WorldWideScience

Sample records for cardiac specification independently

  1. Patient-specific models of cardiac biomechanics

    Science.gov (United States)

    Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

    2013-07-01

    Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

  2. Is a sedentary lifestyle an independent predictor for hospital and early mortality after elective cardiac surgery?

    NARCIS (Netherlands)

    Noyez, L.; Biemans, I.; Verkroost, M.W.; Swieten, H.A. van

    2013-01-01

    OBJECTIVE: This study evaluates whether a sedentary lifestyle is an independent predictor for increased mortality after elective cardiac surgery. METHODS: Three thousand one hundred fifty patients undergoing elective cardiac surgery between January 2007 and June 2012 completed preoperatively the

  3. Gender specific pattern of left ventricular cardiac adaptation to ...

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Some gender specific associations with left ventricular structure and function have been described ... used for analysis. ... risk due to LVH and that cardiac adaptation to ... had history taking, physical examination and ..... between the gender specific differences in cardiac ... A metaanalysis of individual.

  4. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure

    NARCIS (Netherlands)

    D. Westermann (Dirk); A. Riad (Alexander); O. Lettau (Olga); A.J.M. Roks (Anton); K. Sawatis (Konstantinos); P.M. Becher (Peter Moritz); F. Escher (Felicitas); A.H.J. Danser (Jan); H.P. Schultheiss (Heinz-Peter); C. Tschöpe (Carsten)

    2008-01-01

    textabstractPharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac

  5. Gender specific pattern of left ventricular cardiac adaptation to ...

    African Journals Online (AJOL)

    Background: Cardiac adaptation to hypertension and obesity may be related to many factors such as race, gender and haemodynamic status. Some gender specific associations with left ventricular structure and function have been described among Caucasians. Objectives: To describe the sex specific pattern of left ...

  6. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

    Directory of Open Access Journals (Sweden)

    Sujith Dassanayaka

    2018-07-01

    Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

  7. Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death

    Directory of Open Access Journals (Sweden)

    Naira F. Z. Schneider

    2018-03-01

    Full Text Available Cardiac glycosides (CGs are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.

  8. Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.

    Science.gov (United States)

    Reichman, David E; Park, Laura; Man, Limor; Redmond, David; Chao, Kenny; Harvey, Richard P; Taketo, Makoto M; Rosenwaks, Zev; James, Daylon

    2018-01-08

    Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs. © 2018. Published by The Company of Biologists Ltd.

  9. Evaluation of an intervention to increase self-efficacy for independent exercise in cardiac rehabilitation.

    Science.gov (United States)

    Barkley, Sherry A; Fahrenwald, Nancy L

    2013-01-01

    Adherence to independent exercise is an essential outcome of cardiac rehabilitation (CR), yet limited theory-based interventions to improve adherence exist. This study tested the effects of an intervention based on Bandura's conceptualization of self-efficacy. The self-efficacy coaching intervention (SCI), a supplement to standard care, was designed to increase self-efficacy for independent exercise and independent exercise behavior in CR. We examined whether the SCI vs. attention control (AC) resulted in improved exercise self-efficacy (ESE), barriers self-efficacy (BARSE), and minutes of independent exercise for CR participants (n = 65). While between-group differences did not reach significance (p > .10) for any of the outcome measures, significant within-group changes were noted in BARSE scores and independent exercise (p exercise for the AC group was also significant (p =. 006). Further study is needed to explore whether short-term changes translate into maintenance of independent exercise participation after program completion.

  10. Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CT

    International Nuclear Information System (INIS)

    Staniak, Henrique Lane; Sharovsky, Rodolfo; Pereira, Alexandre Costa; Castro, Cláudio Campi de; Benseñor, Isabela M.; Lotufo, Paulo A.; Bittencourt, Márcio Sommer

    2014-01-01

    Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure

  11. Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Staniak, Henrique Lane; Sharovsky, Rodolfo [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil); Pereira, Alexandre Costa [Hospital das Clínicas - Universidade de São Paulo, São Paulo, SP (Brazil); Castro, Cláudio Campi de; Benseñor, Isabela M.; Lotufo, Paulo A. [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil); Faculdade de Medicina - Universidade de São Paulo, São Paulo, SP (Brazil); Bittencourt, Márcio Sommer, E-mail: msbittencourt@mail.harvard.edu [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-01-15

    Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure.

  12. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A

    2009-01-01

    parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function....

  13. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

    Directory of Open Access Journals (Sweden)

    Pujiao Yu

    2016-01-01

    Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

  14. Acute kidney injury is independently associated with higher mortality after cardiac surgery

    DEFF Research Database (Denmark)

    Kandler, Kristian; Jensen, Mathias E; Nilsson, Jens C

    2014-01-01

    OBJECTIVES: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN: Retrospective study with Cox regression analysis to control for possible preoperative......, intraoperative and postoperative confounders. SETTING: University hospital-based single-center study. PARTICIPANTS: All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Acute surgery within 24 hours of coronary angiography.......21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), psurgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent...

  15. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

  16. Is a sedentary lifestyle an independent predictor for hospital and early mortality after elective cardiac surgery?

    Science.gov (United States)

    Noyez, L; Biemans, I; Verkroost, M; van Swieten, H

    2013-10-01

    This study evaluates whether a sedentary lifestyle is an independent predictor for increased mortality after elective cardiac surgery. Three thousand one hundred fifty patients undergoing elective cardiac surgery between January 2007 and June 2012 completed preoperatively the Corpus Christi Heart Project questionnaire concerning physical activity (PA). Based on this questionnaire, 1815 patients were classified as active and 1335 patients were classified as sedentary. The endpoints of the study were hospital mortality and early mortality. The study population had a mean age of 69.7 ± 10.1 (19-95) years and a mean logistic EuroSCORE risk of 5.1 ± 5.6 (0.88-73.8). Sedentary patients were significantly older (p = 0.001), obese (p = 0.001), had a higher EuroSCORE risk (p = 0.001), and a higher percentage of complications. Hospital mortality (1.1 % versus 0.4 % (p = 0.014)) and early mortality (1.5 % versus 0.6 % (p = 0.006)) were significantly higher in the sedentary group compared with the active group. However, a sedentary lifestyle was not identified as an independent predictor for hospital mortality (p = 0.61) or early mortality (p = 0.70). Sedentary patients were older, obese and had a higher EuroSCORE risk. They had significantly more postoperative complications, higher hospital mortality and early mortality. Despite these results, sedentary behaviour could not be identified as an independent predictor for hospital or early mortality.

  17. Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin.

    Science.gov (United States)

    Kolb, Justin; Li, Frank; Methawasin, Mei; Adler, Maya; Escobar, Yael-Natalie; Nedrud, Joshua; Pappas, Christopher T; Harris, Samantha P; Granzier, Henk

    2016-08-01

    Thin filament length (TFL) is an important determinant of the force-sarcomere length (SL) relation of cardiac muscle. However, the various mechanisms that control TFL are not well understood. Here we tested the previously proposed hypothesis that the actin-binding protein nebulin contributes to TFL regulation in the heart by using a cardiac-specific nebulin cKO mouse model (αMHC Cre Neb cKO). Atrial myocytes were studied because nebulin expression has been reported to be most prominent in this cell type. TFL was measured in right and left atrial myocytes using deconvolution optical microscopy and staining for filamentous actin with phalloidin and for the thin filament pointed-end with an antibody to the capping protein Tropomodulin-1 (Tmod1). Results showed that TFLs in Neb cKO and littermate control mice were not different. Thus, deletion of nebulin in the heart does not alter TFL. However, TFL was found to be ~0.05μm longer in the right than in the left atrium and Tmod1 expression was increased in the right atrium. We also tested the hypothesis that the length of titin's spring region is a factor controlling TFL by studying the Rbm20(ΔRRM) mouse which expresses titins that are ~500kDa (heterozygous mice) and ~1000kDa (homozygous mice) longer than in control mice. Results revealed that TFL was not different in Rbm20(ΔRRM) mice. An unexpected finding in all genotypes studied was that TFL increased as sarcomeres were stretched (~0.1μm per 0.35μm of SL increase). This apparent increase in TFL reached a maximum at a SL of ~3.0μm where TFL was ~1.05μm. The SL dependence of TFL was independent of chemical fixation or the presence of cardiac myosin-binding protein C (cMyBP-C). In summary, we found that in cardiac myocytes TFL varies with SL in a manner that is independent of the size of titin or the presence of nebulin. Copyright © 2016. Published by Elsevier Ltd.

  18. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    Science.gov (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  19. Towards functional specification independent of control system suppliers

    International Nuclear Information System (INIS)

    Galara, D.; Leret, E.

    1997-01-01

    For the next nuclear power plant generation, REP 2000, the Engineering and construction Division (ED) and the Research and development Division (R and D) of Electricite de France are working together in the field of Instrumentation and Control (I and C) to improve its engineering method and tools. This method and these tools are defined on the basis of the experience feedback from the N4 nuclear power plant generation and the current information technology, to improve engineering competitiveness and quality of control applications. We intend to decouple the I and C processing from the I and C Human Machine Interface (HMI), because methods and tools are different. In this paper, we only focus on method and tools for I and C processing. We define the I and C processing life cycle into three phases. The first phase is the specification of the control application processing, the product of which is called Functional Requirement Diagrams (FRDs). The second phase is the design of the I and C system. This phase is subdivided into two steps. The step 1 is the distribution of the FRDs into an I and C architecture. The step 2 is the allocation of resources of the I and C system, to support the distributed FRDs. The third phase is the implementation of the distributed FRDs into I and C equipment. The aim of the Engineering Division is to achieve formal FRDs, independent of I and C suppliers. This allows a large improvement for the quality of the specification and the dimensioning of the I and C system before calls for tenders. For the specification phase, studies are almost completed. For the design and the implementation phases, studies and experiments are in progress with European I and C system suppliers. As a conclusion, we present the interest of EDF for standards and especially IEC 1131 improvements. (author). 5 figs

  20. Towards functional specification independent of control system suppliers

    Energy Technology Data Exchange (ETDEWEB)

    Galara, D; Leret, E [Electricite de France, Research and Development Div., Power Plant Control Branch, Chatou (France)

    1997-07-01

    For the next nuclear power plant generation, REP 2000, the Engineering and construction Division (ED) and the Research and development Division (R and D) of Electricite de France are working together in the field of Instrumentation and Control (I and C) to improve its engineering method and tools. This method and these tools are defined on the basis of the experience feedback from the N4 nuclear power plant generation and the current information technology, to improve engineering competitiveness and quality of control applications. We intend to decouple the I and C processing from the I and C Human Machine Interface (HMI), because methods and tools are different. In this paper, we only focus on method and tools for I and C processing. We define the I and C processing life cycle into three phases. The first phase is the specification of the control application processing, the product of which is called Functional Requirement Diagrams (FRDs). The second phase is the design of the I and C system. This phase is subdivided into two steps. The step 1 is the distribution of the FRDs into an I and C architecture. The step 2 is the allocation of resources of the I and C system, to support the distributed FRDs. The third phase is the implementation of the distributed FRDs into I and C equipment. The aim of the Engineering Division is to achieve formal FRDs, independent of I and C suppliers. This allows a large improvement for the quality of the specification and the dimensioning of the I and C system before calls for tenders. For the specification phase, studies are almost completed. For the design and the implementation phases, studies and experiments are in progress with European I and C system suppliers. As a conclusion, we present the interest of EDF for standards and especially IEC 1131 improvements. (author). 5 figs.

  1. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  2. Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Angela S. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); National Heart Centre Singapore, Singapore (Singapore); Murthy, Venkatesh L.; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Wu, Justina [Brigham and Women' s Hospital, Division of Cardiology, Department of Medicine, and the Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Dorbala, Sharmila [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Department of Radiology and the Division of Cardiology, Noninvasive Cardiovascular Imaging Section, Boston, MA (United States)

    2015-09-15

    Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical {sup 82}Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function. (orig.)

  3. Factors independently associated with cardiac troponin I levels in young and healthy adults from the general population.

    Science.gov (United States)

    Bossard, Matthias; Thériault, Sébastien; Aeschbacher, Stefanie; Schoen, Tobias; Kunz, Seraina; von Rotz, Mirco; Estis, Joel; Todd, John; Risch, Martin; Mueller, Christian; Risch, Lorenz; Paré, Guillaume; Conen, David

    2017-02-01

    Determinants of cardiomyocyte injury as quantified by high-sensitivity cardiac troponin I (cTnI) in young and healthy individuals, and sex-specific 99th percentiles are largely unknown. Our study included 2077 adults from the general population aged 25-41 years without cardiovascular disease. cTnI was measured using a high-sensitivity assay. We performed stepwise backward linear regression analyses to identify variables independently associated with hs-cTnI levels, and calculated narrow-sense heritability from 1638-genotyped participants. Median age was 37 years. cTnI was quantifiable in all but 11 participants (99.5 %). Median (interquartile range) cTnI was significantly higher in men than in women [0.99 (0.71; 1.65) versus 0.47 (0.33; 0.71) ng/L, p age, systolic blood pressure, heart rate, left ventricular mass, N-terminal pro B-type natriuretic peptide, and creatine kinase (all p age, and systolic blood pressure belong to the strongest determinants of hs-cTnI in healthy adults. The 99th percentile was three times higher in men compared to women. Hence, sex-specific cut-off values may be preferable when applying hs-cTnI for screening purposes. Our results may also improve the interpretation of cTn levels in daily clinical practice.

  4. Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

    Directory of Open Access Journals (Sweden)

    Shu-ichi Fujita

    Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

  5. A novel fission-independent role of dynamin-related protein 1 in cardiac mitochondrial respiration.

    Science.gov (United States)

    Zhang, Huiliang; Wang, Pei; Bisetto, Sara; Yoon, Yisang; Chen, Quan; Sheu, Shey-Shing; Wang, Wang

    2017-02-01

    Mitochondria in adult cardiomyocytes exhibit static morphology and infrequent dynamic changes, despite the high abundance of fission and fusion regulatory proteins in the heart. Previous reports have indicated that fusion proteins may bear functions beyond morphology regulation. Here, we investigated the role of fission protein, dynamin-related protein 1 (DRP1), on mitochondrial respiration regulation in adult cardiomyocytes. By using genetic or pharmacological approaches, we manipulated the activity or protein level of fission and fusion proteins and found they mildly influenced mitochondrial morphology in adult rodent cardiomyocytes, which is in contrast to their significant effect in H9C2 cardiac myoblasts. Intriguingly, inhibiting endogenous DRP1 by dominant-negative DRP1 mutation (K38A), shRNA, or Mdivi-1 suppressed maximal respiration and respiratory control ratio in isolated mitochondria from adult mouse heart or in adult cardiomyocytes from rat. Meanwhile, basal respiration was increased due to increased proton leak. Facilitating mitofusin-mediated fusion by S3 compound, however, failed to inhibit mitochondrial respiration in adult cardiomyocytes. Mechanistically, DRP1 inhibition did not affect the maximal activity of individual respiratory chain complexes or the assembly of supercomplexes. Knocking out cyclophilin D, a regulator of mitochondrial permeability transition pore (mPTP), abolished the effect of DRP1 inhibition on respiration. Finally, DRP1 inhibition decreased transient mPTP-mediated mitochondrial flashes, delayed laser-induced mPTP opening and suppressed mitochondrial reactive oxygen species (ROS). These results uncover a novel non-canonical function of the fission protein, DRP1 in maintaining or positively stimulating mitochondrial respiration, bioenergetics and ROS signalling in adult cardiomyocyte, which is likely independent of morphological changes. Published on behalf of the European Society of Cardiology. All rights reserved. © The

  6. Maternal Diet-Induced Obesity Programmes Cardiac Dysfunction in Male Mice Independently of Post-Weaning Diet.

    Science.gov (United States)

    Loche, Elena; Blackmore, Heather L; Carpenter, Asha A M; Beeson, Jessica H; Pinnock, Adele; Ashmore, Thomas J; Aiken, Catherine E; de Almeida-Faria, Juliana; Schoonejans, Josca; Giussani, Dino A; Fernandez-Twinn, Denise S; Ozanne, Susan E

    2018-04-04

    Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity. The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure and function was assessed in 8-week old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P<0.0001) and leptin levels (P<0.0001); maternal obesity (P=0.001) and a post-weaning obesogenic diet (P=0.002) increased absolute heart weight; maternal obesity (P=0.01) and offspring obesity (P=0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7:Myh6 ratio; P=0.0004), however these genes were not affected by offspring diet; maternal obesity (P=0.02) and offspring obesity (P=0.05) caused hypertension and effects were additive. Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes and remodelling of cardiac structure. These data highlight that the

  7. Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

    Science.gov (United States)

    Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

    2016-01-01

    We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (Pendurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, Pendurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

  8. Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

    Science.gov (United States)

    Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

    2016-09-01

    We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (Pendurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, Pendurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

  9. Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

    Science.gov (United States)

    Koh, Angela S; Murthy, Venkatesh L; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Wu, Justina; Di Carli, Marcelo F; Dorbala, Sharmila

    2015-09-01

    Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

  10. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  11. Construction and Development of a Cardiac Tissue-Specific and Hypoxia-Inducible Expression Vector

    Directory of Open Access Journals (Sweden)

    Shahrooz Ghaderi

    2018-03-01

    Full Text Available Purpose: Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette. Methods: We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE, cardiac specific promoter, internal ribosome entry site (IRES, and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak. Results: Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2<1% transgene expression. Conclusion: It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter.

  12. Estrogen Therapy, Independent of Timing, Improves Cardiac Structure and Function in Oophorectomized mRen2.Lewis Rats

    Science.gov (United States)

    Jessup, Jewell A.; Wang, Hao; MacNamara, Lindsay M.; Presley, Tennille D.; Kim-Shapiro, Daniel B.; Zhang, Lili; Chen, Alex F.; Groban, Leanne

    2013-01-01

    Objective mRen2.Lewis Rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment following the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide (NO) release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing chronic 17 β-estradiol (E2) therapy on myocardial function, structure, and the cardiac NO system. Methods Oophrectomy (OVX; n=24) or sham-operation (Sham; n=13) was performed in 4-week-old, female mRen2.Lewis rats. Following randomization, OVX rats received E2 immediately (OVX + early E2; n=7), E2 at 11 weeks of age (OVX + late E2 N=8), or no E2 at all (OVX N=9). Results Early E2 was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared to OVX rats without E2 supplementation. Late E2 similarly attenuated the adverse effects of ovarian hormone loss on tissue-Doppler derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation, or mitral annular velocity (e′). Early and late exposure to E2 decreased dihydrobiopterin, but only late E2 yielded significant increases in cardiac nitrite concentrations. Conclusions Although there were some similarities between early and late E2 treatment on preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 was most consistent with late supplementation. The cardioprotective effects of late E2 were independent of blood pressure and may have occurred through regulation of cardiac biopterins and NO production. PMID:23481117

  13. Pathological 99mTc-sestamibi myocardial perfusion scintigraphy is independently associated with emerging cardiac events in elderly patients with known or suspected coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Bucerius, Jan; Joe, Alexius Y.; Herder, Ellen; Brockmann, Holger; Biermann, Kim; Palmedo, Holger; Biersack, Hans-Juergen (Dept. of Nuclear Medicine, Univ. of Bonn (Germany)), e-mail: jan.bucerius@ukb.uni-bonn.de; Tiemann, Klaus (Dept. of Internal Medicine II, Univ. of Bonn (Germany))

    2011-02-15

    Background: Only few data are available regarding the prognostic impact of myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS) regarding emerging cardiac events in elderly patients Purpose: To evaluate the prognostic value of MPS regarding emerging cardiac events in patients aged =70 years with known or suspected coronary artery disease (CAD). Material and Methods: One hundred and thirty-three patients (74.6 +- 3.7 years) who underwent exercise or pharmacological stress/rest MPS were included in this analysis. Semi-quantitative visual interpretation of MPS images was performed and Summed-Stress- (SSS), Summed-Difference- (SDS), and Summed-Rest Scores (SRS) were calculated. Multivariate logistic regression analyses were calculated for evaluation of the independent prognostic impact of MPS results and several cardiac-related patient characteristics with regard to emerging cardiac events. Kaplan-Meier survival- and log rank analyses were calculated for assessment of cardiac event-free survival. Results: Pathological SSS (OR: 3.3), angina (OR: 2.7) and ischemic ECG (OR: 3.0) were independently associated with cardiac events. Patients with pathological SSS (p = 0.005) and ischemic ECG (p = 0.012) had a significantly lower incidence of cardiac event-free survival. Conclusion: Pathological MPS is independently associated with emerging cardiac events predicting a significantly lower incidence of cardiac event-free survival in patients aged =70 years

  14. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen

    2015-01-01

    fibers. Biopsies of left ventricular cardiac muscle and soleus muscle, a type I-rich oxidative skeletal muscle, were obtained from 15 healthy domestic cats. Enzymatic activity of citrate synthase (CS), a biomarker of mitochondrial content, was measured. Mitochondrial OXPHOS capacity with various kinds...

  15. Wnt signaling balances specification of the cardiac and pharyngeal muscle fields

    Science.gov (United States)

    Mandal, Amrita; Holowiecki, Andrew; Song, Yuntao Charlie; Waxman, Joshua S.

    2017-01-01

    Canonical Wnt/β-catenin (Wnt) signaling plays multiple conserved roles during fate specification of cardiac progenitors in developing vertebrate embryos. Although lineage analysis in ascidians and mice has indicated there is a close relationship between the cardiac second heart field (SHF) and pharyngeal muscle (PM) progenitors, the signals underlying directional fate decisions of the cells within the cardio-pharyngeal muscle field in vertebrates are not yet understood. Here, we examined the temporal requirements of Wnt signaling in cardiac and PM development. In contrast to a previous report in chicken embryos that suggested Wnt inhibits PM development during somitogenesis, we find that in zebrafish embryos Wnt signaling is sufficient to repress PM development during anterior-posterior patterning. Importantly, the temporal sensitivity of dorso-anterior PMs to increased Wnt signaling largely overlaps with when Wnt signaling promotes specification of the adjacent cardiac progenitors. Furthermore, we find that excess early Wnt signaling can cell autonomously promote expansion of the first heart field (FHF) progenitors at the expense of PM and SHF within the anterior lateral plate mesoderm (ALPM). Our study provides insight into an antagonistic developmental mechanism that balances the sizes of the adjacent cardiac and PM progenitor fields in early vertebrate embryos. PMID:28087459

  16. Exercise and Type 2 Diabetes Mellitus : Changes in Tissue-specific Fat Distribution and Cardiac Function

    NARCIS (Netherlands)

    Jonker, Jacqueline T.; de Mol, Pieter; de Vries, Suzanna T.; Widya, Ralph L.; Hammer, Sebastiaan; van Schinkel, Linda D.; van der Meer, Rutger W.; Gans, Rijk O. B.; Webb, Andrew G.; Kan, Hermien E.; de Koning, Eelco J. P.; Bilo, Henk J. G.; Lamb, Hildo J.

    2013-01-01

    Purpose: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Materials and Methods: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics

  17. Patient-specific cardiac phantom for clinical training and preprocedure surgical planning.

    Science.gov (United States)

    Laing, Justin; Moore, John; Vassallo, Reid; Bainbridge, Daniel; Drangova, Maria; Peters, Terry

    2018-04-01

    Minimally invasive mitral valve repair procedures including MitraClip ® are becoming increasingly common. For cases of complex or diseased anatomy, clinicians may benefit from using a patient-specific cardiac phantom for training, surgical planning, and the validation of devices or techniques. An imaging compatible cardiac phantom was developed to simulate a MitraClip ® procedure. The phantom contained a patient-specific cardiac model manufactured using tissue mimicking materials. To evaluate accuracy, the patient-specific model was imaged using computed tomography (CT), segmented, and the resulting point cloud dataset was compared using absolute distance to the original patient data. The result, when comparing the molded model point cloud to the original dataset, resulted in a maximum Euclidean distance error of 7.7 mm, an average error of 0.98 mm, and a standard deviation of 0.91 mm. The phantom was validated using a MitraClip ® device to ensure anatomical features and tools are identifiable under image guidance. Patient-specific cardiac phantoms may allow for surgical complications to be accounted for preoperative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.

  18. Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

    Science.gov (United States)

    Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

    2013-11-01

    To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

  19. Characterization and validation of new tools for measuring site-specific cardiac troponin I phosphorylation.

    Science.gov (United States)

    Thoemmes, Stephen F; Stutzke, Crystal A; Du, Yanmei; Browning, Michael D; Buttrick, Peter M; Walker, Lori A

    2014-01-31

    Phosphorylation of cardiac troponin I is a well established mechanism by which cardiac contractility is modulated. However, there are a number of phosphorylation sites on TnI which contribute singly or in combination to influence cardiac function. Accordingly, methods for accurately measuring site-specific TnI phosphorylation are needed. Currently, two strategies are employed: mass spectrometry, which is costly, difficult and has a low throughput; and Western blotting using phospho-specific antibodies, which is limited by the availability of reagents. In this report, we describe a cohort of new site-specific TnI phosphoantibodies, generated against physiologically relevant phosphorylation sites, that are superior to the current commercially available antibodies: to phospho-serine 22/23 which shows a >5-fold phospho-specificity for phosphorylated TnI; to phospho-serine 43, which has >3-fold phospho-specificity for phosphorylated TnI; and phospho-serine 150 which has >2-fold phospho-specificity for phosphorylated TnI. These new antibodies demonstrated greater sensitivity and specificity for the phosphorylated TnI than the most widely used commercially available reagents. For example, at a protein load of 20 μg of total cardiac extract, a commercially available antibody recognized both phosphorylated and dephosphorylated TnI to the same degree. At the same protein load our phospho-serine 22/23 antibody exhibited no cross-reactivity with dephosphorylated TnI. These new tools should allow a more accurate assessment and a better understanding of the role of TnI phosphorylation in the response of the heart to pathologic stress. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

    Science.gov (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-11-07

    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  1. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  2. Patient-reported mental and physical health outcomes are independent predictors of one-year mortality and cardiac events across cardiac diagnoses. Findings from the national DenHeart survey."

    DEFF Research Database (Denmark)

    Berg, Selina Kikkenborg; Thorup, Charlotte Brun; Borregaard, Britt

    2018-01-01

    -reported outcomes at hospital discharge as a predictor of mortality and cardiac events. Design: A cross-sectional survey with register follow-up. Methods: Participants: All patients discharged from April 2013 to April 2014 from five national heart centres in Denmark. Main outcomes: Patient-reported outcomes......Aims: Patient-reported quality of life and anxiety/depression scores provide important prognostic information independently of traditional clinical data. The aims of this study were to describe: (a) mortality and cardiac events one year after hospital discharge across cardiac diagnoses; (b) patient...

  3. Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy

    DEFF Research Database (Denmark)

    Chen, I Y; Gheysens, O; Ray, S

    2010-01-01

    in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery...... genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression...

  4. The independent association of anxiety with non-cardiac chest pain

    DEFF Research Database (Denmark)

    Smeijers, Loes; van de Pas, Harm; Nyklicek, Ivan

    2013-01-01

    the association between anxiety and NCCP is independent of personality factors. Participants with NCCP (N = 46; mean age 44.9 ± 14.7; 67% women) were evaluated for anxiety (Spielberger State-Trait Anxiety Inventory[STAI]), clinical measures and personality factors (negative affectivity and social inhibition...

  5. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  7. Left ventricular long axis function assessed during cine-cardiovascular magnetic resonance is an independent predictor of adverse cardiac events.

    Science.gov (United States)

    Rangarajan, Vibhav; Chacko, Satish Jacob; Romano, Simone; Jue, Jennifer; Jariwala, Nikhil; Chung, Jaehoon; Farzaneh-Far, Afshin

    2016-06-07

    Left ventricular pump function requires a complex interplay involving myocardial fibers orientated in the longitudinal, oblique and circumferential directions. Long axis dysfunction appears to be an early marker for a number of pathological states. We hypothesized that mitral annular plane systolic excursion (MAPSE) measured during cine-cardiovascular magnetic resonance (CMR) reflects changes in long axis function and may be an early marker for adverse cardiovascular outcomes. The aims of this study were therefore: 1) To assess the feasibility and reproducibility of MAPSE measurements during routine cine-CMR; and 2) To assess whether MAPSE, as a surrogate for long axis function, is a predictor of major adverse cardiovascular events (MACE). Four hundred consecutive patients undergoing CMR were prospectively enrolled. MAPSE was measured in the 4-chamber cine view. Patients were prospectively followed for major adverse cardiac events (MACE) - death, non-fatal myocardial infarction, hospitalization for heart failure or unstable angina, and late revascularization. Cox proportional hazards regression modeling was used to identify factors independently associated with MACE. Net reclassification improvement (NRI) was calculated to assess whether addition of MAPSE resulted in improved risk reclassification of MACE. Seventy-two MACE occurred during a median follow-up of 14.5 months. By Kaplan-Meier analysis, patients with lateral MAPSE cine-CMR is an independent predictor of MACE.

  8. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    of beta-blockers, use of psychotropic medication, anxiety, depression, and type D personality were found to be associated with poorer health status in unadjusted analyses. Interestingly, subgroups of patients (12-20 %) who experienced poor health status at baseline improved to stable good health status....... The timely identification of CRT-D patients who present with poor disease-specific health status (i.e., KCCQ score anxiety, depression, and/or type D personality) is paramount, as they may benefit from cardiac rehabilitation in combination...

  9. Expression of a novel cardiac-specific tropomyosin isoform in humans

    International Nuclear Information System (INIS)

    Denz, Christopher R.; Narshi, Aruna; Zajdel, Robert W.; Dube, Dipak K.

    2004-01-01

    Tropomyosins are a family of actin binding proteins encoded by a group of highly conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3, and TPM4, each of which is known to generate multiple isoforms by alternative splicing, promoters, and 3 ' end processing. TPM1 is the most versatile and encodes a variety of tissue specific isoforms. The TPM1 isoform specific to striated muscle, designated TPM1α, consists of 10 exons: 1a, 2b, 3, 4, 5, 6b, 7, 8, and 9a/b. In this study, using RT-PCR with adult and fetal human RNAs, we present evidence for the expression of a novel isoform of the TPM1 gene that is specifically expressed in cardiac tissues. The new isoform is designated TPM1κ and contains exon 2a instead of 2b. Ectopic expression of human GFP.TPM1κ fusion protein can promote myofibrillogenesis in cardiac mutant axolotl hearts that are lacking in tropomyosin

  10. Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging

    International Nuclear Information System (INIS)

    Sandstede, J.; Lipke, C.; Beer, M.; Hofmann, S.; Pabst, T.; Kenn, W.; Hahn, D.; Neubauer, S.

    2000-01-01

    We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 ± 7), women aged under 45 (27 ± 6), men aged over 45 (59 ± 8), and women aged over 45 (57 ± 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 ± 18 and 110 ± 16 g; LV EDV, 118 ± 27 and 96 ± 21 ml; LV ESV, 40 ± 13 and 29 ± 9 ml; RV mass, 52 ± 10 and 39 ± 5 g; RV EDV, 131 ± 28 and 100 ± 23 ml; RV ESV, 53 ± 17 and 33 ± 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4 % and 5.9 % for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values. (orig.)

  11. Automated segmentation and reconstruction of patient-specific cardiac anatomy and pathology from in vivo MRI

    International Nuclear Information System (INIS)

    Ringenberg, Jordan; Deo, Makarand; Devabhaktuni, Vijay; Filgueiras-Rama, David; Pizarro, Gonzalo; Ibañez, Borja; Berenfeld, Omer; Boyers, Pamela; Gold, Jeffrey

    2012-01-01

    This paper presents an automated method to segment left ventricle (LV) tissues from functional and delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) scans using a sequential multi-step approach. First, a region of interest (ROI) is computed to create a subvolume around the LV using morphological operations and image arithmetic. From the subvolume, the myocardial contours are automatically delineated using difference of Gaussians (DoG) filters and GSV snakes. These contours are used as a mask to identify pathological tissues, such as fibrosis or scar, within the DE-MRI. The presented automated technique is able to accurately delineate the myocardium and identify the pathological tissue in patient sets. The results were validated by two expert cardiologists, and in one set the automated results are quantitatively and qualitatively compared with expert manual delineation. Furthermore, the method is patient-specific, performed on an entire patient MRI series. Thus, in addition to providing a quick analysis of individual MRI scans, the fully automated segmentation method is used for effectively tagging regions in order to reconstruct computerized patient-specific 3D cardiac models. These models can then be used in electrophysiological studies and surgical strategy planning. (paper)

  12. Compliant Buckled Foam Actuators and Application in Patient-Specific Direct Cardiac Compression.

    Science.gov (United States)

    Mac Murray, Benjamin C; Futran, Chaim C; Lee, Jeanne; O'Brien, Kevin W; Amiri Moghadam, Amir A; Mosadegh, Bobak; Silberstein, Meredith N; Min, James K; Shepherd, Robert F

    2018-02-01

    We introduce the use of buckled foam for soft pneumatic actuators. A moderate amount of residual compressive strain within elastomer foam increases the applied force ∼1.4 × or stroke ∼2 × compared with actuators without residual strain. The origin of these improved characteristics is explained analytically. These actuators are applied in a direct cardiac compression (DCC) device design, a type of implanted mechanical circulatory support that avoids direct blood contact, mitigating risks of clot formation and stroke. This article describes a first step toward a pneumatically powered, patient-specific DCC design by employing elastomer foam as the mechanism for cardiac compression. To form the device, a mold of a patient's heart was obtained by 3D printing a digitized X-ray computed tomography or magnetic resonance imaging scan into a solid model. From this model, a soft, robotic foam DCC device was molded. The DCC device is compliant and uses compressed air to inflate foam chambers that in turn apply compression to the exterior of a heart. The device is demonstrated on a porcine heart and is capable of assisting heart pumping at physiologically relevant durations (∼200 ms for systole and ∼400 ms for diastole) and stroke volumes (∼70 mL). Although further development is necessary to produce a fully implantable device, the material and processing insights presented here are essential to the implementation of a foam-based, patient-specific DCC design.

  13. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

    Directory of Open Access Journals (Sweden)

    Storm Christian

    2012-01-01

    Full Text Available Abstract Background Neuron specific enolase (NSE has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. Methods In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines. Results The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC of 0.82 (sensitivity 47%, specificity 100%. The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5 was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100% and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100% at 48 hours compared to admission. Conclusion In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

  14. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    Science.gov (United States)

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  15. Performance comparison of independent component analysis algorithms for fetal cardiac signal reconstruction: a study on synthetic fMCG data

    International Nuclear Information System (INIS)

    Mantini, D; II, K E Hild; Alleva, G; Comani, S

    2006-01-01

    Independent component analysis (ICA) algorithms have been successfully used for signal extraction tasks in the field of biomedical signal processing. We studied the performances of six algorithms (FastICA, CubICA, JADE, Infomax, TDSEP and MRMI-SIG) for fetal magnetocardiography (fMCG). Synthetic datasets were used to check the quality of the separated components against the original traces. Real fMCG recordings were simulated with linear combinations of typical fMCG source signals: maternal and fetal cardiac activity, ambient noise, maternal respiration, sensor spikes and thermal noise. Clusters of different dimensions (19, 36 and 55 sensors) were prepared to represent different MCG systems. Two types of signal-to-interference ratios (SIR) were measured. The first involves averaging over all estimated components and the second is based solely on the fetal trace. The computation time to reach a minimum of 20 dB SIR was measured for all six algorithms. No significant dependency on gestational age or cluster dimension was observed. Infomax performed poorly when a sub-Gaussian source was included; TDSEP and MRMI-SIG were sensitive to additive noise, whereas FastICA, CubICA and JADE showed the best performances. Of all six methods considered, FastICA had the best overall performance in terms of both separation quality and computation times

  16. Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter

    Directory of Open Access Journals (Sweden)

    Wolfgang Boecker

    2004-04-01

    Full Text Available Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc reporter gene (Ad.4 × MLC250.Luc. Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 × MLC.Luc or control vectors. For in vivo testing, Ad.4 × MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells was 20.4 versus 0.9 (Ad.4 × MLC250.Luc vs. Ad.CMV. In vivo: Ad.4 × MLC250.Luc significantly reduced luc activity in liver (38.4-fold, lung (16.1-fold, and kidney (21.8-fold versus Ad.CMV (p = .01; whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 × MLC.Luc versus 1:1.4 (Ad.CMV.Luc. Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart.

  17. Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

    Science.gov (United States)

    Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

    2015-01-01

    YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

  18. Cardiac comorbidity is an independent risk factor for radiation-induced lung toxicity in lung cancer patients

    International Nuclear Information System (INIS)

    Nalbantov, Georgi; Kietselaer, Bas; Vandecasteele, Katrien; Oberije, Cary; Berbee, Maaike; Troost, Esther; Dingemans, Anne-Marie; Baardwijk, Angela van; Smits, Kim; Dekker, André; Bussink, Johan; Ruysscher, Dirk De; Lievens, Yolande; Lambin, Philippe

    2013-01-01

    Purpose: To test the hypothesis that cardiac comorbidity before the start of radiotherapy (RT) is associated with an increased risk of radiation-induced lung toxicity (RILT) in lung cancer patients. Material and methods: A retrospective analysis was performed of a prospective cohort of 259 patients with locoregional lung cancer treated with definitive radio(chemo)therapy between 2007 and 2011 (ClinicalTrials.gov Identifiers: NCT00572325 and NCT00573040). We defined RILT as dyspnea CTCv.3.0 grade ⩾2 within 6 months after RT, and cardiac comorbidity as a recorded treatment of a cardiac pathology at a cardiology department. Univariate and multivariate analyses, as well as external validation, were performed. The model-performance measure was the area under the receiver operating characteristic curve (AUC). Results: Prior to RT, 75/259 (28.9%) patients had cardiac comorbidity, 44% of whom (33/75) developed RILT. The odds ratio of developing RILT for patients with cardiac comorbidity was 2.58 (p < 0.01). The cross-validated AUC of a model with cardiac comorbidity, tumor location, forced expiratory volume in 1 s, sequential chemotherapy and pretreatment dyspnea score was 0.72 (p < 0.001) on the training set, and 0.67 (p < 0.001) on the validation set. Conclusion: Cardiac comorbidity is an important risk factor for developing RILT after definite radio(chemo)therapy of lung cancer patients

  19. Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Congying [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Dong, Ruolan [Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Chen, Chen [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hong, E-mail: hong.wang1988@yahoo.com [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Dao Wen, E-mail: dwwang@tjh.tjmu.edu.cn [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-12-25

    Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.

  20. Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

    International Nuclear Information System (INIS)

    Xia, Congying; Dong, Ruolan; Chen, Chen; Wang, Hong; Wang, Dao Wen

    2015-01-01

    Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.

  1. Cardiac-Specific Conversion Factors to Estimate Radiation Effective Dose From Dose-Length Product in Computed Tomography.

    Science.gov (United States)

    Trattner, Sigal; Halliburton, Sandra; Thompson, Carla M; Xu, Yanping; Chelliah, Anjali; Jambawalikar, Sachin R; Peng, Boyu; Peters, M Robert; Jacobs, Jill E; Ghesani, Munir; Jang, James J; Al-Khalidi, Hussein; Einstein, Andrew J

    2018-01-01

    -factors for all scanners and protocols are considerably higher than the k-factor currently used to estimate ED of cardiac CT studies, suggesting that radiation doses from cardiac CT have been significantly and systematically underestimated. Using cardiac-specific factors can more accurately inform the benefit-risk calculus of cardiac-imaging strategies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Safe genetic modification of cardiac stem cells using a site-specific integration technique.

    Science.gov (United States)

    Lan, Feng; Liu, Junwei; Narsinh, Kazim H; Hu, Shijun; Han, Leng; Lee, Andrew S; Karow, Marisa; Nguyen, Patricia K; Nag, Divya; Calos, Michele P; Robbins, Robert C; Wu, Joseph C

    2012-09-11

    Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. We used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (Pmodification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types.

  3. Repeated evolution of fungal cultivar specificity in independently evolved ant-plant-fungus symbioses.

    Science.gov (United States)

    Blatrix, Rumsaïs; Debaud, Sarah; Salas-Lopez, Alex; Born, Céline; Benoit, Laure; McKey, Doyle B; Attéké, Christiane; Djiéto-Lordon, Champlain

    2013-01-01

    Some tropical plant species possess hollow structures (domatia) occupied by ants that protect the plant and in some cases also provide it with nutrients. Most plant-ants tend patches of chaetothyrialean fungi within domatia. In a few systems it has been shown that the ants manure the fungal patches and use them as a food source, indicating agricultural practices. However, the identity of these fungi has been investigated only in a few samples. To examine the specificity and constancy of ant-plant-fungus interactions we characterised the content of fungal patches in an extensive sampling of three ant-plant symbioses (Petalomyrmex phylax/Leonardoxa africana subsp. africana, Aphomomyrmex afer/Leonardoxa africana subsp. letouzeyi and Tetraponera aethiops/Barteria fistulosa) by sequencing the Internal Transcribed Spacers of ribosomal DNA. For each system the content of fungal patches was constant over individuals and populations. Each symbiosis was associated with a specific, dominant, primary fungal taxon, and to a lesser extent, with one or two specific secondary taxa, all of the order Chaetothyriales. A single fungal patch sometimes contained both a primary and a secondary taxon. In one system, two founding queens were found with the primary fungal taxon only, one that was shown in a previous study to be consumed preferentially. Because the different ant-plant symbioses studied have evolved independently, the high specificity and constancy we observed in the composition of the fungal patches have evolved repeatedly. Specificity and constancy also characterize other cases of agriculture by insects.

  4. Repeated evolution of fungal cultivar specificity in independently evolved ant-plant-fungus symbioses.

    Directory of Open Access Journals (Sweden)

    Rumsaïs Blatrix

    Full Text Available Some tropical plant species possess hollow structures (domatia occupied by ants that protect the plant and in some cases also provide it with nutrients. Most plant-ants tend patches of chaetothyrialean fungi within domatia. In a few systems it has been shown that the ants manure the fungal patches and use them as a food source, indicating agricultural practices. However, the identity of these fungi has been investigated only in a few samples. To examine the specificity and constancy of ant-plant-fungus interactions we characterised the content of fungal patches in an extensive sampling of three ant-plant symbioses (Petalomyrmex phylax/Leonardoxa africana subsp. africana, Aphomomyrmex afer/Leonardoxa africana subsp. letouzeyi and Tetraponera aethiops/Barteria fistulosa by sequencing the Internal Transcribed Spacers of ribosomal DNA. For each system the content of fungal patches was constant over individuals and populations. Each symbiosis was associated with a specific, dominant, primary fungal taxon, and to a lesser extent, with one or two specific secondary taxa, all of the order Chaetothyriales. A single fungal patch sometimes contained both a primary and a secondary taxon. In one system, two founding queens were found with the primary fungal taxon only, one that was shown in a previous study to be consumed preferentially. Because the different ant-plant symbioses studied have evolved independently, the high specificity and constancy we observed in the composition of the fungal patches have evolved repeatedly. Specificity and constancy also characterize other cases of agriculture by insects.

  5. High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways.

    Science.gov (United States)

    Kumar, Sandeep; Kain, Vasundhara; Sitasawad, Sandhya L

    2012-07-01

    Cardiac cell apoptosis is the initiating factor of cardiac complications especially diabetic cardiomyopathy. Mitochondria are susceptible to the damaging effects of elevated glucose condition. Calcium overload and oxidative insult are the two mutually non-exclusive phenomena suggested to cause cardiac dysfunction. Here, we examined the effect of high-glucose induced calcium overload in calpain-1 mediated cardiac apoptosis in an in vitro setting. H9c2, rat ventricular myoblast cell line was treated with elevated glucose condition and the cellular consequences were studied. Intracellular calcium trafficking, ROS generation, calpain-1 activation and caspase-12 and caspase-9 pathway were studied using flow cytometry, confocal microscopy and Western blot analysis. High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis. Cardiomyocyte death exhibited several classical markers of apoptosis, including activation of caspases, appearance of annexin V on the outer plasma membrane, increased population of cells with sub-G0/G1 DNA content and nuclear condensation. Key findings include elucidation of cell signaling mechanism of high-glucose induced calcium-dependent cysteine protease calpain-1 activation, which triggers non-conventional caspases as alternate mode of cell death. This information increases the understanding of cardiac cell death under hyperglycemic condition and can possibly be extended for designing new therapeutic strategies for diabetic cardiomyopathy. The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets

    Science.gov (United States)

    Noujaim, Sami F.; Stuckey, Jeanne A.; Ponce-Balbuena, Daniela; Ferrer-Villada, Tania; López-Izquierdo, Angelica; Pandit, Sandeep; Calvo, Conrado J.; Grzeda, Krzysztof R.; Berenfeld, Omer; Sánchez Chapula, José A.; Jalife, José

    2010-01-01

    Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g., inherited gain-of-function mutation channelopathies, ischemia, and chronic and vagally mediated atrial fibrillation). We hypothesize that the antimalarial quinoline chloroquine exerts potent antiarrhythmic effects by interacting with the cytoplasmic domains of Kir2.1 (IK1), Kir3.1 (IKACh), or Kir6.2 (IKATP) and reducing inward rectifier potassium currents. In isolated hearts of three different mammalian species, intracoronary chloroquine perfusion reduced fibrillatory frequency (atrial or ventricular), and effectively terminated the arrhythmia with resumption of sinus rhythm. In patch-clamp experiments chloroquine blocked IK1, IKACh, and IKATP. Comparative molecular modeling and ligand docking of chloroquine in the intracellular domains of Kir2.1, Kir3.1, and Kir6.2 suggested that chloroquine blocks or reduces potassium flow by interacting with negatively charged amino acids facing the ion permeation vestibule of the channel in question. These results open a novel path toward discovering antiarrhythmic pharmacophores that target specific residues of the cytoplasmic domain of inward rectifier potassium channels.—Noujaim, S. F., Stuckey, J. A., Ponce-Balbuena, D., Ferrer-Villada, T., López-Izquierdo, A., Pandit, S., Calvo, C. J., Grzeda, K. R., Berenfeld, O., Sánchez Chapula, J. A., Jalife, J. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. PMID:20585026

  7. Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

    Science.gov (United States)

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-12-02

    Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Quality specification and status of internal quality control of cardiac biomarkers in China from 2011 to 2016.

    Science.gov (United States)

    Li, Tingting; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

    2017-09-07

    This study aimed to investigate the status of internal quality control (IQC) for cardiac biomarkers from 2011 to 2016 so that we can have overall knowledge of the precision level of measurements in China and set appropriate precision specifications. Internal quality control data of cardiac biomarkers, including creatinine kinase MB (CK-MB) (μg/L), CK-MB(U/L), myoglobin (Mb), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and homocysteines (HCY), were collected by a web-based external quality assessment (EQA) system. Percentages of laboratories meeting five precision quality specifications for current coefficient of variations (CVs) were calculated. Then, appropriate precision specifications were chosen for these six analytes. Finally, the CVs and IQC practice were further analyzed with different grouping methods. The current CVs remained nearly constant for 6 years. cTnT had the highest pass rates every year against five specifications, whereas HCY had the lowest pass rates. Overall, most analytes had a satisfactory performance (pass rates >80%), except for HCY, if one-third TEa or the minimum specification were employed. When the optimal specification was applied, the performance of most analytes was frustrating (pass rates < 60%) except for cTnT. The appropriate precision specifications of Mb, cTnI, cTnT and HCY were set as current CVs less than 9.20%, 9.90%, 7.50%, 10.54%, 7.63%, and 6.67%, respectively. The data of IQC practices indicated wide variation and substantial progress. The precision performance of cTnT was already satisfying, while the other five analytes, especially HCY, were still frustrating; thus, ongoing investigation and continuous improvement for IQC are still needed. © 2017 Wiley Periodicals, Inc.

  9. Cardiac-specific overexpression of insulin-like growth factor I (IGF-1) rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling in murine cardiomyocytes.

    Science.gov (United States)

    Zhao, Peng; Turdi, Subat; Dong, Feng; Xiao, Xiaoyan; Su, Guohai; Zhu, Xinglei; Scott, Glenda I; Ren, Jun

    2009-07-01

    Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. Mechanical and intracellular Ca2+ properties were examined in cardiomyocytes from Fast Violet B and cardiac-specific IGF-1 overexpression mice treated with or without LPS (4 mg kg(-1), 6 h). Reactive oxygen species (ROS), protein carbonyl formation and apoptosis were measured. Activation of mitogen-activated protein kinase pathways (p38, c-jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]), ER stress and apoptotic markers were evaluated using Western blot analysis. Our results revealed decreased peak shortening and maximal velocity of shortening/relengthening and prolonged duration of relengthening in LPS-treated Fast Violet B cardiomyocytes associated with reduced intracellular Ca2+ decay. Accumulation of ROS protein carbonyl and apoptosis were elevated after LPS treatment. Western blot analysis revealed activated p38 and JNK, up-regulated Bax, and the ER stress markers GRP78 and Gadd153 in LPS-treated mouse hearts without any change in ERK and Bcl-2. Total protein expression of p38, JNK, and ERK was unaffected by either LPS or IGF-1. Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 microg mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in

  10. Patient-Specific Induced Pluripotent Stem Cell Models: Generation and Characterization of Cardiac Cells.

    Science.gov (United States)

    Zanella, Fabian; Sheikh, Farah

    2016-01-01

    The generation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes has been of utmost interest for the study of cardiac development, cardiac disease modeling, and evaluation of cardiotoxic effects of novel candidate drugs. Several protocols have been developed to guide human stem cells toward the cardiogenic path. Pioneering work used serum to promote cardiogenesis; however, low cardiogenic throughputs, lack of chemical definition, and batch-to-batch variability of serum lots constituted a considerable impediment to the implementation of those protocols to large-scale cell biology. Further work focused on the manipulation of pathways that mouse genetics indicated to be fundamental in cardiac development to promote cardiac differentiation in stem cells. Although extremely elegant, those serum-free protocols involved the use of human recombinant cytokines that tend to be quite costly and which can also be variable between lots. The latest generation of cardiogenic protocols aimed for a more cost-effective and reproducible definition of the conditions driving cardiac differentiation, using small molecules to manipulate cardiogenic pathways overriding the need for cytokines. This chapter details methods based on currently available cardiac differentiation protocols for the generation and characterization of robust numbers of hiPSC-derived cardiomyocytes under chemically defined conditions.

  11. The Efficacy of Goal Setting in Cardiac Rehabilitation-a Gender-Specific Randomized Controlled Trial.

    Science.gov (United States)

    Stamm-Balderjahn, Sabine; Brünger, Martin; Michel, Anne; Bongarth, Christa; Spyra, Karla

    2016-08-08

    Patients with coronary heart disease undergo cardiac rehabilitation in order to reduce their cardiovascular risk factors. Often, however, the benefit of rehabilitation is lost over time. It is unclear whether this happens in the same way to men and women. We studied whether the setting of gender-specific behavior goals with an agreement between the doctor and the patient at the end of rehabilitation can prolong its positive effects. This study was performed with a mixed-method design. It consisted of qualitative interviews and group discussions with patients, doctors and other treating personnel, and researchers, as well as a quantitative, randomized, controlled intervention trial in which data were acquired at four time points (the beginning and end of rehabilitation and then 6 and 12 months later). 545 patients, 262 of them women (48.1%), were included. The patients were assigned to a goal checking group (n = 132), a goal setting group (n = 143), and a control group (n = 270). The primary endpoints were health-related behavior (exercise, diet, tobacco consumption), subjective state of health, and medication adherence. The secondary endpoints included physiological protection and risk factors such as blood pressure, cholesterol (HDL, LDL, and total), blood sugar, HbA1c, and body-mass index. The intervention had no demonstrable effect on the primary or secondary endpoints. The percentage of smokers declined to a similar extent in all groups from the beginning of rehabilitation to 12 months after its end (overall figures: 12.4% to 8.6%, p exercise behavior, diet, and subjective state of health also improved over the entire course of the study. Women had a healthier diet than men. Subgroup analyses indicated a possible effect of the intervention on exercise behavior in women who were employed and in men who were not (pgoal setting was not demonstrated. Therefore, no indication for its routine provision can be derived from the study results.

  12. Overexpression of the muscle-specific protein, melusin, protects from cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Penna, Claudia; Brancaccio, Mara; Tullio, Francesca; Rubinetto, Cristina; Perrelli, Maria-Giulia; Angotti, Carmelina; Pagliaro, Pasquale; Tarone, Guido

    2014-07-01

    Melusin is a muscle-specific protein which interacts with β1 integrin cytoplasmic domain and acts as chaperone protein. Its overexpression induces improved resistance to cardiac overload delaying left ventricle dilation and reducing the occurrence of heart failure. Here, we investigated possible protective effect of melusin overexpression against acute ischemia/reperfusion (I/R) injury with or without Postconditioning cardioprotective maneuvers. Melusin transgenic (Mel-TG) mice hearts were subjected to 30-min global ischemia followed by 60-min reperfusion. Interestingly, infarct size was reduced in Mel-TG mice hearts compared to wild-type (WT) hearts (40.3 ± 3.5 % Mel-TG vs. 59.5 ± 3.8 % WT hearts; n = 11 animals/group; P level of AKT, ERK1/2 and GSK3β phosphorylation, and displayed increased phospho-kinases level after I/R compared to WT mice. Post-ischemic Mel-TG hearts displayed also increased levels of the anti-apoptotic factor phospho-BAD. Importantly, pharmacological inhibition of PI3K/AKT (Wortmannin) and ERK1/2 (U0126) pathways abrogated the melusin protective effect. Notably, HSP90, a chaperone known to protect heart from I/R injury, showed high levels of expression in the heart of Mel-TG mice suggesting a possible collaboration of this molecule with AKT/ERK/GSK3β pathways in the melusin-induced protection. Postconditioning, known to activate AKT/ERK/GSK3β pathways, significantly reduced IS and LDH release in WT hearts, but had no additive protective effects in Mel-TG hearts. These findings implicate melusin as an enhancer of AKT and ERK pathways and as a novel player in cardioprotection from I/R injury.

  13. Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

    Science.gov (United States)

    Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

    2007-10-01

    In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

  14. Gender-specific issues in cardiac rehabilitation: do women with ischaemic heart disease need specially tailored programmes?

    Science.gov (United States)

    Bjarnason-Wehrens, Birna; Grande, Gesine; Loewel, Hannelore; Völler, Heinz; Mittag, Oskar

    2007-04-01

    Ischaemic heart disease (IHD) has changed from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s. Most clinical studies during the past three decades have been conducted with men. Cardiac rehabilitation programmes were also developed with special regard to improving the rate of return to work in middle-aged men. The rehabilitation needs of older patients and women in particular have been largely neglected. The aim of this review is briefly to outline our present knowledge on gender issues in cardiac rehabilitation, and to specify barriers with regard to physical activities especially in (older) women. Coping with a cardiac event, women tend to minimize or play down the impact of their health situation and avoid burdening their social contacts. After a first cardiac event, women report greater psychological distress and lower self-efficacy and self-esteem. In addition, older age, lower exercise levels and reduced functional capacity or co-morbid conditions such as osteoporosis and urinary incontinence are barriers to physical activities in women with IHD. Recent studies on psychosocial intervention revealed less favourable results in women compared with men. These findings have not yet been well explained. This emphasizes our current lack of knowledge about the processes and determinants of successful psychosocial interventions in men and women with IHD. A large (European) trial on gender-specific coping styles, needs, and preferences of older women, and the effects of psychosocial intervention is proposed.

  15. Disinfection By-Product Exposures and the Risk of Specific Cardiac Birth Defects

    Science.gov (United States)

    Wright, J. Michael; Evans, Amanda; Kaufman, John A.; Rivera-Núñez, Zorimar; Narotsky, Michael G.

    2016-01-01

    Background: Epidemiological studies suggest that women exposed to disinfection by-products (DBPs) have an increased risk of delivering babies with cardiovascular defects (CVDs). Objective: We examined nine CVDs in relation to categorical DBP exposures including bromoform, chloroform, dibromochloromethane (DBCM), bromodichloromethane (BDCM), monobromoacetic acid (MBAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and summary DBP measures (HAA5, THMBr, THM4, and DBP9). Methods: We calculated adjusted odds ratios (aORs) in a case–control study of birth defects in Massachusetts with complete quarterly 1999–2004 trihalomethane (THM) and haloacetic acid (HAA) data. We randomly matched 10 controls each to 904 CVD cases based on week of conception. Weight-averaged aggregate first-trimester DBP exposures were assigned to individuals based on residence at birth. Results: We detected associations for tetralogy of Fallot and the upper exposure categories for TCAA, DCAA, and HAA5 (aOR range, 3.34–6.51) including positive exposure–response relationships for DCAA and HAA5. aORs consistent in magnitude were detected between atrial septal defects and bromoform (aOR = 1.56; 95% CI: 1.01, 2.43), as well as DBCM, chloroform, and THM4 (aOR range, 1.26–1.67). Ventricular septal defects (VSDs) were associated with the highest bromoform (aOR = 1.85; 95% CI: 1.20, 2.83), MBAA (aOR = 1.81; 95% CI: 0.85, 3.84), and DBCM (aOR = 1.54; 95% CI: 1.00, 2.37) exposure categories. Conclusions: To our knowledge, this is the first birth defect study to develop multi-DBP adjusted regression models as well as the first CVD study to evaluate HAA exposures and the second to evaluate bromoform exposures. Our findings, therefore, inform exposure specificity for the consistent associations previously reported between THM4 and CVDs including VSDs. Citation: Wright JM, Evans A, Kaufman JA, Rivera-Núñez Z, Narotsky MG. 2017. Disinfection by-product exposures and the risk of specific

  16. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    International Nuclear Information System (INIS)

    King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-01-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

  17. Seismocardiography-Based Cardiac Computed Tomography Gating Using Patient-Specific Template Identification and Detection.

    Science.gov (United States)

    Yao, Jingting; Tridandapani, Srini; Wick, Carson A; Bhatti, Pamela T

    2017-01-01

    To more accurately trigger cardiac computed tomography angiography (CTA) than electrocardiography (ECG) alone, a sub-system is proposed as an intermediate step toward fusing ECG with seismocardiography (SCG). Accurate prediction of quiescent phases is crucial to prospectively gating CTA, which is susceptible to cardiac motion and, thus, can affect the diagnostic quality of images. The key innovation of this sub-system is that it identifies the SCG waveform corresponding to heart sounds and determines their phases within the cardiac cycles. Furthermore, this relationship is modeled as a linear function with respect to heart rate. For this paper, B-mode echocardiography is used as the gold standard for identifying the quiescent phases. We analyzed synchronous ECG, SCG, and echocardiography data acquired from seven healthy subjects (mean age: 31; age range: 22-48; males: 4) and 11 cardiac patients (mean age: 56; age range: 31-78; males: 6). On average, the proposed algorithm was able to successfully identify 79% of the SCG waveforms in systole and 68% in diastole. The simulated results show that SCG-based prediction produced less average phase error than that of ECG. It was found that the accuracy of ECG-based gating is more susceptible to increases in heart rate variability, while SCG-based gating is susceptible to high cycle to cycle variability in morphology. This pilot work of prediction using SCG waveforms enriches the framework of a comprehensive system with multiple modalities that could potentially, in real time, improve the image quality of CTA.

  18. Specificity of secreted proteomes from cardiac stem cells and neonatal myocytes

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Chimenti, I.; Marban, E.; Van Eyk, J.

    2009-01-01

    Roč. 276, Suppl.1 (2009), s. 346 ISSN 1742-464X. [FEBS Congress /34./. 04.07.2009-09.07.2009, Prague] Institutional research plan: CEZ:AV0Z40310501 Keywords : cardiac stem cells * secreted paracrine/autocrine factors * proteomics Subject RIV: CB - Analytical Chemistry, Separation

  19. Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

    International Nuclear Information System (INIS)

    Dotan, Zohar A; Dotan, Aviva; Ramon, Jacob; Avivi, Lydia

    2008-01-01

    random but is independent of the parental origin. The non-disease specific aberrant epigenetic profile displayed in peripheral blood cells of patients with a solid tumour (unlike genetic aberrations) can be reversed, by an epigenetic drug applied in vitro, to the normal. It appears that the cancerous status differentiates between two allelic counterparts in a non-random manner, but independent of the parental origin

  20. Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Maike Marczenke

    2017-07-01

    Full Text Available The ultrarapid delayed rectifier K+ current (IKur, mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF. Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout. This model as well as isogenic wild-type control hiPSCs could selectively be differentiated into ventricular or atrial cardiomyocytes at high efficiency, based on the specific manipulation of retinoic acid signaling. Investigation of electrophysiological properties in Kv1.5-deficient cardiomyocytes compared to isogenic controls revealed a strictly atrial-specific disease phentoype, characterized by cardiac subtype-specific field and action potential prolongation and loss of 4-aminopyridine sensitivity. Atrial Kv1.5-deficient cardiomyocytes did not show signs of arrhythmia under adrenergic stress conditions or upon inhibiting additional types of K+ current. Exposure of bulk cultures to carbachol lowered beating frequencies and promoted chaotic spontaneous beating in a stochastic manner. Low-frequency, electrical stimulation in single cells caused atrial and mutant-specific early afterdepolarizations, linking the loss of KCNA5 function to a putative trigger mechanism in familial AF. These results clarify for the first time the role of Kv1.5 in atrial hiPSC-cardiomyocytes and demonstrate the feasibility of cardiac subtype-specific disease modeling using engineered hiPSCs.

  1. Cardiac-specific activation of Cre expression at late fetal development

    International Nuclear Information System (INIS)

    Opherk, Jan P.; Yampolsky, Peter; Hardt, Stefan E.; Schoels, Wolfgang; Katus, Hugo A.; Koenen, Michael; Zehelein, Joerg

    2007-01-01

    In a first step towards dissecting molecular mechanisms that contribute to the development of cardiac diseases, we have generated transgenic mice that express a Cre-GFP fusion protein under the transcriptional control of a 4.3 kb murine cardiac Troponin I gene (cTnI) promoter. Cre-GFP expression, similar in three transgenic lines, is described in one line. In mouse embryos, transgenic for the Cre-GFP and ROSA lacZ reporter allele, first Cre-mediated recombination appeared at 16.5 dpc selectively at the heart. Like the endogenous cTnI gene, transgenic Cre expression showed a slow rise through fetal development that increased neonatally. Bitransgenic hearts, stained at 30 days of age, showed intense signals in ventricular and atrial myocytes while no recombination occurred in other tissues. The delayed onset of Cre activity in cTnI-Cre mice could provide a useful genetic tool to evaluate the function of loxP targeted cardiac genes without interference of recombination during early heart development

  2. Overexpression of Cardiac-Specific Kinase TNNI3K Promotes Mouse Embryonic Stem Cells Differentiation into Cardiomyocytes.

    Science.gov (United States)

    Wang, Yin; Wang, Shi-Qiang; Wang, Li-Peng; Yao, Yu-Hong; Ma, Chun-Yan; Ding, Jin-Feng; Ye, Jue; Meng, Xian-Min; Li, Jian-Jun; Xu, Rui-Xia

    2017-01-01

    Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days. Further, action potentials and calcium current with/without 5 µM nifedipine were measured by patch clamp for mESC-derived cardiomyocytes. HTNNI3K and mouse-derived siRNA were transfected into mESC using lentivirus vector to induce hTNNI3K overexpression and knock-down, respectively. The number of troponin-T (cTnT) positive cells was greater in the group with TNNI3K overexpression as compared to that in control group, while less such cells were detected in the mTnni3k knock-down group as evaluated on flow cytometry (FCM) and ImageXpress Micro system. After upregulation of connexin43, cardiac troponin-I (Ctni), Ctni, Gata4 were detected in mESCs with TNNI3K overexpression; however, overexpression of α-Actinin and Mlc2v was not detected. Interestingly, Ctnt, connexin40 and connexin45, the markers of ventricular, atrial, and pacemaker cells, respectively, were detected in by real-time PCR in TNNI3K overexpression group. our study indicated that TNNI3K overexpression promoted mESC differentiating into beating cardiomyocytes and induced up-regulating expression of cTnT by PKCε signal pathway, which suggested a modulation of TNNI3K activity as a potential therapeutic approach for ischemic cardiac disease. © 2017 The Author(s) Published by S. Karger AG, Basel.

  3. PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis

    International Nuclear Information System (INIS)

    Aggarwal, Varun; Dobrolet, Nancy; Fishberger, Steven; Zablah, Jenny; Jayakar, Parul; Ammous, Zineb

    2005-01-01

    Mutations in PRKAG2 gene that regulates the γ2 subunit of the adenosine monophosphate (AMP) dependent protein kinase have been associated with the development of atrioventricular (AV) accessory pathways, cardiac hypertrophy, and conduction system abnormalities. These patients can potentially be misdiagnosed as hypertrophic cardiomyopathy (HOCM) and/or Wolf-Parkinson White (WPW) syndrome due to similar clinical phenotype. Early recognition of this disease entity is very important as ablation of suspected accessory pathways is not effective and the natural history of the disease is very different from HOCM and WPW syndrome

  4. THE MASS-INDEPENDENCE OF SPECIFIC STAR FORMATION RATES IN GALACTIC DISKS

    Energy Technology Data Exchange (ETDEWEB)

    Abramson, Louis E.; Gladders, Michael D. [Department of Astronomy and Astrophysics and Kavli Institute for Cosmological Physics, The University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637 (United States); Kelson, Daniel D.; Dressler, Alan; Oemler, Augustus Jr. [The Observatories of the Carnegie Institution for Science, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Poggianti, Bianca [INAF-Osservatorio Astronomico di Padova, Vicolo Osservatorio 5, I-35122 Padova (Italy); Vulcani, Benedetta, E-mail: labramson@uchicago.edu [Kavli Institute for the Physics and Mathematics of the Universe (WPI), Todai Institutes for Advanced Study, University of Tokyo, Kashiwa 277-8582 (Japan)

    2014-04-20

    The slope of the star formation rate/stellar mass relation (the SFR {sup M}ain Sequence{sup ;} SFR-M {sub *}) is not quite unity: specific star formation rates (SFR/M {sub *}) are weakly but significantly anti-correlated with M {sub *}. Here we demonstrate that this trend may simply reflect the well-known increase in bulge mass-fractions—portions of a galaxy not forming stars—with M {sub *}. Using a large set of bulge/disk decompositions and SFR estimates derived from the Sloan Digital Sky Survey, we show that re-normalizing SFR by disk stellar mass (sSFR{sub disk} ≡ SFR/M {sub *,} {sub disk}) reduces the M {sub *} dependence of SF efficiency by ∼0.25 dex per dex, erasing it entirely in some subsamples. Quantitatively, we find log sSFR{sub disk}-log M {sub *} to have a slope β{sub disk} in [ – 0.20, 0.00] ± 0.02 (depending on the SFR estimator and Main Sequence definition) for star-forming galaxies with M {sub *} ≥ 10{sup 10} M {sub ☉} and bulge mass-fractions B/T ≲ 0.6, generally consistent with a pure-disk control sample (β{sub control} = –0.05 ± 0.04). That (SFR/M {sub *,} {sub disk}) is (largely) independent of host mass for star-forming disks has strong implications for aspects of galaxy evolution inferred from any SFR-M {sub *} relation, including manifestations of ''mass quenching'' (bulge growth), factors shaping the star-forming stellar mass function (uniform dlog M {sub *}/dt for low-mass, disk-dominated galaxies), and diversity in star formation histories (dispersion in SFR(M {sub *}, t)). Our results emphasize the need to treat galaxies as composite systems—not integrated masses—in observational and theoretical work.

  5. Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

    Directory of Open Access Journals (Sweden)

    Cecilia Vecoli

    Full Text Available Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD, affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT, eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR was measured at baseline and during infusions of acetylcholine (Ach or sodium-nitroprusside (SNP to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/- showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels

  6. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

    Directory of Open Access Journals (Sweden)

    Takanobu Nagata

    Full Text Available Myocardial ischemia reperfusion injury (IRI adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS-3, an intrinsic negative feedback regulator of the Janus kinase (JAK-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO. The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1 was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

  7. Novel approach for independent control of brain hypothermia and systemic normothermia: cerebral selective deep hypothermia for refractory cardiac arrest.

    Science.gov (United States)

    Wang, Chih-Hsien; Lin, Yu-Ting; Chou, Heng-Wen; Wang, Yi-Chih; Hwang, Joey-Jen; Gilbert, John R; Chen, Yih-Sharng

    2017-08-01

    A 38-year-old man was found unconscious, alone in the driver's seat of his car. The emergency medical team identified his condition as pulseless ventricular tachycardia. Defibrillation was attempted but failed. Extracorporeal membrane oxygenation (ECMO) was started in the emergency room 52 min after the estimated arrest following the extracorporeal cardiopulmonary resuscitation (ECPR) protocol in our center. The initial prognosis under the standard protocol was <25% chance of survival. A novel adjunctive to our ECPR protocol, cerebral selective deep (<30°C) hypothermia (CSDH), was applied. CSDH adds a second independent femoral access extracorporeal circuit, perfusing cold blood into the patient's common carotid artery. The ECMO and CSDH circuits demonstrated independent control of cerebral and core temperatures. Nasal temperature was lowered to below 30°C for 12 hours while core was maintained at normothermia. The patient was discharged without significant neurological deficit 32 days after the initial arrest. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Mitragynine and its potential blocking effects on specific cardiac potassium channels

    Energy Technology Data Exchange (ETDEWEB)

    Tay, Yea Lu; Teah, Yi Fan; Chong, Yoong Min [Malaysian Institute of Pharmaceuticals & Nutraceuticals, NIBM, Ministry of Science, Technology & Innovation (MOSTI), Pulau Pinang (Malaysia); Jamil, Mohd Fadzly Amar [Clinical Research Center, Hospital Seberang Jaya, Kementerian Kesihatan Malaysia, Pulau Pinang (Malaysia); Kollert, Sina [Institute of Physiology, University of Wurzburg, Wurzburg (Germany); Adenan, Mohd Ilham [Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Selangor Darul Ehsan (Malaysia); Wahab, Habibah Abdul [Pharmaceutical Design & Simulation (PhDS) Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang (Malaysia); Döring, Frank; Wischmeyer, Erhard [Institute of Physiology, University of Wurzburg, Wurzburg (Germany); Tan, Mei Lan, E-mail: tanml@usm.my [Malaysian Institute of Pharmaceuticals & Nutraceuticals, NIBM, Ministry of Science, Technology & Innovation (MOSTI), Pulau Pinang (Malaysia); Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang (Malaysia)

    2016-08-15

    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac I{sub Kr} current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, I{sub K1}, a Kir current mediated by Kir2.1 channel and I{sub KACh}, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC{sub 50} value of 1.62 μM and 1.15 μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit I{sub KACh} current with an IC{sub 50} value of 3.32 μM but has no significant effects on I{sub K1}. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. - Highlights: • The potential cardiac potassium channel blocking properties of mitragynine were investigated. • Mitragynine blocks hERG channel and I{sub Kr} in hERG-transfected HEK293 cells and hERG cRNA-injected Xenopus oocytes. • Mitragynine inhibits the hERG protein but not the mRNA expression. • Mitragynine

  9. Mitragynine and its potential blocking effects on specific cardiac potassium channels

    International Nuclear Information System (INIS)

    Tay, Yea Lu; Teah, Yi Fan; Chong, Yoong Min; Jamil, Mohd Fadzly Amar; Kollert, Sina; Adenan, Mohd Ilham; Wahab, Habibah Abdul; Döring, Frank; Wischmeyer, Erhard; Tan, Mei Lan

    2016-01-01

    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, I K1 , a Kir current mediated by Kir2.1 channel and I KACh , a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC 50 value of 1.62 μM and 1.15 μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit I KACh current with an IC 50 value of 3.32 μM but has no significant effects on I K1 . Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. - Highlights: • The potential cardiac potassium channel blocking properties of mitragynine were investigated. • Mitragynine blocks hERG channel and I Kr in hERG-transfected HEK293 cells and hERG cRNA-injected Xenopus oocytes. • Mitragynine inhibits the hERG protein but not the mRNA expression. • Mitragynine inhibits GIRK channel. • Simultaneous

  10. The covariant formulation of Maxwell's equations expressed in a form independent of specific units

    International Nuclear Information System (INIS)

    Heras, Jose A; Baez, G

    2009-01-01

    The covariant formulation of Maxwell's equations can be expressed in a form independent of the usual systems of units by introducing the constants α, β and γ into these equations. Maxwell's equations involving these constants are then specialized to the most commonly used systems of units: Gaussian, SI and Heaviside-Lorentz by giving the constants α, β and γ the values appropriate to each system

  11. Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices.

    Science.gov (United States)

    Takemiya, Kiyoko; Ning, Xinghai; Seo, Wonewoo; Wang, Xiaojian; Mohammad, Rafi; Joseph, Giji; Titterington, Jane S; Kraft, Colleen S; Nye, Jonathan A; Murthy, Niren; Goodman, Mark M; Taylor, W Robert

    2018-04-13

    The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices. Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices. Stainless steel mock-ups of medical devices were implanted subcutaneously in rats. On post-operative day 4, animals were injected with either Staphylococcus aureus around the mock-ups to induce a relatively mild infection or oil of turpentine to induce noninfectious inflammation. Animals with a sterile implant were used as control subjects. On post-operative day 6, either the MDP or F18 fluoromaltohexaose was injected intravenously, and the animals were scanned with the appropriate imaging device. Additional positron emission tomography imaging studies were performed with F18-fluorodeoxyglucose as a comparison of the specificity of our probes (n = 5 to 9 per group). The accumulation of the MDP in the infected rats was significantly increased at 1 h after injection when compared with the control and noninfectious inflammation groups (intensity ratio 1.54 ± 0.07 vs. 1.26 ± 0.04 and 1.20 ± 0.05, respectively; p F18 fluoromaltohexaose and F18 fluorodeoxyglucose significantly accumulated in the infected area 30 min after the injection (maximum standard uptake value ratio 4.43 ± 0.30 and 4.87 ± 0.28, respectively). In control rats, there was no accumulation of imaging probes near the device. In the noninfectious inflammation rats, no significant accumulation was observed with F18 fluoromaltohexaose, but F18 fluorodeoxyglucose accumulated in the mock-up area (maximum standard uptake value 2.53 ± 0.39 vs. 4.74 ± 0.46, respectively; p < 0.05). Our results indicate that maltohexaose-based imaging probes are potentially useful for the

  12. Receptor activity-independent recruitment of βarrestin2 reveals specific signalling modes

    Science.gov (United States)

    Terrillon, Sonia; Bouvier, Michel

    2004-01-01

    The roles of βarrestins in regulating G protein coupling and receptor endocytosis following agonist stimulation of G protein-coupled receptors are well characterised. However, their ability to act on their own as direct modulators or activators of signalling remains poorly characterised. Here, βarrestin2 intrinsic signalling properties were assessed by forcing the recruitment of this accessory protein to vasopressin V1a or V2 receptors independently of agonist-promoted activation of the receptors. Such induction of a stable interaction with βarrestin2 initiated receptor endocytosis leading to intracellular accumulation of the βarrestin/receptor complexes. Interestingly, βarrestin2 association to a single receptor protomer was sufficient to elicit receptor dimer internalisation. In addition to recapitulating βarrestin2 classical actions on receptor trafficking, the receptor activity-independent recruitment of βarrestin2 activated the extracellular signal-regulated kinases. In the latter case, recruitment to the receptor itself was not required since kinase activation could be mediated by βarrestin2 translocation to the plasma membrane in the absence of any interacting receptor. These data demonstrate that βarrestin2 can act as a ‘bonafide' signalling molecule even in the absence of activated receptor. PMID:15385966

  13. Disease-specific and inflammation-independent stromal alterations in spondylarthritis synovitis

    NARCIS (Netherlands)

    Yeremenko, Nataliya; Noordenbos, Troy; Cantaert, Tineke; van Tok, Melissa; van de Sande, Marleen; Cañete, Juan D.; Tak, Paul P.; Baeten, Dominique

    2013-01-01

    The molecular processes driving the distinct patterns of synovial inflammation and tissue remodeling in spondylarthritis (SpA) as compared to rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify novel and unsuspected disease-specific pathways in SpA by a systematic and

  14. Cardiac-specific inducible overexpression of human plasma membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury.

    Science.gov (United States)

    Sadi, Al Muktafi; Afroze, Talat; Siraj, M Ahsan; Momen, Abdul; White-Dzuro, Colin; Zarrin-Khat, Dorrin; Handa, Shivalika; Ban, Kiwon; Kabir, M Golam; Trivieri, Maria G; Gros, Robert; Backx, Peter; Husain, Mansoor

    2018-03-30

    Background: Heart failure (HF) is associated with reduced expression of plasma membrane Ca 2+ -ATPase 4 (PMCA4). Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin. Here we examine temporally regulated cardiac-specific overexpression of hPMCA4b in mouse models of myocardial ischemia reperfusion injury (IRI) ex vivo , and HF following experimental myocardial infarction (MI) in vivo Methods and results: Doxycycline-regulated cardiomyocyte-specific overexpression and activity of hPMCA4b produced adaptive changes in expression levels of Ca 2+ -regulatory genes, and induced hypertrophy without significant differences in Ca 2+ transients or diastolic Ca 2+ concentrations. Total cardiac NOS and nNOS-specific activities were reduced in mice with cardiac overexpression of hPMCA4b while nNOS, eNOS and iNOS protein levels did not differ. hMPCA4b-overexpressing mice also exhibited elevated systolic blood pressure vs. controls, with increased contractility and lusitropy in vivo In isolated hearts undergoing IRI, hPMCA4b overexpression was cardioprotective. NO donor-treated hearts overexpressing hPMCA4b showed reduced LVDP and larger infarct size versus vehicle-treated hearts undergoing IRI, demonstrating that the cardioprotective benefits of hPMCA4b-repressed nNOS are lost by restoring NO availability. Finally, both pre-existing and post-MI induction of hPMCA4b overexpression reduced infarct expansion and improved survival from HF. Conclusions: Cardiac PMCA4b regulates nNOS activity, cardiac mass and contractility, such that PMCA4b overexpression preserves cardiac function following IRI, heightens cardiac performance and limits infarct progression, cardiac hypertrophy and HF, even when induced late post-MI. These data identify PMCA4b as a novel therapeutic target for IRI and HF. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  15. Far red/near infrared light-induced protection against cardiac ischemia and reperfusion injury remains intact under diabetic conditions and is independent of nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Agnes eKeszler

    2014-08-01

    Full Text Available Far red/near-infrared light (NIR promotes a wide range of biological effects including tissue protection but whether and how NIR is capable of acutely protecting myocardium against ischemia and reperfusion injury in vivo is not fully elucidated. Our previous work indicates that NIR exposure immediately before and during early reperfusion protects the myocardium against infarction through mechanisms that are nitric oxide (NO-dependent. Here we tested the hypothesis that NIR elicits protection in a diabetic mouse model where other cardioprotective interventions such as pre- and postconditioning fail, and that the protection is independent of nitric oxide synthase (NOS. NIR reduced infarct size dose dependently. Importantly, NIR-induced protection was preserved in a diabetic mouse model (db/db and during acute hyperglycemia, as well as in endothelial NOS-/- mice and in wild type mice treated with NOS inhibitor L-NAME. In in vitro experiments NIR light liberates NO from nitrosyl hemoglobin (HbNO and nitrosyl myoglobin (MbNO in a wavelength (660-830 nm and dose-dependent manner. Irradiation at 660 nm yields the highest release of NO, while at longer wavelengths a dramatic decrease of NO release can be observed. Similar wavelength dependence was observed for the protection of mice against cardiac ischemia and reperfusion injury in vivo. NIR-induced NO release from deoxymyoglobin in the presence of nitrite mildly inhibits respiration of isolated mitochondria after hypoxia. In summary, NIR applied during reperfusion protects the myocardium against infarction in an NO dependent, but NOS-independent mechanisms, whereby mitochondria may be a target of NO released by NIR, leading to reduced reactive oxygen species generation during reperfusion. This unique mechanism preserves protection even during diabetes where other protective strategies fail.

