT. In our institution, 85-90% of RMVT patients demonstrated runs of ventricular tachycardia or sustained ventricular tachycardia while on a treadmill (exercise test) or during isoproterenol infusion. RMVT was inducible by programmed electrical right ventricular stimulation in only 13% of our patients. Therefore, in patients with suspected RMVT programmed electrophysiological stimulation is only useful to differentiate a ventricular tachycardia from a supraventricular tachycardia with bundle brunch block or in patients with unexplained syncope. The prognosis is considered generally good; in our patients no life threatening ventricular tachyarrhythmias were observed during a follow-up of up to 4 years. Verapamil and beta-adrenoceptor antagonists generally offer symptomatic improvement. In some cases treatment with a class III antiarrhythmic agent is necessary. While drug-refractory paroxysmal sustained idiopathic ventricular tachycardia can be abladed with both immediate and long-term success, catheter

  11. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    PubMed

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior<