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BACKGROUND: Reduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C: a renal leak. We hypothesized that vitamin C renal leak may be associated with disease-mediated renal dysregulation, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. OBJECTIVES: We investigated the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal disease associated with renal tubular dysfunction and low plasma vitamin C concentrations. METHODS: We conducted a non-randomized cross-sectional cohort study of men aged 24-42 y, with Fabry disease (n = 34) and controls without acute or chronic disease (n = 33). To match anticipated plasma vitamin C concentrations, controls were placed on a low-vitamin C diet 3 wk before inpatient admission. To determine the primary outcome of vitamin C renal leak prevalence, subjects were fasted overnight, and matched urine and fasting plasma vitamin C measurements were obtained the following morning. Vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 µM. Exploratory outcomes assessed the association between renal leak and clinical parameters, and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. RESULTS: Compared with controls, the Fabry cohort had 16-fold higher odds of renal leak (6% vs. 52%; OR: 16; 95% CI: 3.30, 162; P < 0.001). Renal leak was associated with higher protein creatinine ratio (P < 0.01) and lower hemoglobin (P = 0.002), but not estimated glomerular filtration rate (P = 0.54). Renal leak, but not plasma vitamin C, was associated with a nonsynonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (OR: 15; 95% CI: 1.6, 777; P = 0.01). CONCLUSIONS: Increased prevalence of renal leak in adult men with Fabry disease may result from dysregulated vitamin C renal physiology and is associated with abnormal clinical outcomes and genomic variation.
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Enfermedad de Fabry , Adulto , Masculino , Humanos , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/orina , Ácido Ascórbico , Estudios Transversales , Riñón/metabolismo , Vitaminas , Genómica , Tasa de Filtración GlomerularRESUMEN
BACKGROUND AND PURPOSE: Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA). METHODS: We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation. α-galactosidase-A gene was sequenced for Fabry diagnosis. National Institutes of Health Stroke Scale score was measured at presentation to quantify stroke severity. Modified Rankin Scale determined functional outcomes ≤7 days after presentation and 6 months later. RESULTS: We enrolled 365 patients with IS and 32 with TIA. α-galactosidase-A sequencing identified a single carrier of a genetic variant of unknown significance (p.R118C) and no well-recognized pathogenic variants. Mean National Institutes of Health Stroke Scale score was 3.1. Proportion of patients with modified Rankin Scale of 0 to 2 was 70.7% at ≤7 days and 87.4% at 6 months. National Institutes of Health Stroke Scale score at presentation and diabetes mellitus predicted 6-month modified Rankin Scale. Thirteen patients experienced 5 recurrent IS and 9 TIA during follow-up. No patient died. Most patients (98.7%) returned home. Among previous workers, 43% had residual working limitations. CONCLUSIONS: In this Canadian cohort of patients with cryptogenic IS or TIA, the prevalence of Fabry was 0.3% if p.R118C variant is considered as pathogenic. This suggests that more cost-effective methods should be applied for diagnosis of Fabry rather than systematic genetic screening in this population. Overall, cryptogenic IS in young adults is associated with favorable outcomes.
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Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/epidemiología , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Adulto , Canadá/epidemiología , Estudios de Cohortes , Enfermedad de Fabry/terapia , Femenino , Estudios de Seguimiento , Humanos , Ataque Isquémico Transitorio/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Accidente Cerebrovascular/terapia , Resultado del TratamientoRESUMEN
Fabry disease is caused by deficient activity of α-galactosidase A and subsequent accumulation of glycosphingolipids (mainly globotriaosylceramide, Gb3), leading to multisystem organ dysfunction. Oxidative stress and nitric oxide synthase (NOS) uncoupling are thought to contribute to Fabry cardiovascular diseases. We hypothesized that decreased tetrahydrobiopterin (BH4) plays a role in the pathogenesis of Fabry disease. We found that BH4 was decreased in the heart and kidney but not in the liver and aorta of Fabry mice. BH4 was also decreased in the plasma of female Fabry patients, which was not corrected by enzyme replacement therapy (ERT). Gb3 levels were inversely correlated with BH4 levels in animal tissues and cultured patient cells. To investigate the role of BH4 deficiency in disease phenotypes, 12-month-old Fabry mice were treated with gene transfer-mediated ERT or substrate reduction therapy (SRT) for 6 months. In the Fabry mice receiving SRT but not ERT, BH4 deficiency was restored, concomitant with ameliorated cardiac and renal hypertrophy. Additionally, glutathione levels were decreased in Fabry mouse tissues in a sex-dependent manner. Renal BH4 levels were closely correlated with glutathione levels and inversely correlated with cardiac and kidney weight. In conclusion, this study showed that BH4 deficiency occurs in Fabry disease and may contribute to the pathogenesis of the disease through oxidative stress associated with a reduced antioxidant capacity of cells and NOS uncoupling. This study also suggested dissimilar efficacy of ERT and SRT in correcting pre-existing pathologies in Fabry disease.
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Biopterinas/análogos & derivados , Terapia de Reemplazo Enzimático , Enfermedad de Fabry/genética , alfa-Galactosidasa/genética , Animales , Biopterinas/deficiencia , Biopterinas/genética , Biopterinas/metabolismo , Modelos Animales de Enfermedad , Enfermedad de Fabry/mortalidad , Enfermedad de Fabry/fisiopatología , Femenino , Glutatión/metabolismo , Glicoesfingolípidos/metabolismo , Humanos , Riñón/metabolismo , Riñón/patología , Ratones , Miocardio/metabolismo , Miocardio/patología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/genética , alfa-Galactosidasa/biosíntesis , alfa-Galactosidasa/metabolismoRESUMEN
BACKGROUND: Given the recent interest in blast injury spurred by returning soldiers from overseas conflicts, we sought to research the early historical descriptions of blast injuries and their treatments. Consideration was given to specific descriptions of survivors of closed head injury and their treatment. METHODS: A review of the medical and nonmedical literature was undertaken, with particular emphasis on pre-1800 descriptions of volcanic eruptions and mining accidents. Compilations of accounts of the Etna eruptions dating from 126 BC were translated into English, and early mining texts from the 1600s and 1700s were reviewed. RESULTS: Accumulations of flammable gases were recorded in many medieval sources and this knowledge of toxic gas which could lead to blast injury was known in the mining community by 1316. No direct attribution of injuries to blast forces was present in the historical record examined before the 1300s, although mining accounts in the 1600s detail deaths due to blast. No specific descriptions of survivors of a closed head injury were found in the mining and volcanic eruption literature. CONCLUSIONS: Descriptions and warnings of blast forces were commonly written about in the medieval and Renaissance mining communities. Personal narratives as early as 1316 recognize the traumatic effects of blast injury. No mining or volcanic blast descriptions before 1800 detailed severe closed head injury survivors, suggesting greater mortality than morbidity from blast injury in the premodern era. This review also uncovered that there was no historical treatment or remedy recommended to survivors of blast injury. Blast explosions resulting in injury or death were frequently described, although in simplistic terminology.
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Traumatismos por Explosión/historia , Minería/historia , Terrorismo , Erupciones Volcánicas/efectos adversos , Traumatismos por Explosión/complicaciones , Lesiones Traumáticas del Encéfalo/etiología , Explosiones/historia , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Historia Medieval , Humanos , Traumatismos Ocupacionales/historia , Erupciones Volcánicas/historia , GuerraRESUMEN
Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.
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Traumatismos por Explosión/complicaciones , Traumatismos por Explosión/patología , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Medición de Riesgo , Animales , Traumatismos por Explosión/fisiopatología , Peso Corporal , Lesiones Encefálicas/fisiopatología , Elasticidad , Análisis de Elementos Finitos , Humanos , Presión Intracraneal , Ratones , Modelos Biológicos , Tamaño de los Órganos , Conejos , Especificidad de la Especie , Sus scrofa , ViscosidadRESUMEN
Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C-associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention.