  16. Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

    OpenAIRE

    Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

    2003-01-01

    For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

  17. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  18. A specific and sensitive HPLC-MS/MS micromethod for milrinone plasma levels determination after inhalation in cardiac patients.

    Science.gov (United States)

    Gavra, Paul; Nguyen, Anne Q-N; Theoret, Yves; Litalien, Catherine; Denault, André Y; Varin, France

    2014-10-01

    Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown to be useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. To address these issues in view of pharmacokinetic studies, this article aims to develop and validate a specific and sensitive analytical assay using high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery. Plasma samples (50 μL) were extracted using ethyl acetate. Milrinone was separated on a C18 analytical column at 50°C. The mobile phase consisted of methanol and 10 mM ammonium acetate (45:55 vol/vol). The electrospray was operated in the negative ionization mode and monitored the following mass transitions: m/z 212.1 → 140.0 at 36 eV for milrinone and m/z 252.1 → 156.1 at 32 eV for olprinone. Calibration curves followed a quadratic regression in the concentration range of 0.3125-640 ng/mL. The lower limit of quantification is 0.3125 ng/mL and is based on a low plasma volume of 50 μL. Mean drug recovery and accuracy were ≥72.3% and 96.0%, respectively. Intraday and interday precision coefficient of variation (%) was ≤7.4% and ≤11.5%, respectively. The specificity allowed milrinone quantification in the multidrug administration conditions of cardiopulmonary bypass. This validated micromethod proved to be highly sensitive and specific while using a low volume of plasma. Its low volume and its lower limit of quantification indicate that this approach is suitable for further characterization of milrinone pharmacokinetics in both adults (inhalation) and neonates.

  19. Muscle specific miRNAs are induced by testosterone and independently upregulated by age

    DEFF Research Database (Denmark)

    Nielsen, Søren; Hvid, Thine; Kelly, Meghan

    2014-01-01

    Age dependent decline in skeletal muscle function leads to impaired metabolic flexibility in elderly individuals. Physical activity and testosterone treatment have proven efficient strategies for delaying this condition. However, a common molecular pathway has not been identified. Muscle specific...... miRNAs (myomiRs) regulate metabolic pathways in skeletal muscle, are regulated by physical activity, and have response elements for testosterone in their promoter region. We therefore hypothesized that myomiRs would be regulated in skeletal muscle during aging. We further investigated any potential...... gender-dependent regulation of these miRNAs. We found that the myomiRs miR-1, miR-133a, and miR-133b were increased in skeletal muscle of elderly men compared to younger men. In addition, miR-133a/133b expression was markedly higher in women compared to men. Elimination of circulating testosterone in men...

  20. Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

    Directory of Open Access Journals (Sweden)

    Hinrich eAbken

    2013-11-01

    Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

  1. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo.

    Science.gov (United States)

    Bueno, O F; De Windt, L J; Lim, H W; Tymitz, K M; Witt, S A; Kimball, T R; Molkentin, J D

    2001-01-19

    Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.

  2. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation

    NARCIS (Netherlands)

    Kamphuis, M.; Zwinderman, K.A.H.; Vogels, T.; Vliegen, H.W.; Kamphuis, R.P.; Ottenkamp, J.; Verloove-Vanhorick, S.P.; Bruil, J.

    2004-01-01

    This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an

  3. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?

    Science.gov (United States)

    Leischik, Roman; Spelsberg, Norman; Niggemann, Hiltrud; Dworrak, Birgit; Tiroch, Klaus

    2014-01-01

    Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the "cardiac fatigue" caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  4. Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

    Directory of Open Access Journals (Sweden)

    Sung-Jun Park

    2017-04-01

    Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

  5. Contrast-enhanced specific absorption rate-efficient 3D cardiac cine with respiratory-triggered radiofrequency gating.

    Science.gov (United States)

    Henningsson, Markus; Chan, Raymond H; Goddu, Beth; Goepfert, Lois A; Razavi, Reza; Botnar, Rene M; Schaeffter, Tobias; Nezafat, Reza

    2013-04-01

    To investigate the use of radiofrequency (RF) gating in conjunction with a paramagnetic contrast agent to reduce the specific absorption rate (SAR) and increase the blood-myocardium contrast in balanced steady-state free precession (bSSFP) 3D cardiac cine. RF gating was implemented by synchronizing the RF-excitation with an external respiratory sensor (bellows), which could additionally be used for respiratory gating. For reference, respiratory-gated 3D cine images were acquired without RF gating. Free-breathing 3D cine images were acquired in eight healthy subjects before and after contrast injection (Gd-BOPTA) and compared to breath-hold 2D cine. RF-gated 3D cine reduced the SAR by nearly 40% without introducing significant artifacts while providing left ventricle (LV) measurements similar to those obtained with 2D cine. The contrast-to-noise ratio (CNR) was significantly higher for 3D cine compared to 2D cine, both before and after contrast injection; however, no statistically significant CNR increase was observed for the postcontrast 3D cine compared to the precontrast acquisitions. Respiratory-triggered RF gating significantly reduces SAR in 3D cine acquisitions, which may enable a more widespread clinical use of 3D cine. Furthermore, CNR of 3D bSSFP cine is higher than of 2D and administration of Gd-BOPTA does not improve the CNR of 3D cine. Copyright © 2012 Wiley Periodicals, Inc.

  6. Increased specificity in human cardiac-myosin radioimmunoassay utilizing two monoclonal antibodies in a double sandwich assay

    International Nuclear Information System (INIS)

    Katus, H.A.; Hurrell, J.G.; Matsueda, G.R.; Ehrlich, P.; Zurawski, V.R. Jr.; Khaw, B.-A.; Haber, E.

    1982-01-01

    An immunoradiometric assay that simultaneously measured two different epitopes on the same molecule was devised to differential between cardiac- and skeletal-myosin light chains. Three monoclonal antibodies were examined that were 100% (lC5), 25% (2B9) and 17% (4F10) cross reactive, respectively, between the two antigens. One antibody of the pair to be studied was immobilized to cyanogen bromide-activated Sepharose 4B while the other was iodinated with 125 I using the lactoperoxidase method. The antigen was mixed with the immobilized antibody, the labeled antibody was added and the precipitate then washed and counted in a gamma counter. When both antibodies of the pair to be studied (immobilized and labeled) were the same (2B9), no radioactivity above background was bound to the precipitate, indicating that the second antibody could not bind to an already occupied epitope. When two different antibodies were employed, the specificity of the assay increased over that of a single antibody. The cross reactivity of a pair approximated the product of the cross reactivities of the individual antibodies. Thus, lC5 and 2B9 were 25% cross reactive together, lC5 and 4F10 17% cross reactive, and 2B9 and 4F10 4.3% cross reactive. (author)

  7. Site-specific issues related to structural/seismic design of an underground independent spent fuel storage installation (ISFSI)

    International Nuclear Information System (INIS)

    Tripathi, B.P.

    2005-01-01

    Utilities owning and operating commercial nuclear power plants (NPP) in USA may choose to build an underground Independent Spent Fuel Storage Installation (ISFSI) to store the spent nuclear fuels. The regulatory requirements and other guidance are based on 10 CFR Part 72, Regulatory Guide RG 3.73, Standard Review Plans NUREG-1536 and NUREG-1567, and Interim staff Guidance (ISG) documents as applicable. Structures, Systems, and Components (SSCs) classified as important to safety are designed to withstand the effects of site-specific environmental conditions and natural phenomena such as earthquake, tornado, flood, etc. An underground ISFSI for storage of spent nuclear fuel, presents some unique analysis and design challenges. This paper will briefly address some of these challenges and discuss site-specific loads, including seismic for the ISFSI design. (authors)

  8. Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Ukwatta, Eranga, E-mail: eukwatt1@jhu.edu; Arevalo, Hermenegild; Pashakhanloo, Farhad; Prakosa, Adityo; Vadakkumpadan, Fijoy [Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland 21205 and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Rajchl, Martin [Department of Computing, Imperial College London, London SW7 2AZ (United Kingdom); White, James [Stephenson Cardiovascular MR Centre, University of Calgary, Calgary, Alberta T2N 2T9 (Canada); Herzka, Daniel A.; McVeigh, Elliot [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Lardo, Albert C. [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 and Division of Cardiology, Johns Hopkins Institute of Medicine, Baltimore, Maryland 21224 (United States); Trayanova, Natalia A. [Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Department of Biomedical Engineering, Johns Hopkins Institute of Medicine, Baltimore, Maryland 21205 (United States)

    2015-08-15

    Purpose: Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. Methods: The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. Results: The accuracy of the LogOdds method in reconstructing 3D

  9. Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Rettmann, Maryam E., E-mail: rettmann.maryam@mayo.edu; Holmes, David R.; Camp, Jon J.; Cameron, Bruce M.; Robb, Richard A. [Biomedical Imaging Resource, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States); Kwartowitz, David M. [Department of Bioengineering, Clemson University, Clemson, South Carolina 29634 (United States); Gunawan, Mia [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C. 20057 (United States); Johnson, Susan B.; Packer, Douglas L. [Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905 (United States); Dalegrave, Charles [Clinical Cardiac Electrophysiology, Cardiology Division Hospital Sao Paulo, Federal University of Sao Paulo, 04024-002 Brazil (Brazil); Kolasa, Mark W. [David Grant Medical Center, Fairfield, California 94535 (United States)

    2014-02-15

    Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved

  10. The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

    Science.gov (United States)

    Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

    To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience

    International Nuclear Information System (INIS)

    Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Joergen; Nyholm, Tufve; Ahnesjoe, Anders; Karlsson, Mikael

    2007-01-01

    Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm 3 ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 ± 1.2% and 0.5 ± 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 ± 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach

  12. Lack of host specificity leads to independent assortment of dipterocarps and ectomycorrhizal fungi across a soil fertility gradient.

    Science.gov (United States)

    Peay, Kabir G; Russo, Sabrina E; McGuire, Krista L; Lim, Zhenyu; Chan, Ju Ping; Tan, Sylvester; Davies, Stuart J

    2015-08-01

    Plants interact with a diversity of microorganisms, and there is often concordance in their community structures. Because most community-level studies are observational, it is unclear if such concordance arises because of host specificity, in which microorganisms or plants limit each other's occurrence. Using a reciprocal transplant experiment, we tested the hypothesis that host specificity between trees and ectomycorrhizal fungi determines patterns of tree and fungal soil specialisation. Seedlings of 13 dipterocarp species with contrasting soil specialisations were seeded into plots crossing soil type and canopy openness. Ectomycorrhizal colonists were identified by DNA sequencing. After 2.5 years, we found no evidence of host specificity. Rather, soil environment was the primary determinant of ectomycorrhizal diversity and composition on seedlings. Despite their close symbiosis, our results show that ectomycorrhizal fungi and tree communities in this Bornean rain forest assemble independently of host-specific interactions, raising questions about how mutualism shapes the realised niche. © 2015 John Wiley & Sons Ltd/CNRS.

  13. Age-specific prognostication after out-of-hospital cardiac arrest - The ethical dilemma between 'life-sustaining treatment' and 'the right to die' in the elderly.

    Science.gov (United States)

    Sulzgruber, Patrick; Sterz, Fritz; Poppe, Michael; Schober, Andreas; Lobmeyr, Elisabeth; Datler, Philip; Keferböck, Markus; Zeiner, Sebastian; Nürnberger, Alexander; Hubner, Pia; Stratil, Peter; Wallmueller, Christian; Weiser, Christoph; Warenits, Alexandra-Maria; van Tulder, Raphael; Zajicek, Andreas; Buchinger, Angelika; Testori, Christoph

    2017-03-01

    While prognostic values on survival after out-of-hospital cardiac arrest have been well investigated, less attention has been paid to their age-specific relevance. Therefore, we aimed to identify suitable age-specific early prognostication in elderly patients suffering out-of-hospital cardiac arrest in order to reduce the burden of unnecessary treatment and harm. In a prospective population-based observational trial on individuals suffering out-of-hospital cardiac arrest, a total of 2223 patients receiving resuscitation attempts by the local emergency medical service in Vienna, Austria, were enrolled. Patients were stratified according to age as follows: young and middle-aged individuals (85 years). There was an increasing rate of 30-day mortality (+21.8%, p 85-year-olds. Frailty was directly associated with mortality (HR 1.22, 95% CI 1.01-1.51, p = 0.049), showing a 30-day survival of 5.6% and a favourable neurological outcome of 1.1% among elderly individuals. An initially shockable electrocardiogram proved to be a suitable tool for risk assessment and decision making in order to predict a successful outcome in elderly victims of out-of-hospital cardiac arrest. However, the outcomes of elderly patients seemed to be exceptionally poor in frail individuals and need to be considered in order to reduce unnecessary treatment decisions.

  14. Measurement of functional capacity requirements to aid in development of an occupation-specific rehabilitation training program to help firefighters with cardiac disease safely return to work.

    Science.gov (United States)

    Adams, Jenny; Roberts, Joanne; Simms, Kay; Cheng, Dunlei; Hartman, Julie; Bartlett, Charles

    2009-03-15

    We designed a study to measure the functional capacity requirements of firefighters to aid in the development of an occupation-specific training program in cardiac rehabilitation; 23 healthy male firefighters with no history of heart disease completed a fire and rescue obstacle course that simulated 7 common firefighting tasks. They wore complete personal protective equipment and portable metabolic instruments that included a data collection mask. We monitored each subject's oxygen consumption (VO(2)) and working heart rate, then calculated age-predicted maximum heart rates (220 - age) and training target heart rates (85% of age-predicted maximum heart rate). During performance of the obstacle course, the subjects' mean working heart rates and peak heart rates were higher than the calculated training target heart rates (t(22) = 5.69 [working vs target, p functional capacity greatly exceeded that typically attained by patients in traditional cardiac rehabilitation programs (5 to 8 METs). In conclusion, our results indicate the need for intense, occupation-specific cardiac rehabilitation training that will help firefighters safely return to work after a cardiac event.

  15. Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

    Science.gov (United States)

    Hung, Rupert K; Al-Mallah, Mouaz H; Qadi, Mohamud A; Shaya, Gabriel E; Blumenthal, Roger S; Nasir, Khurram; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

    2015-08-01

    We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations.

    Science.gov (United States)

    Wang, Tianqi; Zhang, Xiaolong; Li, Ang; Zhu, Meifang; Liu, Shu; Qin, Wen; Li, Jin; Yu, Chunshui; Jiang, Tianzi; Liu, Bing

    2017-01-01

    Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS) was computed. Two independent general populations (N = 360 and N = 323) were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity. Consistent altered functional connectivity was found with the bilateral insula: for the left supplementary motor area and the left superior temporal gyrus with the cross-disorder PGRS, for the left insula and right middle and superior temporal lobe associated with the PGRS for autism, for the bilateral midbrain, posterior cingulate, cuneus, and precuneus associated with the PGRS for BD, and for the left angular gyrus and the left dorsolateral prefrontal cortex associated with the PGRS for schizophrenia. No significant functional connectivity was found associated with the PGRS for ADHD and MDD. Our findings indicated that genetic effects on the cross-disorder and disorder-specific neural connectivity of common genetic risk loci are detectable in the general population. Our findings also indicated that polygenic risk contributes to the main neurobiological phenotypes of psychiatric disorders and that identifying cross-disorder and specific functional connectivity related to polygenic risks may elucidate the neural pathways for these disorders.

  17. Age- and gender-specific differences in left ventricular cardiac function and volumes determined by gated SPET

    International Nuclear Information System (INIS)

    Bondt, P. de; Wiele, C. van de; Winter, F. de; Dierckx, R.A.; Sutter, J. de; Backer, G. de

    2001-01-01

    The aim of this study was to determine normative volumetric data and ejection fraction values derived from gated myocardial single-photon emission tomography (SPET) using the commercially available software algorithm QGS (quantitative gated SPET). From a prospective database of 876 consecutive patients who were referred for a 2-day stress-rest technetium-99m tetrofosmin (925 MBq) gated SPET study, 102 patients (43 men, 59 women) with a low (<10%) pre-test likelihood of coronary disease were included (mean age 57.6 years). For stress imaging, a bicycle protocol was used in 79 of the patients and a dipyridamole protocol in 23. Left ventricular ejection fraction (LVEF) and end-diastolic and -systolic volumes (EDV and ESV) were calculated by QGS. EDV and ESV were corrected for body surface area, indicated by EDVi and ESVi. To allow comparison with previous reports using other imaging modalities, men and women were divided into three age groups (<45 years, ≥45 years but <65 years and ≥65 years). Men showed significantly higher EDVi and ESVi values throughout and lower LVEF values when compared with women in the subgroup ≥65 years (P<0.05, ANOVA). Significant negative and positive correlations were found between age and EDVi and ESVi values for both women and men and between LVEF and age in women (Pearson P≤0.01). LVEF values at bicycle stress were significantly higher than at rest (P=0.000, paired t test), which was the result of a significant decrease in ESV (P=0.003), a phenomenon which did not occur following dipyridamole stress (P=0.409). The data presented suggest that LVEF and EDVi and ESVi as assessed by QGS are strongly gender-specific. Although the physiological significance of these results is uncertain and needs further study, these findings demonstrate that the evaluation of cardiac function and volumes of patients by means of QGS should consider age- and gender-matched normative values. (orig.)

  18. siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

    Science.gov (United States)

    Vickers, Timothy A; Crooke, Stanley T

    2012-07-01

    While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

  19. The accuracy of chest radiographs in the detection of congenital heart disease and in the diagnosis of specific congenital cardiac lesions

    International Nuclear Information System (INIS)

    Laya, Bernard F.; Goske, Marilyn J.; Morrison, Stuart; Reid, Janet R.; Swischuck, Leonard; Ey, Elizabeth H.; Murphy, Daniel J.; Lieber, Michael; Obuchowski, Nancy

    2006-01-01

    Congenital heart disease (CHD) is a significant cause of morbidity and mortality in pediatric patients. Traditional teaching holds that specific types of CHD can be diagnosed on the chest radiograph (CXR) through pattern recognition. To determine the accuracy of radiologists in detecting CHD on the CXR. This study was a blinded retrospective review of chest radiographs from 281 patients (<12 years) by five pediatric radiologists from three institutions. Thirteen groups were evaluated that included 12 categories of CHD and a control group of patients without heart disease. Radiographs were assessed for heart size, heart and mediastinal shape and vascularity. Clinical information, angiography, echocardiograms and surgery were used as the gold standard for definitive diagnosis. The average accuracy of the five readers in distinguishing normal from CHD patients was 78% (range of 72% to 82%). The overall measure of accuracy in distinguishing specific congenital cardiac lesions among 13 groups of patients was 71% (range of 63% to 79%). CXR alone is not diagnostic of specific cardiac lesions, with a low accuracy of only 71%. We believe that less emphasis should be placed on the use of radiographs alone in diagnosing specific congenital cardiac lesions. (orig.)

  20. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs.

    Science.gov (United States)

    Shiri, Fereshteh; Pirhadi, Somayeh; Ghasemi, Jahan B

    2016-03-01

    Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q (2) value of 0.77, an [Formula: see text] of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  1. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

    Directory of Open Access Journals (Sweden)

    Fereshteh Shiri

    2016-03-01

    Full Text Available Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD and the enhanced replacement method (ERM were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND approach. After variable selection, GRIND were correlated with activity values (pIC50 by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q2 value of 0.77, an rpred2 of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  2. Cardiac CT

    International Nuclear Information System (INIS)

    Dewey, Marc

    2011-01-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  3. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  4. Measurement of functional capacity requirements of police officers to aid in development of an occupation-specific cardiac rehabilitation training program.

    Science.gov (United States)

    Adams, Jenny; Schneider, Jonna; Hubbard, Matthew; McCullough-Shock, Tiffany; Cheng, Dunlei; Simms, Kay; Hartman, Julie; Hinton, Paul; Strauss, Danielle

    2010-01-01

    This study was designed to measure the functional capacity of healthy subjects during strenuous simulated police tasks, with the goal of developing occupation-specific training for cardiac rehabilitation of police officers. A calibrated metabolic instrument and an oxygen consumption data collection mask were used to measure the oxygen consumption and heart rates of 30 Dallas Police Academy officers and cadets as they completed an 8-event obstacle course that simulated chasing, subduing, and handcuffing a suspect. Standard target heart rates (85% of age-predicted maximum heart rate, or 0.85 x [220 - age]) and metabolic equivalents (METs) were calculated; a matched-sample t test based on differences between target and achieved heart rate and MET level was used for statistical analysis. Peak heart rates during the obstacle course simulation were significantly higher than the standard target heart rates (those at which treadmill stress tests in physicians' offices are typically stopped) (t(29) = 12.81, P requires a functional capacity greater than that typically attained in traditional cardiac rehabilitation programs. Rehabilitation professionals should consider performing maximal stress tests and increasing the intensity of cardiac rehabilitation workouts to effectively train police officers who have had a cardiac event.

  5. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Brennan, Donal J; Jirstrom, Karin; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm

    2010-01-01

    Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens

  6. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-01-01

    BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  7. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-04-01

    Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  8. Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Based on our recent finding that cardiac myosin binding protein C (cMyBP-C phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302, DAD (Asp273-Ala282-Asp302, SAS (Ser273-Ala282-Ser302, and t/t (cMyBP-C null genotypes, and the results were compared to transgenic mice expressing wide-type (WT cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi, and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc, and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases.

  9. Mouse Nkrp1-Clr gene cluster sequence and expression analyses reveal conservation of tissue-specific MHC-independent immunosurveillance.

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    Full Text Available The Nkrp1 (Klrb1-Clr (Clec2 genes encode a receptor-ligand system utilized by NK cells as an MHC-independent immunosurveillance strategy for innate immune responses. The related Ly49 family of MHC-I receptors displays extreme allelic polymorphism and haplotype plasticity. In contrast, previous BAC-mapping and aCGH studies in the mouse suggest the neighboring and related Nkrp1-Clr cluster is evolutionarily stable. To definitively compare the relative evolutionary rate of Nkrp1-Clr vs. Ly49 gene clusters, the Nkrp1-Clr gene clusters from two Ly49 haplotype-disparate inbred mouse strains, BALB/c and 129S6, were sequenced. Both Nkrp1-Clr gene cluster sequences are highly similar to the C57BL/6 reference sequence, displaying the same gene numbers and order, complete pseudogenes, and gene fragments. The Nkrp1-Clr clusters contain a strikingly dissimilar proportion of repetitive elements compared to the Ly49 clusters, suggesting that certain elements may be partly responsible for the highly disparate Ly49 vs. Nkrp1 evolutionary rate. Focused allelic polymorphisms were found within the Nkrp1b/d (Klrb1b, Nkrp1c (Klrb1c, and Clr-c (Clec2f genes, suggestive of possible immune selection. Cell-type specific transcription of Nkrp1-Clr genes in a large panel of tissues/organs was determined. Clr-b (Clec2d and Clr-g (Clec2i showed wide expression, while other Clr genes showed more tissue-specific expression patterns. In situ hybridization revealed specific expression of various members of the Clr family in leukocytes/hematopoietic cells of immune organs, various tissue-restricted epithelial cells (including intestinal, kidney tubular, lung, and corneal progenitor epithelial cells, as well as myocytes. In summary, the Nkrp1-Clr gene cluster appears to evolve more slowly relative to the related Ly49 cluster, and likely regulates innate immunosurveillance in a tissue-specific manner.

  10. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

    Science.gov (United States)

    Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

    2017-06-13

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

  11. An RNA aptamer specific to Hsp70-ATP conformation inhibits its ATPase activity independent of Hsp40.

    Science.gov (United States)

    Thirunavukarasu, Deepak; Shi, Hua

    2015-04-01

    The highly conserved and ubiquitous molecular chaperone heat shock protein 70 (Hsp70) plays a critical role in protein homeostasis (proteostasis). Controlled by its ATPase activity, Hsp70 cycles between two conformations, Hsp70-ATP and Hsp70-ADP, to bind and release its substrate. Chemical tools with distinct modes of action, especially those capable of modulating the ATPase activity of Hsp70, are being actively sought after in the mechanistic dissection of this system. Here, we report a conformation-specific RNA aptamer that binds only to Hsp70-ATP but not to Hsp70-ADP. We have refined this aptamer and demonstrated its inhibitory effect on Hsp70's ATPase activity. We have also shown that this inhibitory effect on Hsp70 is independent of its interaction with the Hsp40 co-chaperone. As Hsp70 is increasingly being recognized as a drug target in a number of age related diseases such as neurodegenerative, protein misfolding diseases and cancer, this aptamer is potentially useful in therapeutic applications. Moreover, this work also demonstrates the feasibility of using aptamers to target ATPase activity as a general therapeutic strategy.

  12. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

    Science.gov (United States)

    Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2014-02-01

    Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. [Cardiac cachexia].

    Science.gov (United States)

    Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

    2006-05-01

    Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

  14. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  15. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  16. Development of an organ-specific insert phantom generated using a 3D printer for investigations of cardiac computed tomography protocols.

    Science.gov (United States)

    Abdullah, Kamarul A; McEntee, Mark F; Reed, Warren; Kench, Peter L

    2018-04-30

    An ideal organ-specific insert phantom should be able to simulate the anatomical features with appropriate appearances in the resultant computed tomography (CT) images. This study investigated a 3D printing technology to develop a novel and cost-effective cardiac insert phantom derived from volumetric CT image datasets of anthropomorphic chest phantom. Cardiac insert volumes were segmented from CT image datasets, derived from an anthropomorphic chest phantom of Lungman N-01 (Kyoto Kagaku, Japan). These segmented datasets were converted to a virtual 3D-isosurface of heart-shaped shell, while two other removable inserts were included using computer-aided design (CAD) software program. This newly designed cardiac insert phantom was later printed by using a fused deposition modelling (FDM) process via a Creatbot DM Plus 3D printer. Then, several selected filling materials, such as contrast media, oil, water and jelly, were loaded into designated spaces in the 3D-printed phantom. The 3D-printed cardiac insert phantom was positioned within the anthropomorphic chest phantom and 30 repeated CT acquisitions performed using a multi-detector scanner at 120-kVp tube potential. Attenuation (Hounsfield Unit, HU) values were measured and compared to the image datasets of real-patient and Catphan ® 500 phantom. The output of the 3D-printed cardiac insert phantom was a solid acrylic plastic material, which was strong, light in weight and cost-effective. HU values of the filling materials were comparable to the image datasets of real-patient and Catphan ® 500 phantom. A novel and cost-effective cardiac insert phantom for anthropomorphic chest phantom was developed using volumetric CT image datasets with a 3D printer. Hence, this suggested the printing methodology could be applied to generate other phantoms for CT imaging studies. © 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical

  17. Predictive mutagenesis of ligation-independent cloning (LIC) vectors for protein expression and site-specific chemical conjugation

    DEFF Research Database (Denmark)

    Vernet, Erik; Sauer, Jørgen; Andersen, Peter Andreas

    2011-01-01

    Ligation-independent cloning (LIC) allows for cloning of DNA constructs independent of insert restriction sites and ligases. However, any required mutations are typically introduced by additional, time-consuming steps. We present a rapid, inexpensive method for mutagenesis in the 5' LIC site...

  18. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells.

    Science.gov (United States)

    Baldauf, Hanna-Mari; Stegmann, Lena; Schwarz, Sarah-Marie; Ambiel, Ina; Trotard, Maud; Martin, Margarethe; Burggraf, Manja; Lenzi, Gina M; Lejk, Helena; Pan, Xiaoyu; Fregoso, Oliver I; Lim, Efrem S; Abraham, Libin; Nguyen, Laura A; Rutsch, Frank; König, Renate; Kim, Baek; Emerman, Michael; Fackler, Oliver T; Keppler, Oliver T

    2017-03-07

    Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.

  19. Validation of site-specific soil Ni toxicity thresholds with independent ecotoxicity and biogeochemistry data for elevated soil Ni.

    Science.gov (United States)

    Hale, Beverley; Gopalapillai, Yamini; Pellegrino, Amanda; Jennett, Tyson; Kikkert, Julie; Lau, Wilson; Schlekat, Christian; McLaughlin, Mike J

    2017-12-01

    The Existing Substances Regulation Risk Assessments by the European Union (EU RA) generated new toxicity data for soil organisms exposed to Ni added to sixteen field-collected soils with low background concentration of metals and varying physico-chemical soil characteristics. Using only effective cation exchange capacity (eCEC) as a bioavailability correction, chronic toxicity of Ni in soils with a wide range of characteristics could be predicted within a factor of two. The objective of the present study was to determine whether this was also the case for three independent data sets of Ni toxicity thresholds. Two of the data sets were from Community Based Risk Assessments in Port Colborne ON, and Sudbury ON (Canada) for soils containing elevated concentrations of Ni, Co and Cu arising from many decades of Ni mining, smelting and refining. The third data set was the Metals in Asia study of soluble Ni added to field soils in China. These data yielded 72 leached and aged EC 10 /NOEC values for soil Ni, for arthropods, higher plants and woodlot structure and function. These were reduced to nine most sensitive single or geometric mean species/function endpoints, none of which were lower than the HC 5 predicted for a soil with an eCEC of 20 cmol/kg. Most of these leached and aged EC 10 /NOEC values were from soils co-contaminated with Cu, in some cases at its median HC 5 as predicted by the EU RA from soil characteristics. We conclude that the EU RA is protective of Ni toxicity to higher-tier ecological endpoints, including in mixture with Cu, before the assessment factor of 2 is applied. We suggest that for prospective risk assessment, the bioavailability based PNEC (HC 5 /2) be used as a conservative screen, but for retrospective and site-specific risk assessment, the bioavailability based HC 5 is sufficient. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Validation of site-specific soil Ni toxicity thresholds with independent ecotoxicity and biogeochemistry data for elevated soil Ni

    International Nuclear Information System (INIS)

    Hale, Beverley; Gopalapillai, Yamini; Pellegrino, Amanda; Jennett, Tyson; Kikkert, Julie; Lau, Wilson; Schlekat, Christian; McLaughlin, Mike J.

    2017-01-01

    The Existing Substances Regulation Risk Assessments by the European Union (EU RA) generated new toxicity data for soil organisms exposed to Ni added to sixteen field-collected soils with low background concentration of metals and varying physico-chemical soil characteristics. Using only effective cation exchange capacity (eCEC) as a bioavailability correction, chronic toxicity of Ni in soils with a wide range of characteristics could be predicted within a factor of two. The objective of the present study was to determine whether this was also the case for three independent data sets of Ni toxicity thresholds. Two of the data sets were from Community Based Risk Assessments in Port Colborne ON, and Sudbury ON (Canada) for soils containing elevated concentrations of Ni, Co and Cu arising from many decades of Ni mining, smelting and refining. The third data set was the Metals in Asia study of soluble Ni added to field soils in China. These data yielded 72 leached and aged EC 10 /NOEC values for soil Ni, for arthropods, higher plants and woodlot structure and function. These were reduced to nine most sensitive single or geometric mean species/function endpoints, none of which were lower than the HC 5 predicted for a soil with an eCEC of 20 cmol/kg. Most of these leached and aged EC 10 /NOEC values were from soils co-contaminated with Cu, in some cases at its median HC 5 as predicted by the EU RA from soil characteristics. We conclude that the EU RA is protective of Ni toxicity to higher-tier ecological endpoints, including in mixture with Cu, before the assessment factor of 2 is applied. We suggest that for prospective risk assessment, the bioavailability based PNEC (HC 5 /2) be used as a conservative screen, but for retrospective and site-specific risk assessment, the bioavailability based HC 5 is sufficient. - Highlights: • Higher-tier ecotoxicity thresholds calculated for field soils with elevated Ni. • Adjusted for Ni bioavailability using soil eCEC and species-specific

  1. Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

    Science.gov (United States)

    Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

    2013-03-01

    The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Left ventricular dyssynchrony assessed by gated SPECT phase analysis is an independent predictor of death in patients with advanced coronary artery disease and reduced left ventricular function not undergoing cardiac resynchronization therapy

    Energy Technology Data Exchange (ETDEWEB)

    Uebleis, Christopher; Hellweger, Stefan; Lehner, Sebastian; Haug, Alexander; Bartenstein, Peter; Cumming, Paul; Hacker, Marcus [Ludwig-Maximilians University, Department of Nuclear Medicine, Munich (Germany); Laubender, Ruediger Paul [Ludwig-Maximilians University, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); Becker, Alexander [Ludwig-Maximilians University, Medical Department I, Munich (Germany); Sohn, Hae-Young [Ludwig-Maximilians University, Medical Department Innenstadt, Munich (Germany); Van Kriekinge, Serge D.; Slomka, Piotr J. [Cedars-Sinai Medical Center, Los Angeles, CA (United States); UCLA, David Geffen School of Medicine, Los Angeles, CA (United States)

    2012-10-15

    Left ventricular (LV) mechanical dyssynchrony (LVMD) was assessed by gated single-photon emission CT myocardial perfusion imaging (MPI) as an independent predictor of death from any cause in patients with known coronary artery disease (CAD) and reduced LV function. Between 2001 and 2010, 135 patients (64 {+-} 11 years of age, 84 % men) with known CAD, reduced LV ejection fraction (LVEF, 38 {+-} 15 %) and without an implanted cardiac resynchronization therapy device underwent gated MPI at rest. LV functional evaluation, which included phase analysis, was conducted to identify patients with LVMD. Kaplan-Meier survival curves were calculated for death of any cause during a mean follow-up of 2.0 {+-} 1.7 years. Uni- and multivariate Cox proportional hazards regression models were calculated to identify independent predictors of death from any cause. Of the 135 patients, 30 (22 %) died during follow-up (18 cardiac deaths and 12 deaths from other causes). Kaplan-Meier curves showed a significantly shorter survival time in the patients with severely reduced LVEF (<30 %, n = 45) or with LVMD (n = 81, log-rank test P <0.005). Cox models identified LVMD, LVEF <30 % and a total perfusion deficit at rest of {>=}20 % as independent predictors of death from any cause. While patients with LVEF <30 % in conjunction with LVMD had similar survival times irrespective of whether they had early revascularization or medical therapy, those patients with LVEF {>=}30% and LVMD who underwent revascularization had significantly longer survival. In patients with known CAD and reduced LV function, dyssynchrony of the LV is an independent predictor of death from any cause. (orig.)

  3. Cardiac ablation

    Directory of Open Access Journals (Sweden)

    Kelly Ratheal

    2016-01-01

    Full Text Available Cardiac ablation is a procedure that uses either radiofrequency or cryothermal energy to destroy cells in the heart to terminate and/or prevent arrhythmias. The indications for cardiac catheter ablation include refractory, symptomatic arrhythmias, with more specific guidelines for atrial fibrillation in particular. The ablation procedure itself involves mapping the arrhythmia and destruction of the aberrant pathway in an effort to permanently prevent the arrhythmia. There are many types of arrhythmias, and they require individualized approaches to ablation based on their innately different electrical pathways. Ablation of arrhythmias, such as Wolff-Parkinson-White syndrome, AV nodal reentrant tachycardia, and atrial-fibrillation, is discussed in this review. Ablation has a high success rate overall and minimal complication rates, leading to improved quality of life in many patients.

  4. Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

    Science.gov (United States)

    Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi

    2015-12-01

    Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Language-Independent and Language-Specific Aspects of Early Literacy: An Evaluation of the Common Underlying Proficiency Model

    Science.gov (United States)

    Goodrich, J. Marc; Lonigan, Christopher J.

    2017-01-01

    According to the common underlying proficiency model (Cummins, 1981), as children acquire academic knowledge and skills in their first language, they also acquire language-independent information about those skills that can be applied when learning a second language. The purpose of this study was to evaluate the relevance of the common underlying…

  6. Noninvasive detection of cardiac repair after acute myocardial infarction in rats by 111In fab fragment of monoclonal antibody specific for tenascin-C

    International Nuclear Information System (INIS)

    Okada, Kenichi; Uehara, Tomoya; Arano, Yasushi

    2008-01-01

    Left ventricular (LV) remodeling after acute myocardial infarction (MI) causes heart failure, and thus it is important to evaluate cardiac repair as the early stage of LV remodeling. Tenascin-C (TNC), an extracellular matrix glycoprotein, is transiently and abundantly expressed in the heart during the early stage of tissue remodeling after MI. However, it is not expressed in healthy adult heart. This study was undertaken to develop a new noninvasive diagnostic technique to detect cardiac repair after acute MI using 111 In Fab fragment of a monoclonal antibody specific for TNC. 111 In-anti-TNC-Fab was injected intravenously in 13 rats at 1 (D1, n=3), 3 (D3, n=5), and 5 (D5, n=5) days after producing MI and in 5 sham-operated rats (S). We performed autoradiography and dual-isotope single-photon emission computed tomography imaging (SPECT) of 111 In-anti-TNC-Fab and 99m Tc methoxyisobutyl isonitrile (MIBI). The radioactivity in the heart was significantly higher in D (D1, 0.45±0.06% injected-dose/g; D3, 0.64±0.12; D5, 0.38±0.07) than S (0.27±0.06, P 111 In-anti-TNC-Fab, which was complementary to the perfusion image. The results of the present study indicated that we can localize the infarcted region in the heart by ex vivo and in vivo imaging methods using 111 In-anti-TNC-Fab, and suggested the potential usefulness of noninvasive detection of cardiac repair. (author)

  7. Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.

    Directory of Open Access Journals (Sweden)

    Ludger Hauck

    Full Text Available The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1.

  8. The covariant formulation of Maxwell's equations expressed in a form independent of specific units

    Energy Technology Data Exchange (ETDEWEB)

    Heras, Jose A; Baez, G [Departamento de Ciencias Basicas, Universidad Autonoma Metropolitana Unidad Azcapotzalco, Av. San Pablo No. 180, Col. Reynosa, 02200 Mexico DF (Mexico)], E-mail: herasgomez@gmail.com, E-mail: gbaez@correo.azc.uam.mx

    2009-01-15

    The covariant formulation of Maxwell's equations can be expressed in a form independent of the usual systems of units by introducing the constants {alpha}, {beta} and {gamma} into these equations. Maxwell's equations involving these constants are then specialized to the most commonly used systems of units: Gaussian, SI and Heaviside-Lorentz by giving the constants {alpha}, {beta} and {gamma} the values appropriate to each system.

  9. Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

    Science.gov (United States)

    Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

    2010-04-15

    The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

    1988-01-01

    We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

  11. Specific binding of (/sup 3/H)LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

    1989-05-01

    LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for (/sup 3/H)LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound (/sup 3/H)LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that (/sup 3/H)LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs.

  12. Specific binding of [3H]LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

    International Nuclear Information System (INIS)

    Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

    1989-01-01

    LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for [ 3 H]LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound [ 3 H]LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that [ 3 H]LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs

  13. Effects of PPARs agonists on cardiac metabolism in littermate and cardiomyocyte-specific PPAR-γ-knockout (CM-PGKO mice.

    Directory of Open Access Journals (Sweden)

    Michelangela Barbieri

    Full Text Available Understanding the molecular regulatory mechanisms controlling for myocardial lipid metabolism is of critical importance for the development of new therapeutic strategies for heart diseases. The role of PPARγ and thiazolidinediones in regulation of myocardial lipid metabolism is controversial. The aim of our study was to assess the role of PPARγ on myocardial lipid metabolism and function and differentiate local/from systemic actions of PPARs agonists using cardiomyocyte-specific PPARγ -knockout (CM-PGKO mice. To this aim, the effect of PPARγ, PPARγ/PPARα and PPARα agonists on cardiac function, intra-myocyte lipid accumulation and myocardial expression profile of genes and proteins, affecting lipid oxidation, uptake, synthesis, and storage (CD36, CPT1MIIA, AOX, FAS, SREBP1-c and ADPR was evaluated in cardiomyocyte-specific PPARγ-knockout (CM-PGKO and littermate control mice undergoing standard and high fat diet (HFD. At baseline, protein levels and mRNA expression of genes involved in lipid uptake, oxidation, synthesis, and accumulation of CM-PGKO mice were not significantly different from those of their littermate controls. At baseline, no difference in myocardial lipid content was found between CM-PGKO and littermate controls. In standard condition, pioglitazone and rosiglitazone do not affect myocardial metabolism while, fenofibrate treatment significantly increased CD36 and CPT1MIIA gene expression. In both CM-PGKO and control mice submitted to HFD, six weeks of treatment with rosiglitazone, fenofibrate and pioglitazone lowered myocardial lipid accumulation shifting myocardial substrate utilization towards greater contribution of glucose. In conclusion, at baseline, PPARγ does not play a crucial role in regulating cardiac metabolism in mice, probably due to its low myocardial expression. PPARs agonists, indirectly protect myocardium from lipotoxic damage likely reducing fatty acids delivery to the heart through the actions on adipose

  14. A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis

    Science.gov (United States)

    Lee, Chunghee; Clark, Steven E.

    2015-01-01

    The homeostatic maintenance of stem cells that carry out continuous organogenesis at the shoot meristem is crucial for plant development. Key known factors act to signal between the stem cells and an underlying group of cells thought to act as the stem cell niche. In Arabidopsis thaliana the homeodomain transcription factor WUSCHEL (WUS) is essential for stem cell initiation and maintenance at shoot and flower meristems. Recent data suggest that the WUS protein may move from the niche cells directly into the stem cells to maintain stem cell identity. Here we provide evidence for a second, previously unknown, pathway for stem cell specification at shoot and flower meristems that bypasses the requirement for WUS. We demonstrate that this novel stem cell specification pathway is normally repressed by the activity of the HD-zip III transcription factors PHABULOSA (PHB), PHAVOLUTA (PHV) and CORONA (CNA). When de-repressed, this second stem cell pathway leads to an accumulation of stem cells and an enlargement of the stem cell niche. When de-repressed in a wus mutant background, this second stem cell pathway leads to functional meristems with largely normal cell layering and meristem morphology, activation of WUS cis regulatory elements, and extensive, but not indeterminate, organogenesis. Thus, WUS is largely dispensable for stem cell specification and meristem function, suggesting a set of key stem cell specification factors, competitively regulated by WUS and PHB/PHV/CNA, remain unidentified. PMID:26011610

  15. Chironomid-based water depth reconstructions: an independent evaluation of site-specific and local inference models

    NARCIS (Netherlands)

    Engels, S.; Cwynar, L.C.; Rees, A.B.H.; Shuman, B.N.

    2012-01-01

    Water depth is an important environmental variable that explains a significant portion of the variation in the chironomid fauna of shallow lakes. We developed site-specific and local chironomid water-depth inference models using 26 and 104 surface-sediment samples, respectively, from seven

  16. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological...... effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang......II) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains...

  17. Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2015-07-01

    Full Text Available Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD paradigm. Multi-specificity design (MSD, on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON. The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes.

  18. Cardiac rehabilitation

    Science.gov (United States)

    ... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  19. Understanding individual differences in school achievement : the specific and joint impact of motivation and parenting style independent of children's measured intelligence

    OpenAIRE

    Su, Ying

    2015-01-01

    Intelligence explains some variance in students’ school achievement, but not all. Motivation and parenting have been well-documented as non-cognitive predictors and are crucial to students’ school achievement. Better performance of students under Eastern culture could be attributed to motivation and parenting. The present research is dedicated to exploring the associations among motivation and parenting, as well as their specific and joint predictive power for school achievement, independent ...

  20. On the Size Dependence of Molar and Specific Properties of Independent Nano-phases and Those in Contact with Other Phases

    Science.gov (United States)

    Kaptay, George

    2018-05-01

    Nano-materials are materials with at least one nano-phase. A nano-phase is a phase with at least one of its dimensions below 100 nm. It is shown here that nano-phases have at least 1% of their atoms along their surface layer. The ratio of surface atoms is proportional to the specific surface area of the phase, defined as the ratio of its surface area to its volume. Each specific/molar property has its bulk value and its surface value for the given phase, being always different, as the energetic states of the atoms in the bulk and in the surface layer of a phase are different. The average specific/molar property of a nano-phase is modeled here as a linear combination of the bulk and surface values of the same property, scaled with the ratio of the surface atoms. That makes the performance of all nano-phases proportional to their specific surface area. As the characteristic size of the nano-phase is inversely proportional to its specific surface area, all specific/molar properties of nano-phases are inversely proportional to the characteristic size of the phase. This is applied to the size dependence of the molar Gibbs energy of the nano-phase, which appears to be in agreement with the thermodynamics of Gibbs. This agreement proves the general validity of the present model on the size dependence of the specific/molar properties of independent nano-phases. It is shown that the properties of nano-phases are different for independent nano-phases (surrounded only by their equilibrium vapor phase) and for nano-phases in multi-phase situations, such as a liquid nano-droplet in the sessile drop configuration.

  1. Cardiac pacemaker

    International Nuclear Information System (INIS)

    Kolenik, S.A.

    1976-01-01

    The construction of a cardiac pacemaker is described which is characterized by particularly small dimensions, small weight and long life duration. The weight is under 100g, the specific weight under 1.7. Mass inertia forces which occur through acceleration and retardation processes, thus remain below the threshold values, above which one would have to reckon with considerable damaging of the surrounding body tissue. The maintaining of small size and slight weight is achieved by using an oscillator on COSMOS basis, where by considerably lower energy consumption, amongst others the lifetimes of the batteries used - a lithium anode with thionyl chloride electrolyte - is extended to over 5 years. The reliability can be increased by the use of 2 or more batteries. The designed dimension are 20x60x60 mm 3 . (ORU/LH) [de

  2. Cardiac ventriculography

    International Nuclear Information System (INIS)

    Hillis, L.D.; Grossman, W.

    1986-01-01

    Cardiac ventriculography has been used extensively to define the anatomy of the ventricles and related structures in patients with congenital, valvular, coronary, and cardiomyopathic heart disease. Specifically, left ventriculography may provide valuable information about global and segmental left ventricular function, mitral valvular incompetence, and the presence, location, and severity of a number of other abnormalities, including ventricular septal defect and hypertrophic cardiomyopathy. As a result, it should be a routine part of catheterization in patients being evaluated for coronary artery disease, aortic or mitral valvular disease, unexplained left ventricular failure, or congenital heart disease. Similarly, right ventriculography may provide information about global and segmental right ventricular function and can be especially helpful in patients with congenital heart disease

  3. Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Vallabhajosula, Shankar; Goldsmith, Stanley J; Bander, Neil H

    2004-07-01

    To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ((90)Y-J591) in patients with androgen-independent prostate cancer (PC). Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by (90)Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m(2). Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Twenty-nine patients with androgen-independent PC received (90)Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m(2), with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m(2) dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. The recommended dose for (90)Y-J591 is 17.5 mCi/m(2). Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of (90)Y-J591 in the treatment of patients with PC.

  4. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

    DEFF Research Database (Denmark)

    Vrijens, Karen; Winckelmans, Ellen; Tsamou, Maria

    2017-01-01

    Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. Methods: Microarray analyses were performed in 98...... healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women...

  5. Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

    Science.gov (United States)

    Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

    2018-01-01

    To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

  6. Phonological Awareness and Rapid Automatized Naming Are Independent Phonological Competencies With Specific Impacts on Word Reading and Spelling: An Intervention Study.

    Science.gov (United States)

    Vander Stappen, Caroline; Reybroeck, Marie Van

    2018-01-01

    Phonological awareness (PA) and rapid automatized naming (RAN) have been shown to be powerful predictors of reading achievement across many languages. However, literature remains unclear: (a) whether RAN is independent of PA, (b) about the specific influences of PA and RAN on reading and spelling, and (c) about the efficacy of a RAN intervention. This study aims to address these issues by means of an intervention design. Precisely, the objectives are (a) to determine whether training one competence involves or not an effect on the other, (b) to examine whether each intervention based on oral abilities (PA vs. RAN) could improve word reading and word spelling performances, and (c) to assess the efficacy of a RAN-objects' intervention. Thirty-six French-speaking second graders, from two Belgian elementary schools, were divided into two groups, and received either a PA- or a RAN-objects' intervention. Twenty-five-minute lessons took place at school twice a week over a period of 2 months. Both groups were compared on multiple experimental measures (PA, RAN, word reading, and word spelling), before and immediately after the intervention, and 6 months later. Results showed specific efficacy of the two interventions, with participants trained in one ability outperforming those from the other group on this specific ability at post-test. Moreover, the PA intervention revealed transfer effects on the sub-lexical processes of spelling, while the RAN intervention enhanced word reading speed. Finally, the results demonstrated the efficacy of a RAN-objects' intervention for the first time. These findings provide a new piece of evidence showing the independence of PA and RAN, each process influencing the acquisition of literacy skills in a different way. The efficacy and the specific transfer effects of both interventions open up new perspectives for prevention and targeted remediation of reading disabilities.

  7. High specificity but contrasting biodiversity of Sphagnum-associated bacterial and plant communities in bog ecosystems independent of the geographical region.

    Science.gov (United States)

    Opelt, Katja; Berg, Christian; Schönmann, Susan; Eberl, Leo; Berg, Gabriele

    2007-10-01

    Mosses represent ecological niches that harbor a hitherto largely uncharacterized microbial diversity. To investigate which factors affect the biodiversity of bryophyte-associated bacteria, we analyzed the bacterial communities associated with two moss species, which exhibit different ecological behaviors and importance in bog ecosystems, Sphagnum magellanicum and Sphagnum fallax, from six temperate and boreal bogs in Germany and Norway. Furthermore, their surrounding plant communities were studied. Molecular analysis of bacterial communities was determined by single-strand conformation polymorphism (SSCP) analysis using eubacterial and genus-specific primers for the dominant genera Burkholderia and Serratia as well as by sequence analysis of a Burkholderia 16S rRNA gene clone library. Plant communities were analyzed by monitoring the abundance and composition of bryophyte and vascular plant species, and by determining ecological indicator values. Interestingly, we found a high degree of host specificity for associated bacterial and plant communities of both Sphagnum species independent of the geographical region. Calculation of diversity indices on the basis of SSCP gels showed that the S. fallax-associated communities displayed a statistically significant higher degree of diversity than those associated with S. magellanicum. In contrast, analyses of plant communities of Sphagnum-specific habitats resulted in a higher diversity of S. magellanicum-specific habitats for all six sites. The higher content of nutrients in the S. fallax-associated ecosystems can explain higher diversity of microorganisms.

  8. Satisfactory rate of postprocessing visualization of standard fetal cardiac views from 4-dimensional cardiac volumes acquired during routine ultrasound practice by experienced sonographers in peripheral centers.

    Science.gov (United States)

    Rizzo, Giuseppe; Capponi, Alessandra; Pietrolucci, Maria Elena; Capece, Giuseppe; Cimmino, Ernesto; Colosi, Enrico; Ferrentino, Salvatore; Sica, Carmine; Di Meglio, Aniello; Arduini, Domenico

    2011-01-01

    The aim of this study was to evaluate the feasibility of visualizing standard cardiac views from 4-dimensional (4D) cardiac volumes obtained at ultrasound facilities with no specific experience in fetal echocardiography. Five sonographers prospectively recorded 4D cardiac volumes starting from the 4-chamber view on 500 consecutive pregnancies at 19 to 24 weeks' gestation undergoing routine ultrasound examinations (100 pregnancies for each sonographer). Volumes were sent to the referral center, and 2 independent reviewers with experience in 4D fetal echocardiography assessed their quality in the display of the abdominal view, 4-chamber view, left and right ventricular outflow tracts, and 3-vessel and trachea view. Cardiac volumes were acquired in 474 of 500 pregnancies (94.8%). The 2 reviewers respectively acknowledged the presence of satisfactory images in 92.4% and 93.6% of abdominal views, 91.5% and 93.0% of 4-chamber views, in 85.0% and 86.2% of left ventricular outflow tracts, 83.9% and 84.5% of right ventricular outflow tracts, and 85.2% and 84.5% of 3-vessel and trachea views. The presence of a maternal body mass index of greater than 30 altered the probability of achieving satisfactory cardiac views, whereas previous maternal lower abdominal surgery did not affect the quality of reconstructed cardiac views. In conclusion, cardiac volumes acquired by 4D sonography in peripheral centers showed high enough quality to allow satisfactory diagnostic cardiac views.

  9. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response

    Science.gov (United States)

    Eba, Patrick M.; Lim, HyeYoung

    2017-01-01

    Abstract Introduction: AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents’ access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. Methods: A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Results: Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents’ access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents

  10. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response.

    Science.gov (United States)

    Eba, Patrick M; Lim, HyeYoung

    2017-08-11

    AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents' access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents' access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents. Efforts to end legal barriers to access to HIV services

  11. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes? [v1; ref status: indexed, http://f1000r.es/3b4

    Directory of Open Access Journals (Sweden)

    Roman Leischik

    2014-05-01

    Full Text Available Background: Exercise-induced arterial hypertension (EIAH leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM, the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037. The spiroergometric results were: maximum oxygen uptake (relative VO2max 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns. Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034 or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019. Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  12. PsbS-specific zeaxanthin-independent changes in fluorescence emission spectrum as a signature of energy-dependent non-photochemical quenching in higher plants.

    Science.gov (United States)

    Zulfugarov, Ismayil S; Tovuu, Altanzaya; Dogsom, Bolormaa; Lee, Chung Yeol; Lee, Choon-Hwan

    2010-05-01

    The PsbS protein of photosystem II is necessary for the development of energy-dependent quenching of chlorophyll (Chl) fluorescence (qE), and PsbS-deficient Arabidopsis plant leaves failed to show qE-specific changes in the steady-state 77 K fluorescence emission spectra observed in wild-type leaves. The difference spectrum between the quenched and un-quenched states showed a negative peak at 682 nm. Although the level of qE development in the zeaxanthin-less npq1-2 mutant plants, which lacked violaxanthin de-epoxidase enzyme, was only half that of wild type, there were no noticeable changes in this qE-dependent difference spectrum. This zeaxanthin-independent DeltaF682 signal was not dependent on state transition, and the signal was not due to photobleaching of pigments either. These results suggest that DeltaF682 signal is formed due to PsbS-specific conformational changes in the quenching site of qE and is a new signature of qE generation in higher plants.

  13. Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner.

    Science.gov (United States)

    Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

    2017-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cardiac arrest

    Science.gov (United States)

    ... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

  15. Cardiac Ochronosis

    Science.gov (United States)

    Erek, Ersin; Casselman, Filip P.A.; Vanermen, Hugo

    2004-01-01

    We report the case of 67-year-old woman who underwent aortic valve replacement and mitral valve repair due to ochronotic valvular disease (alkaptonuria), which was diagnosed incidentally during cardiac surgery. PMID:15745303

  16. Cardiac catheterization

    Science.gov (United States)

    ... tests. However, it is very safe when done by an experienced team. The risks include: Cardiac tamponade Heart attack Injury to a coronary artery Irregular heartbeat Low blood pressure Reaction to the contrast dye Stroke Possible complications ...

  17. Nuclear cardiac

    International Nuclear Information System (INIS)

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

  18. Distinct cargo-specific response landscapes underpin the complex and nuanced role of galectin-glycan interactions in clathrin-independent endocytosis.

    Science.gov (United States)

    Mathew, Mohit P; Donaldson, Julie G

    2018-05-11

    Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting from the outside, could be a part of that endocytic machinery. We show that the perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects CIE. Interestingly, these changes in glycosylation had cargo-specific effects. For example, in HeLa cells, GlcNAc treatment, which increases glycan branching, increased major histocompatibility complex class I (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule (CD59). The effects of knocking down the expression of galectin 3, a carbohydrate-binding protein and an important player in galectin-glycan interactions, were also cargo-specific and stimulated CD59 uptake. By contrast, inhibition of all galectin-glycan interactions by lactose inhibited CIE of both MHCI and CD59. None of these treatments affected clathrin-mediated endocytosis, implying that glycosylation changes specifically affect CIE. We also found that the galectin lattice tailors membrane fluidity and cell spreading. Furthermore, changes in membrane dynamics mediated by the galectin lattice affected macropinocytosis, an altered form of CIE, in HT1080 cells. Our results suggest that glycans play an important and nuanced role in CIE, with each cargo being affected uniquely by alterations in galectin and glycan profiles and their interactions. We conclude that galectin-driven effects exist on a continuum from stimulatory to inhibitory, with distinct CIE cargo proteins having unique response landscapes and with different cell types starting at different positions on these conceptual landscapes.

  19. Comparison of Usefulness of N-Terminal Pro-Brain Natriuretic Peptide as an Independent Predictor of Cardiac Function Among Admission Cardiac Serum Biomarkers in Patients With Anterior Wall Versus Nonanterior Wall ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

    NARCIS (Netherlands)

    Haeck, Joost D. E.; Verouden, Niels J. W.; Kuijt, Wichert J.; Koch, Karel T.; van Straalen, Jan P.; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G. P.; Krucoff, Mitchell W.; de Winter, Robbert J.

    2010-01-01

    The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial

  20. Nonexercise cardiac stress testing

    International Nuclear Information System (INIS)

    Vacek, J.L.; Baldwin, T.

    1989-01-01

    Many patients who require evaluation for coronary artery disease are unable to undergo exercise stress testing because of physiologic or psychological limitations. Drs Vacek and Baldwin describe three alternative methods for assessment of cardiac function in these patients, all of which have high levels of diagnostic sensitivity and specificity. 23 references

  1. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

    Science.gov (United States)

    Fernandes, T; Soci, U P R; Oliveira, E M

    2011-09-01

    Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  2. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

    Directory of Open Access Journals (Sweden)

    T. Fernandes

    2011-09-01

    Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  3. Antibody-dependent NK cell activation is associated with late kidney allograft dysfunction and the complement-independent alloreactive potential of donor-specific antibodies

    Directory of Open Access Journals (Sweden)

    Tristan Legris

    2016-08-01

    Full Text Available Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs. The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK cells as innate immune effectors of antibody-dependent cellular cytotoxicity, but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years. Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate (eGFR over a 1-year period (hazard ratio: 2.83. In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration

  4. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    Directory of Open Access Journals (Sweden)

    Mani Harika eVemula

    2016-03-01

    Full Text Available Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis (M.tb, the tuberculosis (TB causing bacilli in human is cleared by cell-mediated immunity (CMI with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches towards vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M.tb Zinc metalloprotease-1 (Zmp1, a secretory protein essential for intracellular survival and pathogenesis of M.tb. We observed that Zmp1 was secreted by in vitro grown M.tb under granuloma-like stress conditions (acidic, oxidative, iron deficiency and nutrient deprivation and generated Th2 cytokine microenvironment upon exogenous treatment of Peripheral Blood Mononulear Cells (PBMCs with recombinant Zmp1 (rZmp1. This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n=121 as against healthy control (n=62, household contacts (n=89 and non-specific infection controls (n=23. A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL to paucibacillary smear-negative pulmonary tuberculosis (PTB cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen

  5. Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

    Science.gov (United States)

    Mullooly, Maeve; Murphy, Jeanne; Gierach, Gretchen L; Walsh, Paul M; Deady, Sandra; Barron, Thomas I; Sherman, Mark E; Rosenberg, Philip S; Anderson, William F

    2017-11-01

    The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers. Published by Elsevier Ltd.

  6. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  7. Clinical Utility of Iopamidol (Pamiray 370) for Cardiac CT

    International Nuclear Information System (INIS)

    Kim, Mok Hee; Seon, Hyun Ju; Choi, Song; Kim, Yun Hyeon; Kim, Jae Kyu; Park, Jin Gyoon; Kang, Heong Keun

    2011-01-01

    We evaluated the utility of iopamidol-based nonionic contrast media (Pamiray 370) for cardiac CT, with assessment of its image quality and safety. The study included 100 patients who underwent cardiac CT with Pamiray 370 (experimental group), and 100 patients who underwent cardiac CT with Ultravist 370 (control group). A comparison of the image qualities and degree of vascular contrast enhancement was made between the two groups and evaluated statistically by an independent t-test. Changes in vital signs and adverse events during cardiac CT were evaluated in the experimental group. There were no statistically significant differences in the image quality (image quality score in experimental group vs. control group: 4.26 ± 0.63 vs. 4.24 ± 0.62), and mean attenuation values at the coronary arteries(p > 0.05) between two groups. For the experimental group, 12% experienced adverse events, including mild and transient reactions such as dizziness (7%), nausea (4%), and fatigue (1%). Further, 94% of patients complained of mild to moderate febrile sense just after contrast agent administration, which spontaneously disappeared within 3 minutes without any specific management. For cardiac CT, Pamiray 370 was comparable to the widely-used contrast agent (Ultravist 370) in terms of image quality and safety without any severe adverse reaction.

  8. Specification of requirements to get a license for an Independent Spent Fuel Dry Storage Installation (ISFSI) at the site of the NPP-LV

    International Nuclear Information System (INIS)

    Serrano R, M. L.

    2015-09-01

    This article describes some of the work done in the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS) to define specifically the requirements that the Federal Electricity Commission (CFE) shall meet to submit for consideration of CNSNS an operation request of an Independent Spent Fuel Dry Storage Installation (ISFSI). The project of a facility of this type arose from the need to provide storage capacity for spent nuclear fuel in the nuclear power plant of Laguna Verde (NPP-LV) and to continue the operation at the same facility in a safe manner. The licensing of these facilities in the United States of America has two modes: specific license or general license. The characteristics of these licenses are described in this article. However, in Mexico the existing national legislation is not designed for such license types, in fact there is a lack of standards or regulations in this regard. The regulatory law of Article 27 of the Constitution in the nuclear matter, only generally establishes that this type of facility requires an authorization from the Ministry of Energy. For this reason and because there is not a national legislation, was necessary to use the legislation that provides the Nuclear Regulatory Commission of USA, the US NRC. However, it cannot be applied as is established, so was necessary that the CNSNS analyze one by one the requirements of both types of license and determine what would be required to NPP-LV to submit its operating license of ISFSI. The American regulatory applicable to an ISFSI, the 10-Cfr-72 of the US NRC, establishes the requirements for both types of licenses. Chapter 10-Cfr was analyzed in all its clauses and coupled to the laws, regulations and standards as well as to the requirements established by CNSNS, all associated with a store spent fuel on site; the respective certification of containers for spent fuel dry storage was not included in this article, even though the CNSNS also performed that activity under the

  9. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    Fiandra, O.; Espasandin, W.; Fiandra, H.

    1984-01-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  10. Are Independent Probes Truly Independent?

    Science.gov (United States)

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  11. Ca2+-clock-dependent pacemaking in the sinus node is impaired in mice with a cardiac specific reduction in SERCA2 abundance

    Directory of Open Access Journals (Sweden)

    Sunil Jit Ramamoorthy Jeewanlal Logantha

    2016-06-01

    Full Text Available Background: The sarcoplasmic reticulum Ca2+-ATPase (SERCA2 pump is an important component of the Ca2+-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO as a model for investigating SERCA2’s role in sinus node pacemaking.Methods and Results: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P70% Serca2 downregulation.Conclusions: Serca2 KO mice show a disrupted Ca2+-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.

  12. Discovery and progress of direct cardiac reprogramming.

    Science.gov (United States)

    Kojima, Hidenori; Ieda, Masaki

    2017-06-01

    Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

  13. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  14. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ding, William, E-mail: billyding888@gmail.com [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Lee, John [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Chamberlain, David [Department of Radiation Oncology, St. Mary' s Regional Medical Center, Reno, Nevada (United States); Cunningham, James [Carson Urology, Carson City, Nevada (United States); Yang Lixi [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Tay, Jonathan [Department of Radiation Oncology, St. Mary' s Regional Medical Center, Reno, Nevada (United States)

    2012-11-15

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naieve patients with localized adenocarcinoma of the prostate treated at St. Mary's Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of {<=}1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic

  15. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    International Nuclear Information System (INIS)

    Ding, William; Lee, John; Chamberlain, David; Cunningham, James; Yang Lixi; Tay, Jonathan

    2012-01-01

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naïve patients with localized adenocarcinoma of the prostate treated at St. Mary’s Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of ≤1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic variables for

  16. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  17. Selection of specific inhibitor peptides in enzyme-linked immunosorbent assay (ELISA) of cardiac troponin I using immuno-dominant epitopes as competitor.

    Science.gov (United States)

    Rezaee, Majid Asiabanha; Rasaee, Mohammad Javad; Mohammadnejad, Javad

    2017-01-01

    Human cardiac troponin I (cTni) is the gold marker for early diagnosis of myocardial infarction. In this regard, four immune-dominant epitopes of cTni were predicted and their 3D structures were determined. Thereafter, the competitive performance of the peptides was monitored with the developed polyclonal antibody-based indirect competitive ELISA; a half-maximal inhibitory concentration (IC50) of 0.49 (µg/mL) and detection limit of 0.037 (µg/mL) were achieved for recombinant cTni. The competitive ELISA determined sensitivity levels of 0.306, 0.141, 0.960, and 0.155 (µg/mL), respectively, for each peptide as competitor. We indicated that two of the selected epitopes have significant sensitivity scales and inhibition ability.

  18. Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac Progenitor Cells.

    Science.gov (United States)

    Mochizuki, Michika; Lorenz, Vera; Ivanek, Robert; Della Verde, Giacomo; Gaudiello, Emanuele; Marsano, Anna; Pfister, Otmar; Kuster, Gabriela M

    2017-10-24

    Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (<2 hours). Ninety-four genes were differentially regulated on laminin versus fibronectin, consisting of mostly downregulated genes that were enriched for Yes-associated protein (YAP) conserved signature and TEA domain family member 1 (TEAD1)-related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2 ( Plk2 ). Plk2 expression depended on YAP stability and was enhanced in CPCs transfected with a nuclear-targeted mutant YAP. Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  19. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  20. JTT-130, a Novel Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein, Improves Hyperglycemia and Dyslipidemia Independent of Suppression of Food Intake in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shohei Sakata

    2014-01-01

    Full Text Available We investigated the effects of JTT-130 on glucose and lipid metabolism independent of the suppression of feeding by comparing with pair-fed animals. Male Zucker diabetic fatty (ZDF rats were divided into control, JTT-130 treatment, and pair-fed groups. The rats were fed with a regular powdered diet with or without JTT-130 as a food admixture for 6 weeks. We compared the effects on glucose and lipid metabolism in JTT-130 treatment group with those in pair-fed group. Results. Hyperglycemia in ZDF rats was prevented in both JTT-130 treatment and pair-fed groups, but the prevention in pair-fed group became poor with time. Moreover, reduction in plasma cholesterol levels was observed only in JTT-130 treatment group. JTT-130 treatment group showed improved glucose tolerance at 5 weeks after treatment and significant elevation of portal glucagon-like peptide-1 (GLP-1 levels. The hepatic lipid content in JTT-130 treatment group was decreased as compared with pair-fed group. Furthermore, pancreatic protection effects, such as an increase in pancreatic weight and an elevation of insulin-positive area in islets, were observed after JTT-130 treatment. Conclusions. JTT-130 improves hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake, which is ascribed to an enhancement of GLP-1 secretion and a reduction of lipotoxicity.

  1. Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

    Science.gov (United States)

    Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

    2014-08-01

    Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, ppain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Is Training Essential for Interpreting Cardiac Computed Tomography

    International Nuclear Information System (INIS)

    Ripsweden, J.; Brolin, E. Bacsovics; Brismar, T.; Nilsson, T.; Svensson, A.; Werner, C.; Cederlund, K.; Mir-Akbari, H.; Rueck, A.; Rasmussen, E.; Winter, R.

    2009-01-01

    Background: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. Purpose: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. Material and Methods: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. Results: The mean review time decreased (P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists (P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists (P<0.01). Conclusion: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team

  3. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal

    2017-01-01

    were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5...... of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition....... RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC...

  4. Imaging in cardiac mass lesions

    International Nuclear Information System (INIS)

    Mundinger, A.; Gruber, H.P.; Dinkel, E.; Geibel, A.; Beck, A.; Wimmer, B.; Schlosser, V.

    1992-01-01

    In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two-dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n=13) and thrombus (n=7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results. (author)

  5. Conditional shape models for cardiac motion estimation

    DEFF Research Database (Denmark)

    Metz, Coert; Baka, Nora; Kirisli, Hortense

    2010-01-01

    We propose a conditional statistical shape model to predict patient specific cardiac motion from the 3D end-diastolic CTA scan. The model is built from 4D CTA sequences by combining atlas based segmentation and 4D registration. Cardiac motion estimation is, for example, relevant in the dynamic...

  6. Language Impairments in the Development of Sign: Do They Reside in a Specific Modality or Are They Modality-Independent Deficits?

    Science.gov (United States)

    Woll, Bencie; Morgan, Gary

    2012-01-01

    Various theories of developmental language impairments have sought to explain these impairments in modality-specific ways--for example, that the language deficits in SLI or Down syndrome arise from impairments in auditory processing. Studies of signers with language impairments, especially those who are bilingual in a spoken language as well as a…

  7. Prevalence and predictors of depressive symptoms and wellbeing during and up to nine years after outpatient cardiac rehabilitation.

    Science.gov (United States)

    Koçer, O; Wachter, M; Zellweger, M; Piazzalonga, S; Hoffmann, A

    2011-07-30

    Depression is an important independent prognostic variable in cardiac patients. The prevalence and predictors of depressive symptoms up to nine years after cardiac rehabilitation were studied. Follow-up questionnaires were sent to 2199 patients who had completed a 12-week exercise-based outpatient cardiac rehabilitation (OCR) programme between June 1999 and March 2006. Medical outcome, general wellbeing, and depressive symptoms were assessed, the latter by using two screening questions according to Arrol. Patients with incomplete data due to language problems, lack of compliance and non-response were excluded. Complete data for analysis was available for 710 patients. The median follow up period was 46 months (Interquartile range (IQR) 22-71, min. 6 months). At follow-up, 132 patients (19%) indicated low wellbeing, whereas 81 (11%) were having depressive symptoms. Multivariate analyses revealed impaired quality of life (p wellbeing at follow-up. Persistent smoking (p = 0.045) as well as negative mood (p = 0.022) at the end of OCR were independent predictors of depressive symptoms at follow-up. In a selected patient population a mean of four years after OCR, persistent smoking, diabetes, low exercise capacity and impaired quality of life at the end of OCR were independent long term predictors of low wellbeing and depressive symptoms, rather than specific cardiac variables. This highlights the need for close cooperation between cardiovascular and psychological specialists in cardiac rehabilitation.

  8. Independent preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    1991-01-01

    A simple mathematical result characterizing a subset of a product set is proved and used to obtain additive representations of preferences. The additivity consequences of independence assumptions are obtained for preferences which are not total or transitive. This means that most of the economic ...... theory based on additive preferences - expected utility, discounted utility - has been generalized to preferences which are not total or transitive. Other economic applications of the theorem are given...

  9. Aberrant DNA Methylation in Human iPSCs Associates with MYC-Binding Motifs in a Clone-Specific Manner Independent of Genetics.

    Science.gov (United States)

    Panopoulos, Athanasia D; Smith, Erin N; Arias, Angelo D; Shepard, Peter J; Hishida, Yuriko; Modesto, Veronica; Diffenderfer, Kenneth E; Conner, Clay; Biggs, William; Sandoval, Efren; D'Antonio-Chronowska, Agnieszka; Berggren, W Travis; Izpisua Belmonte, Juan Carlos; Frazer, Kelly A

    2017-04-06

    Induced pluripotent stem cells (iPSCs) show variable methylation patterns between lines, some of which reflect aberrant differences relative to embryonic stem cells (ESCs). To examine whether this aberrant methylation results from genetic variation or non-genetic mechanisms, we generated human iPSCs from monozygotic twins to investigate how genetic background, clone, and passage number contribute. We found that aberrantly methylated CpGs are enriched in regulatory regions associated with MYC protein motifs and affect gene expression. We classified differentially methylated CpGs as being associated with genetic and/or non-genetic factors (clone and passage), and we found that aberrant methylation preferentially occurs at CpGs associated with clone-specific effects. We further found that clone-specific effects play a strong role in recurrent aberrant methylation at specific CpG sites across different studies. Our results argue that a non-genetic biological mechanism underlies aberrant methylation in iPSCs and that it is likely based on a probabilistic process involving MYC that takes place during or shortly after reprogramming. Published by Elsevier Inc.

  10. A photostable near-infrared fluorescent tracker with pH-independent specificity to lysosomes for long time and multicolor imaging.

    Science.gov (United States)

    Zhang, Xinfu; Wang, Chao; Han, Zhuo; Xiao, Yi

    2014-12-10

    A new boron-dipyrromethene-based lysosome tracker, Lyso-NIR, is facilely synthesized. Besides the intensive near-infrared (NIR) fluorescence and high photostability, Lyso-NIR shows the capability to stably localize in lysosomes, which is independent of the local pH. Lyso-NIR does not have the problematic alkalization effect suffered by the commonly used lysotrackers; thus, it shows ignorable cytotoxicity and slightly affects normal physiological functions of lysosomes. The above advantages of Lyso-NIR make it feasible to track lysosomes' dynamic changes in a relatively long time during the full cellular processes such as apoptosis, heavy metal stimulation, and endocytosis, as is demonstrated in this work. Moreover, Lyso-NIR's narrow NIR emission at 740 nm with a full width at half-maximum smaller than 50 nm makes it easy to avoid the crosstalk with the emissions from other common fluorescent probes, which strengthens Lyso-NIR's competitiveness as a standard lysosome tracker for multicolor bioimaging.

  11. Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-specific 99th percentiles based on the third universal definition of myocardial infarction classification system.

    Science.gov (United States)

    Sandoval, Yader; Smith, Stephen W; Schulz, Karen M; Murakami, MaryAnn M; Love, Sara A; Nicholson, Jennifer; Apple, Fred S

    2015-04-01

    The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses. © 2015 American Association for Clinical Chemistry.

  12. A novel begomovirus isolated from sida contains putative cis- and trans-acting replication specificity determinants that have evolved independently in several geographical lineages.

    Science.gov (United States)

    Mauricio-Castillo, J A; Torres-Herrera, S I; Cárdenas-Conejo, Y; Pastor-Palacios, G; Méndez-Lozano, J; Argüello-Astorga, G R

    2014-09-01

    A novel begomovirus isolated from a Sida rhombifolia plant collected in Sinaloa, Mexico, was characterized. The genomic components of sida mosaic Sinaloa virus (SiMSinV) shared highest sequence identity with DNA-A and DNA-B components of chino del tomate virus (CdTV), suggesting a vertical evolutionary relationship between these viruses. However, recombination analysis indicated that a short segment of SiMSinV DNA-A encompassing the plus-strand replication origin and the 5´-proximal 43 codons of the Rep gene was derived from tomato mottle Taino virus (ToMoTV). Accordingly, the putative cis- and trans-acting replication specificity determinants of SiMSinV were identical to those of ToMoTV but differed from those of CdTV. Modeling of the SiMSinV and CdTV Rep proteins revealed significant differences in the region comprising the small β1/β5 sheet element, where five putative DNA-binding specificity determinants (SPDs) of Rep (i.e., amino acid residues 5, 8, 10, 69 and 71) were previously identified. Computer-assisted searches of public databases led to identification of 33 begomoviruses from three continents encoding proteins with SPDs identical to those of the Rep encoded by SiMSinV. Sequence analysis of the replication origins demonstrated that all 33 begomoviruses harbor potential Rep-binding sites identical to those of SiMSinV. These data support the hypothesis that the Rep β1/β5 sheet region determines specificity of this protein for DNA replication origin sequences.

  13. Independent Directors

    DEFF Research Database (Denmark)

    Ringe, Wolf-Georg

    2013-01-01

    This paper re-evaluates the corporate governance concept of ‘board independence’ against the disappointing experiences during the 2007-08 financial crisis. Independent or outside directors had long been seen as an essential tool to improve the monitoring role of the board. Yet the crisis revealed...... that they did not prevent firms' excessive risk taking; further, these directors sometimes showed serious deficits in understanding the business they were supposed to control, and remained passive in addressing structural problems. A closer look reveals that under the surface of seemingly unanimous consensus...

  14. Cardiac regeneration therapy: connections to cardiac physiology.

    Science.gov (United States)

    Takehara, Naofumi; Matsubara, Hiroaki

    2011-12-01

    Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

  15. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-01-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  16. FET-biosensor for cardiac troponin biomarker

    Directory of Open Access Journals (Sweden)

    Md Arshad Mohd Khairuddin

    2017-01-01

    Full Text Available Acute myocardial infarction or myocardial infarction (MI is a major health problem, due to diminished flow of blood to the heart, leads to higher rates of mortality and morbidity. The most specific markers for cardiac injury are cardiac troponin I (cTnI and cardiac troponin T (cTnT which have been considered as ‘gold standard’. Due to higher specificity, determination of the level of cardiac troponins became a predominant indicator for MI. Currently, field-effect transistor (FET-based biosensors have been main interest to be implemented in portable sensors with the ultimate application in point-of-care testing (POCT. In this paper, we review on the FET-based biosensor based on its principle of operation, integration with nanomaterial, surface functionalization as well as immobilization, and the introduction of additional gate (for ambipolar conduction on the device architecture for the detection of cardiac troponin I (cTnI biomarker.

  17. Somatic Arc protein expression in hippocampal granule cells is increased in response to environmental change but independent of task-specific learning.

    Science.gov (United States)

    Cleland, J P; Willis, E F; Bartlett, P F; Vukovic, J

    2017-09-29

    Activated neurons express immediate-early genes, such as Arc. Expression of Arc in the hippocampal granule cell layer, an area crucial for spatial learning and memory, is increased during acquisition of spatial learning; however, it is unclear whether this effect is related to the task-specific learning process or to nonspecific aspects of the testing procedure (e.g. exposure to the testing apparatus and exploration of the environment). Herein, we show that Arc-positive cells numbers are increased to the same extent in the granule cell layer after both acquisition of a single spatial learning event in the active place avoidance task and exploration of the testing environment, as compared to naïve (i.e. caged) mice. Repeated exposure the testing apparatus and environment did not reduce Arc expression. Furthermore, Arc expression did not correlate with performance in both adult and aged animals, suggesting that exploration of the testing environment, rather than the specific acquisition of the active place avoidance task, induces Arc expression in the dentate granule cell layer. These findings thus suggest that Arc is an experience-induced immediate-early gene.

  18. Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Skladchikova, Galina; Lepekhin, Eugene E

    2010-01-01

    lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3). Results: VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk1......ABSTRACT: BACKGROUND: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell....../2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK...

  19. Cardiac and vascular malformations

    International Nuclear Information System (INIS)

    Ley, S.; Ley-Zaporozhan, J.

    2015-01-01

    Malformations of the heart and great vessels show a high degree of variation. There are numerous variants and defects with only few clinical manifestations and are only detected by chance, such as a persistent left superior vena cava or a partial anomalous pulmonary venous connection. Other cardiovascular malformations are manifested directly after birth and need prompt mostly surgical interventions. At this point in time echocardiography is the diagnostic modality of choice for morphological and functional characterization of malformations. Additional imaging using computed tomography (CT) or magnetic resonance imaging (MRI) is only required in a minority of cases. If so, the small anatomical structures, the physiological tachycardia and tachypnea are a challenge for imaging modalities and strategies. This review article presents the most frequent vascular, cardiac and complex cardiovascular malformations independent of the first line diagnostic imaging modality. (orig.) [de

  20. PCR-Independent Detection of Bacterial Species-Specific 16S rRNA at 10 fM by a Pore-Blockage Sensor

    Directory of Open Access Journals (Sweden)

    Leyla Esfandiari

    2016-07-01

    Full Text Available A PCR-free, optics-free device is used for the detection of Escherichia coli (E. coli 16S rRNA at 10 fM, which corresponds to ~100–1000 colony forming units/mL (CFU/mL depending on cellular rRNA levels. The development of a rapid, sensitive, and cost-effective nucleic acid detection platform is sought for the detection of pathogenic microbes in food, water and body fluids. Since 16S rRNA sequences are species specific and are present at high copy number in viable cells, these nucleic acids offer an attractive target for microbial pathogen detection schemes. Here, target 16S rRNA of E. coli at 10 fM concentration was detected against a total RNA background using a conceptually simple approach based on electromechanical signal transduction, whereby a step change reduction in ionic current through a pore indicates blockage by an electrophoretically mobilized bead-peptide nucleic acid probe conjugate hybridized to target nucleic acid. We investigated the concentration detection limit for bacterial species-specific 16S rRNA at 1 pM to 1 fM and found a limit of detection of 10 fM for our device, which is consistent with our previous finding with single-stranded DNA of similar length. In addition, no false positive responses were obtained with control RNA and no false negatives with target 16S rRNA present down to the limit of detection (LOD of 10 fM. Thus, this detection scheme shows promise for integration into portable, low-cost systems for rapid detection of pathogenic microbes in food, water and body fluids.

