39 research outputs found

    Proximal aortic stent migration

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    Challenges in the prenatal and post-natal diagnosis of mediastinal cystic hygroma: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Cystic hygroma is a benign congenital neoplasm that mostly presents as a soft-tissue mass in the posterior triangle of the neck. Pure mediastinal lesions are uncommon; the vast majority are asymptomatic and are an incidental finding in adulthood. The diagnosis is often made intra- or postoperatively. Prenatal identification is exceptional and post-natal diagnosis also proves challenging.</p> <p>Case presentation</p> <p>We report one such case that was mistaken for other entities in both the prenatal and immediate post-natal period. Initial and follow-up antenatal ultrasound scans demonstrated a multicystic lesion in the left chest, and the mother was counselled about the possibility of her baby having a congenital diaphragmatic hernia. Initial post-natal chest radiographs were reported as normal. An echocardiogram and thoracic computed tomography scan confirmed a complex multiloculated cystic mediastinal mass. The working diagnoses were of a mediastinal teratoma or congenital cystic adenomatous malformation. At operation, the lesion was compressed by the left lung and was found to be close to the left phrenic nerve, which was carefully identified and preserved. After excision, histopathological examination of the mass confirmed the diagnosis of cystic hygroma. Postoperative dyspnoea was observed secondary to paradoxical movement of the left hemidiaphragm and probable left phrenic neuropraxia. This settled conservatively with excellent recovery.</p> <p>Conclusion</p> <p>Despite the fact that isolated intrathoracic cystic hygroma is a rare entity, it needs to be considered in the differential diagnosis of foetal and neonatal mediastinal masses, particularly for juxtadiaphragmatic lesions. The phrenic nerve is not identifiable on prenatal ultrasound imaging, and it is therefore understandable that a mass close to the diaphragm may be mistaken for a congenital diaphragmatic hernia because of the location, morphology and potential phrenic nerve compression. Post-natal diagnosis may also be misleading as many mediastinal cystic masses have similar appearances on imaging. Therefore, as well as cystic architecture, special consideration needs to be given to the anatomical location and effect on local structures.</p

    Static Magnetic Field Exposure Reproduces Cellular Effects of the Parkinson's Disease Drug Candidate ZM241385

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    This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009)) established that moderate strength static magnetic field (SMF) exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A(2A) receptor (A(2A)R) in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD).SMF reproduced several responses elicited by ZM241385, a selective A(2A)R antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A(2A)R agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A(2A)R, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth.When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders

    Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

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    Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Asenapine pharmacokinetics and tolerability in a pediatric population

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    Peter Dogterom,1 Robert Riesenberg,2 Rik de Greef,1 Justin Dennie,3 Martin Johnson,1 Venkatesh Pilla Reddy,1 Andr&eacute; MM Miltenburg,1 Robert L Findling,4 Abhijeet Jakate,5 Timothy J Carrothers,5 Matthew D Troyer3 1Early Stage Development, Merck Sharp and Dohme, Oss, the Netherlands; 2Atlanta Center for Medical Research, Atlanta, GA, 3Merck, Kenilworth, NJ, 4Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, 5Allergan, Madison, NJ, USA Purpose: This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders. Methods: Two Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10&ndash;17 years) with schizophrenia or bipolar I disorder. Patients received asenapine 1&ndash;10 mg twice daily for up to 12 days. PK parameters (maximum concentration [Cmax], area under the curve from 0 to 12 hours [AUC0&ndash;12], time to Cmax [Tmax], and half-life) were summarized for asenapine with descriptive statistics, and safety parameters were collected. A population PK model, which included the two Phase I studies and two additional Phase III efficacy studies (asenapine 2.5&ndash;10 mg twice daily for up to 8 weeks, age 10&ndash;17 years), was developed using nonlinear mixed-effect modeling based on a previously developed adult PK model. The final model was used in simulations to obtain asenapine-exposure estimates across pediatric subgroups and to determine if intrinsic covariates warrant dose adjustments. Results: The PK of asenapine showed rapid absorption (Tmax ~1 hour) with an apparent terminal half-life between 16 and 32 hours. Increases in mean Cmax and AUC0&ndash;12 appeared to be dose-proportional in one study and near dose-proportional in the second study. Steady state was attained within 8 days. The most frequently occurring treatment-emergent adverse events were dysgeusia, sedation, and oral hypoesthesia. Simulation-based estimates of Cmax and AUC0&ndash;12 were similar for pediatric and adult patients; age, body-mass index, race, and sex were not associated with changes in asenapine exposure. Conclusion: Asenapine was generally safe and well tolerated in pediatric patients aged 10&ndash;17 years. PK and safety data were similar to that observed in the adult population. Intrinsic factors had no significant impact on asenapine exposure, indicating there is no need for dose adjustments in the pediatric population. Keywords: asenapine, pharmacokinetics, schizophrenia, bipolar disorder, child and adolescent, atypical antipsychoti
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