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BACKGROUND: A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions. AIM: To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients. MATERIALS AND METHODS: Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. RESULTS: Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of Fabry disease. Investigation results suggestive of Fabry disease (idiopathic hypertrophic cardiomyopathy, proteinuria, vertebrobasilar dolichoectasia, and the pulvinar sign) were found only in subjects with normal α-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. CONCLUSIONS: Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening.
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Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/epidemiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Adolescente , Adulto , Isquemia Encefálica/genética , Canadá/epidemiología , Estudios de Cohortes , Enfermedad de Fabry/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Polimorfismo Genético/genética , Prevalencia , Accidente Cerebrovascular/genética , Adulto Joven , alfa-Galactosidasa/genéticaRESUMEN
BACKGROUND: Stroke in young adults is etiologically diverse and may represent a diagnostic challenge remaining cryptogenic in one-fourth of cases. Limited information is available on the prevalence of Fabry's disease, a treatable multisystem inherited lysosomal storage disorder, and disability in young patients with cryptogenic stroke. DESIGN AND METHODS: The Canadian Fabry Stroke Screening Initiative (CFSSI) is a prospective multicenter cohort study of young adults (age 18-55) presenting with an ischemic stroke, transient ischemic attack, or intracerebral haemorrhage of unknown etiology to stroke centres across Canada. Diagnosis of Fabry's disease is made by direct DNA analysis of blood samples for α-galactosidase gene mutations or polymorphisms. Demographics, clinical information, and investigations including brain Magnetic Resonance Imaging (MRI) are collected. Functional neurological assessment includes neurological examination, the National Institutes of Health (NIH) stroke scale, modified Rankin scale, and the Barthel index. A follow-up interview is conducted by telephone or in person approximately six-months after the index stroke/transient ischemic attack/intracerebral haemorrhage to determine patient outcomes, quality of life, and patient use of medications. MAIN OUTCOME: Prevalence of positive DNA mutation or single nucleotide polymorphism screens for Fabry's disease as a proportion of total cryptogenic stroke. Secondary outcomes include incident risk of new or recurrent vascular event at six-months, discharge disposition, disability at six-months as measured by the modified Rankin scale, mean time from symptoms onset to the definite etiological diagnosis, and length of hospital stay. CONCLUSION: This study constitutes the first initiative to determine the prevalence of a positive screen for Fabry's disease in young adults with stroke in Canada. Moreover, the Canadian Fabry Stroke Screening Initiative will provide information on recurrent vascular events, disability at six-months (modified Rankin scale), and disposition in this understudied population.
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Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/genética , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Adolescente , Adulto , Factores de Edad , Canadá/epidemiología , Enfermedad de Fabry/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico , Adulto JovenRESUMEN
Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads.
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Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Modelos Animales de Enfermedad , Hipocampo/patología , Hipocampo/fisiopatología , Enfermedad Aguda , Animales , Lesiones Encefálicas/etiología , Degeneración Nerviosa/etiología , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Técnicas de Cultivo de Órganos , Presión/efectos adversos , Ratas , Ratas Sprague-Dawley , Estrés MecánicoRESUMEN
A new approach for characterization of agarose gel permeability under compression at different loading velocities is proposed. Uniaxial compression tests on thin agarose gel specimens in a rigid porous confinement cell immersed in a water bath are undertaken. The equilibrium response of the gel, which is assumed to be achieved under extremely low-loading velocity (of the order of tens nanometers per second) is considered to be the response of the hydrated gel scaffold. The water exudation behavior from the agarose gel was extracted from the load-displacement response under various loading velocities by subtracting the equilibrium response. It was found that the pressure on water in the gel is not a linear function of loading velocity or volume flow rate and therefore, the permeability of agarose gel was observed to vary with deformation and water flow velocity. In addition, it was inferred from the analysis that at low velocities and large strain levels the gel permeability dominates the compression behavior, and at higher velocities and small strain levels the viscosity of the hydrated matrix may contribute to the load. Finally, permeability variation in agarose gel at different loading velocities is attributed to the two states (free water and bound water) of water molecules in the gel.