  1. Cardiac integrins the ties that bind.

    Science.gov (United States)

    Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

    1998-01-01

    An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

  2. Visual characterization and diversity quantification of chemical libraries: 2. Analysis and selection of size-independent, subspace-specific diversity indices.

    Science.gov (United States)

    Colliandre, Lionel; Le Guilloux, Vincent; Bourg, Stephane; Morin-Allory, Luc

    2012-02-27

    High Throughput Screening (HTS) is a standard technique widely used to find hit compounds in drug discovery projects. The high costs associated with such experiments have highlighted the need to carefully design screening libraries in order to avoid wasting resources. Molecular diversity is an established concept that has been used to this end for many years. In this article, a new approach to quantify the molecular diversity of screening libraries is presented. The approach is based on the Delimited Reference Chemical Subspace (DRCS) methodology, a new method that can be used to delimit the densest subspace spanned by a reference library in a reduced 2D continuous space. A total of 22 diversity indices were implemented or adapted to this methodology, which is used here to remove outliers and obtain a relevant cell-based partition of the subspace. The behavior of these indices was assessed and compared in various extreme situations and with respect to a set of theoretical rules that a diversity function should satisfy when libraries of different sizes have to be compared. Some gold standard indices are found inappropriate in such a context, while none of the tested indices behave perfectly in all cases. Five DRCS-based indices accounting for different aspects of diversity were finally selected, and a simple framework is proposed to use them effectively. Various libraries have been profiled with respect to more specific subspaces, which further illustrate the interest of the method.

  3. Toll-like receptor 9 mediated responses in cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Ingrid Kristine Ohm

    Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

  4. Intraperitoneal injections of low doses of C75 elicit a behaviorally specific and vagal afferent-independent inhibition of eating in rats

    Science.gov (United States)

    Mansouri, Abdelhak; Aja, Susan; Moran, Timothy H.; Ronnett, Gabriele; Kuhajda, Francis P.; Arnold, Myrtha; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

    2008-01-01

    Central and intraperitoneal C75, an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyl-transferase-1, inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether intraperitoneal C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts nonselectively, for example by eliciting illness or aversion. Another issue relates to whether intraperitoneal C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of intraperitoneal C75 on spontaneous meal patterns and the formation of conditioned taste aversion (CTA). We also tested whether the eating inhibitory effect of intraperitoneal C75 is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). Intraperitoneal injection of 3.2 and 7.5 mg/kg of C75 significantly reduced food intake 3, 12, and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg of C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. The eating inhibitory effect of C75 was not diminished in either TVX or SDA rats. We conclude that intraperitoneal injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents. PMID:18667714

  5. Mutations in the testis-specific enhancer of SOX9 in the SRY independent sex-determining mechanism in the genus Tokudaia.

    Directory of Open Access Journals (Sweden)

    Ryutaro Kimura

    Full Text Available SRY (sex-determining region Y is widely conserved in eutherian mammals as a sex-determining gene located on the Y chromosome. SRY proteins bind to the testis-specific enhancer of SOX9 (TES with SF1 to upregulate SOX9 expression in undifferentiated gonads of XY embryos of humans and mice. The core region within TES, named TESCO, is an important enhancer for mammalian sex determination. We show that TESCO of the genus Tokudaia lost enhancer activity caused by mutations in its SRY and SF1 binding sites. Two species of Tokudaia do not have the Y chromosome or SRY, and one species has multiple SRYs located on the neo-Y chromosome consisting of the Y fused with an autosome. The sequence of Tokudaia TESCO exhibited more than 83% identity with mouse TESCO, however, nucleotide substitution(s were found in two out of three SRY binding sites and in five out of six SF1 binding sites. TESCO of all species showed low enhancer activity in cells co-transfected with SRY and SF1, and SOX9 and SF1 in reporter gene assays. Mutated TESCO, in which nucleotide substitutions found in SRY and SF1 binding sites were replaced with mouse sequence, recovered the activity. Furthermore, SRYs of the SRY-positive species could not activate the mutated TESCO or mouse TESCO, suggesting that SRYs lost function as a sex-determining gene any more. Our results indicate that the SRY dependent sex-determining mechanism was lost in a common ancestor of the genus Tokudaia caused by nucleotide substitutions in SRY and SF1 binding sites after emergence of a new sex-determining gene. We present the first evidence for an intermediate stage of the switchover from SRY to a new sex-determining gene in the evolution of mammalian sex-determining mechanism.

  6. Mutations in the testis-specific enhancer of SOX9 in the SRY independent sex-determining mechanism in the genus Tokudaia.

    Science.gov (United States)

    Kimura, Ryutaro; Murata, Chie; Kuroki, Yoko; Kuroiwa, Asato

    2014-01-01

    SRY (sex-determining region Y) is widely conserved in eutherian mammals as a sex-determining gene located on the Y chromosome. SRY proteins bind to the testis-specific enhancer of SOX9 (TES) with SF1 to upregulate SOX9 expression in undifferentiated gonads of XY embryos of humans and mice. The core region within TES, named TESCO, is an important enhancer for mammalian sex determination. We show that TESCO of the genus Tokudaia lost enhancer activity caused by mutations in its SRY and SF1 binding sites. Two species of Tokudaia do not have the Y chromosome or SRY, and one species has multiple SRYs located on the neo-Y chromosome consisting of the Y fused with an autosome. The sequence of Tokudaia TESCO exhibited more than 83% identity with mouse TESCO, however, nucleotide substitution(s) were found in two out of three SRY binding sites and in five out of six SF1 binding sites. TESCO of all species showed low enhancer activity in cells co-transfected with SRY and SF1, and SOX9 and SF1 in reporter gene assays. Mutated TESCO, in which nucleotide substitutions found in SRY and SF1 binding sites were replaced with mouse sequence, recovered the activity. Furthermore, SRYs of the SRY-positive species could not activate the mutated TESCO or mouse TESCO, suggesting that SRYs lost function as a sex-determining gene any more. Our results indicate that the SRY dependent sex-determining mechanism was lost in a common ancestor of the genus Tokudaia caused by nucleotide substitutions in SRY and SF1 binding sites after emergence of a new sex-determining gene. We present the first evidence for an intermediate stage of the switchover from SRY to a new sex-determining gene in the evolution of mammalian sex-determining mechanism.

  7. Cyclosporine-resistant, Rab27a-independent Mobilization of Intracellular Preformed CD40L Mediates Antigen-specific T Cell Help In Vitro

    Science.gov (United States)

    Koguchi, Yoshinobu; Gardell, Jennifer L.; Thauland, Timothy J.; Parker, David C.

    2011-01-01

    CD40L is critically important for the initiation and maintenance of adaptive immune responses. It is generally thought that CD40L expression in CD4+ T cells is regulated transcriptionally and made from new mRNA following antigen recognition. However, recent studies with two-photon microscopy revealed that the majority of cognate interactions between effector CD4+ T cells and APCs are too short for de novo synthesis of CD40L. Given that effector and memory CD4+ T cells store preformed CD40L (pCD40L) in lysosomal compartments and that pCD40L comes to the cell surface within minutes of antigenic stimulation, we and others have proposed that pCD40L might mediate T cell-dependent activation of cognate APCs during brief encounters in vivo. However, it has not been shown that this relatively small amount of pCD40L is sufficient to activate APCs, owing to the difficulty of separating the effects of pCD40L from those of de novo CD40L and other cytokines in vitro. Here we show that pCD40L surface mobilization is resistant to cyclosporine or FK506 treatment, while de novo CD40L and cytokine expression are completely inhibited. These drugs thus provide a tool to dissect the role of pCD40L in APC activation. We find that pCD40L mediates selective activation of cognate but not bystander APCs in vitro and that mobilization of pCD40L does not depend on Rab27a, which is required for mobilization of lytic granules. Therefore, effector CD4+ T cells deliver pCD40L specifically to APCs on the same time scale as the lethal hit of CTLs but with distinct molecular machinery. PMID:21677130

  8. Comparison between In-house developed and Diamond commercial software for patient specific independent monitor unit calculation and verification with heterogeneity corrections.

    Science.gov (United States)

    Kuppusamy, Vijayalakshmi; Nagarajan, Vivekanandan; Jeevanandam, Prakash; Murugan, Lavanya

    2016-02-01

    The study was aimed to compare two different monitor unit (MU) or dose verification software in volumetric modulated arc therapy (VMAT) using modified Clarkson's integration technique for 6 MV photons beams. In-house Excel Spreadsheet based monitor unit verification calculation (MUVC) program and PTW's DIAMOND secondary check software (SCS), version-6 were used as a secondary check to verify the monitor unit (MU) or dose calculated by treatment planning system (TPS). In this study 180 patients were grouped into 61 head and neck, 39 thorax and 80 pelvic sites. Verification plans are created using PTW OCTAVIUS-4D phantom and also measured using 729 detector chamber and array with isocentre as the suitable point of measurement for each field. In the analysis of 154 clinically approved VMAT plans with isocentre at a region above -350 HU, using heterogeneity corrections, In-house Spreadsheet based MUVC program and Diamond SCS showed good agreement TPS. The overall percentage average deviations for all sites were (-0.93% + 1.59%) and (1.37% + 2.72%) for In-house Excel Spreadsheet based MUVC program and Diamond SCS respectively. For 26 clinically approved VMAT plans with isocentre at a region below -350 HU showed higher variations for both In-house Spreadsheet based MUVC program and Diamond SCS. It can be concluded that for patient specific quality assurance (QA), the In-house Excel Spreadsheet based MUVC program and Diamond SCS can be used as a simple and fast accompanying to measurement based verification for plans with isocentre at a region above -350 HU. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  9. Parent and Child Independent Report of Emotional Responses to Asthma-Specific Vignettes: The Relationship Between Emotional States, Self-Management Behaviors, and Symptoms.

    Science.gov (United States)

    Conn, Kelly M; Fisher, Susan G; Rhee, Hyekyun

    2016-01-01

    Little is known about the emotional intelligence (EI) of parents and their children with asthma. Objectives of this study were to assess: 1) parent's and children's report of emotions in response to an asthma vignette (proxy for EI) and 2) the relationship between emotions, self-management behaviors, and symptoms. We conducted a descriptive, mixed methods study of children 7-12 years old with asthma. Parent-Child dyads (n=104) responded to an asthma vignette to gain insight into emotions, symptoms, and self-management behaviors. Additional questions assessed confidence and worry using a 5-point Likert scale. Thematic analyses and descriptive statistics were used to assess qualitative and quantitative outcomes. Children were predominantly male (58%), 7-9 (58%), and White (46%). The most common negative emotions reported by children were scared and sad. Children who sought help from an adult were less likely to report using medications compared to children who did not seek help (39.5% vs. 62.3%, p=.029). Children with low worry and high confidence had fewer symptoms compared to children reporting high worry and low confidence (symptoms: days 3.24 vs. 6.77, p=.012, nights 2.71 vs. 5.36, p=.004). Children provided appropriate emotional responses to the asthma vignette; emotions were related to self-management behaviors and symptoms. More studies are needed to specifically assess EI in this population. Parents and children with greater EI may be better able to understand their needs, engage in self-management behaviors, and communicate with their nurses, to improve their support network and ability to access services. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

    Directory of Open Access Journals (Sweden)

    Lijun Catherine Liu

    2016-09-01

    Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

  12. Clinical Use of Ultrasensitive Cardiac Troponin I Assay in Intermediate- and High-Risk Surgery Patients

    Directory of Open Access Journals (Sweden)

    Flávia Kessler Borges

    2013-01-01

    Full Text Available Background. Cardiac troponin levels have been reported to add value in the detection of cardiovascular complications in noncardiac surgery. A sensitive cardiac troponin I (cTnI assay could provide more accurate prognostic information. Methods. This study prospectively enrolled 142 patients with at least one Revised Cardiac Risk Index risk factor who underwent noncardiac surgery. cTnI levels were measured postoperatively. Short-term cardiac outcome predictors were evaluated. Results. cTnI elevation was observed in 47 patients, among whom 14 were diagnosed as having myocardial infarction (MI. After 30 days, 16 patients had major adverse cardiac events (MACE. Excluding patients with a final diagnosis of MI, predictors of cTnI elevation included dialysis, history of heart failure, transoperative major bleeding, and elevated levels of pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP. Maximal cTnI values showed the highest sensitivity (94%, specificity (75%, and overall accuracy (AUC 0.89; 95% CI 0.80–0.98 for postoperative MACE. Postoperative cTnI peak level (OR 9.4; 95% CI 2.3–39.2 and a preoperative NT-proBNP level ≥917 pg/mL (OR 3.47; 95% CI 1.05–11.6 were independent risk factors for MACE. Conclusions. cTnI was shown to be an independent prognostic factor for cardiac outcomes and should be considered as a component of perioperative risk assessment.

  13. Law enforcement duties and sudden cardiac death among police officers in United States: case distribution study.

    Science.gov (United States)

    Varvarigou, Vasileia; Farioli, Andrea; Korre, Maria; Sato, Sho; Dahabreh, Issa J; Kales, Stefanos N

    2014-11-18

    To assess the association between risk of sudden cardiac death and stressful law enforcement duties compared with routine/non-emergency duties. Case distribution study (case series with survey information on referent exposures). United States law enforcement. Summaries of deaths of over 4500 US police officers provided by the National Law Enforcement Officers Memorial Fund and the Officer Down Memorial Page from 1984 to 2010. Observed and expected sudden cardiac death counts and relative risks for sudden cardiac death events during specific strenuous duties versus routine/non-emergency activities. Independent estimates of the proportion of time that police officers spend across various law enforcement duties obtained from surveys of police chiefs and front line officers. Impact of varying exposure assessments, covariates, and missing cases in sensitivity and stability analyses. 441 sudden cardiac deaths were observed during the study period. Sudden cardiac death was associated with restraints/altercations (25%, n=108), physical training (20%, n=88), pursuits of suspects (12%, n=53), medical/rescue operations (8%, n=34), routine duties (23%, n=101), and other activities (11%, n=57). Compared with routine/non-emergency activities, the risk of sudden cardiac death was 34-69 times higher during restraints/altercations, 32-51 times higher during pursuits, 20-23 times higher during physical training, and 6-9 times higher during medical/rescue operations. Results were robust to all sensitivity and stability analyses. Stressful law enforcement duties are associated with a risk of sudden cardiac death that is markedly higher than the risk during routine/non-emergency duties. Restraints/altercations and pursuits are associated with the greatest risk. Our findings have public health implications and suggest that primary and secondary cardiovascular prevention efforts are needed among law enforcement officers. © Varvarigou et al 2014.

  14. Assessment of cardiac risk before non-cardiac surgery: brain natriuretic peptide in 1590 patients.

    Science.gov (United States)

    Dernellis, J; Panaretou, M

    2006-11-01

    To evaluate the predictive value of brain natriuretic peptide (BNP) for assessment of cardiac risk before non-cardiac surgery. Consecutively treated patients (947 men, 643 women) whose BNP was measured before non-cardiac surgery were studied. Clinical and ECG variables were evaluated to identify predictors of postoperative cardiac events. Events occurred in 6% of patients: 21 cardiac deaths, 20 non-fatal myocardial infarctions, 41 episodes of pulmonary oedema and 14 patients with ventricular tachycardia. All of these patients had raised plasma BNP concentrations (best cut-off point 189 pg/ml). The only independent predictor of postoperative events was BNP (odds ratio 34.52, 95% confidence interval (CI) 17.08 to 68.62, p 300 pg/ml); postoperative event rates were 0%, 5%, 12% and 81%, respectively. In this population of patients evaluated before non-cardiac surgery, BNP is an independent predictor of postoperative cardiac events. BNP > 189 pg/ml identified patients at highest risk.

  15. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    Gulati, Gurpreet S; Kothari, Shyam S

    2011-01-01

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  16. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  17. Cardiac Rotational Mechanics As a Predictor of Myocardial Recovery in Heart Failure Patients Undergoing Chronic Mechanical Circulatory Support: A Pilot Study.

    Science.gov (United States)

    Bonios, Michael J; Koliopoulou, Antigone; Wever-Pinzon, Omar; Taleb, Iosif; Stehlik, Josef; Xu, Weining; Wever-Pinzon, James; Catino, Anna; Kfoury, Abdallah G; Horne, Benjamin D; Nativi-Nicolau, Jose; Adamopoulos, Stamatis N; Fang, James C; Selzman, Craig H; Bax, Jeroen J; Drakos, Stavros G

    2018-04-01

    Impaired qualitative and quantitative left ventricular (LV) rotational mechanics predict cardiac remodeling progression and prognosis after myocardial infarction. We investigated whether cardiac rotational mechanics can predict cardiac recovery in chronic advanced cardiomyopathy patients. Sixty-three patients with advanced and chronic dilated cardiomyopathy undergoing implantation of LV assist device (LVAD) were prospectively investigated using speckle tracking echocardiography. Acute heart failure patients were prospectively excluded. We evaluated LV rotational mechanics (apical and basal LV twist, LV torsion) and deformational mechanics (circumferential and longitudinal strain) before LVAD implantation. Cardiac recovery post-LVAD implantation was defined as (1) final resulting LV ejection fraction ≥40%, (2) relative LV ejection fraction increase ≥50%, (iii) relative LV end-systolic volume decrease ≥50% (all 3 required). Twelve patients fulfilled the criteria for cardiac recovery (Rec Group). The Rec Group had significantly less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably, both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35 degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac recovery. Peak LV torsion before LVAD implantation was found to be an independent predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1 degrees/cm [0.49-0.87]; P =0.014). LV rotational mechanics seem to be useful in selecting patients prone to cardiac recovery after mechanical unloading induced by LVADs. Future studies should investigate the utility of these markers in predicting durable cardiac recovery after the explantation of the cardiac assist device. © 2018 American Heart Association, Inc.

  18. Patient-Specific MRI-Based Right Ventricle Models Using Different Zero-Load Diastole and Systole Geometries for Better Cardiac Stress and Strain Calculations and Pulmonary Valve Replacement Surgical Outcome Predictions.

    Directory of Open Access Journals (Sweden)

    Dalin Tang

    Full Text Available Accurate calculation of ventricular stress and strain is critical for cardiovascular investigations. Sarcomere shortening in active contraction leads to change of ventricular zero-stress configurations during the cardiac cycle. A new model using different zero-load diastole and systole geometries was introduced to provide more accurate cardiac stress/strain calculations with potential to predict post pulmonary valve replacement (PVR surgical outcome.Cardiac magnetic resonance (CMR data were obtained from 16 patients with repaired tetralogy of Fallot prior to and 6 months after pulmonary valve replacement (8 male, 8 female, mean age 34.5 years. Patients were divided into Group 1 (n = 8 with better post PVR outcome and Group 2 (n = 8 with worse post PVR outcome based on their change in RV ejection fraction (EF. CMR-based patient-specific computational RV/LV models using one zero-load geometry (1G model and two zero-load geometries (diastole and systole, 2G model were constructed and RV wall thickness, volume, circumferential and longitudinal curvatures, mechanical stress and strain were obtained for analysis. Pairwise T-test and Linear Mixed Effect (LME model were used to determine if the differences from the 1G and 2G models were statistically significant, with the dependence of the pair-wise observations and the patient-slice clustering effects being taken into consideration. For group comparisons, continuous variables (RV volumes, WT, C- and L- curvatures, and stress and strain values were summarized as mean ± SD and compared between the outcome groups by using an unpaired Student t-test. Logistic regression analysis was used to identify potential morphological and mechanical predictors for post PVR surgical outcome.Based on results from the 16 patients, mean begin-ejection stress and strain from the 2G model were 28% and 40% higher than that from the 1G model, respectively. Using the 2G model results, RV EF changes correlated negatively with

  19. Cardiac Delayed Rectifier Potassium Channels in Health and Disease

    Science.gov (United States)

    Chen, Lei; Sampson, Kevin J.; Kass, Robert S.

    2016-01-01

    Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this chapter, we will review the molecular identities and biophysical properties of these channels. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the possibility and prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID:27261823

  20. Cardiac Delayed Rectifier Potassium Channels in Health and Disease.

    Science.gov (United States)

    Chen, Lei; Sampson, Kevin J; Kass, Robert S

    2016-06-01

    Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this article, we will review their molecular identities and biophysical properties. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Wnt/β-Catenin Signaling during Cardiac Development and Repair

    Directory of Open Access Journals (Sweden)

    Jan W. Buikema

    2014-05-01

    Full Text Available Active Wnt/β-catenin signaling is essential for proper cardiac specification, progenitor expansion and myocardial growth. During development, the mass of the embryonic heart increases multiple times to achieve the dimensions of adult ventricular chambers. Cell division in the embryonic heart is fairly present, whereas cell turnover in the adult myocardium is extremely low. Understanding of embryonic cardiomyocyte cell-replication, therefore, could improve strategies for cardiac regenerative therapeutics. Here, we review which role Wnt signaling plays in cardiac development and highlight a selection of attempts that have been made to modulate Wnt signaling after cardiac ischemic injury to improve cardiac function and reduce infarct size.

  2. Sexual Dysfunction before and after Cardiac Rehabilitation

    Directory of Open Access Journals (Sweden)

    Jörg Schumann

    2010-01-01

    variables. Methods. Analysis of patients participating in a 12-week exercise-based outpatient cardiac rehabilitation program (OCR between April 1999 and December 2007. Exercise capacity (ExC and quality of life including sexual function were assessed before and after OCR. Results. Complete data were available in 896 male patients. No sexual activity at all was indicated by 23.1% at baseline and 21.8% after OCR, no problems with sexual activity by 40.8% at baseline and 38.6% after OCR. Patients showed an increase in specific problems (erectile dysfunction and lack of orgasm from 18% to 23% (<.0001 during OCR. We found the following independent positive and negative predictors of sexual problems after OCR: hyperlipidemia, age, CABG, baseline ExC and improvement of ExC, subjective physical and mental capacity, and sense of affiliation. Conclusions. Sexual dysfunction is present in over half of the patients undergoing OCR with no overall improvement during OCR. Age, CABG, low exercise capacity are independent predictors of sexual dysfunction after OCR.

  3. Cardiac gated ventilation

    International Nuclear Information System (INIS)

    Hanson, C.W. III; Hoffman, E.A.

    1995-01-01

    There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart

  4. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  5. The cardiac patient in Ramadan.

    Science.gov (United States)

    Chamsi-Pasha, Majed; Chamsi-Pasha, Hassan

    2016-01-01

    Ramadan is one of the five fundamental pillars of Islam. During this month, the majority of the 1.6 billion Muslims worldwide observe an absolute fast from dawn to sunset without any drink or food. Our review shows that the impact of fasting during Ramadan on patients with stable cardiac disease is minimal and does not lead to any increase in acute events. Most patients with the stable cardiac disease can fast safely. Most of the drug doses and their regimen are easily manageable during this month and may need not to be changed. Ramadan fasting is a healthy nonpharmacological means for improving cardiovascular risk factors. Most of the Muslims, who suffer from chronic diseases, insist on fasting Ramadan despite being exempted by religion. The Holy Quran specifically exempts the sick from fasting. This is particularly relevant if fasting worsens one's illness or delays recovery. Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, decompensated heart failure, recent cardiac intervention or cardiac surgery or any debilitating diseases should avoid fasting.

  6. The paediatrician and cardiac auscultation

    OpenAIRE

    Roy, Douglas L

    2003-01-01

    The cardiac auscultation (CA) skills of paediatric residents and office-based paediatricians have recently been shown to be suboptimal. CA is known to have a high degree of specificity and sensitivity, and is inexpensive. New teaching aids and availability of surrogate patient heart sounds and murmurs now allow most physicians to acquire CA skills. These teaching aids should be available in all medical schools and in all postgraduate paediatric training programs. While the relationship betwee...

  7. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  8. The evaluation of cardiac tamponade risk in patients with pericardial effusion detected by non-gated chest CT.

    Science.gov (United States)

    Ohta, Yasutoshi; Miyoshi, Fuminori; Kaminou, Toshio; Kaetsu, Yasuhiro; Ogawa, Toshihide

    2016-05-01

    Although pericardial effusion is often identified using non-gated chest computed tomography (CT), findings predictive of cardiac tamponade have not been adequately established. To determine the findings predictive of clinical cardiac tamponade in patients with moderate to large pericardial effusion using non-gated chest CT. We performed a retrospective analysis of 134 patients with moderate to large pericardial effusion who were identified from among 4581 patients who underwent non-gated chest CT. Cardiac structural changes, including right ventricular outflow tract (RVOT), were qualitatively evaluated. The inferior vena cava ratio with hepatic (IVCupp) and renal portions (IVClow) and effusion size were measured. The diagnostic performance of each structural change was calculated, and multivariate analysis was used to determine the predictors of cardiac tamponade. Of the 134 patients (mean age, 70.3 years; 64 men), 37 (28%) had cardiac tamponade. The sensitivity and specificity were 76% and 74% for RVOT compression; 87% and 84% for an IVClow ratio ≥0.77; and 60% and 77% for an effusion size ≥25.5 mm, respectively. Multivariate logistic regression analysis demonstrated that RVOT compression, an IVClow ratio ≥0.77, and an effusion size ≥25.5 mm were independent predictors of cardiac tamponade. The combination of these three CT findings had a sensitivity, specificity, and accuracy of 81%, 95%, and 91%, respectively. In patients with moderate to large pericardial effusion, non-gated chest CT provides additional information for predicting cardiac tamponade. © The Foundation Acta Radiologica 2015.

  9. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Leela K Lella

    Full Text Available The significance of right ventricular ejection fraction (RVEF, independent of left ventricular ejection fraction (LVEF, following isolated coronary artery bypass grafting (CABG and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR, independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery.From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.Forty-eight patients had reduced RVEF (mean 25% and 61 patients had normal RVEF (mean 50% (p<0.001. Fifty-four patients had reduced LVEF (mean 30% and 55 patients had normal LVEF (mean 59% (p<0.001. Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05. Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03. Reduced LVEF did not influence long-term cardiac re-hospitalization.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

  10. Mathematical Models of Cardiac Pacemaking Function

    Science.gov (United States)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  11. Mathematical Models of Cardiac Pacemaking Function

    Directory of Open Access Journals (Sweden)

    Pan eLi

    2013-10-01

    Full Text Available Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  12. Can cardiac surgery cause hypopituitarism?

    Science.gov (United States)

    Francis, Flverly; Burger, Ines; Poll, Eva Maria; Reineke, Andrea; Strasburger, Christian J; Dohmen, Guido; Gilsbach, Joachim M; Kreitschmann-Andermahr, Ilonka

    2012-03-01

    Apoplexy of pituitary adenomas with subsequent hypopituitarism is a rare but well recognized complication following cardiac surgery. The nature of cardiac on-pump surgery provides a risk of damage to the pituitary because the vascular supply of the pituitary is not included in the cerebral autoregulation. Thus, pituitary tissue may exhibit an increased susceptibility to hypoperfusion, ischemia or intraoperative embolism. After on-pump procedures, patients often present with physical and psychosocial impairments which resemble symptoms of hypopituitarism. Therefore, we analyzed whether on-pump cardiac surgery may cause pituitary dysfunction also in the absence of pre-existing pituitary disease. Twenty-five patients were examined 3-12 months after on-pump cardiac surgery. Basal hormone levels for all four anterior pituitary hormone axes were measured and a short synacthen test and a growth hormone releasing hormone plus arginine (GHRH-ARG)-test were performed. Quality of life (QoL), depression, subjective distress for a specific life event, sleep quality and fatigue were assessed by means of self-rating questionnaires. Hormonal alterations were only slight and no signs of anterior hypopituitarism were found except for an insufficient growth hormone rise in two overweight patients in the GHRH-ARG-test. Psychosocial impairment was pronounced, including symptoms of moderate to severe depression in 9, reduced mental QoL in 8, dysfunctional coping in 6 and pronounced sleep disturbances in 16 patients. Hormone levels did not correlate with psychosocial impairment. On-pump cardiac surgery did not cause relevant hypopituitarism in our sample of patients and does not serve to explain the psychosocial symptoms of these patients.

  13. Major Cardiac Events After Non-cardiac Surgery.

    Science.gov (United States)

    Sousa, Gabriela; Lopes, Ana; Reis, Pedro; Carvalho, Vasco; Santos, Alice; Abelha, Fernando José

    2016-08-01

    Postoperative cardiovascular complications might be difficult to assess and are known to be associated with longer hospital stay and increased costs as well as higher morbidity and mortality rates. The aim of this study was to evaluate the predictors for major cardiac events (MCE) after non-cardiac surgery. The study included 4398 patients who were admitted to the Surgical Intensive Care Unit between January 1, 2006 and July 19, 2013. Acute physiology and chronic health evaluation II score and simplified acute physiology score (SAPS II) were calculated, and all variables entered as parameters were evaluated independently. Multivariate logistic regression analysis was performed to assess the independent factors for MCE. A total of 107 people experienced MCE. The independent predictors for postoperative MCE were higher fraction of inspired oxygen (FiO2) (odds ratio [OR] 38.97; 95 % confidence interval [CI] 10.81-140.36), history of ischemic heart disease (OR 3.38; 95 % CI 2.12-5.39), history of congestive heart disease (OR 2.39; 95 % CI 1.49-3.85), history of insulin therapy for diabetes (OR 2.93; 95 % CI 1.66-5.19), and increased SAPS II (OR 1.03; 95 % CI 1.01-1.05). Having a MCE was associated with a longer length of stay in the surgical intensive care unit (OR 1.01, 95 % CI 1.00-1.01). FiO2, ischemic heart disease, congestive heart disease, insulin therapy for diabetes, SAPS II, and length of stay in the surgical intensive care unit were independent predictors for MCE.

  14. Cardiac surgery in the parturient.

    Science.gov (United States)

    Chandrasekhar, Shobana; Cook, Christopher R; Collard, Charles D

    2009-03-01

    Heart disease is the primary cause of nonobstetric mortality in pregnancy, occurring in 1%-3% of pregnancies and accounting for 10%-15% of maternal deaths. Congenital heart disease has become more prevalent in women of childbearing age, representing an increasing percentage (up to 75%) of heart disease in pregnancy. Untreated maternal heart disease also places the fetus at risk. Independent predictors of neonatal complications include a maternal New York Heart Association heart failure classification >2, anticoagulation use during pregnancy, smoking, multiple gestation, and left heart obstruction. Because cardiac surgical morbidity and mortality in the parturient is higher than nonpregnant patients, most parturients with cardiac disease are first managed medically, with cardiac surgery being reserved when medical management fails. Risk factors for maternal mortality during cardiac surgery include the use of vasoactive drugs, age, type of surgery, reoperation, and maternal functional class. Risk factors for fetal mortality include maternal age >35 yr, functional class, reoperation, emergency surgery, type of myocardial protection, and anoxic time. Nonetheless, acceptable maternal and fetal perioperative mortality rates may be achieved through such measures as early preoperative detection of maternal cardiovascular decompensation, use of fetal monitoring, delivery of a viable fetus before the operation and scheduling surgery on an elective basis during the second trimester. Additionally, fetal morbidity may be reduced during cardiopulmonary bypass by optimizing maternal oxygen-carrying capacity and uterine blood flow. Current maternal bypass recommendations include: 1) maintaining the pump flow rate >2.5 L x min(-1) x m(-2) and perfusion pressure >70 mm Hg; 2) maintaining the hematocrit > 28%; 3) using normothermic perfusion when feasible; 4) using pulsatile flow; and 5) using alpha-stat pH management.

  15. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  16. Diagnosis of cardiac allograft rejection with indium-111 labeled platelets in cyclosporin treated rats

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1984-01-01

    Rejection of heart transplants remains difficult to diagnose. Indium-111 (In-111) labeled lymphocytes accumulate in rat cardiac allografts when recipients are treated with Cyclosporin (Cy), even in the absence of clinical rejection. This presumably occurs because of the non-specific 'interstitial infiltration' caused by Cy. This study examines the usefulness of In-111 labeled platelets in differentiating experimental cardiac allograft rejection from Cy-induced tissue changes. The authors initially examined the migration patterns of syngeneic In-111 labeled platelets in groups of Lewis recipients of ACI cardiac allografts treated with IM Cy (10mg/kg) for 6-14 days. In addition, 10 control animals were not immunosuppressed, and 10 were treated with Cy but received Lewis cardiac isografts. Syngeneic In-111 platelets were injected IV into each animal 24 hours prior to sacrifice. Three to five rats from each group were killed at 3 ,7, 14, 21 and 28 days after transplantation and the % ID/gm in the transplanted hearts and native hearts were determined and correlated with histopathology. Untreated Lewis recipients rejected ACI hearts in 6.5 +- 0.4 days while Cy prolonged allograft survival in a variable fashion. In-111 platelet accumulation correlated well with the degree of rejection determined independently by histopathology. No significant In-111 platelet accumulation was detected in non-rejecting cardiac transplants or in native hearts in Cy treated or control animals. The results suggest that In-111 labeled platelets will be an effective agent for diagnosis of cardiac rejection, even in the presence of Cy treatment

  17. Differential protection by wildtype vs. organelle-specific Bcl-2 suggests a combined requirement of both the ER and mitochondria in ceramide-mediated caspase-independent programmed cell death

    Directory of Open Access Journals (Sweden)

    Belka Claus

    2009-10-01

    Full Text Available Abstract Background Programmed cell death (PCD is essential for development and homeostasis of multicellular organisms and can occur by caspase-dependent apoptosis or alternatively, by caspase-independent PCD (ciPCD. Bcl-2, a central regulator of apoptosis, localizes to both mitochondria and the endoplasmic reticulum (ER. Whereas a function of mitochondrial and ER-specific Bcl-2 in apoptosis has been established in multiple studies, corresponding data for ciPCD do not exist. Methods We utilized Bcl-2 constructs specifically localizing to mitochondria (Bcl-2 ActA, the ER (Bcl-2 cb5, both (Bcl-2 WT or the cytosol/nucleus (Bcl-2 ΔTM and determined their protective effect on ceramide-mediated ciPCD in transiently and stably transfected Jurkat cells. Expression of the constructs was verified by immunoblots. Ceramide-mediated ciPCD was induced by treatment with human recombinant tumor necrosis factor and determined by flow cytometric measurement of propidium iodide uptake as well as by optical analysis of cell morphology. Results Only wildtype Bcl-2 had the ability to efficiently protect from ceramide-mediated ciPCD, whereas expression of Bcl-2 solely at mitochondria, the ER, or the cytosol/nucleus did not prevent ceramide-mediated ciPCD. Conclusion Our data suggest a combined requirement for both mitochondria and the ER in the induction and the signaling pathways of ciPCD mediated by ceramide.

  18. Differential protection by wildtype vs. organelle-specific Bcl-2 suggests a combined requirement of both the ER and mitochondria in ceramide-mediated caspase-independent programmed cell death

    International Nuclear Information System (INIS)

    Deerberg, Andrea; Sosna, Justyna; Thon, Lutz; Belka, Claus; Adam, Dieter

    2009-01-01

    Programmed cell death (PCD) is essential for development and homeostasis of multicellular organisms and can occur by caspase-dependent apoptosis or alternatively, by caspase-independent PCD (ciPCD). Bcl-2, a central regulator of apoptosis, localizes to both mitochondria and the endoplasmic reticulum (ER). Whereas a function of mitochondrial and ER-specific Bcl-2 in apoptosis has been established in multiple studies, corresponding data for ciPCD do not exist. We utilized Bcl-2 constructs specifically localizing to mitochondria (Bcl-2 ActA), the ER (Bcl-2 cb5), both (Bcl-2 WT) or the cytosol/nucleus (Bcl-2 ΔTM) and determined their protective effect on ceramide-mediated ciPCD in transiently and stably transfected Jurkat cells. Expression of the constructs was verified by immunoblots. Ceramide-mediated ciPCD was induced by treatment with human recombinant tumor necrosis factor and determined by flow cytometric measurement of propidium iodide uptake as well as by optical analysis of cell morphology. Only wildtype Bcl-2 had the ability to efficiently protect from ceramide-mediated ciPCD, whereas expression of Bcl-2 solely at mitochondria, the ER, or the cytosol/nucleus did not prevent ceramide-mediated ciPCD. Our data suggest a combined requirement for both mitochondria and the ER in the induction and the signaling pathways of ciPCD mediated by ceramide

  19. Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy

    OpenAIRE

    Kohli, Shrey; Ahuja, Suchit; Rani, Vibha

    2011-01-01

    Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and anti-hypertrophic factors. Thi...

  20. Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence.

    Science.gov (United States)

    Steyers, Curtis M; Khera, Rohan; Bhave, Prashant

    2015-01-01

    Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population. We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria. A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6-72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies. Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery.

  1. Safety in cardiac surgery

    NARCIS (Netherlands)

    Siregar, S.

    2013-01-01

    The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for

  2. Cardiac Catheterization (For Kids)

    Science.gov (United States)

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cardiac Catheterization KidsHealth / For Kids / Cardiac Catheterization What's in this article? What Is ...

  3. Augmenter of liver regeneration causes different kinetics of ERK1/2 and Akt/PKB phosphorylation than EGF and induces hepatocyte proliferation in an EGF receptor independent and liver specific manner

    Energy Technology Data Exchange (ETDEWEB)

    Ilowski, Maren; Putz, Christine [Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, Munich (Germany); Weiss, Thomas S. [Department of Surgery, University of Regensburg Hospital, Regensburg (Germany); Brand, Stephan [Department of Internal Medicine II, Ludwig-Maximilians-University of Munich Hospital Grosshadern, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, Munich (Germany); Hengstler, Jan G. [Leibniz Research Centre for Working Environment and Human Factors, TU Dortmund University, Dortmund (Germany); Thasler, Wolfgang Erwin, E-mail: wolfgang.thasler@med.uni-muenchen.de [Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, Munich (Germany)

    2010-04-16

    Background/Aim: Augmenter of liver regeneration (ALR) is a potent growth factor which supports liver regeneration in experimental animals. The aim of this study was to compare proliferation as well as the kinetics of ERK1/2 and Akt/PKB phosphorylation by recombinant human ALR (rhALR) and EGF in human hepatocytes and extrahepatic cells. Methods: Kinetics of ERK1/2 and Akt/PKB phosphorylation were determined in primary human hepatocytes (phh) after stimulation with rhALR and EGF. Induction of proliferation was analyzed in phh and several cell lines of hepatic and extrahepatic origin by the MTT and [{sup 3}H]-thymidine assay. Results: The kinetics of ERK phosphorylation showed clear differences, whereby rhALR caused a transient and EGF a permanent increase during the observation period of 60 min. For both, Akt and ERK phosphorylation, EGF caused a faster effect with maximal levels observed already after 2 min, whereas rhALR caused maximal phosphorylation between 10 and 15 min. Using the EGF receptor inhibitor AG1478 we provide evidence of an EGF receptor independent induction of proliferation by rhALR. Furthermore, rhALR induced proliferation only in phh and the human liver derived cell lines HepG2 and Chang. In contrast, EGF enhanced proliferation in all analyzed cell types including cell lines of colon, bronchial, pancreatic and gastric origin (SW480, BC1, L36PL and GC1). Conclusion: rhALR and EGF induce different kinetics of ERK and Akt phosphorylation in human hepatocytes. The mitogenic effect of rhALR is liver specific and seems to be at least partially independent from EGF receptor mediated signaling.

  4. Metabolic Enhancer Piracetam Attenuates the Translocation of Mitochondrion-Specific Proteins of Caspase-Independent Pathway, Poly [ADP-Ribose] Polymerase 1 Up-regulation and Oxidative DNA Fragmentation.

