DOCSLIB.ORG

2021 ACMT Annual Scientific Meeting Abstracts—Virtual

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
2021 ACMT Annual Scientific Meeting Abstracts—Virtual Journal of Medical Toxicology https://doi.org/10.1007/s13181-021-00832-9 ANNUAL MEETING ABSTRACTS 2021 ACMT Annual Scientific Meeting Abstracts—Virtual Abstract: These are the abstracts of the 2021 American College of 001. Gender-Based Production of N-Acetyl-P-Benzoquinone Imine Medical Toxicology (ACMT) Annual Scientific Meeting. Included here Protein Adduct Formation With Therapeutic Acetaminophen are 178 abstracts that will be presented in April 2021, including research Administration studies from around the globe and the ToxIC collaboration, clinically significant case reports describing toxicologic phenomena, and encore Brandon J Sonn1, Kennon J Heard1,2, Susan M Heard2,Angelo research presentations from other scientific meetings. D'Alessandro1, Kate M Reynolds2, Richard C Dart2, Barry H Rumack1,2,AndrewAMonte1,2 Keywords: Abstracts - Annual Scientific Meeting - Toxicology 1University of Colorado Denver, Aurora, Colorado, USA. 2Rocky Investigators Consortium - Medical Toxicology Foundation Mountain Poison and Drug Center, Denver, Colorado, USA Correspondence: American College of Medical Toxicology (ACMT) Background: Acetaminophen (APAP)-associated transaminase elevation, 10645 N. Tatum Blvd Phoenix, AZ; [email protected] induced by N-acetyl-p-benzoquinone imine (NAPQI) protein adduction, re- mains a global concern. Distinct from known genetic, physiologic, and dos- Introduction: The American College of Medical Toxicology (ACMT) age associations dictating severity of hepatic injury, no known factors predict received 188 eligible research abstracts for consideration for presentation an absence of NAPQI protein adduct formation at therapeutic APAP dosing. at the 2021 Annual Scientific Meeting (ASM), including 85 research Hypothesis: Gender-based physiologies are predictive of APAP-induced studies and 103 case reports. Each abstract was reviewed in a blinded protein adduct formation at therapeutic doses. fashion by at least three Research Committee members. Each abstract Methods: This retrospective study is interrogating serum samples collect- was independently scored based on the clinical question, data source, ed for a prior study investigating fluctuations of alanine aminotransferase analytic method, results/conclusion, and clarity of presentation. A total (ALT) over time with 4 grams daily APAP dosing for ≥ 16 days in of 178 abstracts were accepted. This work would not be possible without subjects from Denver, Colorado. Subjects were grouped by NAPQI ad- the hard work and diligence of our abstract reviewers: Justin Arnold, Katie duct formation (n = 184) vs no adducts (n = 20). Samples were run on Boyle, Jeffrey Brent, Keith Burkhart, Jennifer Carey, Stephanie Carreiro, ultra-high performance liquid chromatography mass spectrometry from James Chenowth, Neeraj Chhabra, Jon Cole, Nick Connors, Fiona days 0, 7, 16, and 31. Significant metabolite expressions were identified Garlich, Spender Greene, Rob Hendrickson, Michelle Hieger, David using t-tests with false discovery rate correction (FDR), partial least Juurlink, Louise Kao, Kenneth Katz, Russ Kerns, Andrew King, Kathy squares discriminant, and ANOVA simultaneous comparison analyses. Kopec, JoAn Laes, Eric Lavonas, Michael Levine, David Liss, Kevin Demographic and clinical data were explored using t-tests with FDR (age, Maskell, William Meggs, Andrew Monte, Elissa Moore, Babak weight, BMI, ALT) and chi-square (gender, ethnicity, race) analyses. Mostafazadeh, Mark Mycyk, Mark Neavyn, Travis Olives, Patricia Results: In pre-treatment samples, relative quantitation caprylic acid was Rosen, Evan Schwarz, Samuel Stellpflug, Mark Su, Manoj Tyagi, expressed nine-fold higher and 6-carboxyhexanoate was expressed three- Shawn Varney, Steven Walsh, Richard Wang, Sage Wiener, Brandon fold lower in subjects who did not develop adducts. Lactate had greater Wills, and Luke Yip. We would also like to thank the Fellows who par- expression in the no adducts group (p = NS). Using absolute quantitation, ticipated in the inaugural review mentorship program: Vincent Calleo, glutathione was expressed 2.6-fold greater among no adduct subjects. Richard Chen, Joseph Kennedy, Jacob Lebin, and Christopher Meaden. Odds of men developing NAPQI protein adducts at therapeutic APAP Equally significant is the contribution of the ACMT staff (Adrienne dosing are 5.91 times lower than women (95% CI=2.3–14.9; p = 0.0001). Dunavin and Sandra Kirilovic) who led the process. Congratulations to Conclusion: Multiple metabolites were significantly expressed within the all the contributors whose work will be presented in April. no adduct group with known greater expression in males, such as lactate. Additionally, metabolites were identified unique to adduct development We look forward to seeing you there. independent of gender such as caprylic acid. At therapeutic APAP dosing, males are less likely to develop NAPQI protein adducts. Further research Christine Murphy, MD, FACMT, Abstract Review Chair; Peter Chai, into lipid biosynthesis and metabolism may provide further insight into MD, FACMT, Abstract Review Co-Chair; Maryann Amirshahi, physiology associated with NAPQI production. PharmD, MD, MPH, PhD, FACMT, Chair, ACMT Research Committee 002. Platelet Mitochondrial Dysfunction in Acute Acetaminophen Toxicity and with 4-Methylpyrazole Treatment 2021 ACMT Annual Scientific Meeting Abstracts—Virtual Carolyn Fox, Michael Ekaney, Michael Runyon, Iain H McKillop, Christine Murphy Day 1: Platforms, Abstracts 001–004 Atrium Health's Carolinas Medical Center, Charlotte, NC, USA J. Med. Toxicol. Background: Clinical and experimental data suggest administration of 4- Results: Injection of 500 mg/kg APAP led to significantly changed methylpyrazole (4-MP) and N-acetylcysteine in severe acetaminophen POC within 12 hours versus both control and 300 mg/kg APAP −7 (APAP) overdoses may improve morbidity and mortality. In the clinical (−2.19 ± 0.45 × 10 μgO2/min/platelet [500 mg-APAP] versus −8 setting, rapidly determining the degree of hepatic damage following −5.52 ± 1.73 × 10 μgO2/min/platelet [Control] and −7.22 ± 0.70 −8 APAP overdose remains challenging. ×10 μgO2/min/platelet [300 mg-APAP]; P < 0.05, 500 mg-APAP Hypothesis: Acetaminophen toxicity is ameliorated by 4-MP in an ex- versus Control and 300 mg-APAP), effects that were maintained at perimental model of APAP-toxicity in vivo, effects that are detectable by 24 hours. Administration of 4-MP did not significantly affect POC in changes in circulating platelet mitochondrial function assessed by control or 300 mg/kg-APAP mice. Conversely, in mice receiving 500 platelet-oxygen consumption (POC). mg/kg-APAP+4-MP, POC changed at both 12 hours (−2.19 ± 0.45 × −7 −7 Methods: Male C57Bl/6 mice (8–12 weeks old) were randomized to 10 μgO2/min/platelet [500 mg-APAP] versus −1.10 ± 0.15 × 10 receive APAP (500 or 300 mg/kg) or vehicle (0.9% [w/v] sodium chlo- μgO2/min/platelet [500 mg-APAP+4-MP]) and 24 hours (−2.22 −7 ride) intraperitoneally (ip) followed by either 4-MP treatment (50 mg/kg) ±0.49 × 10 μgO2/min/platelet [500 mg-APAP] versus −0.81 ± −7 or vehicle ip injection 90 minutes after APAP administration. Mice were 0.12 × 10 μgO2/min/platelet [500 mg-APAP+4-MP]). POC of euthanized 0 (control), 12, or 24 hours after APAP administration, and mice treated with 500 mg/kg-APAP+4-MP were not significantly platelets from cardiac blood were isolated and counted. Using a closed different from time-matched vehicle and vehicle+4MP groups. system to measure POC, mitochondrial function was determined as a ratio Conclusion: Platelet mitochondrial function can be used as an early bio- of total oxygen consumption to platelet number. Differences between marker of acute APAP toxicity, and 4-MP treatment may mitigate the groups at each time point were evaluated by analysis of variance. harmful effects of APAP on platelet mitochondrial function. This research was supported by a 2020 Medical Toxicology Foundation Innovative Research and Teaching Award. 