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Fuerza Compresiva , Ensayo de Materiales/métodos , Sefarosa/química , Geles , Hidrodinámica , Permeabilidad , Porosidad , Estrés Mecánico , Agua/químicaRESUMEN
In this paper, we show that bone piezoelectricity-a phenomenon in which bone polarizes electrically in response to an applied mechanical stress and produces a short-range electric field-may be a source of intense blast-induced electric fields in the brain, with magnitudes and timescales comparable to fields with known neurological effects. We compute the induced charge density in the skull from stress data on the skull from a finite-element full-head model simulation of a typical IED-scale blast wave incident on an unhelmeted human head as well as a human head protected by a kevlar helmet, and estimate the resulting electric fields in the brain in both cases to be on the order of 10 V/m in millisecond pulses. These fields are more than 10 times stronger than the IEEE safety guidelines for controlled environments (IEEE Standards Coordinating Committee 28, 2002) and comparable in strength and timescale to fields from repetitive Transcranial Magnetic Stimulation (rTMS) that are designed to induce neurological effects (Wagner et al., 2006a). They can be easily measured by RF antennas, and may provide the means to design a diagnostic tool that records a quantitative measure of the head's exposure to blast insult.
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Traumatismos por Explosión/fisiopatología , Lesiones Encefálicas/fisiopatología , Campos Electromagnéticos , Modelos Neurológicos , Cráneo/fisiopatología , Fenómenos Biofísicos , Encéfalo/fisiopatología , Análisis de Elementos Finitos , Humanos , Estrés MecánicoRESUMEN
Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.
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Antineoplásicos/uso terapéutico , Política de Salud/legislación & jurisprudencia , Política de Salud/tendencias , Nanomedicina/legislación & jurisprudencia , Nanomedicina/tendencias , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Imagenología Tridimensional/métodos , Nanomedicina/métodos , Nanoestructuras/uso terapéutico , Medicina de Precisión/métodos , Medicina de Precisión/tendenciasRESUMEN
Blast-induced traumatic brain injury is the most prevalent military injury in Iraq and Afghanistan, yet little is known about the mechanical effects of blasts on the human head, and still less is known about how personal protective equipment affects the brain's response to blasts. In this study we investigated the effect of the Advanced Combat Helmet (ACH) and a conceptual face shield on the propagation of stress waves within the brain tissue following blast events. We used a sophisticated computational framework for simulating coupled fluid-solid dynamic interactions and a three-dimensional biofidelic finite element model of the human head and intracranial contents combined with a detailed model of the ACH and a conceptual face shield. Simulations were conducted in which the unhelmeted head, head with helmet, and head with helmet and face shield were exposed to a frontal blast wave with incident overpressure of 10 atm. Direct transmission of stress waves into the intracranial cavity was observed in the unprotected head and head with helmet simulations. Compared to the unhelmeted head, the head with helmet experienced slight mitigation of intracranial stresses. This suggests that the existing ACH does not significantly contribute to mitigating blast effects, but does not worsen them either. By contrast, the helmet and face shield combination impeded direct transmission of stress waves to the face, resulting in a delay in the transmission of stresses to the intracranial cavity and lower intracranial stresses. This suggests a possible strategy for mitigating blast waves often associated with military concussion.
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Traumatismos por Explosión/patología , Lesiones Encefálicas/patología , Encéfalo/patología , Simulación por Computador , Fenómenos Biomecánicos , Traumatismos por Explosión/fisiopatología , Lesiones Encefálicas/fisiopatología , Cabeza/patología , Dispositivos de Protección de la Cabeza , Humanos , Personal Militar , Modelos Biológicos , PresiónRESUMEN
The effects of blast on biological tissue are documented for some organ systems such as the lung. In the central nervous system (CNS) the mechanism of CNS injury following blast wave is unclear. For example is there a selective effect of blast on varying brain region or white matter bundles. The effect of blast on traumatic brain injury (TBI) has come into particular focus with the Global War on Terror and Operation Iraqi Freedom and Operation Enduring Freedom where TBI has become known as the signature injury of these conflicts. The reason for the prominence of TBI in these particular conflicts as opposed to others is unclear but may result from the increased survivability of blast due to improvements in body armor. In the current series of articles in the Journal some developments of current research concepts in relation to military traumatic brain injury (TBI) are highlighted together with many remaining unsolved questions.
