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1.
Aust Vet J ; 99(4): 119-123, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33442884

RESUMO

BACKGROUND: Brain metastases are well known for disseminated hemangiosarcoma involving the right atrium/auricle. CASE REPORT: An 8-year-old male Australian Shepherd Dog presented with a 3-day history of circling to the left. A neurological examination revealed obtunded mentation, right hemi-inattention, bilateral strabismus towards the left side and absent physiological nystagmus. In addition, the dog had muffled heart sounds on auscultation and exercise-induced weakness. Laboratory findings included hypercoagulability and marked elevation in the C-reactive protein concentration. Electrocardiography detected a sinus rhythm with right bundle-branch block and ventricular bigeminy. Echocardiography revealed an extensive interventricular septal mass. Due to the grave prognosis, the owners elected for euthanasia, and a complete necropsy was performed. The main pathological findings were an interventricular septal and left ventricular hemangiosarcoma, with metastases in the brain, lungs, spleen and adrenal glands. No evidence of tumour infiltration was found in the right atrium. CONCLUSION: To the authors' knowledge, this is the first report of neurological signs due to confirmed brain metastases in a dog with interventricular septal hemangiosarcoma. Although the right atrium is the main location for cardiac hemangiosarcoma, the interventricular septum should be evaluated in all cases.


Assuntos
Neoplasias Encefálicas , Doenças do Cão , Hemangiossarcoma , Animais , Austrália , Neoplasias Encefálicas/veterinária , Doenças do Cão/diagnóstico , Cães , Ecocardiografia/veterinária , Eletrocardiografia , Eutanásia Animal , Hemangiossarcoma/veterinária , Masculino
2.
Accid Anal Prev ; 122: 287-294, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30396030

RESUMO

OBJECTIVE: Drugged driving crashes have significantly increased over the past two decades. The objectives of this study were to identify and characterize the drugs present in motor vehicle driver fatalities using multiple surveillance data sources; assess concordance of the data sources in identifying drug presence; and identify demographic and crash factors associated with drug and alcohol screening in fatally injured motor vehicle drivers. METHODS: Fatality Analysis Reporting System (FARS), Collision Report Analysis for Safer Highways (CRASH), and mortality data sets were linked; drug screening and positive drug screens were identified. Chi-square and conditional logistic regression were performed. RESULTS: The use of FARS data identified the majority of positive drug screens in the linked data set. Supplementation of FARS data with death certificate and CRASH data increased identification of specific drugs and drug classes detected among fatally injured motor vehicle drivers, although there was a low concordance among the data sources. Alcohol and depressants such as alprazolam had the highest frequencies among fatally injured drivers. Speeding, lack of occupant restraints, young age, commercial truck drivers, and speeding were all factors associated with increased odds of the fatally injured driver being drug or alcohol screened. CONCLUSIONS: These findings indicate that FARS drug information data may be strengthened through increased autopsy and consultation with medical examiners to better understand and interpret decedent toxicology testing results, and that states with low driver drug testing rates should consider mandatory driver drug testing in fatal crashes.


Assuntos
Acidentes de Trânsito/mortalidade , Dirigir sob a Influência/estatística & dados numéricos , Detecção do Abuso de Substâncias/estatística & dados numéricos , Adolescente , Adulto , Autopsia/estatística & dados numéricos , Coleta de Dados/métodos , Feminino , Humanos , Kentucky/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
3.
Inj Epidemiol ; 5(1): 27, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29961925

RESUMO

BACKGROUND: Private and Public security and law enforcement (SLE) sectors perform multiple overlapping job duties. METHODS: Workers' compensation (WC) SLE first reports of injury (FROI) data (2005-2015) were analyzed to describe injuries, identify differences in awarded WC benefits, and compare the probability of a FROI resulting in awarded benefits between Public and Private SLE. A Pearson's chi-square test was utilized and reverse selection logistic regression was performed to estimate the odds ratio that a FROI would result in an awarded benefit for Private vs. Public SLE, while adjusting for relevant covariates. RESULTS: Private SLE had higher FROI percentages for younger and for older workers, fall injuries, and back injuries, compared to Public SLE. The adjusted odds that a FROI resulted in an awarded benefit was 1.4 times higher for Private SLE compared to Public SLE; (95% confidence interval [CI] = 1.09,1.69). Middle-aged SLE employee adjusted odds of awarded benefits was 3.3 times (95% CI [1.96, 5.39]) higher compared to younger employees. Adjusted odds of awarded benefits was 3.8 times (95% CI [1.34, 10.61]) higher for gunshots and 1.7 times (95% CI [1.22, 2.39]) higher for fractures/dislocations compared to other nature of injuries. Motor vehicle injury, fall/slip, and strain related FROIs had elevated adjusted odds of awarded benefits compared to other injury causes. CONCLUSIONS: Results highlight the importance of injury prevention education and worker safety training for Private and Public SLE sector workers on fall prevention (especially in Private SLE) and strain prevention (especially in Public SLE), as well as motor vehicle safety.

4.
Phys Rev Lett ; 120(24): 245003, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29956968

RESUMO

A series of cryogenic, layered deuterium-tritium (DT) implosions have produced, for the first time, fusion energy output twice the peak kinetic energy of the imploding shell. These experiments at the National Ignition Facility utilized high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums, resulting in a peak hohlraum radiative temperature ∼290 eV. The imploding shell, composed of the nonablated high density carbon and the DT cryogenic layer, is, thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic energy of ∼21 kJ, which once stagnated produced a total DT neutron yield of 1.9×10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ. Time dependent low mode asymmetries that limited further progress of implosions have now been controlled, leading to an increased compression of the hot spot. It resulted in hot spot areal density (ρr∼0.3 g/cm^{2}) and stagnation pressure (∼360 Gbar) never before achieved in a laboratory experiment.

5.
Traffic Inj Prev ; 19(4): 446-453, 2018 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-29381397

RESUMO

OBJECTIVE: Traffic incidents occurring on roadways require the coordinated effort of multiple responder and recovery entities, including communications, law enforcement, fire and rescue, emergency medical services, hazardous materials, transportation agencies, and towing and recovery. The objectives of this study were to (1) identify and characterize transportation incident management (TIM)-related occupational fatalities; (2) assess concordance of surveillance data sources in identifying TIM occupations, driver vs. pedestrian status, and occupational fatality incident location; and (3) determine and compare U.S. occupational fatality rates for TIM industries. METHODS: The Kentucky Fatality Assessment and Control Evaluation (FACE) program analyzed 2005-2016 TIM occupational fatality data using multiple data sources: death certificate data, Collision Report Analysis for Safer Highways (CRASH) data, and media reports, among others. Literal text analysis was performed on FACE data, and a multiple linear regression model and SAS proc sgpanel were used to estimate and visualize the U.S. TIM occupational mortality trend lines and confidence bounds. RESULTS: There were 29 TIM fatalities from 2005 to 2015 in Kentucky; 41% of decedents were in the police protection occupation, and 21% each were in the fire protection and motor vehicle towing industries. Over one half of the TIM decedents were performing work activities as pedestrians when they died. Media reports identified the majority of the occupational fatalities as TIM related (28 of 29 TIM-related deaths); the use of death certificates as the sole surveillance data source only identified 17 of the 29 deaths as TIM related, and the use of CRASH data only identified 4 of the 29 deaths as TIM related. Injury scenario text analysis showed that law enforcement vehicle pursuit, towing and recovery vehicle loading, and disabled vehicle response were particular high-risk activities that led to TIM deaths. Using U.S. data, the motor vehicle towing industry had a significantly higher risk for occupational mortality compared to the fire protection and police protection industries. CONCLUSIONS: Multiple data sources are needed to comprehensively identify TIM fatalities and to examine the circumstances surrounding TIM fatalities, because no one data source in itself was adequate and undercounted the total number of TIM fatalities. The motor vehicle towing industry, in particular, is at elevated risk for occupational mortality, and targeted mandatory TIM training for the motor vehicle towing industry should be considered. In addition, enhanced law enforcement roadside safety training during vehicle pursuit and apprehension of suspects is recommended.


Assuntos
Acidentes de Trabalho/mortalidade , Acidentes de Trânsito/mortalidade , Atestado de Óbito , Veículos Automotores/estatística & dados numéricos , Acidentes de Trabalho/classificação , Adulto , Feminino , Humanos , Kentucky/epidemiologia , Masculino , Pessoa de Meia-Idade
6.
Vet Comp Oncol ; 15(4): 1468-1478, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28194917

