Medical Sciences Commons^™

Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff

Michael A. Rogawski

The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively ...

Ngo's Bpa Report Intended To Frighten, Not Enlighten., Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Validated Automatic Brain Extraction Of Head Ct Images, John Muschelli Iii, Natalie L. Ullman, Daniel F. Hanley, Paul Vespa, Ciprian M. Crainiceanu

John Muschelli III

Background

X-ray Computed Tomography (CT) imaging of the brain is commonly used in diagnostic settings. Al- though CT scans are primarily used in clinical practice, they are increasingly used in research. A fundamental processing step in brain imaging research is brain extraction – the process of separating the brain tissue from all other tissues. Methods for brain extraction have either been validated but not fully automated, or have been fully automated and informally proposed, but never formally validated.

Aim

To systematically analyze and validate the performance of FSL’s brain extraction tool (BET) on head CT images of patients with intracranial ...

A Proposed Framework For Consensus-Based Lung Tumour Volume Auto-Segmentation In 4d Computed Tomography Imaging., Spencer Martin, Mark Brophy, David Palma, Alexander V Louie, Edward Yu, Brian Yaremko, Belal Ahmad, John L Barron, Steven S Beauchemin, George Rodrigues, Stewart Gaede

Medical Biophysics Publications

This work aims to propose and validate a framework for tumour volume auto-segmentation based on ground-truth estimates derived from multi-physician input contours to expedite 4D-CT based lung tumour volume delineation. 4D-CT datasets of ten non-small cell lung cancer (NSCLC) patients were manually segmented by 6 physicians. Multi-expert ground truth (GT) estimates were constructed using the STAPLE algorithm for the gross tumour volume (GTV) on all respiratory phases. Next, using a deformable model-based method, multi-expert GT on each individual phase of the 4D-CT dataset was propagated to all other phases providing auto-segmented GTVs and motion encompassing internal gross target volumes (IGTVs ...

Registration Of In-Vivo To Ex-Vivo Mri Of Surgically Resected Specimens: A Pipeline For Histology To In-Vivo Registration., Maged Goubran, Sandrine De Ribaupierre, Robert R Hammond, Catherine Currie, Jorge G Burneo, Andrew G Parrent, Terry M Peters, Ali R Khan

Medical Biophysics Publications

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology.

NEW METHOD: A combination of image-based and landmark-based 3D ...

Coronary Steal Due To Left Internal Mammary Artery Side Branch – A Dilemma, Vatsal Ladia Md, Puja Sitwala Md, Parag Brahmbhatt Md, Vedang Bhavsar Md, James Halama Md, Vijay Ramu Md, Kais Albalbassi Md, Paul Timir Md

Tennessee Medicine E-Journal

Internal Mammary Artery (IMA) is the best graft for Coronary Artery Bypass Graft surgery (CABG) in terms of long term survival rates and graft patency rates when compared to other grafts^1,2. In traditional CABG, IMA is harvested from 1^st inter-costal space and is skeletonized by ligating all the side branches, which is usually 10 cm long. In 1995, Benneti introduced Minimally Invasive Coronary Artery Bypass Graft surgery (MIDCAB) for various benefits. In this technique Left IMA (LIMA) is harvested from 5^th inter-costal space and long enough to reach Left Anterior Descending Artery (LAD) around 4-6 cm ...

Feasibility Of A Unified Approach To Intensity-Modulated Radiation Therapy And Volume-Modulated Arc Therapy Optimization And Delivery, Jerry J. Battista, Michael Macfarlane, Eugene Wong, Jeff Z. Chen, Douglas A. Hoover

Medical Biophysics Publications

Purpose:

To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT)optimization and delivery to produce superior radiation treatment plans, both in terms of dosedistribution and efficiency of beam delivery when compared with either VMAT or IMRT alone.

Methods:

An inverse planning algorithm for UIMAT was prototyped within the pinnacle treatment planningsystem (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the ...

Reward Enhances Tic Suppression In Children Within Months Of Tic Disorder Onset, Deanna J. Greene, Jonathan M. Koller, Amy Robichaux-Viehoever, Emily C. Bihun, Bradley L. Schlaggar, Kevin J. Black

Kevin J. Black, MD

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would ...

Pulmonary Abnormalities And Carotid Atherosclerosis In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Tamas J Lindenmaier, Khadija Sheikh, Casey E Neron, Daniel G Hackam, J David Spence, Aaron Fenster, Nigel A M Paterson, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Abstract It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- ...

