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1.
Mil Med ; 183(11-12): e571-e579, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788089

RESUMO

Introduction: Although not a "signature injury" of Operation Desert Shield/Desert Storm (i.e., Gulf War, GW), some GW veterans have a history traumatic brain injury (TBI). For example, a previous study found that 12.2% of the GW veterans from the Fort Devens Cohort Study had self-reported TBIs. The present study sought to build upon this finding by examining the relationship between TBI and chronic symptomatic illness in a different sample of GW veterans. Materials and Methods: Participants were 202 GW veterans recruited from 2014 to 2018 at the San Francisco Veterans Affairs Medical Center as part of a VA-funded study on the effects of predicted exposure to low levels of sarin and cyclosarin on brain structure and function. The Ohio State University TBI identification method was used to determine lifetime history of TBI. The Kansas Gulf War Military History and Health Questionnaire was used to assess symptoms and to determine cases of Kansas Gulf War Illness (GWI) and Centers for Disease Control and Prevention (CDC) Chronic Multisymptom Illness (CMI). Results: Nearly half (47%) the sample had a history of TBI, but only 7% of the TBIs were sustained in injuries that occurred during the GW. Most of the TBIs were sustained in injuries that occurred prior to (73%) or after (34%) the GW. History of TBI was not associated with higher rates of symptomatic illness when it was narrowly defined (i.e., Kansas GWI cases or cases of severe CMI). History of TBI was only associated with higher rates of symptomatic illness when it is broadly defined (i.e., CDC CMI or mild-moderate CMI). There was suggestive evidence that veterans who sustained TBIs during the GW (only seven in the present sample) have poorer functional outcomes compared with GW veterans with non-GW related TBIs. Conclusions: While TBIs were uncommon during the GW, many GW veterans sustained TBIs prior or after the GW. Because TBI and GWI/CMI share some overlapping symptoms, history of TBI may appear to be associated with increased rates of chronic symptomatic illness in GW veterans if chronic symptomatic illness is defined broadly (i.e., CDC CMI or mild-moderate CMI). History of pre-GW TBI did not affect the veterans' response to exposures/experiences from the GW; however, there was suggestive evidence that veterans who sustained TBIs during the GW may have poorer functional outcomes that GW veterans without TBI or even GW veterans with non-GW-related TBIs. Future, better powered studies with randomly and systematically select participants from the larger population of GW veterans will need to confirm this finding.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Doença Crônica/reabilitação , Veteranos/estatística & dados numéricos , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/fisiopatologia , Distribuição de Qui-Quadrado , Doença Crônica/epidemiologia , Estudos de Coortes , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Feminino , Guerra do Golfo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organofosforados/efeitos adversos , Psicometria/instrumentação , Psicometria/métodos , Sarina/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans Affairs/organização & administração , United States Department of Veterans Affairs/estatística & dados numéricos , Veteranos/psicologia
2.
Disaster Med Public Health Prep ; 12(2): 249-256, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28514981

RESUMO

Sarin is a potent nerve agent chemical weapon that was originally designed for military purposes as a fast-acting anti-personnel weapon that would kill or disable large numbers of enemy troops. Its potent toxicity, ease of deployment, and rapid degradation allow for rapid deployment by an attacking force, who can safely enter the area of deployment a short while after its release. Sarin has been produced and stockpiled by a number of countries, and large quantities of it still exist despite collective agreements to cease manufacture and destroy stockpiles. Sarin's ease of synthesis, which is easily disseminated across the Internet, increases the risk that terrorist organizations may use sarin to attack civilians. Sarin has been used in a number of terrorist attacks in Japan, and more recently in attacks in the Middle East, where nonmilitary organizations have led much of the disaster relief and provision of medical care. In the present article, we examine and discuss the available literature on sarin's historical use, delivery methods, chemical properties, mechanism of action, decontamination process, and treatment. We present a management guideline to assist with the recognition of an attack and management of victims by medical professionals and disaster relief organizations, specifically in resource-constrained and austere environments. (Disaster Med Public Health Preparedness. 2018;12:249-256).


Assuntos
Recursos em Saúde/provisão & distribução , Sarina/efeitos adversos , Anticonvulsivantes/uso terapêutico , Atropina/uso terapêutico , Terrorismo Químico/estatística & dados numéricos , Países em Desenvolvimento , Diazepam/uso terapêutico , Recursos em Saúde/estatística & dados numéricos , Humanos , Incidentes com Feridos em Massa/prevenção & controle , Antagonistas Muscarínicos/uso terapêutico , Equipamento de Proteção Individual
3.
J Med Chem ; 60(22): 9376-9392, 2017 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-29091431

RESUMO

Recently, a new class of reactivators of chemical warfare agent inhibited acetylcholinesterase (AChE) with promising in vitro potential was developed by the covalent linkage of an oxime nucleophile and a peripheral site ligand. However, the complexity of these molecular structures thwarts their accessibility. We report the compatibility of various oxime-based compounds with the use of the Ugi multicomponent reaction in which four readily accessible building blocks are mixed together to form a product that links a reactivating unit and a potential peripheral site ligand. A small library of imidazole and imidazolium reactivators was successfully synthesized using this method. Some of these compounds showed a promising ability to reactivate AChE inhibited by various types of CWA in vitro. Molecular modeling was used to understand differences in reactivation potential between these compounds. Four compounds were evaluated in vivo using sarin-exposed rats. One of the reactivators showed improved in vivo efficacy compared to the current antidote pralidoxime (2-PAM).


Assuntos
Acetilcolinesterase/metabolismo , Reativadores da Colinesterase/síntese química , Reativadores da Colinesterase/farmacologia , Animais , Encéfalo/metabolismo , Inibidores da Colinesterase/efeitos adversos , Reativadores da Colinesterase/administração & dosagem , Reativadores da Colinesterase/farmacocinética , Humanos , Imidazóis/administração & dosagem , Imidazóis/síntese química , Imidazóis/farmacocinética , Imidazóis/farmacologia , Cinética , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Agentes Neurotóxicos/efeitos adversos , Oximas/administração & dosagem , Oximas/síntese química , Oximas/farmacocinética , Oximas/farmacologia , Compostos de Pralidoxima/farmacologia , Ratos Wistar , Sarina/efeitos adversos
4.
Mil Med ; 182(5): e1625-e1631, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-29087904

RESUMO

INTRODUCTION: Despite the fact that many veterans returned from the 1991 Gulf War (GW) with complaints of memory difficulties, most neuropsychological studies to date have found little evidence of a correspondence between subjective and objective measures of cognitive function in GW veterans. However, if GW veterans complain about memory problems, it is likely that they experience memory problems in their daily lives. In this respect, it is notable that the past studies that have investigated the relationship between subjective and objective measures of cognitive function in GW veterans used composite measures to quantify subjective complaints and batteries of neuropsychological tests that assessed multiple domains to objectively measure cognitive function. The study's focus on memory was motivated by the suggestive evidence that subjective memory complaint may be a harbinger of further cognitive decline and increased risk for dementia. MATERIALS AND METHODS: This study examined the association between subjective memory complaint (probed with single question: "Do you have difficulty remembering things?") and performance on a single objective test of verbal learning and memory (i.e., California Verbal Learning Test, CVLT-II) in a sample of 428 deployed GW veterans. RESULTS: GW veterans who endorsed memory difficulties performed more poorly on CVLT-II measures of total learning, retention, and delayed recall than GW veterans without subjective memory complaints (p < 0.001), even after accounting for demographic (e.g., age, sex, education) and clinical variables (e.g., diagnoses of current post-traumatic stress disorder [PTSD], depressive disorder, and/or anxiety disorder) that could potentially contribute to memory deficits. Among GW veterans who met the Centers for Disease Control and Prevention criteria for chronic multisymptom illness (N = 272), subjective memory complaint significantly predicted CVLT-II retention scores (ß = -0.12, p = 0.04) and marginally predicted CVLT-II delayed recall scores (ß = -0.11, p = 0.05) over and above potentially confounding demographic and clinical variables. CONCLUSION: This study suggests that deployed GW veterans with subjective memory complaints have objective memory impairments. In light of the evidence linking subjective memory complaint to increased risk for dementia in the elderly, these findings suggest that aging GW veterans with subjective memory complaints should be closely monitored for further cognitive decline.


Assuntos
Transtornos da Memória/etiologia , Veteranos/psicologia , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , California/epidemiologia , Substâncias para a Guerra Química/efeitos adversos , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Guerra do Golfo , Humanos , Masculino , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/etiologia , Testes Neuropsicológicos/estatística & dados numéricos , Compostos Organofosforados/efeitos adversos , Síndrome do Golfo Pérsico/complicações , Síndrome do Golfo Pérsico/epidemiologia , Sarina/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/epidemiologia
5.
Neurotoxicology ; 48: 239-48, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25929683

RESUMO

BACKGROUND: We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity. METHODS: Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. RESULTS: There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure. CONCLUSIONS: The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/GF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF).


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Guerra do Golfo , Leucoencefalopatias/induzido quimicamente , Compostos Organofosforados/efeitos adversos , Sarina/efeitos adversos , Saúde dos Veteranos , Substância Branca/efeitos dos fármacos , Adulto , Anisotropia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Exposição por Inalação/efeitos adversos , Leucoencefalopatias/patologia , Leucoencefalopatias/fisiopatologia , Leucoencefalopatias/psicologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/efeitos dos fármacos , Substância Branca/patologia , Substância Branca/fisiopatologia
6.
Disaster Med Public Health Prep ; 3(2): 75-87, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19491602

RESUMO

OBJECTIVE: To develop and apply a novel modeling approach to support medical and public health disaster planning and response using a sarin release scenario in a metropolitan environment. METHODS: An agent-based disaster simulation model was developed incorporating the principles of dose response, surge response, and psychosocial characteristics superimposed on topographically accurate geographic information system architecture. The modeling scenarios involved passive and active releases of sarin in multiple transportation hubs in a metropolitan city. Parameters evaluated included emergency medical services, hospital surge capacity (including implementation of disaster plan), and behavioral and psychosocial characteristics of the victims. RESULTS: In passive sarin release scenarios of 5 to 15 L, mortality increased nonlinearly from 0.13% to 8.69%, reaching 55.4% with active dispersion, reflecting higher initial doses. Cumulative mortality rates from releases in 1 to 3 major transportation hubs similarly increased nonlinearly as a function of dose and systemic stress. The increase in mortality rate was most pronounced in the 80% to 100% emergency department occupancy range, analogous to the previously observed queuing phenomenon. Effective implementation of hospital disaster plans decreased mortality and injury severity. Decreasing ambulance response time and increasing available responding units reduced mortality among potentially salvageable patients. Adverse psychosocial characteristics (excess worry and low compliance) increased demands on health care resources. Transfer to alternative urban sites was possible. CONCLUSIONS: An agent-based modeling approach provides a mechanism to assess complex individual and systemwide effects in rare events.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Defesa Civil/métodos , Planejamento em Desastres/métodos , Emergências/epidemiologia , Modelos Teóricos , Sarina/efeitos adversos , Simulação por Computador , Emergências/psicologia , Serviço Hospitalar de Emergência , Exposição Ambiental/efeitos adversos , Comportamentos Relacionados com a Saúde , Humanos , Mortalidade , Modelos de Riscos Proporcionais , Estresse Psicológico/etiologia , Triagem
7.
Rev. neurol. (Ed. impr.) ; 47(2): 99-106, 14 jul., 2008. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-69648

RESUMO

Introducción. El descubrimiento y desarrollo de los denominados ‘agentes nerviosos’ (sustancias neurotóxicas destinadas al arsenal bélico) tuvieron lugar en la Alemania del Tercer Reich, gracias, en gran medida, al enorme desarrollo de la farmacología en este país, tanto en el ámbito académico como industrial. Asimismo, la organización por parte de los sucesivos gobiernos nacionalsocialistas de una red colaborativa entre el estamento académico, la industria química y los responsables militares favoreció esta línea de investigación. Desarrollo. En la incorporación del primer agente neurotóxico a la categoría de ‘arma de guerra química’ influyó decisivamente el azar. En el marco de investigaciones sobre pesticidas e insecticidasde naturaleza organofosforada, Gerhard Schrader, químico de la compañía I.G. Farben, sintetizó el tabún (etil-N,N-dimetil- fosforamidocianidato), y una contaminación accidental del personal del laboratorio con esta sustancia puso de manifiesto su potencialidad tóxica. Este mismo grupo sintetizó posteriormente otra sustancia dotada de las mismas propiedades, el sarín(isopropil-metil-fosfonofluoridato). Ambos agentes fueron estudiados como armas químicas por Wolfgang Wirth. Simultáneamente, el grupo liderado por Richard Kuhn, premio Nobel de Química en 1938, sintetizó el pinacolil-metil-fosfonofluoridato, conocido como somán. Conclusión. Los estudios farmacológicos confirmaron que el mecanismo de acción neurotóxico de estassustancias era la inhibición irreversible de la enzima acetilcolinesterasa, responsable de la metabolización de la acetilcolina, y que el exceso de este neurotransmisor ocasionaba una sobreestimulación continuada de los receptores colinérgicos (nicotínicos y muscarínicos), responsable de la aparición del amplio espectro de síntomas de intoxicación y de su rápido efecto letal