RESUMO

Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment. Diuresis using furosemide is effective in canines when maximally tolerated dosed cyclophosphamide is administered. This retrospective study aimed to determine whether orally administered furosemide decreased the incidence of SHC. Secondary aims were to identify predisposing factors for SHC. One-hundred and fifteen dogs treated with metronomic cyclophosphamide were analysed retrospectively. Populations were not randomized. 25 dogs (21.7%) developed SHC. Furosemide administration significantly reduced the likelihood of SHC development (P = 0.010, where SHC was diagnosed in 30.3% of dogs administered cyclophosphamide without furosemide, and 10.2% of dogs administered cyclophosphamide with furosemide). Age, gender, breed, bodyweight, number of cyclophosphamide treatments, piroxicam use and previous or pre-existing disease were not found to be associated with SHC development. This study demonstrates furosemide is effective in the prevention of SHC and its use may be considered when implementing metronomic cyclophosphamide therapy.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Cistite/veterinária , Doenças do Cão/tratamento farmacológico , Furosemida/uso terapêutico , Administração Metronômica , Animais , Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Cistite/induzido quimicamente , Cistite/prevenção & controle , Doenças do Cão/induzido quimicamente , Doenças do Cão/prevenção & controle , Cães , Feminino , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Estudos Retrospectivos , Fatores de Risco
8.
Phys Rev Lett ; 117(7): 075002, 2016 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-27563971

RESUMO

Direct measurements of hydrodynamic instability growth at the fuel-ablator interface in inertial confinement fusion (ICF) implosions are reported for the first time. These experiments investigate one of the degradation mechanisms behind the lower-than-expected performance of early ICF implosions on the National Ignition Facility. Face-on x-ray radiography is used to measure instability growth occurring between the deuterium-tritium fuel and the plastic ablator from well-characterized perturbations. This growth starts in two ways through separate experiments-either from a preimposed interface modulation or from ablation front feedthrough. These experiments are consistent with analytic modeling and radiation-hydrodynamic simulations, which say that a moderately unstable Atwood number and convergence effects are causing in-flight perturbation growth at the interface. The analysis suggests that feedthrough from outersurface perturbations dominates the interface perturbation growth at mode 60.

9.
Am J Ind Med ; 58(10): 1114-25, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26305997

RESUMO

BACKGROUND: Heat-related illness (HRI) is an occupational health risk for many outdoor, and some indoor, workers. METHODS: Emergency department (ED) and inpatient hospitalization (IH) data for 2007-2011 from nine southeast states were analyzed to identify occupational HRI numbers and rates, demographic characteristics, and co-morbid conditions. RESULTS: There were 8,315 occupational HRI ED visits (6.5/100,000 workers) and 1,051 IHs (0.61/100,000) in the southeast over the study period. Out-of-state residents comprised 8% of ED visits and 12% of IHs. Rates for both, ED visits and IHs were significantly elevated in males and blacks. Younger workers had elevated rates for ED visits, while older workers had higher IH rates. CONCLUSIONS: This is the first study to evaluate occupational HRI ED visits and IHs in the southeast region and indicates the need for enhanced heat-stress prevention policies in the southeast. Findings from this study can be used to direct state health department tracking and evaluation of occupational HRI.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Transtornos de Estresse por Calor/epidemiologia , Hospitalização/estatística & dados numéricos , Doenças Profissionais/epidemiologia , Adulto , Idoso , Feminino , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Doenças Profissionais/terapia , Estudos Retrospectivos , Fatores de Risco , Sudeste dos Estados Unidos/epidemiologia
10.
Traffic Inj Prev ; 14(7): 680-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23944873

RESUMO

OBJECTIVE: Prescription drug overdoses, abuse, and sales have increased dramatically in the United States in the last decade. The purpose of the present study was to link crash data with emergency department (ED) and inpatient hospitalization data to assess the concordance between the data sets in the identification of the presence of drugs among injured motor vehicle drivers (passenger cars, passenger trucks, light trucks, and semi-trucks) in Kentucky. METHODS: Kentucky CRASH data were probabilistically linked to ED data sets for years 2008-2010 and to inpatient hospitalization data sets for years 2000-2010. Statistical analyses were performed. RESULTS: Of the 72,529 linked crash/ED visits, there were 473 drivers with an associated nondependent abuse of drugs diagnosis in the ED, and 930 drivers had drug involvement recorded in the CRASH data (only 163 cases overlapped with drug involvement both recorded in CRASH data and coded as nondependent abuse of drugs in the ED); 64 drivers had multiple drug types present in their system. Of the 20,860 total linked crash/inpatient hospitalization cases, there were 973 drivers diagnosed with nondependent abuse of drugs in the inpatient hospitalization record and 499 drivers had drug involvement recorded in the CRASH data (only 207 overlapped); 250 drivers were diagnosed with multiple drugs in their system. CONCLUSIONS: Surveillance data from multiple public health data sets is necessary to identify the presence of drugs in injured drivers involved in motor vehicle crashes. The use of a single surveillance data set alone may significantly underreport the number of drugged drivers who were injured in a motor vehicle collision.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Vigilância da População/métodos , Detecção do Abuso de Substâncias/estatística & dados numéricos , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Humanos , Kentucky , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/terapia , Adulto Jovem
11.
Accid Anal Prev ; 47: 140-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22405242

RESUMO

A retrospective population-based case-control study was performed to determine the association between vehicle fires, and vehicle, collision, and driver factors on highways with a posted speed limit of at least 55mph. Data were obtained from the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic files for 2000-2009 from the Kentucky State Police Records Sections. The results from the final multiple logistic regression show that large trucks were at a higher risk for a collision involving a fire than passenger vehicles and pickup trucks. When controlling for all other variables in the model, vehicles 6 years old and older, driving straight down the highway, and single vehicle collisions were also identified as factors that increase the risk of motor vehicle collision fires on roadways with a posted speed limit of ≥55mph. Of the 2096 vehicles that caught fire, there were 632 (30%) non-fatally injured drivers and 224 (11%) fatally injured drivers. The results of this study have the potential to inform public health messages directed to the transportation industry, particularly semi truck drivers, in regard to fire risk.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Incêndios/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Acidentes de Trânsito/mortalidade , Condução de Veículo , Humanos , Kentucky/epidemiologia , Veículos Automotores , Estudos Retrospectivos , Fatores de Risco
12.
Traffic Inj Prev ; 10(3): 266-72, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19452368

RESUMO

OBJECTIVE: A retrospective population-based case control study was conducted to determine whether semi truck driver age and gender and the presence of passengers affect the likelihood that a semi truck driver will be at fault in a semi truck collision (STC) with another vehicle. METHODS: Cases were identified as semi truck drivers in at-fault STCs with other vehicles and controls were semi truck drivers in not-at-fault STCs with other vehicles, using the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic database from 2000-2006. Multiple logistic regression was performed. RESULTS: The results from the final multiple logistic regression show that solo semi truck drivers, aged 65 and over, were the age group at highest risk for at-fault STCs with other vehicles. However, the presence of passengers in the semi truck had a protective effect for semi truck drivers aged 65 and older. When controlling for all other variables in the model, female semi truck drivers were at higher risk than male drivers, and curvy and graded/hillcrest roads increased the odds that the semi truck driver would be at fault in an STC with another vehicle. Daytime driving and driving on roads with low posted speed limits (35 mph and less) were associated with a higher probability of being at fault in an STC with another vehicle. CONCLUSIONS: The results of this study have the potential to inform public policy in regard to the presence of passengers and their positive protective effect on older (aged 65 and older) semi truck drivers, particularly in long-distance driving performed by solo semi truck drivers vs. team semi truck drivers.


Assuntos
Acidentes de Trânsito , Conscientização , Veículos Automotores , Acidentes de Trânsito/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Bases de Dados como Assunto , Feminino , Humanos , Kentucky , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
13.
Accid Anal Prev ; 37(5): 862-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15921653

RESUMO

A retrospective population-based case-control study was conducted to determine whether driver sleepiness/fatigue and inattention/distraction increase the likelihood that a commercial motor vehicle collision (CVC) will be fatal. Cases were identified as CVC drivers who died (fatal) and controls were drivers who survived (nonfatal) an injury collision using the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic database from 1998-2002. Cases and controls were matched on unit type and roadway type. Conditional logistic regression was performed. Driver sleepiness/fatigue, distraction/inattention, age of 51 years of age and older, and nonuse of safety belts increase the odds that a CVC will be fatal. Primary safety belt law enactment and enforcement for all states, commercial vehicle driver education addressing fatigue and distraction and other approaches including decreased hours-of-service, rest breaks and policy changes, etc. may decrease the probability that a CVC will be fatal.


Assuntos
Acidentes de Trabalho/mortalidade , Acidentes de Trânsito/mortalidade , Atenção , Fadiga/epidemiologia , Transtornos do Sono do Ritmo Circadiano/epidemiologia , Adulto , Distribuição por Idade , Estudos de Casos e Controles , Humanos , Kentucky/epidemiologia , Modelos Logísticos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Cintos de Segurança/estatística & dados numéricos
14.
Hum Exp Toxicol ; 21(9-10): 479-85, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12458904

RESUMO

While the history of immunotoxicology research involving experimental animals of immature ages dates back over several decades, there exist remarkably little data, to date, directly comparing the impact of developmental status on immunotoxicological risk. Given the size of the nonadult human population and the potential for differential vulnerability among the various ages, this represents a serious gap of knowledge in efforts to minimize environmentally linked health risks. This article frames the issues surrounding developmental immunotoxicological evaluations. In particular, the issues introduced include those of potential animal models, strain/genotype selection, gender, age of exposure, and age of assessment. Recent research results involving early exposure to lead (Pb) and other chemicals are discussed to highlight the nature of the decisions that are available and the potential cost-benefit associated with various approaches to evaluation.


Assuntos
Exposição Ambiental/efeitos adversos , Substâncias Perigosas/toxicidade , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/crescimento & desenvolvimento , Adolescente , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/prevenção & controle , Criança , Pré-Escolar , Modelos Animais de Doenças , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Exposição Ambiental/legislação & jurisprudência , Guias como Assunto , Humanos , Lactente , Recém-Nascido , Neoplasias/induzido quimicamente , Neoplasias/prevenção & controle , Projetos de Pesquisa , Medição de Risco , Testes de Toxicidade/normas , Toxicologia/métodos , Toxicologia/normas , Estados Unidos
15.
J Toxicol Environ Health A ; 64(3): 223-40, 2001 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-11594701

RESUMO

Gender-based differences in immunotoxicity induced by the heavy metal lead (Pb) have been observed both in the juvenile chicken and the adult rat following low-level exposure during embryonic development. To better define the gender-based differences, as related to dose following in utero exposure to Pb, potential differential sensitivities were examined after exposure of F344 rats to low concentrations of Pb (0, 50, 100, or 250 ppm Pb) ad libitum throughout gestation. Immune assessment was performed in juveniles (5 wk old) and young adults (13 wk old). At the highest (250 ppm) Pb concentration examined, the delayed-type hypersensitivity (DTH) response was depressed in females relative to gender-matched controls at both ages; relative spleen weights and relative neutrophil numbers were increased while relative and absolute monocyte numbers and relative basophil numbers were decreased at 13 but not 5 wk of age. In contrast, 250 ppm Pb-treated males did not differ in these endpoints. With in utero exposure to 100 ppm Pb, 13-wk-old females again had decreased relative and absolute monocyte numbers and increased relative neutrophil numbers, although the DTH response was unchanged. Males (with 100 ppm Pb) had increased relative neutrophil numbers, decreased relative lymphocytes, and transiently increased nitrite production seen at 5, but not 13, wk of age. After gestational exposure to 50 ppm Pb, minimal immunotoxic effects were observed in either males or females at either developmental age assessed. These results suggest that differential gender-based immunotoxicity profiles exist after gestational Pb exposure depending on the concentration of Pb administered to the dam. In utero exposure of dams to 250 ppm Pb results in more profound immunotoxicity in females than males. Males arenot more sensitive to lower concentrations of Pb than females. Since the 50 ppm exposure produced minimal changes, these data may provide information to establish a no-observed-adverse-effect level (NOAEL) for in utero exposure to Pb. Additionally, while most effects were evident at both juvenile and adult ages, some changes were not fully evident until measured in the adult. Most changes were persistent with only one exception (male nitrite levels at 100 ppm).


Assuntos
Envelhecimento/imunologia , Imunidade/efeitos dos fármacos , Chumbo/toxicidade , Envelhecimento/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade Tardia , Masculino , Óxido Nítrico/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Ratos , Ratos Endogâmicos F344 , Caracteres Sexuais , Baço/citologia , Baço/imunologia
16.
Toxicol Sci ; 64(1): 57-66, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11606801