    Science.gov (United States)

    Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Sivarama Raju, K; Wahajuddin, Mu; Singh, Sarika

    2018-03-12

    Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment. Cells co-treated with LPS and piracetam exhibited significant uptake of piracetam in comparison to only piracetam-treated cells as estimated by liquid chromatography-mass spectrometry (LC-MSMS). LPS treatment caused significant translocation of AIF and endonuclease-G in neuronal N2A cells which were significantly attenuated with piracetam co-treatment. Significant over-expression of proinflammatory cytokines was also observed after treatment of LPS to cells which was inhibited with piracetam co-treatment demonstrating its anti-inflammatory property. LPS-treated cells exhibited significant oxidative DNA fragmentation and poly [ADP-ribose] polymerase-1 (PARP-1) up-regulation in nucleus, both of which were attenuated with piracetam treatment. Antioxidant melatonin but not z-VAD offered the inhibited LPS-induced DNA fragmentation indicating the involvement of oxidative DNA fragmentation. Further, we did not observe the altered caspase-3 level after LPS treatment initially while at a later time point, significantly augmented level of caspase-3 was observed which was not inhibited with piracetam treatment. In total, our findings indicate the interference of piracetam in mitochondrion-mediated caspase-independent pathway, as well as its anti-inflammatory and antioxidative properties. Graphical Abstract Graphical abstract indicating the novel interference of metabolic enhancer piracetam (P) in neuronal death

  5. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Neeraj Parakh

    2015-01-01

    Full Text Available Sudden cardiac death is one of the most common cause of mortality worldwide. Despite significant advances in the medical science, there is little improvement in the sudden cardiac death related mortality. Coronary artery disease is the most common etiology behind sudden cardiac death, in the above 40 years population. Even in the apparently healthy population, there is a small percentage of patients dying from sudden cardiac death. Given the large denominator, this small percentage contributes to the largest burden of sudden cardiac death. Identification of this at risk group among the apparently healthy individual is a great challenge for the medical fraternity. This article looks into the causes and methods of preventing SCD and at some of the Indian data. Details of Brugada syndrome, Long QT syndrome, Genetics of SCD are discussed. Recent guidelines on many of these causes are summarised.

  6. CARDIAC LYMPHOMA IN DOG

    Directory of Open Access Journals (Sweden)

    G. D. Cruz

    2016-11-01

    Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

  7. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  8. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  9. Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

    Science.gov (United States)

    Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

    2017-10-19

    Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    Science.gov (United States)

    Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

    2016-01-01

    Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

  11. Pathological links between stroke and cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Shaila Ghanekar; Sydney Corey; Trenton Lippert; Cesar V.Borlongan

    2017-01-01

    There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

  12. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  13. Agent independent task planning

    Science.gov (United States)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  14. [Cardiac rehabilitation: current status and future challenges].

    Science.gov (United States)

    Hahmann, H W

    2012-02-01

    The goal of cardiac rehabilitation is to support heart patients using a multidisciplinary team in order to obtain the best possible physical and mental health and achieve long-term social reintegration. In addition to improving physical fitness, cardiac rehabilitation restores self-confidence, thus better equipping patients to deal with mental illness and improving their social reintegration ("participation"). Once the causes of disease have been identified and treated as effectively as possible, drug and lifestyle changes form the focus of cardiac rehabilitation measures. In particular diseases, rehabilitation offers the opportunity for targeted educational courses for diabetics or drug dose escalation, as well as special training for heart failure patients. A nationwide network of outpatient heart groups is available for targeted follow-up. Cardiac patients predominantly rehabilitated in follow-up rehabilitation are older and have greater morbidity than in the past; moreover, they generally come out of acute clinical care earlier and are discharged from hospital more quickly. The proportion of severely ill and multimorbid patients presents a diagnostic and therapeutic challenge in cardiac rehabilitation, although cardiac rehabilitation was not initially conceived for this patient group. The benefit of cardiac rehabilitation has been a well documented reduction in morbidity and mortality. However, hurdles remain, partly due to the patients themselves, partly due to the health insurers. Some insurance providers still refuse rehabilitation for non-ST-segment elevation infarction. In principle rehabilitation can be carried out in an inpatient or an outpatient setting. Specific allocation criteria have not yet been established, but the structure and process quality of outpatient rehabilitation should correspond to that of the inpatient setting. The choice between the two settings should be based on pragmatic criteria. Both settings should be possible for an individual

  15. Diagnosis of cardiac allograft rejection with MR imaging

    International Nuclear Information System (INIS)

    Soulen, R.L.; Fraser, C.D.; Hutchins, G.M.; Baumgartner, W.A.; Reitz, B.A.

    1987-01-01

    Serial MR images and endomyocardial biopsy specimens of heterotopic cervical cardiac allotransplants were obtained in six dogs during 2 weeks of immunosuppression followed by 1 week without such therapy. A surface coil and gated spin-echo technique were used. Myocardial intensity (MI) measurements and histopathologic interpretations were performed independently. All six dogs showed a decrease in MI between their first and second MR studies, while showing no rejection. One dog had no rejection and died; in five dogs studies gated to every other beat showed progressive increase in MI that correlated significantly with increasing rejection, though absolute MI values did not correlated with a specific biopsy score. Severe rejection also caused overt increase in myocardial mass. The MI in the early postoperative period may reflect reperfusion injury. Absolute intensity values cannot predict rejection. Serial studies in transplant patients may prove clinically useful

  16. Cardiac complications in diphtheria and predictors of outcomes.

    Science.gov (United States)

    Samdani, Sunil; Jain, Avani; Meena, Vinod; Meena, C B

    2018-01-01

    To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. Single centre prospective analysis of cardiac complications in diphtheria patients. In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses. Copyright © 2017. Published by Elsevier B.V.

  17. Cardiac damage in athlete's heart: When the "supernormal" heart fails!

    Science.gov (United States)

    Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

    2017-06-26

    Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

  18. How is cardiac troponin released from injured myocardium?

    DEFF Research Database (Denmark)

    Mair, Johannes; Lindahl, Bertil; Hammarsten, Ola

    2017-01-01

    Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and eliminatio...

  19. Cardiac surgery with cardiopulmonary bypass: does aprotinin affect outcome?

    NARCIS (Netherlands)

    van der Linden, P. J.; Hardy, J.-F.; Daper, A.; Trenchant, A.; de Hert, S. G.

    2007-01-01

    BACKGROUND: Aprotinin, a non-specific serine protease inhibitor, has been used for two decades to reduce perioperative blood loss and the risk for allogeneic transfusion in cardiac surgery. This study evaluated the effects of aprotinin on outcome (mortality, cardiac events, renal failure, and

  20. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  1. Dual energy cardiac CT.

    Science.gov (United States)

    Carrascosa, Patricia; Deviggiano, Alejandro; Rodriguez-Granillo, Gastón

    2017-06-01

    Conventional single energy CT suffers from technical limitations related to the polychromatic nature of X-rays. Dual energy cardiac CT (DECT) shows promise to attenuate and even overcome some of these limitations, and might broaden the scope of patients eligible for cardiac CT towards the inclusion of higher risk patients. This might be achieved as a result of both safety (contrast reduction) and physiopathological (myocardial perfusion and characterization) issues. In this article, we will review the main clinical cardiac applications of DECT, that can be summarized in two core aspects: coronary artery evaluation, and myocardial evaluation.

  2. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Emil D Bartels

    Full Text Available Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP; the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease.

  3. Biomarkers for cardiac cachexia: reality or utopia.

    Science.gov (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Cardiac Catheterization (For Parents)

    Science.gov (United States)

    ... cases, the doctor might call for a cardiac magnetic resonance imaging (MRI) scan or a CAT scan . ... first couple of days. This means no heavy lifting (more than 10 pounds) and no sports. After ...

  5. Cardiac Catheterization (For Teens)

    Science.gov (United States)

    ... doctor may also call for a cardiac MRI (magnetic resonance imaging) scan or a CT (computerized tomography) ... first couple of days. This means no heavy lifting (nothing over 10 pounds) and no sports. After ...

  6. Cardiac Anxiety - When the heart is (thought to be) in danger-

    NARCIS (Netherlands)

    Beek, M.H.C.T. van

    2016-01-01

    When the heart is (thought to be) in danger - like after a myocardial infarction (MI) or in patients with Non Cardiac Chest Pain (NCCP)- , this may provoke specific fears related to the heart: cardiac anxiety. This anxiety is often not acknowledged nor treated. The present thesis showed that cardiac

  7. Autonomic cardiac innervation

    Science.gov (United States)

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  8. Cardiac imaging in adults

    International Nuclear Information System (INIS)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority

  9. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  10. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  11. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  12. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  13. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    Directory of Open Access Journals (Sweden)

    Olivia Chen

    2015-01-01

    Full Text Available Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

  14. Cardiac troponins in dogs and cats

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob

    2016-01-01

    Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conven...

  15. Quadripolar leads in cardiac resynchronization therapy

    NARCIS (Netherlands)

    Van Everdingen, Wouter M.; Cramer, MJ; Doevendans, Pieter A.; Meine, Mathias

    2015-01-01

    Despite the benefit of cardiac resynchronization therapy (CRT) in patients with heart failure and conduction delay, a considerable number of patients do not respond substantially. Left ventricular lead position is an important factor in response, restricted by the patient's specific anatomy and

  16. Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells

    Science.gov (United States)

    Arshi, Armin; Nakashima, Yasuhiro; Nakano, Haruko; Eaimkhong, Sarayoot; Evseenko, Denis; Reed, Jason; Stieg, Adam Z.; Gimzewski, James K.; Nakano, Atsushi

    2013-04-01

    While adult heart muscle is the least regenerative of tissues, embryonic cardiomyocytes are proliferative, with embryonic stem (ES) cells providing an endless reservoir. In addition to secreted factors and cell-cell interactions, the extracellular microenvironment has been shown to play an important role in stem cell lineage specification, and understanding how scaffold elasticity influences cardiac differentiation is crucial to cardiac tissue engineering. Though previous studies have analyzed the role of matrix elasticity on the function of differentiated cardiomyocytes, whether it affects the induction of cardiomyocytes from pluripotent stem cells is poorly understood. Here, we examine the role of matrix rigidity on cardiac differentiation using mouse and human ES cells. Culture on polydimethylsiloxane (PDMS) substrates of varied monomer-to-crosslinker ratios revealed that rigid extracellular matrices promote a higher yield of de novo cardiomyocytes from undifferentiated ES cells. Using a genetically modified ES system that allows us to purify differentiated cardiomyocytes by drug selection, we demonstrate that rigid environments induce higher cardiac troponin T expression, beating rate of foci, and expression ratio of adult α- to fetal β- myosin heavy chain in a purified cardiac population. M-mode and mechanical interferometry image analyses demonstrate that these ES-derived cardiomyocytes display functional maturity and synchronization of beating when co-cultured with neonatal cardiomyocytes harvested from a developing embryo. Together, these data identify matrix stiffness as an independent factor that instructs not only the maturation of already differentiated cardiomyocytes but also the induction and proliferation of cardiomyocytes from undifferentiated progenitors. Manipulation of the stiffness will help direct the production of functional cardiomyocytes en masse from stem cells for regenerative medicine purposes.

  17. Postmortem cardiac imaging in fetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Andrew M. [Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, Level 7, Old Nurses Home, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Sebire, Neil J. [UCL Institute of Cardiovascular Science, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2015-04-01

    Fetal and pediatric cardiac autopsies have a crucial role in the counseling of parents with regard to both the cause of death of their child and the implications of such findings for future pregnancies, as well as for quality assurance of antenatal screening programs and antemortem diagnostic procedures. Postmortem imaging allows an opportunity to investigate the heart in situ prior to dissection, and both postmortem CT and postmortem MRI have shown excellent accuracy in detecting the majority of clinically significant cardiac lesions in the perinatal and pediatric population. As less-invasive autopsy becomes increasingly popular, clinical guidelines for maximal diagnostic yield in specific circumstances can be developed. (orig.)

  18. Postmortem cardiac imaging in fetuses and children

    International Nuclear Information System (INIS)

    Taylor, Andrew M.; Arthurs, Owen J.; Sebire, Neil J.

    2015-01-01

    Fetal and pediatric cardiac autopsies have a crucial role in the counseling of parents with regard to both the cause of death of their child and the implications of such findings for future pregnancies, as well as for quality assurance of antenatal screening programs and antemortem diagnostic procedures. Postmortem imaging allows an opportunity to investigate the heart in situ prior to dissection, and both postmortem CT and postmortem MRI have shown excellent accuracy in detecting the majority of clinically significant cardiac lesions in the perinatal and pediatric population. As less-invasive autopsy becomes increasingly popular, clinical guidelines for maximal diagnostic yield in specific circumstances can be developed. (orig.)

  19. Acquired valvar disease and cardiac tumours

    International Nuclear Information System (INIS)

    Ruttley, M.

    1985-01-01

    Investigation must determine the severity of the valve fault or faults, the effect on cardiac function and the significance of any associated cardiac disease in order that surgical referral can be made when appropriate with knowledge of operative risk and prognosis; radiology plays an important part in this. Radiological features will depend on the valve or valves affected, the type and severity of the haemodynamic disturbance and its time scale of development and duration. They may be modified by embolism or infection and there may be specific radiological manifestations of the underlying disease

  20. Trends and determinant factors in the use of cardiac resynchronization therapy devices in Japan: Analysis of the Japan cardiac device treatment registry database

    Directory of Open Access Journals (Sweden)

    Hisashi Yokoshiki

    2016-12-01

    Conclusions: Younger age, male sex, reduced LVEF, and a history of NSVT were independently associated with the choice of CRT-D for primary prevention of sudden cardiac death in patients with heart failure in Japan.

  1. Independence and Product Systems

    OpenAIRE

    Skeide, Michael

    2003-01-01

    Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

  2. Raf-mediated cardiac hypertrophy in adult Drosophila

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  3. The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Güínever Eustáquio do Império

    2015-08-01

    Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

  4. Cardiac radiology: centenary review.

    Science.gov (United States)

    de Roos, Albert; Higgins, Charles B

    2014-11-01

    During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

  5. Isolated Cardiac Hydatid Cyst

    International Nuclear Information System (INIS)

    Shakil, U.; Rehman, A. U.; Shahid, R.

    2015-01-01

    Hydatid cyst disease is common in our part of the world. Cardiac hydatid cyst is its rare manifestation. We report this case of 48-year male having isolated cardiac hydatid cyst, incidentally found on computed tomography. This patient presented in medical OPD of Combined Military Hospital, Lahore with one month history of mild retrosternal discomfort. His general physical and systemic examinations as well as ECG were unremarkable. Chest X-ray showed an enlarged cardiac shadow with mildly irregular left heart border. Contrast enhanced CT scan of the chest showed a large well defined multiloculated non-enhancing cystic lesion with multiple daughter cysts involving wall of left ventricle and overlying pericardium. Serology for echinococcus confirmed the diagnosis of hydatid cyst. Patient was offered the surgical treatment but he opted for medical treatment only. Albendezol was prescribed. His follow-up echocardiography after one month showed no significant decrease in size of the cyst. (author)

  6. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  7. Association of morning blood pressure surge with carotid intima-media thickness and cardiac dysfunction in patients with cardiac syndrome-X.

    Science.gov (United States)

    Mahfouz, Ragab A; Goda, Mohammad; Galal, Islam; Ghareb, Mohamed S

    2018-05-23

    Background & hypothesis: We hypothesized that exaggerated morning blood pressure surge, may contribute in cardiac dysfunction and arterial stiffness in patients with cardiac syndrome X. Thus we investigated the impact of morning blood pressure surge on cardiac function and carotid intima-media thickness in subjects with cardiac syndrome X. We studied patients with cardiac syndrome X using ambulatory blood pressure monitoring and investigated the association of morning blood pressure surge with carotid intima thickness, left atrial volume index and left ventricular filling (E/e'). Seventy patients with cardiac syndrome X were enrolled for the study and compared with 70 age and sex matched controls. Patients with cardiac syndrome X were stratified based on the systolic morning blood pressure surge value of control subjects to patients with exaggerated blood pressure surge (n = 42) and those with normal morning blood pressure surge (n = 28). Basal heart rate (p blood pressure surge group than those with morning blood pressure surge group. Morning blood pressure surge was significantly correlated with carotid intima-media thickness, high sensitive C-reactive protein, left atrial volume index and E/e' ratio in patients with cardiac syndrome X. In multivariate analysis, exaggerated morning blood pressure surge was the only independent predictor of increased carotid intima-media thickness (OR = 2.379; p blood pressure surge is an independent predictor for arterial stiffness and diastolic dysfunction in patients with cardiac syndrome X.

  8. Role of cardiac biomarkers (troponin I and CK-MB as predictors of quality of life and long-term outcome after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Bignami Elena

    2009-01-01

    Full Text Available Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life. Markers such as troponin effectively predict short-term outcome. In a prospective cohort study in a University Hospital we assessed the role of cardiac biomarkers, also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery. Patients were interviewed via phone calls with a structured questionnaire examining general health, functional status, activities of daily living, perception of life quality and need for hospital readmission. Descriptive statistics and multivariate analysis were performed. Out of 252 consecutive patients, 8 (3.2% died at the three years follow up: 7 for cardiac complications and 1 for cancer. Thirty-six patients (13.5% had hospital readmission for cardiac causes (mostly for atrial fibrillation or other arrhythmias (9.3%, but none needed cardiac surgical reintervention; 21 patients (7.9% were hospitalised for non-cardiac causes. No limitation in function activities of daily living was reported by most patients (94%, 92% perceived their general health as excellent, very good or good and none considered it insufficient; 80% were NYHA I, 17% NYHA II, 3% NYHA III and none NYHA IV. Multivariate analysis indicated preoperative treatment with digitalis or nitrates, and postoperative cardiac biomarkers release was independently associated to death. Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study.

  9. Home-based versus centre-based cardiac rehabilitation.

    Science.gov (United States)

    Taylor, Rod S; Dalal, Hayes; Jolly, Kate; Moxham, Tiffany; Zawada, Anna

    2010-01-20

    The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Traditionally centre-based cardiac rehabilitation (CR) programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. To determine the effectiveness of home-based cardiac rehabilitation programmes compared with supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life and modifiable cardiac risk factors in patients with coronary heart disease. We updated the search of a previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2007, Issue 4), MEDLINE, EMBASE and CINAHL from 2001 to January 2008. We checked reference lists and sought advice from experts. No language restrictions were applied. Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes, in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. Studies were selected independently by two reviewers, and data extracted by a single reviewer and checked by a second one. Authors were contacted where possible to obtain missing information. Twelve studies (1,938 participants) met the inclusion criteria. The majority of studies recruited a lower risk patient following an acute myocardial infarction (MI) and revascularisation. There was no difference in outcomes of home- versus centre-based cardiac rehabilitation in mortality risk ratio (RR) was1.31 (95% confidence interval (C) 0.65 to 2.66), cardiac events, exercise capacity standardised mean difference (SMD) -0.11 (95% CI -0.35 to 0.13), as well as in modifiable risk factors (systolic blood pressure; diastolic blood pressure; total cholesterol

  10. Quantitative cardiac computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Thelen, M.; Dueber, C.; Wolff, P.; Erbel, R.; Hoffmann, T.

    1985-06-01

    The scope and limitations of quantitative cardiac CT have been evaluated in a series of experimental and clinical studies. The left ventricular muscle mass was estimated by computed tomography in 19 dogs (using volumetric methods, measurements in two axes and planes and reference volume). There was good correlation with anatomical findings. The enddiastolic volume of the left ventricle was estimated in 22 patients with cardiomyopathies; using angiography as a reference, CT led to systematic under-estimation. It is also shown that ECG-triggered magnetic resonance tomography results in improved visualisation and may be expected to improve measurements of cardiac morphology.

  11. Cardiac output measurement

    Directory of Open Access Journals (Sweden)

    Andreja Möller Petrun

    2014-02-01

    Full Text Available In recent years, developments in the measuring of cardiac output and other haemodynamic variables are focused on the so-called minimally invasive methods. The aim of these methods is to simplify the management of high-risk and haemodynamically unstable patients. Due to the need of invasive approach and the possibility of serious complications the use of pulmonary artery catheter has decreased. This article describes the methods for measuring cardiac output, which are based on volume measurement (Fick method, indicator dilution method, pulse wave analysis, Doppler effect, and electrical bioimpedance.

  12. Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

    Directory of Open Access Journals (Sweden)

    Gro Egholm

    2015-01-01

    Full Text Available The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury.

  13. NUCLEAR IMAGING IN THE DIAGNOSIS OF CARDIAC AMYLOIDOSIS

    Directory of Open Access Journals (Sweden)

    V. B. Sergienko

    2018-01-01

    Full Text Available Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis but has its limitations. Accordingly, there is a need for noninvasive techniques to cardiac amyloidosis diagnostics. Echocardiography and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Recently, new opportunities of nuclear imaging in risk stratification and assessment of prognosis for patients with cardiac amyloidosis have appeared. During the last two decades different classes of radiopharmaceuticals have been developed based on compounds tropic to the components of amyloid infiltrates. In this paper we describe the current possibilities and perspectives of nuclear medicine techniques in patients with cardiac amyloidosis, including osteotropic and neurotropic scintigraphy, single-photon and positron emission tomography

  14. Blood transfusion in cardiac surgery does increase the risk of 5-year mortality: results from a contemporary series of 1714 propensity-matched patients.

    Science.gov (United States)

    Shaw, Richard E; Johnson, Christopher K; Ferrari, Giovanni; Brizzio, Mariano E; Sayles, Kathleen; Rioux, Nancy; Zapolanski, Alex; Grau, Juan B

    2014-04-01

    Studies have found that cardiac surgery patients receiving blood transfusions are at risk for increased mortality during the first year after surgery, but risk appears to decrease after the first year. This study compared 5-year mortality in a propensity-matched cohort of cardiac surgery patients. Between July 1, 2004, and June 30, 2011, 3516 patients had cardiac surgery with 1920 (54.6%) requiring blood transfusion. Propensity matching based on 22 baseline characteristics yielded two balanced groups (blood transfusion group [BTG] and nontransfused control group [NCG]) of 857 patients (1714 in total). The type and number of blood products were compared in the BTG. Operative mortality was higher in BTG versus NCG (2.3% vs. 0.4%; p blood (79.6% vs. 88.0%; p transfusion was independently associated with increased risk for 5-year mortality. Patients receiving cryoprecipitate products had a twofold mortality risk increase (adjusted hazard ratio, 2.106; p = 0.002). Blood transfusion, specifically cryoprecipitates, was independently associated with increased 5-year mortality. Transfusion during cardiac surgery should be limited to patients who are in critical need of blood products. © 2013 American Association of Blood Banks.

  15. Are Independent Fiscal Institutions Really Independent?

    Directory of Open Access Journals (Sweden)

    Slawomir Franek

    2015-08-01

    Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

  16. Quality of Life After Cardiac Surgery Based on the Minimal Clinically Important Difference Concept.

    Science.gov (United States)

    Grand, Nathalie; Bouchet, Jean Baptiste; Zufferey, Paul; Beraud, Anne Marie; Awad, Sahar; Sandri, Fabricio; Campisi, Salvator; Fuzellier, Jean François; Molliex, Serge; Vola, Marco; Morel, Jerome

    2018-03-23

    Health-related quality of life (HRQOL) is an increasingly important issue in assessing the consequences of any surgical or medical intervention. Our study aimed to evaluate change in HRQOL 6 months after elective cardiac surgery and to identify specific predictors of poor HRQOL. In this prospective, single-center study, HRQOL was evaluated before and 6 months after surgery using the SF-36 questionnaire and its two components: the physical component summary (PCS) and the mental component summary (MCS). We distinguished patients with worsening of HRQOL according to the minimal clinically important difference. All consecutive adult patients undergoing cardiac surgery were included. 326 patients completed the preoperative and postoperative SF-36 questionnaires and 24 patients died before completing follow-up questionnaires. Based on the definition used, clinically significant deterioration of HRQOL was observed in 93 patients (26.6%) for PCS and 99 patients (28.2%) for MCS. Renal replacement for acute renal failure and mechanical ventilation for longer than 48 hours were independent risk factors for PCS and MCS worsening or death. Although our study showed overall improvement of QOL after cardiac surgery, over a quarter of the patients manifested deterioration of HRQOL at 6 months post-surgery. The findings from this study should help clinicians to inform patients about their likely postoperative functional status and quality of life. Copyright © 2018. Published by Elsevier Inc.

  17. Functional modulation of cardiac form through regionally confined cell shape changes.

    Directory of Open Access Journals (Sweden)

    Heidi J Auman

    2007-03-01

    Full Text Available Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

  18. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I

    2009-01-01

    Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via...... secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...... remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression...

  19. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

    Directory of Open Access Journals (Sweden)

    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

  20. Trauma-induced secondary cardiac injury is associated with hyperacute elevations in inflammatory cytokines.

    Science.gov (United States)

    De'Ath, Henry D; Manson, Joanna; Davenport, Ross; Glasgow, Simon; Renfrew, Ian; Davies, L Ceri; Uppal, Rakesh; Brohi, Karim

    2013-05-01

    Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients. A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid-binding protein and the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality. Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-α (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1β (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid-binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-α (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8-66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9-101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1-72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values. There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

  1. Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lamare, F., E-mail: frederic.lamare@chu-bordeaux.fr; Fernandez, P. [Univ. Bordeaux, INCIA, UMR 5287, F-33400 Talence (France); CNRS, INCIA, UMR 5287, F-33400 Talence (France); Service de Médecine Nucléaire, Hôpital Pellegrin, CHU de Bordeaux, 33076 Bordeaux (France); Le Maitre, A.; Visvikis, D. [INSERM, UMR1101, LaTIM, Université de Bretagne Occidentale, 29609 Brest (France); Dawood, M.; Schäfers, K. P. [European Institute for Molecular Imaging, University of Münster, Mendelstr. 11, 48149 Münster (Germany); Rimoldi, O. E. [Vita-Salute University and Scientific Institute San Raffaele, Milan, Italy and CNR Istituto di Bioimmagini e Fisiologia Molecolare, Milan (Italy)

    2014-07-15

    observed in the performance of the two motion models considered. Superior image SNR and contrast were seen using the affine respiratory motion model in combination with the diastole cardiac bin in comparison to the use of the whole cardiac cycle. In contrast, when simultaneously correcting for cardiac beating and respiration, the elastic respiratory motion model outperformed the affine model. In this context, four cardiac bins associated with eight respiratory amplitude bins seemed to be adequate. Conclusions: Considering the compensation of respiratory motion effects only, both affine and elastic based approaches led to an accurate resizing and positioning of the myocardium. The use of the diastolic phase combined with an affine model based respiratory motion correction may therefore be a simple approach leading to significant quality improvements in cardiac PET imaging. However, the best performance was obtained with the combined correction for both cardiac and respiratory movements considering all the dual-gated bins independently through the use of an elastic model based motion compensation.

  2. Specification of a system for planning and analysis of independent generator connection impact on the electric distribution system; Especificacao de um sistema de planeamento e analise do impacto da conexao de geradores independentes no sistema electrico da distribuicao

    Energy Technology Data Exchange (ETDEWEB)

    Proenca, Luis Miguel; Matos, Manuel Antonio [Instituto de Engenharia de Sistemas e Computadores (INESC), Porto (Portugal); Campos, Manuel Luis Borges [Centro para a Excelencia na Distribuicao (CED), Sao Paulo, SP (Brazil)

    1999-07-01

    This paper describes a system for planning and analysis of the independent generator connection impact on the electric distribution system. This system is being developed under a contract signed between the Center for Excellency in the Distribution (CED), state of Sao Paulo - Brazil and the INESC, Porto - Portugal - energy unit.

  3. Influence of cardiac decentralization on cardioprotection.

    Directory of Open Access Journals (Sweden)

    John G Kingma

    Full Text Available The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization (surgical modulates coronary flow reserve and myocardial protection in preconditioned dogs subject to ischemia-reperfusion. Experiments were conducted on four groups of anesthetised, open-chest dogs (n = 32: 1- controls (CTR, intact cardiac nerves, 2- ischemic preconditioning (PC; 4 cycles of 5-min IR, 3- cardiac decentralization (CD and 4- CD+PC; all dogs underwent 60-min coronary occlusion and 180-min reperfusion. Coronary blood flow and reactive hyperemic responses were assessed using a blood volume flow probe. Infarct size (tetrazolium staining was related to anatomic area at risk and coronary collateral blood flow (microspheres in the anatomic area at risk. Post-ischemic reactive hyperemia and repayment-to-debt ratio responses were significantly reduced for all experimental groups; however, arterial perfusion pressure was not affected. Infarct size was reduced in CD dogs (18.6 ± 4.3; p = 0.001, data are mean ± 1 SD compared to 25.2 ± 5.5% in CTR dogs and was less in PC dogs as expected (13.5 ± 3.2 vs. 25.2 ± 5.5%; p = 0.001; after acute CD, PC protection was conserved (11.6 ± 3.4 vs. 18.6 ± 4.3%; p = 0.02. In conclusion, our findings provide strong evidence that myocardial protection against ischemic injury can be preserved independent of extrinsic cardiac nerve inputs.

  4. Neonatal cardiac emergencies

    African Journals Online (AJOL)

    flow) or require intervention (surgical or catheter) within the first ... Cardiac. History. Risk factors, e.g. meconium-stained liquor, prematurity, ... 'snowman' sign for supracardiac total anomalous pulmonary venous drainage (TAPVD), cardiomegaly with plethora for ... central cyanosis and on auscultation you hear no murmurs.

  5. Comparative cardiac imaging

    International Nuclear Information System (INIS)

    Brundage, B.H.

    1990-01-01

    This book is designed to compare all major cardiac imaging techniques. All major imaging techniques - including conventional angiography, digital angiography, echocardiography and Doppler imaging, conventional radioisotope techniques, computed tomography, and magnetic resonance imaging - are covered in this text as they apply to the major cardiovascular disorders. There is brief coverage of positron emission tomography and an extensive presentation of ultrafast computed tomography

  6. Advanced Cardiac Life Support.

    Science.gov (United States)

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document contains materials for an advanced college course in cardiac life support developed for the State of Iowa. The course syllabus lists the course title, hours, number, description, prerequisites, learning activities, instructional units, required text, six references, evaluation criteria, course objectives by units, course…

  7. Cardiac Pacemakers; Marcapasos Cardiacos

    Energy Technology Data Exchange (ETDEWEB)

    Fiandra, O [Universidad de la Republica, Facultad de Maedicina, Departamento de Cardiologia, Montevideo(Uruguay); Espasandin, W [Universidad de la Republica, Facultad de Medicina, Departamento de Cirugia Cardiaca, Montevideo (Uruguay); Fiandra, H [Instituto Nacional de Cirugia Cardiaca, Departamento de Hemodinamia y Marcapasos, Montevideo (Uruguay); and others

    1984-07-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control.

  8. Cardiac magnetic resonance imaging

    African Journals Online (AJOL)

    2011-03-06

    Mar 6, 2011 ... Cardiac magnetic resonance imaging. Cardiovascular magnetic resonance imaging is becoming a routine diagnostic technique. BRUCE s sPOTTiswOOdE, PhD. MRC/UCT Medical Imaging Research Unit, University of Cape Town, and Division of Radiology, Stellenbosch University. Bruce Spottiswoode ...

  9. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU

    2012-08-01

    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  10. Organizing Independent Student Work

    Directory of Open Access Journals (Sweden)

    Zhadyra T. Zhumasheva

    2015-03-01

    Full Text Available This article addresses issues in organizing independent student work. The author defines the term “independence”, discusses the concepts of independent learner work and independent learner work under the guidance of an instructor, proposes a classification of assignments to be done independently, and provides methodological recommendations as to the organization of independent student work. The article discusses the need for turning the student from a passive consumer of knowledge into an active creator of it, capable of formulating a problem, analyzing the ways of solving it, coming up with an optimum outcome, and proving its correctness. The preparation of highly qualified human resources is the primary condition for boosting Kazakhstan’s competitiveness. Independent student work is a means of fostering the professional competence of future specialists. The primary form of self-education is independent work.

  11. Maternal cardiac metabolism in pregnancy

    Science.gov (United States)

    Liu, Laura X.; Arany, Zolt

    2014-01-01

    Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

  12. What to do when you question cardiac troponin values

    DEFF Research Database (Denmark)

    Mair, Johannes; Lindahl, Bertil; Müller, Christian

    2017-01-01

    High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches...... for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic...... of the work-up for such a clinical setting....

  13. Cardiac computed tomography in patients with acute coronary syndrome

    International Nuclear Information System (INIS)

    Schlett, C.L.; Bamberg, F.

    2014-01-01

    Currently, cardiac computed tomography (CT) is increasingly being implemented into clinical algorithms, primarily due to substantial technical advances over the last decade. Its use in the setting of suspected acute coronary syndrome is of particular relevance, given the high degree of accumulating scientific evidence of improving patient outcomes. Performing cardiac CT requires specific knowledge on the available scan acquisitions and patient preparation. Also, expertise is required in order to interpret the coronary and extra-coronary findings adequately. The present article provides an overview of the different aspects on the use of cardiac CT in the setting of acute coronary syndrome.

  14. Cardiac nuclear medicine, part II: diagnosis of coronary artery diseas

    International Nuclear Information System (INIS)

    Polak, J.F.; Holman, B.L.

    1981-01-01

    Diagnosing coronary artery disease is difficult and requires careful consideration of the roles and limitations of the tests used. Standard ECG tests are not reliable indicators of the presence of disease in asymptomatic patients. Thallium stress testing to assess ischemia and exercise ventriculography to assess functional status of the heart are limited in sensitivity and specificity. This is the second of a three-part series on cardiac nuclear medicine. Part I (Med. Instrum., May-June, 1981) focused on the commonly used examinations in cardiac physiology and pathophysiology. Part III will focus on myocardial infarction and other cardiac diseases

  15. Establishing a clinical cardiac MRI service

    International Nuclear Information System (INIS)

    O'Regan, D.P.; Schmitz, S.A.

    2006-01-01

    After several years of research development cardiovascular MRI has evolved into a widely accepted clinical tool. It offers important diagnostic and prognostic information for a variety of clinical indications, which include ischaemic heart disease, cardiomyopathies, valvular dysfunction and congenital heart disorders. It is a safe non-invasive technique that employs a variety of imaging sequences optimized for temporal or spatial resolution, tissue-specific contrast, flow quantification or angiography. Cardiac MRI offers specific advantages over conventional imaging techniques for a significant number of patients. The demand for cardiac MRI studies from cardiothoracic surgeons, cardiologists and other referrers is likely to continue to rise with pressure for more widespread local service provision. Setting up a cardiac MRI service requires careful consideration regarding funding issues and how it will be integrated with existing service provision. The purchase of cardiac phased array coils, monitoring equipment and software upgrades must also be considered, as well as the training needs of those involved. The choice of appropriate imaging protocols will be guided by operator experience, clinical indication and equipment capability, and is likely to evolve as the service develops. Post-processing and offline analysis form a significant part of the time taken to report studies and an efficient method of providing quantitative reports is an important requirement. Collaboration between radiologists and cardiologists is needed to develop a successful service and multi-disciplinary meetings are key component of this. This review will explore these issues from our perspective of a new clinical cardiac MRI service operating over its first year in a teaching hospital imaging department

  16. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

    2014-09-15

    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  17. Sudden Cardiac Arrest during Participation in Competitive Sports.

    Science.gov (United States)

    Landry, Cameron H; Allan, Katherine S; Connelly, Kim A; Cunningham, Kris; Morrison, Laurie J; Dorian, Paul

    2017-11-16

    The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac

  18. Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2.

    Science.gov (United States)

    Bylund, Jeffery B; Trinh, Linh T; Awgulewitsch, Cassandra P; Paik, David T; Jetter, Christopher; Jha, Rajneesh; Zhang, Jianhua; Nolan, Kristof; Xu, Chunhui; Thompson, Thomas B; Kamp, Timothy J; Hatzopoulos, Antonis K

    2017-05-01

    Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling.

  19. Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2

    Science.gov (United States)

    Bylund, Jeffery B.; Trinh, Linh T.; Awgulewitsch, Cassandra P.; Paik, David T.; Jetter, Christopher; Jha, Rajneesh; Zhang, Jianhua; Nolan, Kristof; Xu, Chunhui; Thompson, Thomas B.; Kamp, Timothy J.

    2017-01-01

    Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling. PMID:28125926

  20. Does firm performance affect board independence?

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2010-07-01

    Full Text Available This paper seeks to shed some light on the antecedents of board independence. Specifically, it attempts to test the conceptual frameworks which make different predictions about the effect of firm performance on the level of board independence. The results provide support for the perspective that appointing more independent members to the boards may merely represent firms’ attempts to comply with institutional pressures. It is found that higher blockholder shareholdings lead to lower independence on the board, and audit and remuneration committees. Moreover, larger firms have relatively more independent directors sitting on nomination and remuneration committees.

  1. Antimyosin imaging in cardiac transplant rejection

    International Nuclear Information System (INIS)

    Johnson, L.L.; Cannon, P.J.

    1991-01-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  2. Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Koczor, Christopher A., E-mail: ckoczor@emory.edu; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

    2015-11-01

    This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

  3. Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

    International Nuclear Information System (INIS)

    Koczor, Christopher A.; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

    2015-01-01

    This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

  4. Direct and simultaneous estimation of cardiac four chamber volumes by multioutput sparse regression.

    Science.gov (United States)

    Zhen, Xiantong; Zhang, Heye; Islam, Ali; Bhaduri, Mousumi; Chan, Ian; Li, Shuo

    2017-02-01

    Cardiac four-chamber volume estimation serves as a fundamental and crucial role in clinical quantitative analysis of whole heart functions. It is a challenging task due to the huge complexity of the four chambers including great appearance variations, huge shape deformation and interference between chambers. Direct estimation has recently emerged as an effective and convenient tool for cardiac ventricular volume estimation. However, existing direct estimation methods were specifically developed for one single ventricle, i.e., left ventricle (LV), or bi-ventricles; they can not be directly used for four chamber volume estimation due to the great combinatorial variability and highly complex anatomical interdependency of the four chambers. In this paper, we propose a new, general framework for direct and simultaneous four chamber volume estimation. We have addressed two key issues, i.e., cardiac image representation and simultaneous four chamber volume estimation, which enables accurate and efficient four-chamber volume estimation. We generate compact and discriminative image representations by supervised descriptor learning (SDL) which can remove irrelevant information and extract discriminative features. We propose direct and simultaneous four-chamber volume estimation by the multioutput sparse latent regression (MSLR), which enables jointly modeling nonlinear input-output relationships and capturing four-chamber interdependence. The proposed method is highly generalized, independent of imaging modalities, which provides a general regression framework that can be extensively used for clinical data prediction to achieve automated diagnosis. Experiments on both MR and CT images show that our method achieves high performance with a correlation coefficient of up to 0.921 with ground truth obtained manually by human experts, which is clinically significant and enables more accurate, convenient and comprehensive assessment of cardiac functions. Copyright © 2016 Elsevier

  5. Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls

    NARCIS (Netherlands)

    van der Klaauw, Agatha A.; Bax, Jeroen J.; Bleeker, Gabe B.; Holman, Eduard R.; Delgado, V.; Smit, Johannes W. A.; Romijn, Johannes A.; Pereira, Alberto M.

    2008-01-01

    Both GH excess and GH deficiency (GHD) lead to specific cardiac pathology. The aim of this study was to evaluate cardiac morphology and function in patients with GHD after treatment for acromegaly. Cross-sectional study. Cardiac parameters were studied by conventional two-dimensional

  6. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt

    2012-01-01

    in recruitment and participation among low educated and socially vulnerable patients must be addressed to lower inequality in post-MI health. Our aim was to improve referral, attendance, and adherence rates among socially vulnerable patients by systematic screening and by offering a socially differentiated...... to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social...

  7. Ictal Cardiac Ryhthym Abnormalities.

    Science.gov (United States)

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy.