003. Late Hemotoxicity following North American Rattlesnake venom for rattlesnake envenomation. Cases were excluded for Envenomation Treated with Crotalidae Immune F(ab’)2 (Equine) incomplete data and if less than one set of follow-up laboratory Antivenom (Anavip®) values was obtained. Data collected included demographics, en- venomation characteristics, laboratory values, and treatment ad- Meghan B Spyres1,2, Gabriel Padilla3, Richard D Gerkin1,2,Anne- ministered. Statistics: t-test and Fisher’s exact test. Hemotoxicity Michelle Ruha1,2, On Behalf of the ToxIC Investigators Consortium was defined as platelets <120 K/mm3 or fibrinogen < 170 mg/dL; (ToxIC) hemotoxicity was considered late on follow-up if values met 1Banner University Medical Center Phoenix, Phoenix, AZ, USA. threshold and were decreased from discharge value. 2University of Arizona College of Medicine Phoenix, Phoenix, AZ, Results: One hundred thirteen rattlesnake bites receiving antivenom were USA. 3University of Southern California Keck Medical School, Los reported to the NASBR in 2019, 111 were included. Twenty-seven received Angeles, CA, USA Anavip® alone, 50 received Crofab® alone, and 34 received both antivenoms. Baseline patient and envenomation characteristics were similar Background: Late hemotoxicity is common following rattlesnake en- between the groups. For single antivenom cases, Anavip® cases received venomation treated with Fab antivenom (CroFab®). Clinical trials more vials than Crofab® cases (17 vs. 11; p < 0.001), but discrete dosing showed Anavip® to be superior
Load more

Recommended publications
  • Poisoning – Investigative and Management Protocols
    UNIT-1 Management of Common Clinical Poisoning Dr. Pallav Shekhar Asstt. Professor Veterinary Medicine Suspection Common Symptoms exhibited by large no. of animals at a time. ➢ Sudden death ➢ Salivation ➢ Vomition ➢ Neurological signs ➢ Presence of mouldy feeds ➢ Presence of house hold waste and medicaments ➢ Sewage water contamination ➢ Presence of dead rat or rat wait ➢ Spray of insecticides, weedicides. ➢ Use of paint Principal of treatment Prevention of further exposure Alkalis are more dangerous than acids. Acids form insoluble acid proteinates and hence its effect is partially self limiting Alkalis form alkali proteinates along with soaps which will penetrate rapidly into tissues. Inhaled poisons can be eliminated by providing assisted ventilation. Topical applied toxicant can be removed by washing with plenty of water and soap. Skin contact can be eliminated by washing with plenty of water and soap if the poison is water soluble and with organic solvents like Benzene, alcohol if they are fat soluble Conti…. Clipping of hair or wool may be necessary Emesis is of value in dogs, cats and pigs if done within few hours of ingestion. Emesis is contraindicated when ▪ The swallowing reflex is absent ▪ Animal is convulsive ▪ Corrosive agent or volatile hydrocarbons or petroleum product ingested Conti…. Emetics: a) Oral: I. Syrup of ipecac; 10-20ml in dogs II. Hydrogen peroxide: 2ml/kg b) Parenteral: Apomorphine can be used in dogs at dosage of 0.05-0.1mg/kg Conti… Gastric lavage: This is done in mono-gastric animals and 10ml lavage fluid/kg body weight should be given. Potassium permanganate solution This is done with Endotracheal tube and stomach tube Conti… Insertion of stomach tube in cattle for gastric lavage Conti.