Introduction. The discovery and development of the so-called ‘nerve agents’ (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research.Development. The first neurotoxic substance to be incorporated into the category of ‘chemical warfare agent’ did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, achemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researcherslater synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. Conclusions. Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that anexcess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect


Assuntos
Humanos , Guerra Biológica , Neurotoxinas/efeitos adversos , Neurofarmacologia/história , Sarina/efeitos adversos , Soman/efeitos adversos
8.
J Neurol Sci ; 249(1): 76-85, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16962140

RESUMO

Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events. Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In Tokyo, two died in station yards and another ten victims died in hospitals within a few hours to 3 months after poisoning. Six victims with serum ChE below 20% of the lowest normal were resuscitated from cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered completely and one remained in vegetative state due to anoxic brain damage. EEG abnormalities persisted for up to 5 years. Miosis and copious secretions from the respiratory and GI tracts (muscarinic effects) were common in severely to slightly affected victims. Weakness and twitches of muscles (nicotinic effects) appeared in severely affected victims. Neuropathy and ataxia were observed in small number (less than 10%) of victims, which findings disappeared between 3 days and 3 months. Leukocytosis and high serum CK levels were common. Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in severely affected victims, which abnormalities were attributed to damage of the adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase and symptoms quickly even if administered 6 h after exposure. Post Traumatic Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological symptoms continue in victims of both incidents. In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan.


Assuntos
Terrorismo Químico/história , Inibidores da Colinesterase/envenenamento , Doenças do Sistema Nervoso/induzido quimicamente , Sarina/efeitos adversos , Doença Aguda/mortalidade , Doença Aguda/psicologia , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Reativadores da Colinesterase/uso terapêutico , Cuidados Críticos/normas , História do Século XX , Humanos , Japão , Doenças do Sistema Nervoso/mortalidade , Doenças do Sistema Nervoso/fisiopatologia , Tempo
9.
Med Tr Prom Ekol ; (11): 14-9, 2006.
Artigo em Russo | MEDLINE | ID: mdl-17217221

RESUMO

The authors summarized study results on chronic effects caused by products of leaching from bituminous-salt masses obtained through destruction of sarin, soman and RVX. State of experimental rats was evaluated with integral informative tests (physiologic, biochemical, hematologic and morphologic) presenting changes in objective health parameters and revealing every disorder in organs and systems functioning.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Resíduos Perigosos/efeitos adversos , Hidrocarbonetos/efeitos adversos , Organotiofosfatos/efeitos adversos , Sais , Sarina/efeitos adversos , Soman/efeitos adversos , Animais , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/metabolismo , Hidrocarbonetos/análise , Hidrocarbonetos/sangue , Masculino , Organotiofosfatos/análise , Organotiofosfatos/sangue , Ratos , Ratos Wistar , Sarina/análise , Sarina/sangue , Soman/análise , Soman/sangue , Água/química
10.
Respir Care Clin N Am ; 10(1): 59-74, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15062227

RESUMO

The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Pneumopatias/induzido quimicamente , Pneumopatias/prevenção & controle , Lesão Pulmonar , Planejamento em Desastres , Humanos , Organofosfatos/efeitos adversos , Compostos Organotiofosforados/efeitos adversos , Sarina/efeitos adversos , Soman/efeitos adversos , Estados Unidos
11.
Mil Med ; 168(8): 606-13, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12943034