  8. Fetal cardiac assessment

    International Nuclear Information System (INIS)

    Greene, K.R.

    1983-01-01

    The better understanding of fetal cardiovascular physiology coupled with improved technology for non-invasive study of the fetus now enable much more detailed assessment of fetal cardiac status than by heart rate alone. Even the latter, relatively simple, measurement contains much more information than was previously realized. It is also increasingly clear that no single measurement will provide the answer to all clinical dilemmas either on cardiac function or the welfare of the fetus as a whole. There are obvious clinical advantages in measuring several variables from one signal and the measurement of heart rate, heart rate variation and waveform from the ECG in labour is a potentially useful combination. Systolic time intervals or flow measurements could easily be added or used separately by combining real-time and Doppler ultrasound probes

  9. Cardiac nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Gerson, M.C.

    1987-01-01

    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

  10. Cardiac nuclear medicine

    International Nuclear Information System (INIS)

    Gerson, M.C.

    1987-01-01

    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma

  11. Cardiac function studies

    International Nuclear Information System (INIS)

    Horn, H.J.

    1986-01-01

    A total of 27 patients were subjected tointramyocardial sequential scintiscanning (first pass) using 99m-Tc human serum albumin. A refined method is described that is suitable to analyse clinically relevant parameters like blood volume, cardiac output, ejection fraction, stroke volume, enddiastolic and endsystolic volumes as well as pulmonal transition time and uses a complete camaracomputer system adapted to the requirements of a routine procedure. Unless there is special hardware available, the method does not yet appear mature enough to be put into general practice. Its importance recently appeared in a new light due to the advent of particularly shortlived isotopes. For the time being, however, ECG-triggered equilibrium studies are to be preferred for cardiac function tests. (TRV) [de

  12. CSI cardiac prevent 2015

    OpenAIRE

    S Ramakrishnan; Manisha Kaushik

    2015-01-01

    The CSI Cardiac Prevent 2015 was held at Hotel Taj Palace, New Delhi, on September 25-27, 2015. The major challenge was to create interest among cardiologists and physicians on preventive cardiology, a neglected area. The theme of the conference was "Innovations in Heart Disease Prevention.′′ This conference included "CSI at WHF Roadmap Workshop, Inauguration Ceremony, scientific program, plenary sessions, Nursing/Dietician track, Industry Exhibition, Social Events," Great India blood pressur...

  13. Multifractality in Cardiac Dynamics

    Science.gov (United States)

    Ivanov, Plamen Ch.; Rosenblum, Misha; Stanley, H. Eugene; Havlin, Shlomo; Goldberger, Ary

    1997-03-01

    Wavelet decomposition is used to analyze the fractal scaling properties of heart beat time series. The singularity spectrum D(h) of the variations in the beat-to-beat intervals is obtained from the wavelet transform modulus maxima which contain information on the hierarchical distribution of the singularities in the signal. Multifractal behavior is observed for healthy cardiac dynamics while pathologies are associated with loss of support in the singularity spectrum.

  14. Integrative Cardiac Health Project

    Science.gov (United States)

    2014-10-01

    primary cardiac arrest. Circulation. 1998;97(2):155Y160. 8. Sesso HD, Lee IM, Gaziano JM, Rexrode KM, Glynn RJ, Buring JE. Maternal and paternal ...to signal transduction, inflammation, and host–pathogen interactions .27 Whole blood RNA isolation systems such as PAXgene accurately capture in vivo...the effect of healthy behaviors on leukocyte function and leukocyte–endothelium interactions that are important for cardiovascular health

  15. Molecular nuclear cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soo; Paeng, Jin Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2004-04-01

    Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

  16. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-05-15

    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  17. Cardiac Cachexia Syndrome

    Directory of Open Access Journals (Sweden)

    Teresa Raposo André

    2017-10-01

    Full Text Available Heart failure is a chronic, progressive, and incurable disease. Cardiac cachexia is a strong predictor of poor prognosis, regardless of other important variables. This review intends to gather evidence to enable recognition of cardiac cachexia, identification of early stages of muscle waste and sarcopenia, and improve identification of patients with terminal heart failure in need of palliative care, whose symptoms are no longer controlled by usual medical measures. The pathophysiology is complex and multifactorial. There are many treatment options to prevent or revert muscle waste and sarcopenia; although, these strategies are less effective in advanced stages of cardiac cachexia. In these final stages, symptomatic palliation plays an important role, focussing on the patient’s comfort and avoiding the ‘acute model’ treatment of aggressive, disproportionate, and inefficient care. In order to provide adequate care and attempt to prevent this syndrome, thus reducing its impact on healthcare, there should be improved communication between general practitioners, internal medicine physicians, cardiologists, and palliative care specialists since heart failure has an unforeseeable course and is associated with an increasing number of deaths and different levels of suffering.

  18. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  19. Molecular nuclear cardiac imaging

    International Nuclear Information System (INIS)

    Lee, Dong Soo; Paeng, Jin Chul

    2004-01-01

    Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect

  20. "Just-In-Time" Simulation Training Using 3-D Printed Cardiac Models After Congenital Cardiac Surgery.

    Science.gov (United States)

    Olivieri, Laura J; Su, Lillian; Hynes, Conor F; Krieger, Axel; Alfares, Fahad A; Ramakrishnan, Karthik; Zurakowski, David; Marshall, M Blair; Kim, Peter C W; Jonas, Richard A; Nath, Dilip S

    2016-03-01

    High-fidelity simulation using patient-specific three-dimensional (3D) models may be effective in facilitating pediatric cardiac intensive care unit (PCICU) provider training for clinical management of congenital cardiac surgery patients. The 3D-printed heart models were rendered from preoperative cross-sectional cardiac imaging for 10 patients undergoing congenital cardiac surgery. Immediately following surgical repair, a congenital cardiac surgeon and an intensive care physician conducted a simulation training session regarding postoperative care utilizing the patient-specific 3D model for the PCICU team. After the simulation, Likert-type 0 to 10 scale questionnaire assessed participant perception of impact of the training session. Seventy clinicians participated in training sessions, including 22 physicians, 38 nurses, and 10 ancillary care providers. Average response to whether 3D models were more helpful than standard hand off was 8.4 of 10. Questions regarding enhancement of understanding and clinical ability received average responses of 9.0 or greater, and 90% of participants scored 8 of 10 or higher. Nurses scored significantly higher than other clinicians on self-reported familiarity with the surgery (7.1 vs. 5.8; P = .04), clinical management ability (8.6 vs. 7.7; P = .02), and ability enhancement (9.5 vs. 8.7; P = .02). Compared to physicians, nurses and ancillary providers were more likely to consider 3D models more helpful than standard hand off (8.7 vs. 7.7; P = .05). Higher case complexity predicted greater enhancement of understanding of surgery (P = .04). The 3D heart models can be used to enhance congenital cardiac critical care via simulation training of multidisciplinary intensive care teams. Benefit may be dependent on provider type and case complexity. © The Author(s) 2016.

  1. Initial Efficacy of a Cardiac Rehabilitation Transition Program: Cardiac TRUST

    Science.gov (United States)

    Zullo, Melissa; Boxer, Rebecca; Moore, Shirley M.

    2012-01-01

    Patients recovering from cardiac events are increasingly using postacute care, such as home health care and skilled nursing facility services. The purpose of this pilot study was to test the initial efficacy, feasibility, and safety of a specially designed postacute care transitional rehabilitation intervention for cardiac patients. Cardiac Transitional Rehabilitation Using Self- Management Techniques (Cardiac TRUST) is a family-focused intervention that includes progressive low-intensity walking and education in self-management skills to facilitate recovery following a cardiac event. Using a randomized two-group design, exercise self-efficacy, steps walked, and participation in an outpatient cardiac rehabilitation program were compared in a sample of 38 older adults; 17 who received the Cardiac TRUST program and 21 who received usual care only. At discharge from postacute care, the intervention group had a trend for higher levels of self-efficacy for exercise outcomes (X=39.1, SD=7.4) than the usual care group (X=34.5; SD=7.0) (t-test 1.9, p=.06). During the 6 weeks following discharge, compared with the usual care group, the intervention group had more attendance in out-patient cardiac rehabilitation (33% compared to 11.8%, F=7.1, p=.03) and a trend toward more steps walked during the first week (X=1,307, SD=652 compared to X=782, SD=544, t-test 1.8, p=.07). The feasibility of the intervention was better for the home health participants than for those in the skilled nursing facility and there were no safety concerns. The provision of cardiac-focused rehabilitation during postacute care has the potential to bridge the gap in transitional services from hospitalization to outpatient cardiac rehabilitation for these patients at high risk for future cardiac events. Further evidence of the efficacy of Cardiac TRUST is warranted. PMID:22084960

  2. Perspectives on Current Training Guidelines for Cardiac Imaging and Recommendations for the Future.

    Science.gov (United States)

    Arrighi, James A; Kilic, Sena; Haines, Philip G

    2018-04-23

    To summarize current training guidelines for cardiac imaging and provide recommendations for future guidelines. The current structure of training in cardiac imaging is largely dictated by modality-specific guidelines. While there has been debate on how to define the advanced cardiac imager for over a decade, a uniform consensus has not emerged. We report the perspectives of three key stakeholders in this debate: a senior faculty member-former fellowship program director, a cardiology fellow, and an academic junior faculty imaging expert. The observations of these stakeholders suggest that there is no consensus on the definition of advanced cardiac imaging, leading to ambiguity in training guidelines. This may have negative impact on recruitment of fellows into cardiac imaging careers. Based on the current status of training in cardiac imaging, the authors suggest that the relevant professional groups reconvene to form a consensus in defining advanced cardiac imaging, in order to guide future revisions of training guidelines.

  3. Neuromuscular blockade in cardiac surgery: An update for clinicians

    Directory of Open Access Journals (Sweden)

    Hemmerling Thomas

    2008-01-01

    Full Text Available There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

  4. Accounting for Independent Schools.

    Science.gov (United States)

    Sonenstein, Burton

    The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

  5. Commonwealth of (Independent States

    Directory of Open Access Journals (Sweden)

    Vrućinić Dušan

    2013-01-01

    Full Text Available Following the stages from the establishment itself to the present day of the functioning of such a specific regional organization as the Commonwealth of Independent States (CIS, the article seeks to further explain the meaning of its existence, efficiency and functioning. The CIS was created in order to make the dissolution of a major world super-power, which throughout the 20th century together with the USA defined the bipolar world, as painless as possible, especially for the new countries and its nationally and ethnically diverse population. During the early years after the dissolution of the USSR, the CIS played a major role in a more flexible and less severe dissolution of the Soviet empire, alleviating the consequences for its people. A more efficient functioning among the republics in all fields was also one of the tasks of the Commonwealth, to which it was devoted to the extent which was permitted by the then, not too favourable circumstances. Difficult years of economic crisis did not allow the CIS to mutually integrate its members as much as possible on the economy level. Thanks to the economic recovery of the post-Soviet states in the early 21st century, the Commonwealth has also been transformed, reformed, and renewed, and all this in order to achieve better and more fruitful cooperation between the members. The CIS may serve as a proper example of how the former Soviet Union states are inextricably linked by social, security-political, economic, cultural, communication-transport, and other ties, thanks to the centuries-long existence of the peoples of these states in this area, despite both internal and external factors which occasionally, but temporarily halt the post-Soviet integration. Mathematically expressed, the CIS members are naturally predisposed, to be reciprocally depended on each other, just as they also have the capacity for successful cooperation in the future times and epochs brought on by the modern world.

  6. Cardiac telomere length in heart development, function, and disease.

    Science.gov (United States)

    Booth, S A; Charchar, F J

    2017-07-01

    Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

  7. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline

    2013-01-01

    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

  8. Motion of the esophagus due to cardiac motion.

    Directory of Open Access Journals (Sweden)

    Jacob Palmer

    Full Text Available When imaging studies (e.g. CT are used to quantify morphological changes in an anatomical structure, it is necessary to understand the extent and source of motion which can give imaging artifacts (e.g. blurring or local distortion. The objective of this study was to assess the magnitude of esophageal motion due to cardiac motion. We used retrospective electrocardiogram-gated contrast-enhanced computed tomography angiography images for this study. The anatomic region from the carina to the bottom of the heart was taken at deep-inspiration breath hold with the patients' arms raised above their shoulders, in a position similar to that used for radiation therapy. The esophagus was delineated on the diastolic phase of cardiac motion, and deformable registration was used to sequentially deform the images in nearest-neighbor phases among the 10 cardiac phases, starting from the diastolic phase. Using the 10 deformation fields generated from the deformable registration, the magnitude of the extreme displacements was then calculated for each voxel, and the mean and maximum displacement was calculated for each computed tomography slice for each patient. The average maximum esophageal displacement due to cardiac motion for all patients was 5.8 mm (standard deviation: 1.6 mm, maximum: 10.0 mm in the transverse direction. For 21 of 26 patients, the largest esophageal motion was found in the inferior region of the heart; for the other patients, esophageal motion was approximately independent of superior-inferior position. The esophagus motion was larger at cardiac phases where the electrocardiogram R-wave occurs. In conclusion, the magnitude of esophageal motion near the heart due to cardiac motion is similar to that due to other sources of motion, including respiratory motion and intra-fraction motion. A larger cardiac motion will result into larger esophagus motion in a cardiac cycle.

  9. Measuring cardiac efficiency using PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, Grand [Lawrence Berkeley National Laboratory (United States); Aparici, Carina Mari; Brooks, Gabriel [University of California San Francisco (United States); Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes [Lawrence Berkeley National Laboratory (United States)

    2015-05-18

    Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

  10. Measuring cardiac efficiency using PET/MRI

    International Nuclear Information System (INIS)

    Gullberg, Grand; Aparici, Carina Mari; Brooks, Gabriel; Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes

    2015-01-01

    Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

  11. Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

    Science.gov (United States)

    Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

    2017-04-01

    Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to both stable cirrhotic patients and healthy controls. This pattern is observed even in the absence of hepatic encephalopathy suggesting that blood-CSF barrier impairment is manifest even in absence of overt

  12. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    Science.gov (United States)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

  13. Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yao Song

    Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

  14. Probabilistic conditional independence structures

    CERN Document Server

    Studeny, Milan

    2005-01-01

    Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

  15. An architecture for device independent interfacing

    International Nuclear Information System (INIS)

    Pace, D.M.

    1990-01-01

    Achieving device independence for software applications is required for all but a small number of critical real time applications. Device independence is achieved by establishing protocols and building protocol interpreters for the specific devices. Data structures containing pointers to functions provide a flexible architecture for implementing protocol translation. 3 refs., 5 figs

  16. Institutional independence and the constitutionality of legislation ...

    African Journals Online (AJOL)

    The test for determining whether judicial independence is safeguarded is an objective one based on public confidence in the structure of the court and the ... in the analysis of the application of the principles of judicial independence to specific legislative schemes where the structure of the tribunal thereby established had ...

  17. Accounting for Independent Schools. Second Edition.

    Science.gov (United States)

    National Association of Independent Schools, Boston, MA.

    This is a thoroughly revised edition of the 1969 publication, "Accounting for Independent Schools," a guide that attempted to codify basic accounting principles and practices for specific application to independent schools. The focus of the second edition is more on refining practices than on initiating them, and more on extending the managerial…

  18. Antifibrinolytics in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Achal Dhir

    2013-01-01

    Full Text Available Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA or epsilon amino caproic acid (EACA. While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

  19. Alternans promotion in cardiac electrophysiology models by delay differential equations.

    Science.gov (United States)

    Gomes, Johnny M; Dos Santos, Rodrigo Weber; Cherry, Elizabeth M

    2017-09-01

    Cardiac electrical alternans is a state of alternation between long and short action potentials and is frequently associated with harmful cardiac conditions. Different dynamic mechanisms can give rise to alternans; however, many cardiac models based on ordinary differential equations are not able to reproduce this phenomenon. A previous study showed that alternans can be induced by the introduction of delay differential equations (DDEs) in the formulations of the ion channel gating variables of a canine myocyte model. The present work demonstrates that this technique is not model-specific by successfully promoting alternans using DDEs for five cardiac electrophysiology models that describe different types of myocytes, with varying degrees of complexity. By analyzing results across the different models, we observe two potential requirements for alternans promotion via DDEs for ionic gates: (i) the gate must have a significant influence on the action potential duration and (ii) a delay must significantly impair the gate's recovery between consecutive action potentials.

  20. Alternans promotion in cardiac electrophysiology models by delay differential equations

    Science.gov (United States)

    Gomes, Johnny M.; dos Santos, Rodrigo Weber; Cherry, Elizabeth M.

    2017-09-01

    Cardiac electrical alternans is a state of alternation between long and short action potentials and is frequently associated with harmful cardiac conditions. Different dynamic mechanisms can give rise to alternans; however, many cardiac models based on ordinary differential equations are not able to reproduce this phenomenon. A previous study showed that alternans can be induced by the introduction of delay differential equations (DDEs) in the formulations of the ion channel gating variables of a canine myocyte model. The present work demonstrates that this technique is not model-specific by successfully promoting alternans using DDEs for five cardiac electrophysiology models that describe different types of myocytes, with varying degrees of complexity. By analyzing results across the different models, we observe two potential requirements for alternans promotion via DDEs for ionic gates: (i) the gate must have a significant influence on the action potential duration and (ii) a delay must significantly impair the gate's recovery between consecutive action potentials.

  1. Dealing with existential anxiety in exercise-based cardiac rehabilitation

    DEFF Research Database (Denmark)

    Simonÿ, Charlotte; Pedersen, Birthe D; Dreyer, Pia

    2015-01-01

    rehabilitation. Focus group interviews were conducted at the programme end, and individual interviews were performed one to two months later. The interpretation comprised three methodological steps: naïve reading, structural analysis, and comprehensive interpretation and discussion. Findings Although both......Aims and objectives To investigate patients' lived experiences of exercise-based cardiac rehabilitation. Background Exercise-based cardiac rehabilitation is used to enable patients with cardiac problems to move forward to lead satisfying lives. However, knowledge of patients' concerns while...... it requires specific care. Recognising this anxiety also highlights how participating in the programme can be very demanding, which can help us understand aspects of adherence problems. Of greatest importance is that exercise-based cardiac rehabilitation enables patients to find a new foothold, which...

  2. Exercise-related cardiac arrest in cardiac rehabilitation - The ...

    African Journals Online (AJOL)

    Prescribed physical activity plays a major role in the rehabilitation of patients with coronary artery disease, and as with any other form of treatment its benefits must be weighed against its possible risks. This study attempted to establish the safety of cardiac rehabilitation as a medical intervention at the Johannesburg Cardiac ...

  3. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Eren, B.; Turkmen, N.; Fedakar, R.; Cetin, V.

    2010-01-01

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  4. CSI cardiac prevent 2015

    Directory of Open Access Journals (Sweden)

    S Ramakrishnan

    2015-01-01

    Full Text Available The CSI Cardiac Prevent 2015 was held at Hotel Taj Palace, New Delhi, on September 25-27, 2015. The major challenge was to create interest among cardiologists and physicians on preventive cardiology, a neglected area. The theme of the conference was "Innovations in Heart Disease Prevention.′′ This conference included "CSI at WHF Roadmap Workshop, Inauguration Ceremony, scientific program, plenary sessions, Nursing/Dietician track, Industry Exhibition, Social Events," Great India blood pressure Survey, and CSI Smart Heart App. A total of 848 delegates/faculties attended this conference against a total of 1140 people registered for the meeting.

  5. Hypertension and Cardiac Arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y H; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation......) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit of comprehensively reviewing the available evidence...

  6. Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

    Science.gov (United States)

    Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

    2002-11-15

    Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

  7. Cardiac Arrest: MedlinePlus Health Topic

    Science.gov (United States)

    ... Handouts Cardiac arrest (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Cardiac Arrest updates ... this? GO MEDICAL ENCYCLOPEDIA Cardiac arrest Related Health Topics Arrhythmia CPR Pacemakers and Implantable Defibrillators National Institutes ...

  8. Factors influencing the cardiac MIBG accumulation

    International Nuclear Information System (INIS)

    Takatsu, Hisato; Fujiwara, Hisayoshi

    1997-01-01

    Following factors possibly influencing the cardiac MIBG accumulation were examined mainly in mice. 1. The specific activity of the MIBG (meta-iodo-benzyl guanidine) on the neuronal and non-neuronal fractions. 2. Motor restriction stress on MIBG accumulation and washout. 3. Loading and restriction of sodium chloride on the accumulation and effect of suppression of renin-angiotensin system. 4. Examinations in Dahl rats. 125I- or 131I-MIBG was intravenously administered to mice at 74 kBq. At 30 min or 4 hr after administration, mice were sacrificed and their left ventricles were dissected out for measurement of radioactivity in a liquid scintillation counter. Salt-sensitive and -resistant Dahl rats were given with 37 MBq of 123I-MIBG and cardiac radioactivity was measured externally for calculation of washout. Factors examined were found highly correlated with the accumulation of MIBG and measurement of its washout was considered useful for evaluating sympathetic activity. (K.H.)

  9. Recovery of the cardiac frequency to the minute post effort as early indicator of myocardial ischemia

    International Nuclear Information System (INIS)

    Jimenez M, L.

    2007-01-01

    The objective of the work was to evaluate the recovery cardiac frequency like ischemia indicator, due to the immediate reactivity of the parasympathetic nervous system in the post-effort. It is obtained as conclusion that a slow descent of the cardiac frequency to the first minute of the post-effort is a predictor ischemia index when correlating it with the risk evaluated by cardiac SPECT with a high specificity; being this a marker of simple calculating in the daily practice. (Author)

  10. The paediatrician and cardiac auscultation.

    Science.gov (United States)

    Roy, Douglas L

    2003-11-01

    The cardiac auscultation (CA) skills of paediatric residents and office-based paediatricians have recently been shown to be suboptimal. CA is known to have a high degree of specificity and sensitivity, and is inexpensive. New teaching aids and availability of surrogate patient heart sounds and murmurs now allow most physicians to acquire CA skills. These teaching aids should be available in all medical schools and in all postgraduate paediatric training programs. While the relationship between musicality and CA skill has not been proven, the author assumes this relationship to be valid. Specific learning objectives in CA should be established. Recognizing that the current trend is away from clinical examinations, students frequently are unaware that a CA learning deficit exists. Therefore, students' CA skills should be evaluated before medical school graduation and at the Royal College of Physicians and Surgeons specialty examination. Students with amusia (inability to distinguish pitch of sound) should be identified and consideration should be given to directing them away from a clinical specialty in which CA is important. Further study is required in the physiology of learning of CA. Appropriate action by medical school and paediatric postgraduate program directors and the Royal College will effect a higher standard of patient care by increasing CA skills, resulting in a more financially efficient system - something everyone is trying to achieve in these times of increasing medical care costs.

  11. Cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Jacobson, M.S.; Ambudkar, I.S.; Young, E.P.; Naseem, S.M.; Heald, F.P.; Shamoo, A.E.

    1985-01-01

    The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca 2+ -Mg 2+ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life. (author)

  12. Cardiac chamber scintiscanning

    International Nuclear Information System (INIS)

    Goretzki, G.

    1981-01-01

    The two methods of cardiac chamber scintiscanning, i.e. 'first pass' and 'ECG-triggered' examinations, are explained and compared. Two tables indicate the most significant radiation doses of the applied radio tracers, i.e. 99m-Tc-pertechnetate and 99m-Tc-HSA, to which a patient is exposed. These averaged values are calculated from various data given in specialised literature. On the basis of data given in literature, an effective half-life of approximately 5 hours in the intravascular space was calculated for the erythrocytes labelled with technetium 99m. On this basis, the radiation doses for the patients due to 99m-Tc-labelled erythrocytes are estimated. The advantages and disadvantages of the two methods applied for cardiac chamber scintiscanning are put into contrast and compared with the advantages and disadvantages of the quantitative X-ray cardiography of the left heart. The still existing problems connected with the assessment of ECG-triggered images are discussed in detail. The author performed investigations of his own, which concerned the above-mentioned problems. (orig./MG) [de

  13. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  14. Lentiginosis, Deafness and Cardiac Abnormalities*

    African Journals Online (AJOL)

    1973-01-06

    Jan 6, 1973 ... His height. mass. intelligence and genitalia were normal. The aSSOCiatIOn between deafness and disturbance of cardiac conduction and between pigmented skin lesions and cardiac abnormalities, has been well described. Should. ~I patient present with multiple lentigines and/or familial sensineural ...

  15. Health Instruction Packages: Cardiac Anatomy.

    Science.gov (United States)

    Phillips, Gwen; And Others

    Text, illustrations, and exercises are utilized in these five learning modules to instruct nurses, students, and other health care professionals in cardiac anatomy and functions and in fundamental electrocardiographic techniques. The first module, "Cardiac Anatomy and Physiology: A Review" by Gwen Phillips, teaches the learner to draw…

  16. Neuromuscular diseases after cardiac transplantation

    NARCIS (Netherlands)

    Mateen, Farrah J.; van de Beek, Diederik; Kremers, Walter K.; Daly, Richard C.; Edwards, Brooks S.; McGregor, Christopher G. A.; Wijdicks, Eelco F. M.

    2009-01-01

    BACKGROUND: Cardiac transplantation is a therapeutic option in end-stage heart failure. Peripheral nervous system (PNS) disease is known to occur in cardiac transplant recipients but has not been fully characterized. METHODS: This retrospective cohort review reports the PNS-related concerns of 313

  17. Hypokalemia and sudden cardiac death

    DEFF Research Database (Denmark)

    Kjeldsen, Keld

    2010-01-01

    Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient...... of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis....

  18. Gender-specific independent and combined dose-response association of napping and night sleep duration with type 2 diabetes mellitus in rural Chinese adults: the RuralDiab study.

    Science.gov (United States)

    Liu, Ruihua; Li, Yuqian; Mao, Zhenxing; Liu, Xiaotian; Zhang, Haiqing; Yang, Kaili; Zhang, Honglei; Tu, Runqi; Qian, Xinling; Jiang, Jingjing; Bie, Ronghai; Wang, Chongjian

    2018-05-01

    The aim of this study was to explore the independent and combined dose-response association of napping and night sleep duration with type 2 diabetes mellitus (T2DM) among different genders in the rural Chinese population. For this research, a total of 19,257 participants were enrolled in the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study. Napping and night sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). Restricted cubic splines and logistic regression were used to estimate the relationship between napping and night sleep duration with T2DM. A linear dose-response relationship between napping duration and T2DM as well as a U-shaped relationship between night sleep duration and T2DM were found. Compared with those who reported no napping, participants who had a napping duration of ≥91 min were associated with a 19% increase in prevalence of T2DM. Adjusted odds ratios (ORs) (95% confidence intervals (CIs)) for T2DM were 1.48 (1.03, 2.14) and 1.50 (1.22, 1.85) for shorter (≤5 h) and longer (>9 h) night sleep duration compared with the referential group. Additionally, the combination of longer napping duration (≥91 min) and night sleep duration (>9 h) increased 104% (95% CI: 45%, 128%) prevalence for T2DM. These associations were not found in males but were evident in females. Longer napping duration and extreme night sleep duration increased the prevalence of T2DM. Meanwhile, longer napping and night sleep duration might be jointly associated with a higher prevalence of T2DM. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study.

    Science.gov (United States)

    Power, John A; Thompson, Diane V; Rayarao, Geetha; Doyle, Mark; Biederman, Robert W W

    2016-05-01

    Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis

  20. Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

    Science.gov (United States)

    Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

    2018-01-01

    Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

  1. Cardiac changes in anorexia nervosa.

    Science.gov (United States)

    Spaulding-Barclay, Michael A; Stern, Jessica; Mehler, Philip S

    2016-04-01

    Introduction Anorexia nervosa is an eating disorder, which is associated with many different medical complications as a result of the weight loss and malnutrition that characterise this illness. It has the highest mortality rate of any psychiatric disorder. A large portion of deaths are attributable to the cardiac abnormalities that ensue as a result of the malnutrition associated with anorexia nervosa. In this review, the cardiac complications of anorexia nervosa will be discussed. A comprehensive literature review on cardiac changes in anorexia nervosa was carried out. There are structural, functional, and rhythm-type changes that occur in patients with anorexia nervosa. These become progressively significant as ongoing weight loss occurs. Cardiac changes are inherent to anorexia nervosa and they become more life-threatening and serious as the anorexia nervosa becomes increasingly severe. Weight restoration and attention to these cardiac changes are crucial for a successful treatment outcome.

  2. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well....... An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  3. Depression, not anxiety, is independently associated with 5-year hospitalizations and mortality in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Hoogwegt, Madelein T; Hansen, Tina B

    2013-01-01

    The objective of the current study was to examine whether depression and anxiety are independently associated with 5-year cardiac-related hospitalizations and all-cause mortality in patients with ischemic heart disease (IHD)....

  4. Independent technical review, handbook

    International Nuclear Information System (INIS)

    1994-02-01

    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project

  5. Independent technical review, handbook

    Energy Technology Data Exchange (ETDEWEB)

    1994-02-01

    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.

  6. Living cardiac patch: the elixir for cardiac regeneration.

    Science.gov (United States)

    Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2012-12-01

    A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

  7. Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hye-Joung; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae-Hee; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan [University of Ulsan College of Medicine, Department of Cardiology and Heart Institute, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won [University of Ulsan College of Medicine, Department of Cardiothoracic surgery, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of)

    2015-06-01

    We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. (orig.)

  8. Incorporating Comorbidity Within Risk Adjustment for UK Pediatric Cardiac Surgery.

    Science.gov (United States)

    Brown, Katherine L; Rogers, Libby; Barron, David J; Tsang, Victor; Anderson, David; Tibby, Shane; Witter, Thomas; Stickley, John; Crowe, Sonya; English, Kate; Franklin, Rodney C; Pagel, Christina

    2017-07-01

    When considering early survival rates after pediatric cardiac surgery it is essential to adjust for risk linked to case complexity. An important but previously less well understood component of case mix complexity is comorbidity. The National Congenital Heart Disease Audit data representing all pediatric cardiac surgery procedures undertaken in the United Kingdom and Ireland between 2009 and 2014 was used to develop and test groupings for comorbidity and additional non-procedure-based risk factors within a risk adjustment model for 30-day mortality. A mixture of expert consensus based opinion and empiric statistical analyses were used to define and test the new comorbidity groups. The study dataset consisted of 21,838 pediatric cardiac surgical procedure episodes in 18,834 patients with 539 deaths (raw 30-day mortality rate, 2.5%). In addition to surgical procedure type, primary cardiac diagnosis, univentricular status, age, weight, procedure type (bypass, nonbypass, or hybrid), and era, the new risk factor groups of non-Down congenital anomalies, acquired comorbidities, increased severity of illness indicators (eg, preoperative mechanical ventilation or circulatory support) and additional cardiac risk factors (eg, heart muscle conditions and raised pulmonary arterial pressure) all independently increased the risk of operative mortality. In an era of low mortality rates across a wide range of operations, non-procedure-based risk factors form a vital element of risk adjustment and their presence leads to wide variations in the predicted risk of a given operation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Yang, Chunbo; Al-Aama, Jumana; Stojkovic, Miodrag; Keavney, Bernard; Trafford, Andrew; Lako, Majlinda; Armstrong, Lyle

    2015-09-01

    Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling. © AlphaMed Press.

  10. The economics of cardiac biomarker testing in suspected myocardial infarction.

    Science.gov (United States)

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. The definition of exertion-related cardiac events.

    Science.gov (United States)

    Rai, M; Thompson, P D

    2011-02-01

    Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

  12. Pneumothorax in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard

    2012-01-01

    AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort.METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish...... age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary...

  13. Sudden Cardiac Death

    DEFF Research Database (Denmark)

    Risgaard, Bjarke; Winkel, Bo Gregers; Jabbari, Reza

    2017-01-01

    Objectives This study sought to describe the use of pharmacotherapy in a nationwide cohort of young patients with sudden cardiac death (SCD). Background Several drugs have been associated with an increased risk of SCD and sudden arrhythmic death syndrome (SADS). It remains unclear how...... pharmacotherapy may contribute to the overall burden of SCD in the general population. Methods This was a nationwide study that included all deaths that occurred between 2000 and 2009 and between 2007 and 2009 in people age 1 to 35 years and 36 to 49 years, respectively. Two physicians identified all SCDs through...... review of death certificates. Autopsy reports were collected. Pharmacotherapy prescribed within 90 days before SCD was identified in the Danish Registry of Medicinal Product Statistics. Results We identified 1,363 SCDs; median age was 38 years (interquartile range: 29 to 45 years), and 72% (n = 975) were men...

  14. Cardiac Rehabilitation Series: Canada

    Science.gov (United States)

    Grace, Sherry L.; Bennett, Stephanie; Ardern, Chris I.; Clark, Alexander

    2015-01-01

    Cardiovascular disease is among the leading causes of mortality and morbidity in Canada. Cardiac rehabilitation (CR) has a long robust history here, and there are established clinical practice guidelines. While the effectiveness of CR in the Canadian context is clear, only 34% of eligible patients participate, and strategies to increase access for under-represented groups (e.g., women, ethnic minority groups) are not yet universally applied. Identified CR barriers include lack of referral and physician recommendation, travel and distance, and low perceived need. Indeed there is now a national policy position recommending systematic inpatient referral to CR in Canada. Recent development of 30 CR Quality Indicators and the burgeoning national CR registry will enable further measurement and improvement of the quality of CR care in Canada. Finally, the Canadian Association of CR is one of the founding members of the International Council of Cardiovascular Prevention and Rehabilitation, to promote CR globally. PMID:24607018

  15. Hypertension and cardiac arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y.H.; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both...... supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia......, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society...

  16. Model-Independent Diffs

    DEFF Research Database (Denmark)

    Könemann, Patrick

    just contain a list of strings, one for each line, whereas the structure of models is defined by their meta models. There are tools available which are able to compute the diff between two models, e.g. RSA or EMF Compare. However, their diff is not model-independent, i.e. it refers to the models...

  17. All Those Independent Variables.

    Science.gov (United States)

    Meacham, Merle L.

    This paper presents a case study of a sixth grade remedial math class which illustrates the thesis that only the "experimental attitude," not the "experimental method," is appropriate in the classroom. The thesis is based on the fact that too many independent variables exist in a classroom situation to allow precise measurement. The case study…

  18. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...

  19. Independent safety organization

    International Nuclear Information System (INIS)

    Kato, W.Y.; Weinstock, E.V.; Carew, J.F.; Cerbone, R.J.; Guppy, J.G.; Hall, R.E.; Taylor, J.H.

    1985-01-01

    Brookhaven National Laboratory has conducted a study on the need and feasibility of an independent organization to investigate significant safety events for the Office for Analysis and Evaluation of Operational Data, USNRC. The study consists of three parts: the need for an independent organization to investigate significant safety events, alternative organizations to conduct investigations, and legislative requirements. The determination of need was investigated by reviewing current NRC investigation practices, comparing aviation and nuclear industry practices, and interviewing a spectrum of representatives from the nuclear industry, the regulatory agency, and the public sector. The advantages and disadvantages of alternative independent organizations were studied, namely, an Office of Nuclear Safety headed by a director reporting to the Executive Director for Operations (EDO) of NRC; an Office of Nuclear Safety headed by a director reporting to the NRC Commissioners; a multi-member NTSB-type Nuclear Safety Board independent of the NRC. The costs associated with operating a Nuclear Safety Board were also included in the study. The legislative requirements, both new authority and changes to the existing NRC legislative authority, were studied. 134 references

  20. Is it time for cardiac innervation imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, J. [Turku Univ., Turku (Finland) Turku PET Center; Sipola, P. [Kuopio Univ., Kuopio (Finland)

    2005-03-01

    The autonomic nervous system plays an important role in the regulation of cardiac function and the regional distribution of cardiac nerve terminals can be visualized using scintigraphic techniques. The most commonly used tracer is iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts is used as an index of tracer uptake, and regional distribution is also assessed from tomographic images. The rate of clearance of the tracer can also be measured and indicates the function of the adrenergic system. Innervation imaging has been applied in patients with susceptibility to arrythmias, coronary artery disease, hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity. Abnormal adrenergic innervation or function appear to exist in many pathophysiological conditions indicating that sympathetic neurons are very susceptible to damage. Abnormal findings in innervation imaging also appear to have significant prognostic value especially in patients with cardiomyopathy. Recently, it has also been shown that innervation imaging can monitor drug-induced changes in cardiac adrenergic activity. Although innervation imaging holds great promise for clinical use, the method has not received wider clinical acceptance. Larger randomized studies are required to confirm the value of innervation imaging in various specific indications.

  1. Illicit drugs and cardiac arrhythmias in athletes.

    Science.gov (United States)

    Furlanello, Francesco; Serdoz, Laura Vitali; Cappato, Riccardo; De Ambroggi, Luigi

    2007-08-01

    The current management of athletes with cardiac arrhythmias has become complicated by the widespread use of illicit drugs, which can be arrhythmogenic. The World Anti-Doping Agency annually updates a list of prohibited substances and methods banned by the International Olympic Committee that includes different classes of substances namely, anabolic androgenic steroids, hormones and related substances, beta2-agonists, diuretics, stimulants, narcotics, cannabinoids, glucocorticosteroids, alcohol, beta-blockers and others. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular) that can even be lethal and which are frequently sport activity related. A large use of illicit drugs has been documented in competitive athletes, but the arrhythmogenic effect of specific substances is not precisely known. Precipitation of cardiac arrhythmias, particularly in the presence of a latent electrophysiologic substrate including some inherited cardiomyopathies, at risk of sudden death or due to long-term consumption of the substances, should raise the suspicion that illicit drugs may be a possible cause and lead cardiologists to investigate carefully this relationship and appropriately prevent the clinical consequences.

  2. Lysophosphatidylcholine (LPC) metabolism and cardiac arrhythmias

    International Nuclear Information System (INIS)

    Giffin, D.M.; Man, R.Y.K.; Arthur, G.; Choy, P.C.

    1986-01-01

    The effect of LPC in the production of cardiac arrhythmias in isolated mammalian hearts has been well-documented. Cardiac arrhythmias are initiated by the accumulation of the lysolipid in the cardiac membrane. When isolated rat hearts were perfused in 10 μM LPC for 10 min, severe arrhythmias were observed in all experiments. In isolated guinea pig hearts that were perfused under identical conditions, the development of severe arrhythmias was never observed, and mild arrhythmias were produced in less than 50% of the hearts used. When the hearts of both species were perfused with [ 14 C-palmitate]-LPC, the labellings found in the microsomal fractions (expressed in mg protein) were similar. However, a higher amount of labelled LPC (2-fold) was found in rat heart microsomes, whereas a higher amount of labelled fatty acid was located in the guinea pig heart microsomes. Determination of lysophospholipase activities in these microsomal fractions revealed that the specific activity of the enzyme was much higher in the guinea pig heart than the rat heart. The authors conclude that the differential effect of LPC-induced arrhythmias between the rat and guinea pig heart may be a direct result of the lysophospholipase activities in these hearts. The ability to catabolize LPC more rapidly in the guinea pig heart may decrease the accumulation of LPC in the membrane, and hence, reduce the production of arrhythmias

  3. Skills of primary healthcare physicians in paediatric cardiac auscultation.

    Science.gov (United States)

    Germanakis, Ioannis; Petridou, Eleni T H; Varlamis, George; Matsoukis, Ioannis L; Papadopoulou-Legbelou, Kiriaki; Kalmanti, Maria

    2013-02-01

    To evaluate the performance of primary healthcare physicians in paediatric cardiac auscultation and the impact of a multimedia-based teaching intervention. A total of 106 primary healthcare physicians (77 paediatricians, 14 general practitioners and 15 medical graduates) attended four paediatric cardiac auscultation teaching courses based on virtual patients' presentation (digital phonocardiography). Their auscultatory performance was documented at the beginning of each course and at the end of two of the courses. Participants initially detected 73% of abnormal murmurs and 17% of additional sounds, while 22% of innocent murmurs were interpreted as abnormal. Overall cardiac auscultation performance, assessed by a combined auscultation score, was low and independent of training level (graduates: 39.5/trainees: 42.8/board certified: 42.6, p = 0.89) or specialty (paediatricians: 42.7/general practitioners: 43.1, p = 0.89). Multimedia-based teaching was associated with a significant improvement in abnormal murmur (92.5%) and additional sound (40%) detection (p auscultation, independent of training level or specialty, still leave potential for improvement. Multimedia-based teaching interventions represent an effective means of improving paediatric cardiac auscultatory skills. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

  4. Inhibition of cardiac sodium currents by toluene exposure

    Science.gov (United States)

    Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

    2003-01-01

    Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

  5. Mediastinitis after cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Noedir A. G. Stolf

    2000-05-01

    Full Text Available OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6% of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3±10.0 years and 10 (83.3% patients were males. Seven (58.3% patients showed sternal stability on palpation, 4 (33.3% patients had pleural empyema, and 2 (16.7% patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7% patients. Staphylococcus epidermidis was identified in 2 (16.7% patients, Enterococcus faecalis in 1 (8.3% patient, and the cause of mediastinitis could not be determined in 1 (8.3% patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7% patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3% patient. Out of this series, 5 (41.7% patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3% patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

  6. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-08-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid /sup 14/C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

  7. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    International Nuclear Information System (INIS)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-01-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14 C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides. (orig.)