    [Show full text]
  • The In¯Uence of Medication on Erectile Function
    International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 The in¯uence of medication on erectile function W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4 1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands Keywords: impotence; side-effect; antipsychotic; antihypertensive; physiology; erectile function Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the drug registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion-drugs on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing priapism will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted.
    [Show full text]
  • Automated Kappa Number Determination of Pulp
    Application Note YSI, a Xylem Brand • XA00077 Automated Kappa Number Determination of Pulp PULP & PAPER SERIES Introduction The Kappa number describes the Lignin content of pulp which gives information about the bleaching process of the pulp. The longer the pulp was cooked and bleached the lower the Kappa number is. For the determination of the Kappa number a sample weight adjusted to the expected result is chopped and inserted into a beaker, then 400 ml of water is added. The sample/water mixture is stirred for 10 minutes. Afterwards 50 ml of potassium permanganate (KMnO4, 0.02 mol/L) and 50 ml sulfuric acid (H2SO4, 2 mol/L) are added simultaneously. The mixture is stirred for another 10 minutes. The reaction is stopped by adding 10 ml potassium iodide (KI, 1mol/l). The excess of KMnO4 reacts with Iodide to Iodine, which is titrated with sodium thiosulfate (Na2S2O3, 0.2 mol/L). Chemical Equations: The weight is adjusted to a consumption of about 50% of the MnO4- . - + ➔ - Lignin + MnO4 + 4 H oxidised Lignin + MnO4 (excess) + MnO2 + 2 H2O The reaction is stopped by adding KI. - - + ➔ 2+ 2 MnO4 + 10 I + 16 H 2 Mn + 5 I2 + 8 H2O The formed Iodine is titrated with Na2S2O3. 2- ➔ - 2 S2O3 + I2 S4O6 + 2 I Calculation of the Kappa number: 1. Calculation of the consumed volume Va of KMnO4: 2. Calculation of a correction factor d, which corrects the consumption of permanganate depending on Va to a V1 – V2)c Va = consumption of 50%. 0.1 with d= 100.00093 (2Va – 50) In(10) • 0.00093 (2Va– 50)) V1 = Consumption of Na2S2O3 during blank titration = e V2 = Consumption of Na2S2O3 during sample titration c = Concentration of Na2S2O3 3.
    [Show full text]
  • Page 1 of 7 Analyst
    Analyst Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/analyst Page 1 of 7 Analyst 1 2 Analyst RSC Publishing 3 4 5 ARTICLE 6 7 8 9 Enhancing permanganate chemiluminescence 10 detection for the determination of glutathione and 11 Cite this: DOI: 10.1039/x0xx00000x 12 glutathione disulfide in biological matrices 13 14 a a a b 15 Zoe M. Smith, Jessica M. Terry, Neil W. Barnett, Laura J. Gray, Dean J. Received 00th January 2012, Wright c and Paul S. Francis a* 16 Accepted 00th January 2012 17 18 DOI: 10.1039/x0xx00000x Acidic potassium permanganate chemiluminescence enables direct post-column detection of 19 glutathione, but its application to assess the redox state of a wider range of biological fluids www.rsc.org/ 20 and tissues is limited by its sensitivity.