RESUMO

It is unlikely that Gulf War veterans are suffering chronic effects from illnesses caused by chemical warfare nerve agent exposure. Extensive investigation and review by several expert panels have determined that no evidence exists that chemical warfare nerve agents were used during the Gulf War. At no time before, during, or after the war was there confirmation of symptoms among anyone, military or civilian, caused by chemical warfare nerve agent exposure. However, studies of Gulf War veterans have found belief that chemical weapons were used, significantly associated with both severe and mild-moderate illnesses. The psychological impact of a chemical warfare attack, either actual or perceived, can result in immediate and long-term health consequences. The deployment or war-related health impact from life-threatening experiences of the Gulf War, including the perceived exposure to chemical warfare agents, should be considered as an important cause of morbidity among Gulf War veterans.


Assuntos
Guerra Química/psicologia , Militares , Transtornos de Estresse Pós-Traumáticos/psicologia , Guerra , Substâncias para a Guerra Química/efeitos adversos , Humanos , Iraque , Masculino , Sarina/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologia
13.
Eur J Pharmacol ; 471(2): 97-104, 2003 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-12818696

RESUMO

Organophosphate poisoning can result in seizures and subsequent neuropathology. One possible therapeutic approach would be to employ adenosine A(1) receptor agonists, which have already been shown to have protective effects against organophosphate poisoning. Using an in vitro model of organophosphate-induced seizures, we have investigated the ability of several adenosine A(1) receptor agonists to inhibit epileptiform activity induced by the organophosphate sarin, in the CA1 stratum pyramidale of the guinea pig hippocampal slice. Application of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) or the partial adenosine A(1) receptor agonists 2-deoxy-N(6)-cyclopentyladenosine (2-deoxy-CPA) and 8-butylamino-N(6)-cyclopentyladenosine (8-butylamino-CPA) abolished epileptiform activity in a concentration-related manner. The rank order of potency was CPA (IC(50) 4-5 nM) >2-deoxy-CPA (IC(50) 113-119 nM)=8-butylamino-CPA (IC(50) 90-115 nM). These data suggest that partial adenosine A(1) receptor agonists, which have fewer cardiovascular effects, should be further evaluated in vivo as potential treatments for organophosphate poisoning.


Assuntos
Agonistas do Receptor A1 de Adenosina , Adenosina/análogos & derivados , Hipocampo/efeitos dos fármacos , Receptor A1 de Adenosina/uso terapêutico , Sarina/efeitos adversos , Sarina/antagonistas & inibidores , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Potenciais de Ação/efeitos dos fármacos , Adenosina/farmacocinética , Antagonistas do Receptor A1 de Adenosina , Animais , Desoxiadenosinas/farmacocinética , Cobaias , Hipocampo/citologia , Masculino , Microeletrodos , Neurônios , Soman/efeitos adversos , Soman/antagonistas & inibidores , Relação Estrutura-Atividade , Xantinas/farmacocinética
14.
Mil Med ; 168(3): 239-45, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12685692

RESUMO

In a telephone survey of 4,022 military volunteers for a 1955-1975 program of experimental exposures to chemical agents at Edgewood, Maryland, the current health of those exposed to anticholinesterase agents was compared with that of men exposed to no active chemicals (no chemical test) and to two or more other types of chemical agents (other chemical tests). The survey posed questions about general health and about neurological and psychological deficits. There were only two statistically significant differences: volunteers in anticholinesterase agent tests reported fewer attention problems than those in other chemical tests and greater sleep disturbance than those in no chemical tests. In contrast, volunteers who reported exposure to civilian or military chemical agents outside of their participation in the Edgewood program reported many statistically significant adverse neurological and psychological effects, regardless of their experimental exposure. In this study, the health effects of self-reported, nonexperimental exposure, which are subject to recall bias, were greater than the health effects of experimental exposure.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Inibidores da Colinesterase/efeitos adversos , Sarina/efeitos adversos , Veteranos , Distribuição de Qui-Quadrado , Humanos , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Estados Unidos
15.
Postgrad Med ; 112(4): 90-6; quiz 4, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12400151

RESUMO

Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Guerra Química/prevenção & controle , Descontaminação/métodos , Irritantes/efeitos adversos , Antídotos/uso terapêutico , Arsenicais/efeitos adversos , Inibidores da Colinesterase/efeitos adversos , Humanos , Serviços de Informação , Internet , Gás de Mostarda/efeitos adversos , Organofosfatos/efeitos adversos , Compostos Organotiofosforados/efeitos adversos , Prevenção Primária/métodos , Roupa de Proteção , Sarina/efeitos adversos , Soman/efeitos adversos
16.
Regul Toxicol Pharmacol ; 35(3): 347-56, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12202050

RESUMO

The U.S. Army has estimated acute lethality guideline levels for inhalation of the chemical warfare agents mustard, GB, and VX. These levels are expressed as dosages measured in milligram-minutes per cubic meter (mg-min/m(3)). The National Advisory Council has also proposed acute emergency guideline levels (AEGLs) for the agents. The AEGLs are threshold exposure limits for the general public for mild effects, serious adverse effects, and lethality. They are expressed as air concentrations (in units of mg/m(3)) and are applicable to emergency exposure periods ranging from 10 min to 8 h. The report discusses strengths and deficiencies in the levels, important parameters (i.e., exposure time, breathing rate) that need to be explicitly addressed in deriving the guideline levels, and possible impacts that could result from using AEGLs instead of guideline dosages in future assessments.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Medicina Militar/normas , Gás de Mostarda/efeitos adversos , Compostos Organotiofosforados/efeitos adversos , Sarina/efeitos adversos , Substâncias para a Guerra Química/normas , Planejamento em Desastres , Relação Dose-Resposta a Droga , Guias como Assunto , Exposição por Inalação , Concentração Máxima Permitida , Gás de Mostarda/normas , Compostos Organotiofosforados/normas , Saúde Pública , Medição de Risco/normas , Sarina/normas
17.
Environ Health Perspect ; 109(11): 1169-73, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11713003

RESUMO

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Auxiliares de Emergência , Transtornos da Memória/induzido quimicamente , Médicos , Polícia , Sarina/efeitos adversos , Adulto , Estudos Transversais , Relação Dose-Resposta a Droga , Exposição Ambiental , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/efeitos dos fármacos , Testes Neuropsicológicos , Percepção , Trabalho de Resgate , Transtornos de Estresse Pós-Traumáticos , Terrorismo , Transportes , Vibração
18.
Int J Occup Environ Health ; 7(2): 79-89, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11373050

RESUMO

During the 1991 Gulf War, some Allied troops were potentially exposed to sarin/cyclosarin as the result of the destruction of Iraqi munitions at Khamisiyah. To evaluate the prevalence of past and current symptoms known to be associated with exposure to these chemical warfare agents, the authors conducted a computer-assisted telephone survey of 2,918 U.S. Gulf War veterans. Veterans who had participated in or witnessed the demolition in 1991 were more likely to report historical or extant symptoms than were veterans from other military units. These results should be viewed cautiously because they are based on symptoms recalled nine years after the event without precise characterization of exposure. Nonetheless, the findings suggest that symptoms consistent with low-level sarin exposure may have initially occurred, and health effects may have persisted in the veterans who were nearest to the demolition activity. Further research is warranted.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Sarina/efeitos adversos , Veteranos/estatística & dados numéricos , Adulto , Coleta de Dados , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Nível de Saúde , Humanos , Iraque , Masculino , Estados Unidos , Guerra
20.
Mil Med ; 166(12 Suppl): 23-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11778423

RESUMO

The investigation describes the follow-up of the victims of the 1995 Tokyo sarin attack who were followed by a team at the St. Luke's International Hospital. A symptom questionnaire ("St. Luke's Questionnaire") was developed and given 2, 3, and 5 years following the sarin attack. Somatic and psychological symptoms have continued for 5 years after the incident. New post-traumatic stress disorder diagnostic criteria, which include physical symptoms, were developed and applied for assessment of the outcomes. The St. Luke's cohort was also compared with other Japanese sarin attack cohorts. Interventions, including counseling, medical treatments, and support group activities, were associated with fewer symptoms among the victims.


Assuntos
Substâncias para a Guerra Química/efeitos adversos , Sarina/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Terrorismo/psicologia , Adulto , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Fatores de Tempo , Tóquio
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