  8. Real-time MRI guidance of cardiac interventions.

    Science.gov (United States)

    Campbell-Washburn, Adrienne E; Tavallaei, Mohammad A; Pop, Mihaela; Grant, Elena K; Chubb, Henry; Rhode, Kawal; Wright, Graham A

    2017-10-01

    Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow. 1 Technical Efficacy: Stage 5 J

  9. Cardiac function in acute hypothyroidism

    International Nuclear Information System (INIS)

    Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

    1985-01-01

    It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

  10. Trends in Cardiac Pacemaker Batteries

    Directory of Open Access Journals (Sweden)

    Venkateswara Sarma Mallela

    2004-10-01

    Full Text Available Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future.

  11. Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

    Science.gov (United States)

    Govindsamy, Annelene; Naidoo, Strinivasen

    2018-01-01

    Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology. PMID:29484207

  12. Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

    2004-01-01

    Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

  13. Cardiac cone-beam CT

    International Nuclear Information System (INIS)

    Manzke, Robert

    2005-01-01

    This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net

  14. Acupuncture therapy related cardiac injury.

    Science.gov (United States)

    Li, Xue-feng; Wang, Xian

    2013-12-01

    Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

  15. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Fac. de Medicina. Instituto do Coracao. Servico de Medicina Nuclear e Imagem Molecular

    2008-07-01

    . Cardiac amyloidosis is often under diagnosed due to unspecific and varied signs and symptoms. The diagnosis is confirmed by endomyocardial biopsy, an invasive procedure with inherent risks to this technique. Pyrophosphate-{sup 99m}Tc scintigraphy is a simple, non-invasive, low cost, with good sensitivity method for detection of cardiac amyloidosis. The scintigraphy pattern observed in cardiac amyloidosis cases is abnormal diffuse tracer uptake in both heart ventricles. Planar and/or tomographic imaging may be performed. It is considered a highly sensitive test, with low rates of false-negative results despite the existing little literature. Therefore the scintigraphy can be useful to select patients for biopsy. Conclusion: Scintigraphy can be of great assistance in cardiac amyloidosis, despite its low specificity. Due to its high sensibility, it can be a useful test to early discriminate patients who should undergo biopsy, allowing treatment optimization. (author)

  16. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    International Nuclear Information System (INIS)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C.

    2008-01-01

    amyloidosis is often under diagnosed due to unspecific and varied signs and symptoms. The diagnosis is confirmed by endomyocardial biopsy, an invasive procedure with inherent risks to this technique. Pyrophosphate- 99m Tc scintigraphy is a simple, non-invasive, low cost, with good sensitivity method for detection of cardiac amyloidosis. The scintigraphy pattern observed in cardiac amyloidosis cases is abnormal diffuse tracer uptake in both heart ventricles. Planar and/or tomographic imaging may be performed. It is considered a highly sensitive test, with low rates of false-negative results despite the existing little literature. Therefore the scintigraphy can be useful to select patients for biopsy. Conclusion: Scintigraphy can be of great assistance in cardiac amyloidosis, despite its low specificity. Due to its high sensibility, it can be a useful test to early discriminate patients who should undergo biopsy, allowing treatment optimization. (author)

  17. Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP quantitative trait loci (QTLs that co-localized with navigational performance (Nav-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5, diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5, and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5 compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05. The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  18. Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

    Science.gov (United States)

    Herrera, Victoria L; Pasion, Khristine A; Tan, Glaiza A; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2013-01-01

    Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5)), diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5)), and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5)) compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05). The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  19. NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

    Science.gov (United States)

    Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

    2012-12-01

    To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Regulation of cardiac microRNAs by serum response factor

    Directory of Open Access Journals (Sweden)

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  1. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2005-01-01

    This volume is the first of two volumes containing the revised and completed notes lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald during the period March 9 – 22, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present first volume contains the following lectures: "Lévy Processes in Euclidean Spaces and Groups" by David Applebaum, "Locally Compact Quantum Groups" by Johan Kustermans, "Quantum Stochastic Analysis" by J. Martin Lindsay, and "Dilations, Cocycles and Product Systems" by B.V. Rajarama Bhat.

  2. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2006-01-01

    This is the second of two volumes containing the revised and completed notes of lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald in March, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present second volume contains the following lectures: "Random Walks on Finite Quantum Groups" by Uwe Franz and Rolf Gohm, "Quantum Markov Processes and Applications in Physics" by Burkhard Kümmerer, Classical and Free Infinite Divisibility and Lévy Processes" by Ole E. Barndorff-Nielsen, Steen Thorbjornsen, and "Lévy Processes on Quantum Groups and Dual Groups" by Uwe Franz.

  3. Independent random sampling methods

    CERN Document Server

    Martino, Luca; Míguez, Joaquín

    2018-01-01

    This book systematically addresses the design and analysis of efficient techniques for independent random sampling. Both general-purpose approaches, which can be used to generate samples from arbitrary probability distributions, and tailored techniques, designed to efficiently address common real-world practical problems, are introduced and discussed in detail. In turn, the monograph presents fundamental results and methodologies in the field, elaborating and developing them into the latest techniques. The theory and methods are illustrated with a varied collection of examples, which are discussed in detail in the text and supplemented with ready-to-run computer code. The main problem addressed in the book is how to generate independent random samples from an arbitrary probability distribution with the weakest possible constraints or assumptions in a form suitable for practical implementation. The authors review the fundamental results and methods in the field, address the latest methods, and emphasize the li...

  4. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1991-01-01

    Recent industry trends indicate that the smaller US independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. It is usually accepted that foreign finding costs per barrel are substantially lower than domestic because of the large reserve potential of international plays. To get involved overseas requires, however, an adaptation to different cultural, financial, legal, operational, and political conditions. Generally foreign exploration proceeds at a slower pace than domestic because concessions are granted by the government, or are explored in partnership with the national oil company. First, a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company, must be prepared; it must be followed by an ongoing evaluation of quality prospects in various sedimentary basins, and a careful planning and conduct of the operations. To successfully explore overseas also requires the presence on the team of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work, having had a considerable amount of onsite experience in various geographical and climatic environments. Independents that are best suited for foreign expansion are those that have been financially successful domestically, and have a good discovery track record. When properly approached foreign exploration is well within the reach of smaller US independents and presents essentially no greater risk than domestic exploration; the reward, however, can be much larger and can catapult the company into the big leagues

  5. International exploration by independent

    International Nuclear Information System (INIS)

    Bertragne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. Foreign finding costs per barrel usually are accepted to be substantially lower than domestic costs because of the large reserve potential of international plays. To get involved in overseas exploration, however, requires the explorationist to adapt to different cultural, financial, legal, operational, and political conditions. Generally, foreign exploration proceeds at a slower pace than domestic exploration because concessions are granted by a country's government, or are explored in partnership with a national oil company. First, the explorationist must prepare a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company; next, is an ongoing evaluation of quality prospects in various sedimentary basins, and careful planning and conduct of the operations. To successfully explore overseas also requires the presence of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work. Ideally, these team members will have had a considerable amount of on-site experience in various countries and climates. Independents best suited for foreign expansion are those who have been financially successful in domestic exploration. When properly approached, foreign exploration is well within the reach of smaller U.S. independents, and presents essentially no greater risk than domestic exploration; however, the reward can be much larger and can catapult the company into the 'big leagues.'

  6. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. The problems of communications and logistics caused by different cultures and by geographic distances must be carefully evaluated. A mid-term to long-term strategy tailored to the goals and the financial capabilities of the company should be prepared and followed by a careful planning of the operations. This paper addresses some aspects of foreign exploration that should be considered before an independent venture into the foreign field. It also provides some guidelines for conducting successful overseas operations. When properly assessed, foreign exploration is well within the reach of smaller U.S. independents and presents no greater risk than domestic exploration; the rewards, however, can be much larger. Furthermore, the Oil and Gas Journal surveys of the 300 largest U.S. petroleum companies show that companies with a consistent foreign exploration policy have fared better financially during difficult times

  7. Limiting excessive postoperative blood transfusion after cardiac procedures. A review.

    OpenAIRE

    Ferraris, V A; Ferraris, S P

    1995-01-01

    Analysis of blood product use after cardiac operations reveals that a few patients ( 80%). The risk factors that predispose a minority of patients to excessive blood use include patient-related factors, transfusion practices, drug-related causes, and procedure-related factors. Multivariate studies suggest that patient age and red blood cell volume are independent patient-related variables that predict excessive blood product transfusion aft...

  8. Cardiac damage after treatment of childhood cancer: A long-term follow-up

    International Nuclear Information System (INIS)

    Velensek, Veronika; Mazic, Uros; Krzisnik, Ciril; Demšar, Damjan; Jazbec, Janez; Jereb, Berta

    2008-01-01

    With improved childhood cancer cure rate, long term sequelae are becoming an important factor of quality of life. Signs of cardiovascular disease are frequently found in long term survivors of cancer. Cardiac damage may be related to irradiation and chemotherapy. We have evaluated simultaneous influence of a series of independent variables on the late cardiac damage in childhood cancer survivors in Slovenia and identified groups at the highest risk. 211 long-term survivors of different childhood cancers, at least five years after treatment were included in the study. The evaluation included history, physical examination, electrocardiograpy, exercise testing and echocardiograpy. For analysis of risk factors, beside univariate analysis, multivariate classification tree analysis statistical method was used. Patients treated latest, from 1989–98 are at highest risk for any injury to the heart (73%). Among those treated earlier are at the highest risk those with Hodgkin's disease treated with irradiation above 30 Gy and those treated for sarcoma. Among specific forms of injury, patients treated with radiation to the heart area are at highest risk of injury to the valves. Patients treated with large doses of anthracyclines or concomitantly with anthracyclines and alkylating agents are at highest risk of systolic function defect and enlarged heart chambers. Those treated with anthracyclines are at highest risk of diastolic function defect. The time period of the patient's treatment is emerged as an important risk factor for injury of the heart

  9. Applicability of myocardial perfusion scintigraphy in the evaluation of cardiac synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Christiane Cigagna Wiefels; Nascimento, Erivelton Alessandro do; Dias, Fernanda Baptista Ribeiro; Ribeiro, Mario Luiz; Wanderley, Annelise Passos Bispo; Batista, Layanara Albino; Nunes, Thais Helena Peixoto; Mesquita, Claudio Tinoco, E-mail: chriswreis@gmail.com [Universidade Federal Fluminense (UFF), Niterói, RJ (Brazil). Hospital Universitário Antônio Pedro

    2017-07-15

    To systematically assess the literature on the applicability of myocardial perfusion scintigraphy with phase analysis in the investigation of cardiac dyssynchrony and in the selection of patients for cardiac resynchronization therapy (CRT), manuscripts published on the PubMed database over the past five years have been reviewed. The following MeSH terms were used: heart failure, left ventricular, dyssynchrony, gated-SPECT, phase analysis and resynchronization therapy. Altogether, 99 manuscripts were included for discussion. Speckle-tracking echocardiography is still widely used in the evaluation of dyssynchrony, but the advent of myocardial perfusion scintigraphy with the phase analysis technique has been gaining ground, as besides being operator independent, it can evaluate myocardial viability in the same test. Its use became more widespread in patients with left bundle branch block, with recommendation of CRT. Phase analysis also allows evaluating, in a highly reproducible way, the last ventricular segment to contract, hence allowing the best positioning of the CRT electrode. Knowing that the presence, location and extent of fibrosis in the left ventricle, associated with dyssynchrony are determinants of response to resynchronization therapy, GATED- SPECT can provide this information in a single test and in a reproducible and accurate way. Phase histogram offers several parameters that provide greater sensitivity and specificity to the method. It seems that the technique is able to add value both in the selection and in the evaluation of response of patients eligible to CRT. Further studies are being conducted to demonstrate its clinical applicability. (author)

  10. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery.

    Science.gov (United States)

    Van der Linden, P; De Hert, S; Daper, A; Trenchant, A; Jacobs, D; De Boelpaepe, C; Kimbimbi, P; Defrance, P; Simoens, G

    2001-10-01

    Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. This prospective non randomized observational study evaluated the effects of a standardized multidisciplinary transfusion strategy on allogeneic blood products exposure in patients undergoing non-emergent cardiac surgery. The developed strategy involved a standardized blood conservation program and a multidisciplinary allogeneic blood transfusion policy based mainly on clinical judgement, not only on a specific hemoglobin concentration. Data obtained in a first group including patients operated from September 1997 to August 1998 (Group pre: n=321), when the transfusion strategy was progressively developed, were compared to those obtained in a second group, including patients operated from September 1998 to August 1999 (Group post: n=315) when the transfusion strategy was applied uniformly. Patient populations and surgical procedures were similar. Patients in Group post underwent acute normovolemic hemodilution more frequently, had a higher core temperature at arrival in the intensive care unit and presented lower postoperative blood losses at day one. Three hundred forty units of packed red blood cells were transfused in 33% of the patients in Group pre whereas 161 units were transfused in 18% of the patients in Group post (P <0.001). Pre- and postoperative hemoglobin concentrations, mortality and morbidity were not different among groups. Development of a standardized multidisciplinary transfusion strategy markedly reduced the exposure of cardiac surgery patients to allogeneic blood.

  11. The Johannesburg cardiac rehabilitation programme

    African Journals Online (AJOL)

    1991-02-16

    Feb 16, 1991 ... sion 72,9% of patients were smokers, 26,3% had hypertension and 34,3% had ... Cardiac rehabilitation, including supervised exercise therapy, has become a .... sions on risk factor modification, diet, aspects of heart disease,.

  12. Recent developments in cardiac pacing.

    Science.gov (United States)

    Rodak, D J

    1995-10-01

    Indications for cardiac pacing continue to expand. Pacing to improve functional capacity, which is now common, relies on careful patient selection and technical improvements, such as complex software algorithms and diagnostic capabilities.

  13. Robotic Applications in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alan P. Kypson

    2008-11-01

    Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

  14. Optimal Technique in Cardiac Anesthesia Recovery

    OpenAIRE

    Svircevic, V.

    2014-01-01

    The aim of this thesis is to evaluate fast-track cardiac anesthesia techniques and investigate their impact on postoperative mortality, morbidity and quality of life. The following topics will be discussed in the thesis. (1.) Is fast track cardiac anesthesia a safe technique for cardiac surgery? (2.) Does thoracic epidural anesthesia have an effect on mortality and morbidity after cardiac surgery? (3.) Does thoracic epidural anesthesia have an effect on quality of life after cardiac surgery? ...

  15. Normal values of left ventricularmass and cardiac chamber volumes assessed by 320-detector computed tomography angiography in the Copenhagen General Population Study

    DEFF Research Database (Denmark)

    Fuchs, Andreas; Mejdahl, Mads Rams; Kühl, J Tobias

    2016-01-01

    Aims Normal values of left ventricular mass (LVM) and cardiac chamber sizes are prerequisites for the diagnosis of individuals with heart disease. LVM and cardiac chamber sizes may be recorded during cardiac computed tomography angiography (CCTA), and thus modality specific normal values are need...

  16. Cardiac effects of noncardiac neoplasms

    International Nuclear Information System (INIS)

    Schoen, F.J.; Berger, B.M.; Guerina, N.G.

    1984-01-01

    Clinically significant cardiovascular abnormalities may occur as secondary manifestations of noncardiac neoplasms. The principal cardiac effects of noncardiac tumors include the direct results of metastases to the heart or lungs, the indirect effects of circulating tumor products (causing nonbacterial thrombotic endocarditis, myeloma-associated amyloidosis, pheochromocytoma-associated cardiac hypertrophy and myofibrillar degeneration, and carcinoid heart disease), and the undesired cardiotoxicities of chemotherapy and radiotherapy. 89 references

  17. The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    Hess, Paul L; Al-Khalidi, Hussein R; Friedman, Daniel J; Mulder, Hillary; Kucharska-Newton, Anna; Rosamond, Wayne R; Lopes, Renato D; Gersh, Bernard J; Mark, Daniel B; Curtis, Lesley H; Post, Wendy S; Prineas, Ronald J; Sotoodehnia, Nona; Al-Khatib, Sana M

    2017-08-23

    Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987-2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow-up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37-2.12, P metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19-1.44, P metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Non-cardiac findings on coronary computed tomography and magnetic resonance imaging

    International Nuclear Information System (INIS)

    Dewey, Marc; Schnapauff, Dirk; Teige, Florian; Hamm, Bernd

    2007-01-01

    Both multislice computed tomography (CT) and magnetic resonance imaging (MRI) are emerging as methods to detect coronary artery stenoses and assess cardiac function and morphology. Non-cardiac structures are also amenable to assessment by these non-invasive tests. We investigated the rate of significant and insignificant non-cardiac findings using CT and MRI. A total of 108 consecutive patients suspected of having coronary artery disease and without contraindications to CT and MRI were included in this study. Significant non-cardiac findings were defined as findings that required additional clinical or radiological follow-up. CT and MR images were read independently in a blinded fashion. CT yielded five significant non-cardiac findings in five patients (5%). These included a pulmonary embolism, large pleural effusions, sarcoid, a large hiatal hernia, and a pulmonary nodule (>1.0 cm). Two of these significant non-cardiac findings were also seen on MRI (pleural effusions and sarcoid, 2%). Insignificant non-cardiac findings were more frequent than significant findings on both CT (n = 11, 10%) and MRI (n = 7, 6%). Incidental non-cardiac findings on CT and MRI of the coronary arteries are common, which is why images should be analyzed by radiologists to ensure that important findings are not missed and unnecessary follow-up examinations are avoided. (orig.)

  19. Non-cardiac findings on coronary computed tomography and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc; Schnapauff, Dirk; Teige, Florian; Hamm, Bernd [Charite-Universitaetsmedizin Berlin, Humboldt-Universitaet zu Berlin, Department of Radiology, Chariteplatz 1, P.O. Box 10098, Berlin (Germany)

    2007-08-15

    Both multislice computed tomography (CT) and magnetic resonance imaging (MRI) are emerging as methods to detect coronary artery stenoses and assess cardiac function and morphology. Non-cardiac structures are also amenable to assessment by these non-invasive tests. We investigated the rate of significant and insignificant non-cardiac findings using CT and MRI. A total of 108 consecutive patients suspected of having coronary artery disease and without contraindications to CT and MRI were included in this study. Significant non-cardiac findings were defined as findings that required additional clinical or radiological follow-up. CT and MR images were read independently in a blinded fashion. CT yielded five significant non-cardiac findings in five patients (5%). These included a pulmonary embolism, large pleural effusions, sarcoid, a large hiatal hernia, and a pulmonary nodule (>1.0 cm). Two of these significant non-cardiac findings were also seen on MRI (pleural effusions and sarcoid, 2%). Insignificant non-cardiac findings were more frequent than significant findings on both CT (n = 11, 10%) and MRI (n = 7, 6%). Incidental non-cardiac findings on CT and MRI of the coronary arteries are common, which is why images should be analyzed by radiologists to ensure that important findings are not missed and unnecessary follow-up examinations are avoided. (orig.)

  20. Cardiac imaging. A multimodality approach

    Energy Technology Data Exchange (ETDEWEB)

    Thelen, Manfred [Johannes Gutenberg University Hospital, Mainz (Germany); Erbel, Raimund [University Hospital Essen (Germany). Dept. of Cardiology; Kreitner, Karl-Friedrich [Johannes Gutenberg University Hospital, Mainz (Germany). Clinic and Polyclinic for Diagnostic and Interventional Radiology; Barkhausen, Joerg (eds.) [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiology and Nuclear Medicine

    2009-07-01

    An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

  1. Cardiac imaging. A multimodality approach

    International Nuclear Information System (INIS)

    Thelen, Manfred; Erbel, Raimund; Kreitner, Karl-Friedrich; Barkhausen, Joerg

    2009-01-01

    An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

  2. Churg-Strauss Syndrome with Cardiac Involvement: A Case Report with CT and MRI Findings

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seong Joo; Cho, Young Jun; Kim, Keum; Hwang, Cheol Mok; Kim, Dae Ho [Dept. of Radiology, Konyang University College of Medicine, Daegu (Korea, Republic of); Choi, Eu Gene [Dept. of Internal Medicine, Konyang University College of Medicine, Daegu (Korea, Republic of)

    2012-02-15

    This is a case report of Churg-Strauss Syndrome (CSS) associated with cardiac involvement which is demonstrated in chest CT and cardiac MRI (CMR) without specific cardiac symptoms. A 32-year-old woman had a 3-year history of bronchial asthma, chronic sinusitis, and otitis media. The patient had various typical findings of CSS. The patient had no specific cardiac symptoms or signs such as chest pain, palpitations, syncope, or murmur, but she had diffuse low attenuation lesions in the inner wall of the left ventricle (LV) in contrast-enhanced CT. This corresponded to the area of subendocardial hyperenhancement in delayed contrast-enhanced CMR images. She was treated with steroids for 2 months. Follow-up delayed contrast-enhanced CMR of the LV showed a decrease in the size of the subendocardial enhancement area, and she had no symptoms. Therefore, the radiologist and clinician both should pay careful attention to observe possible cardiac involvement in case of CSS.

  3. Churg-Strauss Syndrome with Cardiac Involvement: A Case Report with CT and MRI Findings

    International Nuclear Information System (INIS)

    Lim, Seong Joo; Cho, Young Jun; Kim, Keum; Hwang, Cheol Mok; Kim, Dae Ho; Choi, Eu Gene

    2012-01-01

    This is a case report of Churg-Strauss Syndrome (CSS) associated with cardiac involvement which is demonstrated in chest CT and cardiac MRI (CMR) without specific cardiac symptoms. A 32-year-old woman had a 3-year history of bronchial asthma, chronic sinusitis, and otitis media. The patient had various typical findings of CSS. The patient had no specific cardiac symptoms or signs such as chest pain, palpitations, syncope, or murmur, but she had diffuse low attenuation lesions in the inner wall of the left ventricle (LV) in contrast-enhanced CT. This corresponded to the area of subendocardial hyperenhancement in delayed contrast-enhanced CMR images. She was treated with steroids for 2 months. Follow-up delayed contrast-enhanced CMR of the LV showed a decrease in the size of the subendocardial enhancement area, and she had no symptoms. Therefore, the radiologist and clinician both should pay careful attention to observe possible cardiac involvement in case of CSS.

  4. Cardiac output during exercise

    DEFF Research Database (Denmark)

    Siebenmann, C; Rasmussen, P.; Sørensen, H.

    2015-01-01

    Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from...... the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2  = 12%). While all four methods reported...... a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0...

  5. Recurrent late cardiac tamponade following cardiac surgery : a deceiving and potentially lethal complication

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Meuzelaar, Jacobus J.

    2010-01-01

    Background - Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. Case report - We present a case of recurrent cardiac tamponade following valve surgery. At first presentation,

  6. Recurrent late cardiac tamponade following cardiac surgery: a deceiving and potentially lethal complication

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Meuzelaar, Jacobus J.

    2010-01-01

    Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. We present a case of recurrent cardiac tamponade following valve surgery. At first presentation, diagnosis was delayed because of

  7. Cardiac function and cognition in older community-dwelling cardiac patients

    NARCIS (Netherlands)

    Eggermont, Laura H.P.; Aly, Mohamed F.A.; Vuijk, Pieter J.; de Boer, Karin; Kamp, Otto; van Rossum, Albert C.; Scherder, Erik J.A.

    2017-01-01

    Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older

  8. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    permanent damage to the heart, we note that the individuals showing the highest hs-TNT levels are not the same as those showing the highest NT-proBNP levels. This suggests that independent mechanisms explain these unusually high levels. In one individual showing a high hs-TNT level, renal impairment may be at least partially to blame. We could make the assumption that our results highlight the existence of high and low responders for the cardiac biomarkers as for the CK.

  9. Independence in appearance

    DEFF Research Database (Denmark)

    Warming-Rasmussen, Bent; Quick, Reiner; Liempd, Dennis van

    2011-01-01

    In the wake of the financial crisis, the EU Commission has published a Green Paper on the future role of the audit function in Europe. The Green Paper lists a number of proposals for tighter rules for audits and auditors in order to contribute to stabilizing the financial system. The present...... article presents research contributions to the question whether the auditor is to continue to provide both audit and non-audit services (NAS) to an audit client. Research results show that this double function for the same audit client is a problem for stakeholders' confidence in auditor independence...

  10. Protection by 6-aminonicotinamide against oxidative stress in cardiac cells

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Sigurdardottir, Kristin Sigridur; Treiman, Marek

    2006-01-01

    necrosis following global ischemia in an isolated rat heart, apparently by limiting the oxidative injury component. We therefore explored the antioxidative potential of 6AN in a model using H9C2(2-1) rat cardiac myoblasts exposed to H2O2 stress. Dependent on the specific protocol, 6AN pretreatment for 6...

  11. An Annotated Dataset of 14 Cardiac MR Images

    DEFF Research Database (Denmark)

    Stegmann, Mikkel Bille

    2002-01-01

    This note describes a dataset consisting of 14 annotated cardiac MR images. Points of correspondence are placed on each image at the left ventricle (LV). As such, the dataset can be readily used for building statistical models of shape. Further, format specifications and terms of use are given....

  12. RIPE [robot independent programming environment]: A robot independent programming environment

    International Nuclear Information System (INIS)

    Miller, D.J.; Lennox, R.C.

    1990-01-01

    Remote manual operations in radiation environments are typically performed very slowly. Sensor-based computer-controlled robots hold great promise for increasing the speed and safety of remote operations; however, the programming of robotic systems has proven to be expensive and difficult. Generalized approaches to robot programming that reuse available software modules and employ programming languages which are independent of the specific robotic and sensory devices being used are needed to speed software development and increase overall system reliability. This paper discusses the robot independent programming environment (RIPE) developed at Sandia National Laboratories (SNL). The RIPE is an object-oriented approach to robot system architectures; it is a software environment that facilitates rapid design and implementation of complex robot systems for diverse applications. An architecture based on hierarchies of distributed multiprocessors provides the computing platform for a layered programming structure that models applications using software objects. These objects are designed to support model-based automated programming of robotic and machining devices, real-time sensor-based control, error handling, and robust communication

  13. A computer case definition for sudden cardiac death.

    Science.gov (United States)

    Chung, Cecilia P; Murray, Katherine T; Stein, C Michael; Hall, Kathi; Ray, Wayne A

    2010-06-01

    To facilitate studies of medications and sudden cardiac death, we developed and validated a computer case definition for these deaths. The study of community dwelling Tennessee Medicaid enrollees 30-74 years of age utilized a linked database with Medicaid inpatient/outpatient files, state death certificate files, and a state 'all-payers' hospital discharge file. The computerized case definition was developed from a retrospective cohort study of sudden cardiac deaths occurring between 1990 and 1993. Medical records for 926 potential cases had been adjudicated for this study to determine if they met the clinical definition for sudden cardiac death occurring in the community and were likely to be due to ventricular tachyarrhythmias. The computerized case definition included deaths with (1) no evidence of a terminal hospital admission/nursing home stay in any of the data sources; (2) an underlying cause of death code consistent with sudden cardiac death; and (3) no terminal procedures inconsistent with unresuscitated cardiac arrest. This definition was validated in an independent sample of 174 adjudicated deaths occurring between 1994 and 2005. The positive predictive value of the computer case definition was 86.0% in the development sample and 86.8% in the validation sample. The positive predictive value did not vary materially for deaths coded according to the ICO-9 (1994-1998, positive predictive value = 85.1%) or ICD-10 (1999-2005, 87.4%) systems. A computerized Medicaid database, linked with death certificate files and a state hospital discharge database, can be used for a computer case definition of sudden cardiac death. Copyright (c) 2009 John Wiley & Sons, Ltd.

  14. Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

    Science.gov (United States)

    Belmonte, Stephen L; Ram, Rashmi; Mickelsen, Deanne M; Gertler, Frank B; Blaxall, Burns C

    2013-09-15

    Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

  15. Halogenated anaesthetics and cardiac protection in cardiac and non-cardiac anaesthesia

    Directory of Open Access Journals (Sweden)

    Landoni Giovanni

    2009-01-01

    Full Text Available Volatile anaesthetic agents have direct protective properties against ischemic myocardial damage. The implementation of these properties during clinical anaesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotrope support, time on mechanical ventilation, intensive care unit and overall hospital stay. Multicentre, randomised clinical trials had previously demonstrated that the use of desflurane can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalisation following coronary artery bypass graft surgery either with and without cardiopulmonary bypass. The American College of Cardiology/American Heart Association Guidelines recommend volatile anaesthetic agents during non-cardiac surgery for the maintenance of general anaesthesia in patients at risk for myocardial infarction. Nonetheless, e vidence in non-coronary surgical settings is contradictory and will be reviewed in this paper together with the mechanisms of cardiac protection by volatile agents.

  16. Cardiac Rehabilitation Enhancing Programs in Patients with Myocardial Infarction: A literature Review

    Directory of Open Access Journals (Sweden)

    Ahyana Ahyana

    2013-01-01

    Full Text Available Background: Cardiac rehabilitation (CR is a process that involves a multidisciplinary team of health professionals in order to optimize the status of patients’ physical, psychological, social, and vocational well being. The CR program has been proven to influence health outcomes in patients with cardiac diseases, particularly myocardial infarction (MI and stable angina. However, patients’ compliance with cardiac rehabilitation programs remains a challenge.Purpose: The purpose of this study is to review and identify interventions that enhance cardiac rehabilitation behaviors in MI patients.Method: A literature review was conducted by analyzing related research reports published since 2000 to 2012. Only English language articles were included.Result: There were 10 experimental studies and 2 meta-analysis studies. Interventions widely used to enhance cardiac rehabilitation behaviors in MI patients were self-efficacy and self management derived programs. These programs involved interventions that enhance cardiac rehabilitation behaviors, including training exercise, behavioral change, education and psychological support, and lifestyle changing strategies. None have reported the use of culturally tailored intervention. Four phases of cardiac rehabilitation were accepted as each phase represents a different aspect of care: inpatient care, early post discharge period, exercise training, and long term follow up. Critical factors for patients in maintaining an optimum health condition after a cardiac event are, in order, status of patient’s physical, psychological, social, and vocational well being.Conclusion: Cardiac Rehabilitation program has been shown to improve quality of life and decrease mortality in MI patients. The development of culturally specific interventions to increase cardiac rehabilitation behaviors will provide a significant improvement for cardiac patient’s care that ultimately results in better health outcomes. Health care

  17. [Structure and functional organization of integrated cardiac intensive care].

    Science.gov (United States)

    Scherillo, Marino; Miceli, Domenico; Tubaro, Marco; Guiducci, Umberto

    2007-05-01

    The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.

  18. Fluorescent Reporters in Human Pluripotent Stem Cells: Contributions to Cardiac Differentiation and Their Applications in Cardiac Disease and Toxicity

    NARCIS (Netherlands)

    den Hartogh, Sabine C.; Passier, Petrus Christianus Johannes Josephus

    2016-01-01

    In the last decade, since the first report of induced pluripotent stem cells, the stem cell field has made remarkable progress in the differentiation to specialized cell-types of various tissues and organs, including the heart. Cardiac lineage- and tissue-specific human pluripotent stem cell (hPSC)

  19. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    Copaja, Miguel; Venegas, Daniel; Aranguiz, Pablo; Canales, Jimena; Vivar, Raul; Catalan, Mabel; Olmedo, Ivonne; Rodriguez, Andrea E.; Chiong, Mario; Leyton, Lisette; Lavandero, Sergio; Diaz-Araya, Guillermo

    2011-01-01

    Several clinical trials have shown the beneficial effects of statins in the prevention of coronary heart disease. Additionally, statins promote apoptosis in vascular smooth muscle cells, in renal tubular epithelial cells and also in a variety of cell lines; yet, the effects of statins on cardiac fibroblast and myofibroblast, primarily responsible for cardiac tissue healing are almost unknown. Here, we investigated the effects of simvastatin on cardiac fibroblast and myofibroblast viability and studied the molecular cell death mechanism triggered by simvastatin in both cell types. Methods: Rat neonatal cardiac fibroblasts and myofibroblasts were treated with simvastatin (0.1-10 μM) up to 72 h. Cell viability and apoptosis were evaluated by trypan blue exclusion method and by flow cytometry, respectively. Caspase-3 activation and Rho protein levels and activity were also determined by Western blot and pull-down assay, respectively. Results: Simvastatin induces caspase-dependent apoptosis of cardiac fibroblasts and myofibroblasts in a concentration- and time-dependent manner, with greater effects on fibroblasts than myofibroblasts. These effects were prevented by mevalonate, farnesylpyrophosphate and geranylgeranylpyrophosphate, but not squalene. These last results suggest that apoptosis was dependent on small GTPases of the Rho family rather than Ras. Conclusion: Simvastatin triggered apoptosis of cardiac fibroblasts and myofibroblasts by a mechanism independent of cholesterol synthesis, but dependent of isoprenilation of Rho protein. Additionally, cardiac fibroblasts were more susceptible to simvastatin-induced apoptosis than cardiac myofibroblasts. Thus simvastatin could avoid adverse cardiac remodeling leading to a less fibrotic repair of the damaged tissues. - Research Highlights: → Simvastatin decreases CF and CMF viability independent of cholesterol synthesis. → Simvastatin induces CF and CMF apoptosis in a caspase-dependent manner being CMF more resistant

  20. Cardiac rehabilitation costs.

    Science.gov (United States)

    Moghei, Mahshid; Turk-Adawi, Karam; Isaranuwatchai, Wanrudee; Sarrafzadegan, Nizal; Oh, Paul; Chessex, Caroline; Grace, Sherry L

    2017-10-01

    Despite the clinical benefits of cardiac rehabilitation (CR) and its cost-effectiveness, it is not widely received. Arguably, capacity could be greatly increased if lower-cost models were implemented. The aims of this review were to describe: the costs associated with CR delivery, approaches to reduce these costs, and associated implications. Upon finalizing the PICO statement, information scientists were enlisted to develop the search strategy of MEDLINE, Embase, CDSR, Google Scholar and Scopus. Citations identified were considered for inclusion by the first author. Extracted cost data were summarized in tabular format and qualitatively synthesized. There is wide variability in the cost of CR delivery around the world, and patients pay out-of-pocket for some or all of services in 55% of countries. Supervised CR costs in high-income countries ranged from PPP$294 (Purchasing Power Parity; 2016 United States Dollars) in the United Kingdom to PPP$12,409 in Italy, and in middle-income countries ranged from PPP$146 in Venezuela to PPP$1095 in Brazil. Costs relate to facilities, personnel, and session dose. Delivering CR using information and communication technology (mean cost PPP$753/patient/program), lowering the dose and using lower-cost personnel and equipment are important strategies to consider in containing costs, however few explicitly low-cost models are available in the literature. More research is needed regarding the costs to deliver CR in community settings, the cost-effectiveness of CR in most countries, and the economic impact of return-to-work with CR participation. A low-cost model of CR should be standardized and tested for efficacy across multiple healthcare systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Patch in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alireza Alizadeh Ghavidel

    2014-06-01

    Full Text Available Introduction: Excessive bleeding presents a risk for the patient in cardiovascular surgery. Local haemostatic agents are of great value to reduce bleeding and related complications. TachoSil (Nycomed, Linz, Austria is a sterile, haemostatic agent that consists of an equine collagen patchcoated with human fibrinogen and thrombin. This study evaluated the safety and efficacy of TachoSil compared to conventional technique.Methods: Forty-two patients scheduled for open heart surgeries, were entered to this study from August 2010 to May 2011. After primary haemostatic measures, patients divided in two groups based on surgeon’s judgment. Group A: 20 patients for whom TachoSil was applied and group B: 22 patients that conventional method using Surgicel (13 patients or wait and see method (9 cases, were performed in order to control the bleeding. In group A, 10 patients were male with mean age of 56.95±15.67 years and in group B, 9 cases were male with mean age of 49.95±14.41 years. In case group 70% (14/20 of the surgeries were redo surgeries versus 100% (22/22 in control group.Results: Baseline characteristics were similar in both groups. In TachoSil group 75% of patients required transfusion versus 90.90% in group B (P=0.03.Most transfusions consisted of packed red blood cell; 2±1.13 units in group A versus 3.11±1.44 in group B (P=0.01, however there were no significant differences between two groups regarding the mean total volume of intra and post-operative bleeding. Re-exploration was required in 10% in group A versus 13.63% in group B (P=0.67.Conclusion: TachoSil may act as a superior alternative in different types of cardiac surgery in order to control the bleeding and therefore reducing transfusion requirement.

  2. The importance of board independence

    NARCIS (Netherlands)

    Zijl, N.J.M.

    2012-01-01

    Although the attributed importance of board independence is high, a clear definition of independence does not exist. Furthermore, the aim and consequences of independence are the subject of discussion and empirical evidence about the impact of independence is weak and disputable. Despite this lack

  3. Autonomy, Independence, Inclusion

    Directory of Open Access Journals (Sweden)

    Filippo Angelucci

    2015-04-01

    Full Text Available The living environment must not only meet the primary needs of living, but also the expectations of improvement of life and social relations and people’s work. The need for a living environment that responds to the needs of users with their different abilities, outside of standardizations, is increasingly felt as autonomy, independence and well-being are the result of real usability and adaptability of the spaces. The project to improve the inclusivity of living space and to promote the rehabilitation of fragile users need to be characterized as an interdisciplinary process in which the integration of specialized contributions leads to adaptive customization of space solutions and technological that evolve with the changing needs, functional capacities and abilities of individuals.

  4. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    Science.gov (United States)

    Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

    2016-12-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  5. Serum cardiac troponin I in canine syncope and seizures.

    Science.gov (United States)

    Dutton, E; Dukes-McEwan, J; Cripps, P J

    2017-02-01

    To determine if serum cardiac troponin I (cTnI) concentration distinguishes between cardiogenic syncope and collapsing dogs presenting with either generalized epileptic seizures (both with and without cardiac disease) or vasovagal syncope. Seventy-nine prospectively recruited dogs, grouped according to aetiology of collapse: generalized epileptic seizures (group E), cardiogenic syncope (group C), dogs with both epileptic seizures and cardiac disease (group B), vasovagal syncope (group V) or unclassified (group U). Most patients had ECG (n = 78), echocardiography (n = 78) and BP measurement (n = 74) performed. Dogs with a history of intoxications, trauma, evidence of metabolic disorders or renal insufficiency (based on serum creatinine concentrations >150 μmol/L and urine specific gravity disease) or vasovagal syncope. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Wireless cardiac action potential transmission with ultrasonically inserted silicon microprobes

    International Nuclear Information System (INIS)

    Shen, C J; Ramkumar, A; Lal, A; Gilmour, R F Jr

    2011-01-01

    This paper reports on the integration of ultrasonically inserted horn-shaped cardiac probes with wireless transmission of 3D cardiac action potential measurement for applications in ex vivo preparations such as monitoring the onset of ventricular fibrillation. Ultrasonically inserted silicon horn probes permit reduced penetr