    [Show full text]
  • University of Colorado Denver Anschutz Medical Campus Msa Capstone Presenations
    UNIVERSITY OF COLORADO DENVER ANSCHUTZ MEDICAL CAMPUS ANNUAL STUDENT MSA CAPSTONE PRESENTATIONS MARCH 2, 2017 ANSCHUTZ MEDICAL CAMPUS HEALTH AND SCIENCES LIBRARY UNIVERSITY OF COLORADO DENVER ANSCHUTZ MEDICAL CAMPUS MSA CAPSTONE PRESENATIONS Thursday, March 2, 2017 Poster Sessions Session A: 1:00 pm – 2:00 pm Session B: 2:15 pm – 3:15 pm Session C: 3:30 pm – 4:30 pm ANSCHUTZ MEDICAL CAMPUS Health Sciences Library The MSA Directors to acknowledge, with gratitude, the support for medical student research provided by: The University of Colorado Denver School of Medicine Dean’s Office And Undergraduate Medical Education Office Poster Session Judges The organizing committee wishes to acknowledge their appreciation to the following serving as judges for the MSA Capstone Presentations. Without their generous contribution of time and talent the forum would not be possible. Thank you! Madiha Abdel-Maksoud, MP, MSPH, PhD Rooban Nahomi, PhD David Ammar, PhD Matthew Nalty, BA Ilango Balakrishnan, PhD Kristen Nowak, PhD, MPH Carl Barnes, MD David Orlicky, Ph.D. Adria Boucharel, MD David Orlicky, Ph.D. Joseph Brzezinski, PhD Clare Paterson, PhD William Cornwell. MD Karin Payne, PhD Colleen Dingmann, R.N, Ph.D. Mark Petrash, PhD Michele Doucette, Ph.D. Miriam Post, MD Charles Edelstein, MD, PhD Allan Prochazka, MD, MSc Adit Ginde, MD, MPH Laura Pyle, PhD Jackie Glover, Ph.D Cordelia Robinson Rosenberg, PhD, RN Daniel Goldberg, JD, PhD Joseph Sakai, MD Maryam Guiahi, MD, MSc David Schwartz, MD Pearce Korb, MD Robert Sclafani, PhD Luidmila Kulik, PhD Deb Seymour, PsyD Rita Lee, MD Nicole Tartaglia, MS, MD Steven Lowenstein, MD, MPH Jean Tsai, MD, PhD Wendy Macklin, PhD Catherine Velopulos, MD, MHS Sandy Martin, PhD Laura Wiley, PhD Leana May DO, MPH Seonghwan Yee, PhD Jose Mayordomo, Ph.D.
    [Show full text]
  • 615.9Barref.Pdf
    INDEX Abortifacient, abortifacients bees, wasps, and ants ginkgo, 492 aconite, 737 epinephrine, 963 ginseng, 500 barbados nut, 829 blister beetles goldenseal blister beetles, 972 cantharidin, 974 berberine, 506 blue cohosh, 395 buckeye hawthorn, 512 camphor, 407, 408 ~-escin, 884 hypericum extract, 602-603 cantharides, 974 calamus inky cap and coprine toxicity cantharidin, 974 ~-asarone, 405 coprine, 295 colocynth, 443 camphor, 409-411 ethanol, 296 common oleander, 847, 850 cascara, 416-417 isoxazole-containing mushrooms dogbane, 849-850 catechols, 682 and pantherina syndrome, mistletoe, 794 castor bean 298-302 nutmeg, 67 ricin, 719, 721 jequirity bean and abrin, oduvan, 755 colchicine, 694-896, 698 730-731 pennyroyal, 563-565 clostridium perfringens, 115 jellyfish, 1088 pine thistle, 515 comfrey and other pyrrolizidine­ Jimsonweed and other belladonna rue, 579 containing plants alkaloids, 779, 781 slangkop, Burke's, red, Transvaal, pyrrolizidine alkaloids, 453 jin bu huan and 857 cyanogenic foods tetrahydropalmatine, 519 tansy, 614 amygdalin, 48 kaffir lily turpentine, 667 cyanogenic glycosides, 45 lycorine,711 yarrow, 624-625 prunasin, 48 kava, 528 yellow bird-of-paradise, 749 daffodils and other emetic bulbs Laetrile", 763 yellow oleander, 854 galanthamine, 704 lavender, 534 yew, 899 dogbane family and cardenolides licorice Abrin,729-731 common oleander, 849 glycyrrhetinic acid, 540 camphor yellow oleander, 855-856 limonene, 639 cinnamomin, 409 domoic acid, 214 rna huang ricin, 409, 723, 730 ephedra alkaloids, 547 ephedra alkaloids, 548 Absorption, xvii erythrosine, 29 ephedrine, 547, 549 aloe vera, 380 garlic mayapple amatoxin-containing mushrooms S-allyl cysteine, 473 podophyllotoxin, 789 amatoxin poisoning, 273-275, gastrointestinal viruses milk thistle 279 viral gastroenteritis, 205 silibinin, 555 aspartame, 24 ginger, 485 mistletoe, 793 Medical Toxicology ofNatural Substances, by Donald G.
    [Show full text]
  • The Pharmacology of Calcium and ATP-Dependent Potassium
    THE PHARMACOLOGY OF CALCHJM AND ATP-DEPENDENT POTASSHJM CHANNELS IN ERYTHROCYTES AND IN SMOOTH AND SKELETAL MUSCLE D. C H. Benton A thesis submitted for the degree of Doctor of Philosophy Department of Pharmacology University College London Gower Street LONDON WCIE 6BT 1995 ProQuest Number: 10044587 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10044587 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Potassium channels are a diverse class of membrane proteins found in virtually all cells. The first part of this study concerns the pharmacology of the calcium activated potassium channel found in mammalian erythrocytes. This channel is blocked by cetiedil, an anti-sickling agent, and the initial section of the thesis explores the structure activity relationship (SAR) of compounds related to cetiedil, investigates their mechanism of action and compares them with other blocking agents. This was studied by measuring the effects of the test compounds on the K^a -mediated net K'*' loss which results from the application of A23187 to a suspension of rabbit erythrocytes.
    [Show full text]
  • Question of the Day Archives: Monday, December 5, 2016 Question: Calcium Oxalate Is a Widespread Toxin Found in Many Species of Plants
    Question Of the Day Archives: Monday, December 5, 2016 Question: Calcium oxalate is a widespread toxin found in many species of plants. What is the needle shaped crystal containing calcium oxalate called and what is the compilation of these structures known as? Answer: The needle shaped plant-based crystals containing calcium oxalate are known as raphides. A compilation of raphides forms the structure known as an idioblast. (Lim CS et al. Atlas of select poisonous plants and mushrooms. 2016 Disease-a-Month 62(3):37-66) Friday, December 2, 2016 Question: Which oral chelating agent has been reported to cause transient increases in plasma ALT activity in some patients as well as rare instances of mucocutaneous skin reactions? Answer: Orally administered dimercaptosuccinic acid (DMSA) has been reported to cause transient increases in ALT activity as well as rare instances of mucocutaneous skin reactions. (Bradberry S et al. Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning. 2009 Q J Med 102:721-732) Thursday, December 1, 2016 Question: What is Clioquinol and why was it withdrawn from the market during the 1970s? Answer: According to the cited reference, “Between the 1950s and 1970s Clioquinol was used to treat and prevent intestinal parasitic disease [intestinal amebiasis].” “In the early 1970s Clioquinol was withdrawn from the market as an oral agent due to an association with sub-acute myelo-optic neuropathy (SMON) in Japanese patients. SMON is a syndrome that involves sensory and motor disturbances in the lower limbs as well as visual changes that are due to symmetrical demyelination of the lateral and posterior funiculi of the spinal cord, optic nerve, and peripheral nerves.
    [Show full text]
  • The Example of Short QT Syndrome Jules C
    Hancox et al. Journal of Congenital Cardiology (2019) 3:3 Journal of https://doi.org/10.1186/s40949-019-0024-7 Congenital Cardiology REVIEW Open Access Learning from studying very rare cardiac conditions: the example of short QT syndrome Jules C. Hancox1,4* , Dominic G. Whittaker2,3, Henggui Zhang4 and Alan G. Stuart5,6 Abstract Background: Some congenital heart conditions are very rare. In a climate of limited resources, a viewpoint could be advanced that identifying diagnostic criteria for such conditions and, through empiricism, effective treatments should suffice and that extensive mechanistic research is unnecessary. Taking the rare but dangerous short QT syndrome (SQTS) as an example, this article makes the case for the imperative to study such rare conditions, highlighting that this yields substantial and sometimes unanticipated benefits. Genetic forms of SQTS are rare, but the condition may be under-diagnosed and carries a risk of sudden death. Genotyping of SQTS patients has led to identification of clear ion channel/transporter culprits in < 30% of cases, highlighting a role for as yet unidentified modulators of repolarization. For example, recent exome sequencing in SQTS has identified SLC4A3 as a novel modifier of ventricular repolarization. The need to distinguish “healthy” from “unhealthy” short QT intervals has led to a search for additional markers of arrhythmia risk. Some overlap may exist between SQTS, Brugada Syndrome, early repolarization and sinus bradycardia. Genotype-phenotype studies have led to identification of arrhythmia substrates and both realistic and theoretical pharmacological approaches for particular forms of SQTS. In turn this has increased understanding of underlying cardiac ion channels.
    [Show full text]
  • Vasoplegic Syndrome After Pediatric Cardiac Surgery
    Journal of Anesthesia & Critical Care: Open Access Review Article Open Access Vasoplegic syndrome after pediatric cardiac surgery Abstract Volume 12 Issue 3 - 2020 Vasoplegic syndrome (VS) is a form of vasodilatory shock that occurs in the early period in Pınar Yıldırım Özkan,1 Ahmet Akyol,1 pek patients who undergo cardiac surgery requiring cardiopulmonary bypass (CBP). Vasoplegic 2 1 1 syndrome, reported between 9 and 44%, is characterized by severe hypotension,severe Erus, AhuBaysal Çitil, Ayşe Duygu Kavas, 3 decrease in systemic vascular resistance, decreased arteriolar reactivity, need for increased Ahmet Ero lu İ 1 volume, and decreased response to norepinephrine, despite normal ardiac outflow. The University of Health Sciences, Ümraniye Training and Vasoplegia is associated with high mortality and morbidity, especially in pediatric patients. Research Hospital,ğ Clinic of Anesthesiology and Intensive Care, The pathophysiology of vasoplegic syndrome includes disruption of the arteriolar tone, Turkey 2Koc University, Medical Faculty, Clinic of Anesthesiology and which is regulated by endothelial function and neurohumoral system.Methylene blue is Intensive Care, Turkey safely used when administered at a dose below 2mg/kg while more prospective randomized 3KTU, Medical Faculty, Clinic of Anesthesiology and Intensive controlled trials are needed to determine the effective dose range. Care, Turkey Keywords: vasoplegic syndrome, pediatric, cardiac surgery, methylene blue, Correspondence: Assoc. Prof.Dr.Ahmet AKYOL, The cardiyopulmoner bypass, prostaglandin infusion, pleth variability index, cross clamp University of Health Sciences, Ümraniye Training and Research Hospital, Clinic of Anesthesiology and Intensive Care, ElmalikentMah. AdemYavuz Cad. No: 1. (34764) Ümraniye, stanbul, Turkey, Tel +90 533 6331369, Email İ Received: April 29, 2020 | Published: May 21, 2020 Introduction min), SpO2 was 85%, BP 69/37 mmHg, and pulse 168/min at room temperature.
    [Show full text]
  • Thiruttu Tuomittur
    THIRUTTUUS009782416B2 TUOMITTUR (12 ) United States Patent ( 10 ) Patent No. : US 9 ,782 ,416 B2 Cowen (45 ) Date of Patent: Oct. 10 , 2017 ( 54 ) PHARMACEUTICAL FORMULATIONS OF 4 , 880 , 830 A 11/ 1989 Rhodes POTASSIUM ATP CHANNEL OPENERS AND 4 ,894 , 448 A 1 / 1990 Pelzer 5 ,063 , 208 A 11/ 1991 Rosenberg et al . USES THEREOF 5 , 284 ,845 A 2 / 1994 Paulsen 5 ,356 ,775 A 10 / 1994 Hebert et al . (71 ) Applicant: Essentialis , Inc. , Carlsbad , CA (US ) 5 ,376 , 384 A 12 / 1994 Eichel et al. 5 , 378 , 704 A 1 / 1995 Weller, III (72 ) Inventor: Neil Madison Cowen , Carlsbad , CA 5 , 399 , 359 A 3 / 1995 Baichwal 5 ,415 , 871 A 5 / 1995 Pankhania et al . (US ) 5 ,629 , 045 A 5 / 1997 Veech 5 , 733 , 563 A 3 / 1998 Fortier (73 ) Assignee : Essentialis , Inc. , Redwood City , CA 5 , 744 , 594 A 4 / 1998 Adelman et al . (US ) 5 , 965 ,620 A 10 / 1999 Sorgente et al . 6 ,022 , 562 A 2 /2000 Autant et al . 6 , 140 , 343 A 10 / 2000 Deninno et al . ( * ) Notice : Subject to any disclaimer , the term of this 6 , 146 ,662 A 11/ 2000 Jao et al . patent is extended or adjusted under 35 6 , 197, 765 B1 3 / 2001 Vardi et al. U . S . C . 154 (b ) by 0 days . 6, 197, 976 B1 3 / 2001 Harrington et al . 6 , 225, 310 B1 5 / 2001 Nielsen et al. (21 ) Appl. No. : 14 / 458 ,032 6 , 255 , 459 B1 7 / 2001 Lester et al . 6 , 277, 366 B1 8 / 2001 Goto et al .
    [Show full text]
  • When Fluids Are Not Enough: Inopressor Therapy Problems in Neonatology
    When Fluids are Not Enough: Inopressor Therapy Problems in Neonatology • Neonatal problem: hypoperfusion Severe sepsis Hallmark of septic shock Secondary to neonatal encephalopathy Vasoplegia Syndrome?? • First line therapy Fluid loading – 20 ml/kg boluses • Inopressor therapy Inotropic therapy Pressor therapy Treating Hypoperfusion • GOAL: return of perfusion Not to achieve a given set of blood pressure values • Measure of perfusion Flow is proportional to left ventricular output Flow is inversely proportional to vascular resistance BP is a measure of these • But… High blood pressure ≠ flow Low blood pressure ≠ no flow BP and Capillary Perfusion Clinical Experience • BP does not correlate with microcirculatory flow • Increasing BP with noradrenaline Unpredictable effects on capillary perfusion • Normalizing BP with pure vasoconstrictor Phenylephrine Decrease microcirculatory perfusion • Impaired cardiac function Vasopressor increases afterload Reduce cardiac output with increase BP No benefit global perfusion Perfusion Physiology • Normal foal BP ≠ perfusion (tissue blood flow) • Microcirculation controlled by metabolic demand + • ADP, K, H or NO (shear stress), O2 levels • When decrease BP Sympathetic control • Overrides tissue-driven blood flow regulation • Baroreceptors response Peripheral vasoconstriction to preserve • Preserve heart and brain perfusion • At expense of global tissue hypoperfusion • Shock Hydrostatic Pressure A = arteriolar constriction B = arteriolar dilation Dünser et al. Critical Care 2013, 17:326 Permissive Hypotension
    [Show full text]