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Abington, PA, United States

Dementovych N.,Abington Memorial Hospital | Mishra R.,Abington Memorial Hospital | Shah Q.A.,Neurosciences Institute
Journal of NeuroInterventional Surgery | Year: 2012

Giant cell arteritis (GCA) is the most common form of systemic vasculitis in adults. Patients usually present with headache and visual symptoms, and have an elevated erythrocyte sedimentation rate. It has been reported that 3-4% of patients with GCA develop ischemic events secondary to vertebral artery stenosis or occlusion. The mainstay of therapy of GCA is high dose steroid and/or methotrexate. A case is described of a patient who initially presented with intermittent double vision, mild headache and unremarkable MRI and MR angiography of the head and neck. The patient was diagnosed and treated for ocular myasthenia. The patient was readmitted 2 months later with imbalance and worsening headache, and workup suggested bilateral cerebellar infarction, complete occlusion of the left vertebral artery and a high grade stenosis of the right vertebral artery. Erythrocyte sedimentation rate and C reactive protein were elevated. Temporal artery biopsy demonstrated changes consistent with GCA. During the course of the treatment with corticosteroids and immunosuppressant, the patient developed dysarthria, left facial droop and left hemiplegia, and was found to have complete occlusion of both vertebral arteries. The patient was emergently taken for revascularization of the occluded segment using angioplasty and stent placement. The patient had significant improvement of neurological symptoms within 3 days after the procedure and continued to improve during hospitalization. Endovascular treatment of vasculitis affecting the intracranial vessels is not yet established. Our experience with successful treatment of complete occlusion of the vertebral artery secondary to GCA using endovascular intracranial angioplasty and stent placement is reported.

Gual A.,Neurosciences Institute | He Y.,Lundbeck | Torup L.,Lundbeck | van den Brink W.,University of Amsterdam | Mann K.,University of Heidelberg
European Neuropsychopharmacology | Year: 2013

This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence. Seven hundred and eighteen patients (placebo=360; nalmefene=358), ≥18 years of age, with a diagnosis of alcohol dependence, ≥6 heavy drinking days and an average alcohol consumption ≥WHO medium drinking risk level in the 4 weeks preceding screening, were randomised (1:1) to 24 weeks of as-needed placebo or nalmefene 18. mg/day.The co-primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days (group difference: -1.7 days/month [95% CI -3.1; -0.4]; p=0.012) and a better but not significant effect in reducing total alcohol consumption (group difference: -5.0. g/day last month [95% CI -10.6; 0.7]; p=0.088). A subgroup analysis showed that patients who did not reduce their drinking prior to randomisation benefitted more from nalmefene. Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group. Adverse events were more common with nalmefene; the incidence of adverse events leading to dropout was similar in both groups.This study provides evidence for the efficacy of nalmefene, which constitutes a new pharmacological treatment paradigm in terms of treatment goal (reduced drinking) and dosing regimen (as-needed), in alcohol dependent patients unable to reduce alcohol consumption on their own. © 2013 Elsevier B.V. and ECNP.

Makarenkova H.P.,Scripps Research Institute | Makarenkova H.P.,Neurosciences Institute | Meech R.,University of South Australia
International Review of Cell and Molecular Biology | Year: 2012

Homeobox transcription factors are key intrinsic regulators of myogenesis. In studies spanning several years, we have characterized the homeobox factor Barx2 as a novel marker for muscle progenitor cells and an important regulator of muscle growth and repair. In this review, we place the expression and function of Barx2 and its paralogue Barx1 in context with other muscle-expressed homeobox factors in both embryonic and adult myogenesis. We also describe the structure and regulation of Barx genes and possible gene/disease associations. The functional domains of Barx proteins, their molecular interactions, and cellular functions are presented with particular emphasis on control of genes and processes involved in myogenic differentiation. Finally, we describe the patterns of Barx gene expression in vivo and the phenotypes of various Barx gene perturbation models including null mice. We focus on the Barx2 null mouse model, which has demonstrated the critical roles of Barx2 in postnatal myogenesis including muscle maintenance during aging, and regeneration of acute and chronic muscle injury. © 2012 Elsevier Inc.

Anderson P.,Public Health Consultant | Gual A.,Neurosciences Institute
Addiction | Year: 2011

Aims To consider, briefly, science's role in informing alcohol policy, and how science could help reframe the present governance of alcohol policy. Design Expression of the two project coordinators' reflections based on discussions during project meetings of the Alcohol Measures for Public Health Research Alliance (AMPHORA) project. Results Three endeavours are considered important for science's role in informing alcohol policy: modelling studies that help predict the outcomes of differing policy approaches; studying the impact of live policy changes as a powerful set of natural experiments; and, improved study of the impact of integrated, coordinated and joined up alcohol policies, as opposed to the impact of individual alcohol policy measures. Three areas where science can contribute to strengthened alcohol policy governance include: analysis of different governance architectures that might promote joined-up actions between different sectors; the design of better metrics that measure the impact of public and private sector actions on health; and, by identifying incentives that help consumers make choices on the use of alcohol that improve health. Conclusions The impact of science on better alcohol policy governance can only happen if there is more and better dialogue between scientists and those who design alcohol policy. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Ropireddy D.,George Mason University | Scorcioni R.,George Mason University | Scorcioni R.,Neurosciences Institute | Lasher B.,George Mason University | And 3 more authors.
Brain Structure and Function | Year: 2011

Axonal arbors of principal neurons form the backbone of neuronal networks in the mammalian cortex. Three-dimensional reconstructions of complete axonal trees are invaluable for quantitative analysis and modeling. However, digital data are still sparse due to labor intensity of reconstructing these complex structures. We augmented conventional tracing techniques with computational approaches to reconstruct fully labeled axonal morphologies. We digitized the axons of three rat hippocampal pyramidal cells intracellularly filled in vivo from different CA3 sub-regions: two from areas CA3b and CA3c, respectively, toward the septal pole, and one from the posterior/ventral area (CA3pv) near the temporal pole. The reconstruction system was validated by comparing the morphology of the CA3c neuron with that traced from the same cell by a different operator on a standard commercial setup. Morphometric analysis revealed substantial differences among neurons. Total length ranged from 200 (CA3b) to 500 mm (CA3c), and axonal branching complexity peaked between 1 (CA3b and CA3pv) and 2 mm (CA3c) of Euclidean distance from the soma. Length distribution was analyzed among sub-regions (CA3a,b,c and CA1a,b,c), cytoarchitectonic layers, and longitudinal extent within a three-dimensional template of the rat hippocampus. The CA3b axon extended thrice more collaterals within CA3 than into CA1. On the contrary, the CA3c projection was double into CA1 than within CA3. Moreover, the CA3b axon extension was equal between strata oriens and radiatum, while the CA3c axon displayed an oriens/radiatum ratio of 1:6. The axonal distribution of the CA3pv neuron was intermediate between those of the CA3b and CA3c neurons both relative to sub-regions and layers, with uniform collateral presence across CA3/CA1 and moderate preponderance of radiatum over oriens. In contrast with the dramatic sub-region and layer differences, the axon longitudinal spread around the soma was similar for the three neurons. To fully characterize the axonal diversity of CA3 principal neurons will require higher-throughput reconstruction systems beyond the threefold speed-up of the method adopted here. © 2010 Springer-Verlag.

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