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Traumatismos por Explosión/complicaciones , Lesiones Encefálicas/etiología , Personal Militar , Campaña Afgana 2001- , HumanosRESUMEN
This article will provide an overview of the initial evaluation and management of traumatic brain injury (TBI). In cases of mild injury, conventional imaging in the absence of focal neurologic deficits is generally unrevealing. In the case of moderate or severe TBI, a review of neurocritical care is provided.
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BACKGROUND: The aim of the Oklahoma City (OKC) bombing retrospective review was to investigate the relationship between physical injury, environmental contributors, and psychiatric disorders such as posttraumatic stress disorder (PTSD) in an event-based, matched design study focused on injury. METHODS: The 182 selected participants were a random subset of the 1,092 direct survivors from the OKC bombing. Only 124 of these 182 cases had a full complement of medical/clinical data in the OKC database. These 124 cases were assessed to explore relationships among PTSD diagnoses, levels of blast exposure, and physical injuries. Associations among variables were statistically tested using contingency analysis and logistic regression. RESULTS: Comparison of the PTSD cases to symptoms/diagnoses reported in the medical records reveals a statistically significant association between PTSD and head/brain injuries associated with head acceleration. PTSD was not highly correlated with other injuries. Although blast pressure and impulse were highly correlated with head injuries, the correlation with PTSD was not statistically significant. Thus, a correlation between blast pressure and PTSD may exist, but higher fidelity pressure calculations are required to elucidate this potential relationship. CONCLUSIONS: This study provides clear evidence that head injury is associated with subsequent PTSD, giving caregivers' information on what physical injuries may suggest the development of psychologic disorders to aid them in developing a profile for the identification of future survivors of terrorist attacks and Warfighters with brain injuries and potential PTSD.
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Bombas (Dispositivos Explosivos) , Traumatismos Craneocerebrales/complicaciones , Explosiones , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/psicología , Sobrevivientes/psicología , Terrorismo/psicología , Adulto , Distribución de Chi-Cuadrado , Femenino , Humanos , Modelos Logísticos , Masculino , Oklahoma , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Primary blast injury of the central nervous system is described in a service-member exposed to a large ordinance explosion. Neuroimaging abnormalities are described together with normalization of the fractional anisotrophy on diffusion tensor imaging after follow-up imaging studies.
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Traumatismos por Explosión/patología , Bombas (Dispositivos Explosivos) , Lesiones Encefálicas/patología , Anisotropía , Lesiones Encefálicas/etiología , Imagen de Difusión por Resonancia Magnética , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Personal MilitarRESUMEN
OBJECTIVES: Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain injury (TBI). The reason for the prominence of TBI in these particular conflicts as opposed to others is unclear but may result from the increased survivability of blast due to improvements in body armor. In the military context blunt, ballistic and blast effects may all contribute to CNS injury, however blast in particular, has been suggested as a primary cause of military TBI. While blast effects on some biological tissues, such as the lung, are documented in terms of injury thresholds, this is not the case for the CNS. We hypothesized that using bio-fidelic models, allowing for fluid-solid interaction and basic material properties available in the literature, a blast wave would interact with CNS tissue and cause a possible concussive effect. METHODS: The modeling approach employed for this investigation consisted of a computational framework suitable for simulating coupled fluid-solid dynamic interactions. The model included a complex finite element mesh of the head and intra-cranial contents. The effects of threshold and 50% lethal blast lung injury were compared with concussive impact injury using the full head model allowing upper and lower bounds of tissue injury to be applied using pulmonary injury as the reference tissue. RESULTS: The effects of a 50% lethal dose blast lung injury (LD(50)) were comparable with concussive impact injury using the DVBIC-MIT full head model. INTERPRETATION: CNS blast concussive effects were found to be similar between impact mild TBI and the blast field associated with LD(50) lung blast injury sustained without personal protective equipment. With the ubiquitous use of personal protective equipment this suggests that blast concussive effects may more readily ascertained in personnel due to enhanced survivability in the current conflicts.