56 research outputs found

    Asymptomatic recurrence after AF ablation: is all lost?

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    Abstract not availableAnand Thiyagarajah, Rajiv Mahajan, Dennis H. Lau, Prashanthan Sander

    SANS of bulk metallic ZrTiCuNiBe glasses

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    The evolution of decomposition and succeeding primary crystallization in the bulk amorphous Zr{sub 41.2}Ti{sub 13.8}Cu{sub 12.5}Ni{sub 10}Be{sub 22.5} alloy have been studied by small angle neutron scattering. Samples annealed isothermally in the supercooled liquid and in the solid state exhibit correlation peaks indicating quasiperiodic inhomogeneities in the scattering length density. The peak positions vary as a function of temperature as predicted by the linear Cahn-Hilliard theory of spinodal decomposition. Variations of the Be-Ti composition ratio of the alloy leads to significant changes in scattering signals. The initially homogeneous alloy separates into two amorphous phases. In the decomposed regions, crystallization probability increases leading to polymorphic crystallization

    Complex interaction of obesity, intentional weight loss and heart failure: a systematic review and meta-analysis

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    OBJECTIVE:The aim of the meta-analysis was to determine the association of obesity and heart failure (HF) and the cardiac impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obese subjects. METHODS:MEDLINE, Embase and Web of Science were searched up to 3 April 2018. Studies reporting association and prognostic impact of obesity in HF and the impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obesity were included in the meta-analysis. RESULTS:4959 citations were reviewed. After exclusions, 29 studies were analysed. A 'J curve' relationship was observed between body mass index (BMI) and risk of HF with maximum risk in the morbidly obese (1.73 (95% CI 1.30 to 2.31), p<0.001, n=11). Although 'obesity paradox' was observed for all-cause mortality, the overweight group was associated with lower cardiovascular (CV) mortality (OR=0.86 (95% CI 0.79 to 0.94), n=11) with no significant differences across other BMI groups. Intentional weight loss induced by bariatric surgery in obese patients (n=9) without established HF, atrial fibrillation or known coronary artery disease, was associated with a reduction in left ventricular mass index (p<0.0001), improvement in left ventricular diastolic function (p≤0.0001) and a reduction in left atrial size (p=0.02). CONCLUSIONS:Despite the increased risk of HF with obesity, an 'obesity paradox' is observed for all-cause mortality. However, the nadir for CV mortality is observed in the overweight group. Importantly, intentional weight loss was associated with improvement in indices of cardiac structure and myocardial function in obese patients. TRIAL REGISTRATION NUMBER:APP 74412.Rajiv Mahajan, Michael Stokes, Adrian Elliott, Dian A Munawar, Kashif B Khokhar, Anand Thiyagarajah, Jeroen Hendriks, Dominik Linz, Celine Gallagher, David Kaye, Dennis Lau, Prashanthan Sander

    Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR

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    Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow-up is presented. After 19.4 (range: 0 to 27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; P 12, 646, or >6 months), or cytogenetic risk. Minimal residual disease-negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow-up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse

    The (Ca2+ + Mg2+)-stimulated ATPase of the rat parotid endoplasmic reticulum.

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    A membrane fraction enriched in endoplasmic reticulum was prepared from rat parotid glands by using sucrose-gradient centrifugation. The fraction showed a 10-fold increase in specific activity of NADPH: cytochrome c reductase activity over that of tissue homogenates and minimal contamination with plasma membranes or mitochondria. The endoplasmic reticulum fraction possessed both Mg2+ -stimulated ATPase as well as Ca2+, Mg2+-ATPase [( Ca2+ + Mg2+)-stimulated ATPase]activity. The Ca2+, Mg2+-ATPase required 2-5 mM-Mg2+ for optimal activity and was stimulated by submicromolar concentrations of free Ca2+. The Km for free Ca2+ was 0.55 microM and the average Vmax. was 60 nmol/min per mg of protein. The Km for ATP was 0.11 mM. Other nucleotides, such as GTP, CTP or ADP, could not substitute for ATP in supporting the Ca2+-activated nucleotidase activity. Increasing the K+ concentration from 0 to 100 mM caused a 2-fold activation of the Ca2+, Mg2+-ATPase. Trifluoperazine, W7 [N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide] and vanadate inhibited the enzyme. The concentration of trifluoperazine and vanadate required for 50% inhibition of the ATPase were 52 microM and 28 microM respectively. Calmodulin, cyclic AMP, cyclic AMP-dependent protein kinase and inositol 1,4,5-trisphosphate had no effect on the ATPase. The properties of the Ca2+, Mg2+ -ATPase were distinct from those of the Mg2+-ATPase, but comparable with those reported for the parotid endoplasmic-reticulum Ca2+-transport system [Kanagasuntheram & Teo (1982) Biochem. J. 208, 789-794]. The results suggest that the Ca2+, Mg2+-ATPase is responsible for driving the ATP-dependent Ca2+ accumulation by this membrane

    Phosphatidylinositol 4,5-biphosphate stimulates parotid endoplasmic reticulum (Ca2++ Mg2+)-ATP'ase

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    Biochemistry International95625-630BIIN

    Characterisation of a high affinity Ca2+-stimulated Mg2+-dependent ATPase in the rat parotid plasma membrane

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    Biochimica et Biophysica Acta - Biomembranes9452202-210BBBM

    Atrial fibrillation and conduction system disease: the roles of catheter ablation and permanent pacing

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    Atrial fibrillation (AF) and diseases of the cardiac conduction system frequently co-exist, and interactions between these rhythm disturbances can adversely impact patient outcomes. Concurrent AF and sinus node disease often manifests as the tachy-brady syndrome wherein the underlying sinus node dysfunction can pose a challenge to AF management. Similarly, the combination of AF and left bundle branch block increases mortality in individuals with co-existent heart failure and hampers effective delivery of cardiac resynchronization therapy. A thorough understanding of the therapeutic interventions available for these conditions, including the role of catheter ablation and permanent pacemaker programming, is crucial for optimal management in affected patients.Anand Thiyagarajah, Dennis H. Lau, Prashanthan Sander

    Magnetically labeled GMR biosensor with a single immobilized ferrimagnetic particle agent for the detection of extremely low concentration of biomolecules

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    10.1109/JSEN.2010.2102349IEEE Sensors Journal1191927-193
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