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Electroencephalographic Recordings in the Canine: Effects of Low Dose Medetomidine or Dexmedetomidine Followed by Atipamezole

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Open Journal of Veterinary Medicine 2014年第2期4卷 7-13页

作者： Laura C. Tepper andy shores Bay Street Animal Hospital Staten Island NY USA Veterinary Specialty Center Starkville MS USA College of Veterinary Medicine Mississippi State University Mississippi State MS USA

Objectives: 1) To describe electroencephalogram (EEG) appearance in the awake dog and compare these results with EEG recordings after low dose medetomidine (2 μg/kg IV) followed by atipamezole (10 μg/kg, IM);2) To institute EEG recordings after low dose medetomidine or dexmedetomidine as a standard of practice if focal abnormalities and amplitudes were not significantly altered by pharmaceuticals in Phase 1 of this study. Methods: Electroencephalograms were performed on eight clinical canine patients with suspected intracranial disease involving the prosencephalon. A five lead montage was used to record the EEGs. Each dog had an awake, baseline recording followed by an EEG performed after administration of low dose medetomidine (2 μg/kg IV) then atipamezole (10 μg/kg, IM). In the second phase of this study, the same dose of medetomidine or dexmedetomidine at 1 μg/kg IV and atipamezole (10 μg/kg, IM) were used in the evaluation of 20 clinical patients with suspected neurologic disease. Results: In Phase 1, awake recordings were laced with movement artifacts. After medetomidine and atipamezole, EEG waveforms were slower. Following atipamezole, however, the frequencies were observed to increase with time. Statistical evaluation revealed significantly more artifacts in baseline recordings. No statistically significant change was observed in focal abnormalities or amplitude. In Phase 2, the a2-adrenoreceptor agonists followed by atipamezole without the use of lidocaine produced clinically reliable results. Clinical Significance: Quality and diagnostic electroencephalogram (EEG) recordings are frequently inconvenient to obtain in the awake dog. Movement results in artifacts and dislodged leads. Administration of low dose medetomidine or dexmedetomidine followed by atipamezole reliably reduced the impact of movement artifacts and produced clinically valid EEG recordings in dogs.

关键词： Dog Brain Electroencephalogram Medetomidine Atipamezole Dexmedetomidine

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Festosterone treatment and cardiovascular events in prescription database studies

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Asian Journal of Andrology 2018年第2期20卷 138-144页

作者： Molly M shores Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine VA Puget Sound Health Care System 1660 South Columbian Way Seattle WA 98108 USA

Over the past decade, there has been a substantial increase in the number of men who are treated with testosterone. Despite this increase in the use of testosterone, the risks of adverse cardiovascular events are unclear as meta-analyses have reported conflicting findings and no clinical studies have been large enough or long enough to adequately assess for cardiovascular risks. The goal of this paper is to review large prescription database studies of testosterone treatment and adverse cardiovascular events and mortality with the aim of providing some guidance for clinicians and researchers in this controversial area.

关键词： cardiovascular diseases cohort studies myocardial infarction stroke testosterone/adverse effects thrombosis

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Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

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World Journal of Gastroenterology 2020年第33期26卷 4889-4899页

作者： Ronald Neil Kostoff Michael Brandon Briggs Darla Roye shores School of Public Policy Georgia Institute of TechnologyGainesvilleVA 20155United States Independent Consultant RoscommonMI 48653United States The Hopkins Resource for Intestinal Vitality and Enhancement the Johns Hopkins University School of MedicineBaltimoreMD 21287United States

Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed *** often includes lifelong immunosuppressive therapy and *** is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential *** of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug *** study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of *** searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from *** most recent 350 records were further analyzed for *** 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD *** of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and *** further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three ***-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.

关键词： Treatment repurposing Treatment repositioning Inflammatory bowel disease Literature-based discovery Text mining Crohn’s disease Ulcerative colitis Novel treatments

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Methylene blue enhances polyethylene glycol-fusion repair of completely severed rat sciatic nerves

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Neural Regeneration Research 2021年第10期16卷 2056-2063页

作者： Cameron L.Ghergherehchi Jaimie T.shores Joseph Alderete Erik K.Weitzel George D.Bittner Institute for Cellular and Molecular Biology University of Texas at AustinAustinTXUSA Department of Plastic and Reconstructive Surgery Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Surgery RESTOR LaboratorySan AntonioTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

Complete transection of peripheral mixed nerves immediately produces loss of sensory perception,muscle contractions and voluntary behavior mediated by the severed distal *** contrast to natural regeneration(~1 mm/d)of proximal axons that may eventually reinnervate denervated targets,re-innervation is restored within minutes by PEG-fusion that consists of neurorrhaphy and a sequence of well specified hypo-and isotonic calcium-free or calcium-containing solutions,the anti-oxidant methylene blue(MB)and the membrane fusogen polyethylene glycol(PEG).In this study,we examined the relative efficacy of PEG-fusion with no MB(0%),0.5%MB,or 1%MB on the recovery of voluntary behaviors by female Sprague-Dawley rats with a complete mid-thigh severance of their sciatic nerve bathed in extracellular fluid or calcium-containing isotonic *** recovery of voluntary behaviors is the most relevant measure of success of any technique to repair peripheral nerve *** assessed recovery by the sciatic functional index,a commonly used measure of voluntary hindlimb behaviors following complete sciatic *** reported that both 1%MB and 0.5%MB in sterile distilled water in our PEG-fusion protocol with neurorrhaphy significantly increased the rate and extent of behavioral recovery compared to PEG plus neurorrhaphy ***,0.5%MB was as effective as 1%MB in voluntary behavioral recovery as assessed by the sciatic functional *** sterile 1%MB is no longer clinically available,we therefore recommend that 0.5%MB be included in upcoming human clinical trials to evaluate the safety and efficacy of *** animal procedures were approved by the University of Texas Institutional Animal Care and Use Committee(AUP-2019-00225)on September 9,2020.

关键词： axotomy methylene blue nerve repair neurorrhaphy peripheral nerve injury polyethylene glycol fusion sciatic nerve

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Recent laser upgrades at Sandia's Z-backlighter facility in order to accommodate new requirements for magnetized liner inertial fusion on the Z-machine

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High Power Laser Science and Engineering 2016年第4期4卷 1-12页

作者： Jens Schwarz Patrick Rambo Darrell Armstrong Marius Schollmeier Ian Smith Jonathan shores Matthias Geissel Mark Kimmel John Porter Sandia National Laboratories

The Z-backlighter laser facility primarily consists of two high energy, high-power laser systems. Z-Beamlet laser(ZBL)(Rambo et al., Appl. Opt. 44, 2421(2005)) is a multi-kJ-class, nanosecond laser operating at 1054 nm which is frequency doubled to 527 nm in order to provide x-ray backlighting of high energy density events on the Z-machine. Z-Petawatt(ZPW)(Schwarz et al., J. Phys.: Conf. Ser. 112, 032020(2008)) is a petawatt-class system operating at 1054 nm delivering up to 500 J in 500 fs for backlighting and various short-pulse laser experiments(see also Figure 10 for a facility overview). With the development of the magnetized liner inertial fusion(MagLIF) concept on the Z-machine, the primary backlighting missions of ZBL and ZPW have been adjusted accordingly. As a result, we have focused our recent efforts on increasing the output energy of ZBL from 2 to 4 kJ at 527 nm by modifying the fiber front end to now include extra bandwidth(for stimulated Brillouin scattering suppression). The MagLIF concept requires a well-defined/behaved beam for interaction with the pressurized fuel. Hence we have made great efforts to implement an adaptive optics system on ZBL and have explored the use of phase plates. We are also exploring concepts to use ZPW as a backlighter for ZBL driven MagLIF experiments. Alternatively, ZPW could be used as an additional fusion fuel pre-heater or as a temporally flexible high energy pre-pulse. All of these concepts require the ability to operate the ZPW in a nanosecond long-pulse mode, in which the beam can co-propagate with ZBL. Some of the proposed modifications are complete and most of them are well on their way.

关键词： adaptive optics high energy lasers MagLIF OPCPA petawatt lasers SBS suppression

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Upper Gastrointestinal Bleeding at a Public Referal Hospital in Malawi

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Surgical Science 2014年第11期5卷 501-507页

作者： Gift Mulima Javeria S.Qureshi Carol shores Salim Tamimi Helena Klackenberg Ake Andren-Sandberg Department of Surgery Kamuzu Central HospitalLilongweMalawi Department of Surgery University of North CarolinaChapel HillUSA Department of Otolaryngology/Head&Neck Surgery University of North CarolinaChapel HillUSA Department of Surgery Karolinska UniversityStockholmSweden

Background: Upper gastrointestinal bleeding (UGIB) is a medical emergency. Timely and appropriate treatment can be lifesaving. Where medical equipment and supplies are inadequate, management of upper gastrointestinal bleeding is challenging. Methods: A retrospective review of charts of patients who were admitted during the year 2010, with a diagnosis of Upper Gastrointestinal Bleeding (UGIB), was done at Kamuzu Central Hospital, Lilongwe, Malawi. A Rockall score was applied to determine mortality risk. Results: A total number of 187 records (119 men and 68 women, mean age of 40.7 ± 15.3 years) were reviewed. The mortality rate was 23.5%, with a non-significant gender difference. Bleeding oesophageal varices were the most common clinical cause of UGIB (42.8%), with more males (63.1%) than females affected. About 40% of patients had no cause of UGIB indicated in their records. 14 (7.5%) patients had a normal oesophagogastroduodenoscopy (OGD). Oesophageal tumor was present in 2.7% of the subjects as a cause of UGIB. Access to endoscopy, for diagnosis and therapeutic intervention, and surgery (Hassab procedure) was available to less than 50% of the patients. Sixteen patients (9.5%) had surgery after endoscopy due to lack of variceal banding materials.?Conclusion:?Upper gastrointestinal bleeding is an important and common clinical problem at Kamuzu Central Hospital. Oesophageal varices seem to be the commonest cause of UGIB. Inadequacy of resuscitation materials and perhaps timely diagnostic and therapeutic endoscopic and surgical interventions are important limiting factors to favourable patient outcome. Work towards regular provision and supply of interventional resources regarding UGIB management may improve patient outcome.

关键词： Upper Gastrointestinal Bleeding(UGIB) Oesophageal Varices Oesophageal Tumor Endoscopy

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Mastabol induced acute cholestasis: A case report

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World Journal of Hepatology 2013年第3期5卷 133-136页

作者： Brett M Hymel David W Victor Luis Alvarez Nathan J shores Luis A Balart Department of Gastroenterology Louisiana State University School of Medicine Department of Gastroenterology and Hepatology Tulane University School of Medicine

A 26-year-old male presented with three weeks of jaundice after the self-initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3one propionate)]. He reported dark urine, light stools, and pruritus. He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL, alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine aminotransferase were 70 units/L and 117 units/L respectively. A working diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia consistent with acute drug induced cholestasis. The patient' s clinical symptoms resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized. Anabolic steroids with 17 alpha carbon substitutions have been associated with a bland variety of cholestatic injury with little hepatocellular injury. Cholestasis, under these circumstances, may be secondary to the binding of drugs to canalicular membrane transporters, accumulation of toxic bile acids from canalicular pump failure, or genetic defects in canalicular transport proteins. Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups at the 17 carbon position. As such, it has been reported to have little potential toxic effects on the liver. This is the first known reported case of Mastabolinduced cholestatic liver injury. It highlights the need for physicians to consider such widely available substances when faced with hepatic injury of unclear etiology.

关键词： Cholestatic Mastabol Hepatic Anabolic Steroids

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Portal vein thrombosis in liver transplantation: radiologic evaluation, risk factors, and occult diagnosis

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Hepatoma Research 2016年第1期2卷 36-41页

作者： Adam Hauch Carl Winkler Eric Katz Peter W.Lundberg Mary Killackey Anil S.Paramesh Luis A.Balart Nathan J.shores Martin Moehlen Ward Miller Douglas P.Slakey Joseph F.Buell Bob H.Saggi Tulane Transplant Institute Tulane University School of MedicineNew OrleansLA 70112USA Department of Gastroenterology Section of HepatologyTulane University School of MedicineNew OrleansLA 70112USA

Aim:Portal vein thrombosis(PVT)in the liver transplant recipient poses many ***,the risk factors and effects on outcomes of PVT are not ***:This study analyzed the experience with PVT in liver transplant program from 2007 to *** included the effectiveness of PVT diagnostics and its risk factors using logistical *** primary endpoints were Kaplan-Meir patient and graft *** secondary endpoints were the length of stay(LOS),transfusion rate,and overall *** predictors of survival were identified using a Cox’s proportional hazards ***:Two hundred and sixteen consecutive liver transplant recipients were examined,and 30(13.8%)had either a total or partial *** hundred and five patients had imaging within 1 year of liver transplantation with only 7(23.3%)of the 30 PVTs identified *** sensitivity(4.8-50%)and negative predictive values(10.5-22.2%)were ***,age significantly predicted PVT[P=0.037/hazard ratio(HR)=0.95].Ninety-day-patient and graft survival for PVT was similar at 6 months,although 1-year survival was significantly lower.“Occult”PVT was not associated with inferior *** for end-stage liver disease score>25(P=0.001,HR=0.49/P=0.004,HR=0.52)and age>60 years(P=0.017,HR=0.64/P=0.013,HR=0.67)were significant predictors of patient and graft *** the transfusion rate was significantly greater with PVT,LOS,and morbidity were ***:Older recipients had a greater likelihood of *** studies were not effective at excluding PVT,and occult diagnosis did not affect the *** was not an independent predictor of mortality or graft loss,but was associated with greater blood loss but not increased LOS or morbidity.

关键词： Advanced age graft survival patient survival post-transplant outcomes resource utilization

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Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*

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Open Journal of Preventive Medicine 2020年第6期10卷 126-150页

作者： George P. Albaugh Sudhir K. Dutta Vasantha Iyengar Samina Shami Althaf Lohani Eduardo Sainz George Kessie Prasanna Nair Sara Lagerholm Alka Kamra J.-H. Joshua Chen Shilpa Kalavapudi Rakesh Vinayek Robert shores Laila E. Phillips Ram Nair Padmanabhan P. Nair Beltsville Human Nutrition Research Centre Agricultural Research Service Beltsville MD USA Division of Gastroenterology Sinai Hospital of Baltimore Baltimore MD USA Department of International Health Johns Hopkins University Bloomberg School of Public Health Baltimore MD USA NonInvasive Technologies LLC Elkridge MD USA Department of Pediatrics University of Maryland School of Medicine Baltimore MD USA

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

关键词： Colon Epithelial Cells CXCR-4 IgA/IgG Chimeric Immunoglobulin Heterodimer COX-2 LGR-5 Musashi-1 Dedifferentiation Cellular Engraftment Oncoly-sis Gastrointestinal Progenitor Stem Cells (GIP-C)

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神经纤维瘤病1型患儿认知功能缺陷的性质和发生率

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世界核心医学期刊文摘（神经病学分册） 2006年第3期2卷 27-27页

作者： Hyman S.L. shores A. North K.N. 王孝文 Children's Hospital at Westmead Clinical Sciences Building Locked Bag 4001 Westmead NSW 2145 Australia

Objective: To assess the frequency and severity of specific cognitive deficits in children with neurofibromatosis type 1 (NF1) in a large unbiased cohort. Methods: Extensive cognitive assessments were performed in 81 children with NF1 ages 8 to 16 years and their performance was compared with that of 49 unaffected sibling controls. Results: Eighty-one percent of the children with NF1 had moderate to severe impairment in one or more areas of cognitive functioning. Although 51%of children with NF1 performed poorly on tasks of reading, spelling, and mathematics, specific learning disabilities (as defined by IQ achievement discrepancies) were present in only 20%of the children. Sustained attention difficulties were present in 63%of children with NF1, with 38%of children with NF1 fulfilling the diagnostic criteria for attention deficit-hyperact- ivity disorder. The NF1 neuropsychological profile is characterized by deficits in perceptual skills (visuospatial and visuoperceptual), executive functioning (planning and abstract concept formation), and attention (sustained and switching). Interestingly, both verbal and visual memory was unaffected in NF1 children, and their memory skills were in general stronger than their level of general intellectual function. Although both expressive and receptive language skills were significantly impaired in NF1 children, they appeared to be relatively better preserved than visuospatial abilities once IQ is taken into account. Conclusion: There is an extremely high frequency of cognitive problems in children with neurofibromatosis type 1, making cognitive dysfunction the most common complication to affect quality of life in these children.

关键词：神经纤维瘤病认知功能执行功能神经心理视知觉重度损伤全面认知功能评估数学能力空间感觉

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