Browsing by Subject "abnormalities"

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    Cavopulmonary assist for the failing Fontan circulation: impact of ventricular function on mechanical support strategy
    (Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-11) Giridharan, Guruprasad A.; Ising, Mickey; Sobieski, Michael A.; Koenig, Steven C.; Chen, Jun; Frankel, Steven C.; Rodefeld, Mark D.; Department of Surgery, IU School of Medicine
    Mechanical circulatory support--either ventricular assist device (VAD, left-sided systemic support) or cavopulmonary assist device (CPAD, right-sided support)--has been suggested as treatment for Fontan failure. The selection of left- versus right-sided support for failing Fontan has not been previously defined. Computer simulation and mock circulation models of pediatric Fontan patients (15-25 kg) with diastolic, systolic, and combined systolic and diastolic dysfunction were developed. The global circulatory response to assisted Fontan flow using VAD (HeartWare HVAD, Miami Lakes, FL) support, CPAD (Viscous Impeller Pump, Indianapolis, IN) support, and combined VAD and CPAD support was evaluated. Cavopulmonary assist improves failing Fontan circulation during diastolic dysfunction but preserved systolic function. In the presence of systolic dysfunction and elevated ventricular end-diastolic pressure (VEDP), VAD support augments cardiac output and diminishes VEDP, while increased preload with cavopulmonary assist may worsen circulatory status. Fontan circulation can be stabilized to biventricular values with modest cavopulmonary assist during diastolic dysfunction. Systemic VAD support may be preferable to maintain systemic output during systolic dysfunction. Both systemic and cavopulmonary support may provide best outcome during combined systolic and diastolic dysfunction. These findings may be useful to guide clinical cavopulmonary assist strategies in failing Fontan circulations.
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    Extended Treatment with a High Dosage of EGCG to Rescue Appendicular Bone Abnormalities in a Down Syndrome Mouse Model
    (Office of the Vice Chancellor for Research, 2015-04-17) Singh, Prabhjot; Roper, Randall J.; Abeysekera, Irushi
    Individuals with Down syndrome (DS) show significant abnormalities in cognitive abilities, muscle tone, and bone homeostasis. DS is caused by a triplication of the 21st human chromosome (Hsa21). Previous research conducted by our lab using mouse models indicates that three copies of Dyrk1a causes the appendicular skeletal deficits associated with DS. Ts65Dn mouse model carries 50% of the genes homologous to Hsa21, and exhibit excellent phenotypic model for the skeletal deficits seen in individuals with DS, such as low bone mineral density, altered bone structure, and decreased cortical bone. Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol that inhibits Dyrk1a activity. In a previous study, we showed that a three-week, low dose (10mg/kg/day) treatment of EGCG rescued bone mineral density, and trabecular bone to that of euploid levels, but not cortical bone. We hypothesize that increasing the concentration and duration of the treatment will be sufficient enough to more fully restore bone abnormalities by rescuing femoral bone mineral density, bone volume, and improving overall bone strength. This project explores the effects of using a prolonged seven-week, high dosage (100mg/kg/day) treatment on specific bone phenotypes. Dual Energy X-ray absorptiometry (DXA), MicroCT, and mechanical testing will be used as our means of analysis of the treated and untreated bones.