David A Jett

National Institutes of Health, 베서스다, Maryland, United States

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Publications (13)39.92 Total impact

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    David A. Jett, David T. Yeung
    Handbook of Toxicology of Chemical Warfare Agents, 2nd edited by Ramesh C. Gupta, 01/2015: chapter 70: pages 1049-56; Academic Press., ISBN: 978-0-12-800159-2
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    ABSTRACT: The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl2, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes.
    Toxicology and Applied Pharmacology 10/2014; 281(3):254-65. DOI:10.1016/j.taap.2014.10.009 · 3.63 Impact Factor
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    ABSTRACT: Dose-lethality response curves were characterized in non-sedated, atropinized Dunkin-Hartley male guinea pigs for the nerve agents tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VX, the pesticides aldicarb and methomyl, and the oxon metabolites paraoxon, phorate oxon (PHO), and chlorpyrifos oxon (CPO) administered by subcutaneous (SC) injection in guinea pigs that subsequently received atropine free base at 0.4 mg/kg, the guinea pig human-equivalent dose of atropine after administration of three Atropen® or DuoDote® autoinjectors. Lethality rates were obtained at 24 hr after challenge by percutaneous challenge. Probit analysis was used to calculate the median lethal dose (LD50). Protective ratios (PR) for atropine were calculated as the LD50 for a challenge material (CM) in atropinized guinea pigs divided by the LD50 for the same CM in no-therapy guinea pigs using data from either the literature or concurrent experiments. Statistically significant (p < 0.05) therapy in terms of survival was attributed to atropine therapy against a SC challenge of GA, aldicarb, and methomyl. Atropine alone at 0.4 mg/kg did not improve survivability against any other CM exposure by SC injection. These data suggest that the recommended dose of atropine alone administered in the pre-hospital setting may not be a sufficient medical countermeasure for most OP nerve agents and some important pesticides.
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    ABSTRACT: The Chemical Events Working Group of the Global Health Security Initiative has developed a flexible screening tool for chemicals that present a risk when accidentally or deliberately released into the atmosphere. The tool is generic, semi-quantitative, independent of site, situation and scenario, encompasses all chemical hazards (toxicity, flammability and reactivity), and can be easily and quickly implemented by non-subject matter experts using freely available, authoritative information. Public health practitioners and planners can use the screening tool to assist them in directing their activities in each of the five stages of the disaster management cycle.
    BMC Public Health 03/2013; 13(1):253. DOI:10.1186/1471-2458-13-253 · 2.32 Impact Factor
  • David A Jett
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    ABSTRACT: Seizurogenic chemicals include a variety of toxic agents, including chemical warfare agents, toxic industrial chemicals, and natural toxins. Chemical weapons such as sarin and VX, and pesticides such as parathion and carbaryl cause hyperstimulation of cholinergic receptors and an increase in excitatory neurotransmission. Glutamatergic hyperstimulation can occur after exposure to excitatory amino acid toxins such as the marine toxin domoic acid. Other pesticides such as lindane and strychnine do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory GABA and glycine synapses. In this article is a discussion of chemicals that cause seizures by a variety of molecular mechanisms and pathways.
    NeuroToxicology 10/2012; 33(6). DOI:10.1016/j.neuro.2012.10.005 · 3.05 Impact Factor
  • David A Jett
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    ABSTRACT: Pesticides represent one of the largest classes of toxic chemicals produced, stored, and used in the United States and abroad. These chemicals are designed to be toxic and many, besides being toxic to the pests they are intended to control, are also toxic to nontarget species including humans. The article gives a brief review of their toxicity to humans with emphasis on their effects on the nervous system. Examples of case studies are included to illustrate their toxicity. A discussion of the possible contribution of occupational and other pesticide exposures to neurologic diseases and disorders is also included.
    Neurologic Clinics 08/2011; 29(3):667-77. DOI:10.1016/j.ncl.2011.06.002 · 1.61 Impact Factor
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    David A Jett, David T Yeung
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    ABSTRACT: The National Institutes of Health has developed a comprehensive research program that includes research centers of excellence, individual research projects, small business projects, contracts, and interagency agreements to conduct basic, translational, and clinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents. Chemical threats include chemical warfare agents, toxic industrial and agricultural chemicals, and toxins and other chemicals that could be used intentionally as an act of terror or by large-scale accidents or natural disasters. The overarching goal of this research program is to enhance our medical response capabilities during an emergency. The program is named Countermeasures Against Chemical Threats (CounterACT). It supports translational research, applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of mortality and morbidity caused by chemical threat agents. The categories of research supported under this program include creation and development of screening assays and animal models for therapy development, identification of candidate therapeutics, obtaining preliminary proof-of-principle data on the efficacy of candidate therapeutics, advanced efficacy and preclinical safety studies with appropriate animal models using Good Laboratory Practices (GLP), and clinical studies, including clinical trials with new drugs. Special consideration is given to research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions.
    Proceedings of the American Thoracic Society 07/2010; 7(4):254-6. DOI:10.1513/pats.201001-003SM
  • David A Jett
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    ABSTRACT: The National Institutes of Health (NIH) supports research about and the development of better therapies for treating exposure to toxic chemicals that could be used in a terrorist attack or released during an industrial accident. A review of recent research published by NIH investigators working in this field indicates that scientific advances in this area also have implications for reducing the burden of other neurological diseases and disorders. Some key examples discussed include studies on the development of therapeutic drugs to treat seizures and the neuropathology caused by chemical nerve agents, which may help find better cures for epilepsy, stroke, and neurodegenerative diseases.
    Science translational medicine 03/2010; 2(23):23ps12. DOI:10.1126/scitranslmed.3000752 · 14.41 Impact Factor
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    David A Jett, David T Yeung
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    ABSTRACT: The use of chemical warfare agents (CWAs) has historically been a primary concern of military personnel due to their devastating physical and psychological effects when employed on the battlefield. As a result of these new threats, agencies within the Department of Health and Human Services (DHHS) and other federal agencies have sustained a highly focused effort to assess and, if necessary, improve upon current emergency response capabilities in the event of an actual terrorist event. These efforts include both nonmedical countermeasures such as personal protective equipment for first responders who must enter a contaminated site, and medical capabilities such as safe and effective antidotes and diagnostic tools to reduce mortality and morbidity after a chemical attack or accident. In 2006, the US Congress appropriated funds to the National Institutes of Health (NIH) to implement the National Strategic Plan and Research Agenda for Medical Chemical Countermeasures. The goal of the CounterACT program is to develop safer and more effective therapeutics to treat victims exposed during a chemical incident. Complementing this goal, the CounterACT program also supports the research and development of novel diagnostic technologies, which could be utilized after a chemical incident to determine the proper course of medical intervention.
    Handbook of Toxicology of Chemical Warfare Agents, 1st edited by Ramesh C. Gupta, 03/2009: chapter 59: pages 889-895; Academic Press., ISBN: 978-0-12-374484-5
  • David A Jett
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    ABSTRACT: Presented below is a brief description of research supported by the National Institutes of Health (NIH) on cholinesterases that was discussed at the IXth International Meeting on Cholinesterases in Suzhou, China. It is a partial description of the research conducted by researchers at academic and other institutions supported by the NIH, and by some of the researchers in NIH intramural laboratories. It does not represent a comprehensive survey of all research supported by the NIH related to cholinesterases, but rather a brief discussion of some of the studies discussed at the IXth International Meeting on Cholinesterases. The article describes exciting basic, translational and clinical research on therapies for neurological and other diseases. In addition, cholinesterases that may treat substance abuse are discussed, and pesticide and chemical warfare agents that inhibit cholinesterases are highlighted as part of the NIH portfolio. It is the intent of this article to share with the international community some of the research being supported by the NIH on cholinesterases that complements many of the studies being conducted elsewhere. The information was obtained only from published articles or from abstracts available to the public within the NIH CRISP database (http://crisp.cit.nih.gov/).
    Chemico-Biological Interactions 05/2008; 175(1-3):22-5. DOI:10.1016/j.cbi.2008.04.021 · 2.98 Impact Factor
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    David A Jett
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    ABSTRACT: he Centers for Disease Control and Prevention urge physicians to become familiar with chemical and biological weapons. Preparedness among neurologists is especially im- portant because several of these agents affect the nervous system. This article reviews 4 agents that have a history of military or terrorist use: cyanide poisons, organophos- phate poisons, botulinum toxin, and anthrax. Cyanide and organophosphate poisons are charac- terized by dose-dependent impairment of neurological function with nonspecific symptoms such as headache or dizziness at one end of the spectrum and convulsions and coma at the other. Neu- rological examinations help clinicians to differentiate these agents from other intoxications. Botu- linum toxin has a delayed onset of action and results in descending paralysis and prominent cra- nialnervepalsies.Anthraxfrequentlycausesfulminatinghemorrhagicmeningitis.Earlyrecognition of these chemical and biological weapons is key to instituting specific therapy and preventing ca- sualties within the health care team and the community at large. Arch Neurol. 2003;60:21-25 Several chemical and biological weapons affect the nervous system, increasing the likelihood of a neurological consulta- tion.Ofthemanyagentsthatmightbeem- ployed,thisarticlefocusesoncyanide,cho- linesteraseinhibitors,botulinumtoxin,and anthraxbecausetheyhaveprominentneu- rological manifestations. This article re- views the weapon applications, clinical manifestations, and treatments of these agents.
    Annals of Neurology 01/2007; 61(1):9-13. DOI:10.1002/ana.21072 · 11.91 Impact Factor
  • D. Jett
    NeuroRx 07/2006; 3(3):409-409. DOI:10.1016/j.nurx.2006.05.016
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    NeuroRx 07/2006; 3(3). DOI:10.1016/j.nurx.2006.05.010