Load Transfer At The Distal Ulna Following Simulated Distal Radius Fracture Malalignment., Louis M Ferreira, Gillian S Greeley, James A Johnson, Graham J W King

Medical Biophysics Publications

PURPOSE: To measure the effects of distal radius malalignment on loading at the distal ulna.

METHODS: Using an adjustable mechanism to simulate angulated and translated malalignments, clinically relevant distal radius deformities were simulated in a cadaveric model. A custom-built load cell was inserted just proximal to the native ulna head to measure the resultant force and torque in the distal ulna. Loads were measured before and after transecting the triangular fibrocartilage complex (TFCC).

RESULTS: There was an increase in distal ulna load and torque with increasing dorsal translation and angulation. Combined conditions of angulation and translation increased force and torque ...

Rapid Desiccation Hardening Changes The Cuticular Hydrocarbon Profile Of Drosophila Melanogaster., Joseph R Stinziano, Richard J Sové, Howard D Rundle, Brent J Sinclair

Medical Biophysics Publications

The success of insects in terrestrial environments is due in large part to their ability to resist desiccation stress. Since the majority of water is lost across the cuticle, a relatively water-impermeable cuticle is a major component of insect desiccation resistance. Cuticular permeability is affected by the properties and mixing effects of component hydrocarbons, and changes in cuticular hydrocarbons can affect desiccation tolerance. A pre-exposure to a mild desiccation stress increases duration of desiccation survival in adult female Drosophila melanogaster, via a decrease in cuticular permeability. To test whether this acute response to desiccation stress is due to a change ...

Iron Alters Cell Survival In A Mitochondria-Dependent Pathway In Ovarian Cancer Cells., Edward Haller

Edward Haller

ABSTRACT The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although levels of intracellular iron, ferritin/CD71 protein and reactive oxygen species did not correlate with iron-induced cell survival changes, we identified mitochondrial damage (via TEM) and reduced expression of outer mitochondrial membrane proteins (translocase of outer membrane: TOM20 and TOM70) in cell lines sensitive to iron. Interestingly, Ru360 (an inhibitor of the mitochondrial calcium uniporter) reversed ...

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A

Association Between Body Surface Area And Outcomes After Percutaneous Coronary Intervention, Kambiz Shetabi, Tonga Nfor, Fengyi Shen, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose

Obesity is a well-known risk factor for adverse cardiovascular events, but some studies suggest higher body mass index (BMI) is associated with better outcomes after ST-segment elevation myocardial infarction (STEMI). We sought to determine the effect of body surface area (BSA) on adverse events after primary percutaneous coronary intervention (PCI) for STEMI and how this relates to the reported obesity paradox theory.

Methods

We analyzed a prospective registry of patients with STEMI who underwent primary PCI at a tertiary care hospital from 2003 to 2009. Post-PCI complications and 1-year all-cause mortality were compared across BSA quartiles. Relationship with 1-year ...

The Onchocerciasis Vaccine For Africa-Tova-Initiative., Peter J Hotez, Maria Elena Bottazzi, Bin Zhan, Benjamin L Makepeace, Thomas R Klei, David Abraham, David W Taylor, Sara Lustigman

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

"Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines" Data Files, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag

Pharmacy Faculty Data Sets

The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division ...

Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag

Pharmacy Faculty Articles and Research

The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division ...

Skeletal Muscle Fibrosis In The Mdx/Utrn+/- Mouse Validates Its Suitability As A Murine Model Of Duchenne Muscular Dystrophy, Lisa M. Hoffman, William T. Hrinivich, Kelly M. Gutpell

Medical Biophysics Publications

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and ...

Pyruvate Carboxylase Is Critical For Non-Small-Cell Lung Cancer Proliferation, Katherine Sellers, Matthew P. Fox, Michael Bousamra Ii, Stephen P. Slone, Richard M. Higashi, Donald M. Miller, Yali Wang, Jun Yan, Mariia O. Yuneva, Rahul Deshpande, Andrew N. Lane, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity ...

Memory T Cells Specific For Murine Cytomegalovirus Re-Emerge After Multiple Challenges And Recapitulate Immunity In Various Adoptive Transfer Scenarios., Michael Quinn, Holly Turula, Mayank Tandon, Berthony Deslouches, Toktam Moghbeli, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8(+) T cells become terminally differentiated effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8(+) T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections ...