496 research outputs found

    255 In vivo detection of non-occlusive thrombi in drug-eluting stents by scintigraphy and radio-labelled annexin V in a rabbit model

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    IntroductionThrombi in contact with non re-endothelialized stent struts associated with drug-eluting stent (DES) thrombosis. Hence, detection of thrombi in DES could help to evaluate the risk of DES thrombosis. Annexin V radio-labelled with 99mTechnetium (99mTc) is a radio-tracer with a high affinity for activated platelets.ObjectivesOur objectives were: 1) to develop an animal model of non-occlusive thrombosis of stents, 2) to evaluate the ability of annexin V 99mTc for the detection of in-stent thrombi using scintigraphy.MethodsRight carotid arteries of NZW rabbits (n=14) fed a high cholesterol diet were implanted with overlapping DES (n=7) or bare-metal stents (BMS; n=7). Four weeks after stent implantation, rabbits underwent a first scintigraphy 3 hours after injection of 200 MBq of radio-labelled annexin V 99mTc. At the end of the first scintigraphy, a suture was placed surgically proximal to the stented carotid arteries in order to induce a thrombus-prone flow limiting stenosis. Four days later, a second scintigraphy was performed. After the second scintigraphy, stents were excised, imaged ex vivo and then fixed for histological examination and scanning electron microscopy (SEM).ResultsActivities measured in vivo in the stented carotid arteries after injection of annexin V 99mTc were higher on the second scintigraphy after creation of a surgical stenosis as compared to the first scintigraphy (0.24 vs. 0.15 counts/pixel/MBq, respectively; p<0.05). On the second scintigraphy, activities were higher in DES vs. BMS (0.26 vs. 0.19 counts/pixel/MBq, respectively; p < 0.005). High activities measured in stents in vivo were associated with the detection of thrombi on corresponding histological sections and SEM.ConclusionsIn this work, we developed a rabbit model of non-occlusive thrombosis of stents in carotid arteries. In this model, in-stent thrombi could be detected using annexin V 99mTc scintigraphy

    Peristrut microhemorrhages: a possible cause of in-stent neoatherosclerosis?

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    AbstractBackgroundIn-stent neoatherosclerosis is characterized by the delayed appearance of markers of atheroma in the subintima, but the pathophysiology underlying this new disease entity remains unclear.Methods and resultsWe collected 20 human coronary artery stents by removal from explanted hearts. The mean duration of stent implantation was 34 months. In all samples, neoatherosclerosis was detected, particularly in peristrut areas. It consisted of foam cells and cholesterol clefts, with or without calcification, associated with neovascularization. Iron and glycophorin-A were present in peristrut areas, as well as autofluorescent ceroids. Moreover, in response to neoatherosclerosis, tertiary lymphoid organs (tissue lymphoid clusters) often developed in the adventitia. Some of these features could be reproduced in an experimental carotid stenting model in rabbits fed a high-cholesterol diet. Foam cells were present in all samples, and peristrut red blood cells (RBCs) were also detected, as shown by iron deposits and Bandeiraea simplicifiola isolectin-B4 staining of RBC membranes. Finally, in silico models were used to evaluate the compliance mismatch between the rigid struts and the distensible arterial wall using finite element analysis. They show that stenting approximately doubles the local von Mises stress in the intimal layer.ConclusionsWe show here that stent implantation both in human and in rabbit arteries is characterized by local peristrut microhemorrhages and finally by both cholesterol accumulation and oxidation, triggering together in-stent neoatherosclerosis. Our data indicate that these processes are likely initiated by an increased mechanical stress due to the compliance mismatch between the rigid stent and the soft wall

    Anaplastic large cell lymphoma in paediatric and young adult patients.

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    Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial.Supported in part by the Pediatric Cancer Research Foundation and Fondazione Giacomo Ascoli. S.D.T. is supported with funding from BloodwiseThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1111/bjh.1395

    Discovery of VHE gamma-rays from the high-frequency-peaked BL Lac object RGB J0152+017

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    Aims: The BL Lac object RGB J0152+017 (z=0.080) was predicted to be a very high-energy (VHE; > 100 GeV) gamma-ray source, due to its high X-ray and radio fluxes. Our aim is to understand the radiative processes by investigating the observed emission and its production mechanism using the High Energy Stereoscopic System (H.E.S.S.) experiment. Methods: We report recent observations of the BL Lac source RGB J0152+017 made in late October and November 2007 with the H.E.S.S. array consisting of four imaging atmospheric Cherenkov telescopes. Contemporaneous observations were made in X-rays by the Swift and RXTE satellites, in the optical band with the ATOM telescope, and in the radio band with the Nancay Radio Telescope. Results: A signal of 173 gamma-ray photons corresponding to a statistical significance of 6.6 sigma was found in the data. The energy spectrum of the source can be described by a powerlaw with a spectral index of 2.95+/-0.36stat+/-0.20syst. The integral flux above 300 GeV corresponds to ~2% of the flux of the Crab nebula. The source spectral energy distribution (SED) can be described using a two-component non-thermal synchrotron self-Compton (SSC) leptonic model, except in the optical band, which is dominated by a thermal host galaxy component. The parameters that are found are very close to those found in similar SSC studies in TeV blazars. Conclusions: RGB J0152+017 is discovered as a source of VHE gamma-rays by H.E.S.S. The location of its synchrotron peak, as derived from the SED in Swift data, allows clearly classification it as a high-frequency-peaked BL Lac (HBL).Comment: Accepted for publication in A&A Letters (5 pages, 4 figures

    Cortisol coregulation in fish

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    Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations

    The geography of snake reproductive mode: a global analysis of the evolution of snake viviparity

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    Aim : Although most reptiles are oviparous, viviparity is a commonmode of reproduction in squamates and has evolved multiple times in different lineages.We test two prevailing hypotheses regarding the biogeography of reptile reproductive modes to evaluate the selective forces driving the evolution of viviparity in snakes. The cold climate hypothesis posits that viviparity is selected for in cold climates, whereas the climatic predictability hypothesis predicts that viviparity is advantageous in seasonal climates. Methods : We collated detailed distribution maps and reproductive mode data for 2663 species of the world’s terrestrial alethinophidian snakes.We studied the relationship between snake reproductive mode and environmental predictors. We applied both an ecological and an evolutionary approach to study snake reproductive mode by performing the analyses at the assemblage level and species level, respectively. We analysed our data at the global and continental scales to learn whether tendencies to viviparity are similar world-wide. Results : We found strong support for the cold climate hypothesis and the assumption that viviparity is an adaptation to cold environments. There was little support for the climatic predictability hypothesis. Nonetheless, viviparous species are not restricted to cold environments. Main conclusions : We conclude that viviparity is adaptive in cold climates, but not necessarily in unpredictable/seasonal climates. Current distributions may not reflect the climate at the time and place of speciation.We suspect many viviparous snakes inhabiting warm climates are members of lineages that originated in colder regions, and their occurrence in maladaptive environments is a result of phylogenetic conservatism
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