RESUMO

Previous rat studies with lead (Pb) have shown that exposure throughout the full gestational period results in persistent immunotoxicity detectable in both juvenile and adult offspring. Gender differences are also evident. However, little is known about the persistent immunotoxic effects of Pb when administered during specific stages of embryonic development. Adult Sprague-Dawley female rats were administered Pb acetate (or control acetate) in their drinking water early in gestation (days 3-9) or late in gestation (days 15-21). Significantly depressed delayed type hypersensitivity (DTH) responses as well as elevated IL-10 production, relative monocyte numbers, and increased relative thymic weights were observed in late-gestation Pb-exposed female offspring assessed as adults. In contrast, late-gestation Pb-treated male offspring had significantly increased IL-12 production and decreased IL-10 production, while the DTH response, relative monocyte numbers and thymic weights were unchanged. With early exposure, the primary alteration was decreased nitric oxide production in Pb-treated males, whereas in Pb-treated females nitrite production was unaltered. These results suggest that at the Pb dosage employed, the embryo may be more sensitive to the full range of Pb-induced immunotoxic effects with late gestational Pb exposure, and the effects of Pb on DTH function are more pronounced in females. The data also indicate that adherent splenocytes (probably macrophages) and T lymphocytes are the primary immune cells affected during fetal Pb exposure, and that gender may influence the impact of Pb exposure on these cells. Therefore, additional developmental immunotoxicity studies are needed to examine critical windows of immune development for immunotoxicity and differential susceptibility based on gender.


Assuntos
Citocinas/metabolismo , Embrião de Mamíferos/efeitos dos fármacos , Hipersensibilidade Tardia , Chumbo/toxicidade , Compostos Organometálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Adjuvantes Imunológicos , Animais , Osso e Ossos/química , Células Cultivadas , Concanavalina A/imunologia , Desenvolvimento Embrionário e Fetal , Feminino , Idade Gestacional , Hemocianinas/imunologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-2/metabolismo , Chumbo/sangue , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Nitritos/metabolismo , Tamanho do Órgão , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacologia , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo , Timo/imunologia , Timo/fisiologia
17.
Ann Neurol ; 50(2): 258-61, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11506411

RESUMO

A case of sporadic Creutzfeldt-Jakob disease (sCJD) is described in a young Dutch protein prion gene (PRNP) codon 129 valine homozygote. Certain clinical and molecular features of this case overlap those of variant CJD. The case highlights possible difficulties in the differential diagnosis of vCJD and the more rare sCJD subtypes based on molecular features alone.


Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Adulto , Feminino , Lobo Frontal/patologia , Homozigoto , Humanos , Imuno-Histoquímica , Países Baixos , Fenótipo
18.
Neuropathol Appl Neurobiol ; 26(5): 463-72, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11054187

RESUMO

The naturally occurring polymorphism at codon 129 of the human prion protein gene (PRNP) influences susceptibility to sporadic Creutzfeldt-Jakob Disease (CJD); the majority of the patients are methionine homozygotes at this locus, while valine homozygotes represent only 10% of cases. The aim was to study the clinical and neuropathological phenotype of sporadic CJD in valine homozygotes, to estimate the reliability of current clinical diagnostic criteria, and to identify any consistent and distinct features. Twelve cases of sporadic CJD with a codon 129 valine homozygote genotype were identified at the National CJD Surveillance Unit in Edinburgh. In addition to a retrospective clinical analysis, tissue blocks were stained by conventional techniques and by immunocytochemistry for prion protein. Frozen brain tissue was available from five cases for Western blot analysis of PrPRES, which in all cases showed a type 2 mobility. The cases included four males and eight females, average age 63.6 years, with a mean duration of illness of 6 months. Eleven patients presented with ataxia, and none had the characteristic EEG changes found in sporadic CJD. The neuropathological phenotype comprised spongiform change and prion protein immunopositivity most marked in the subcortical grey matter and cerebellum, prion protein positive plaque-like deposits in all regions, laminar deposition of prion protein in the cerebral cortex, and hippocampal involvement (which is seldom reported in sporadic CJD). In conclusion, these cases exhibited a fairly uniform phenotype, which is relatively distinct from sporadic CJD in methionine homozygotes, and thus diagnosis may be difficult using existing clinical criteria.


Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Homozigoto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Encéfalo/metabolismo , Encéfalo/patologia , Códon , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteínas PrPSc/metabolismo , Valina
19.
J Toxicol Environ Health A ; 61(8): 677-93, 2000 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-11132697

RESUMO

Lead has been shown previously to induce immunotoxic effects on macrophage and T-cell-associated functions after full-gestational exposure. To gain a better understanding of a single developmental exposure and the potential role of gender in immunotoxic responses to low levels of lead, 5-d-old avian embryos were injected once with lead acetate (5 or 10 microg). As juveniles (4 wk of age), animals were immunized with a foreign antigen, bovine serum albumin (BSA). At 6 and 8 wk, animals were sensitized with a self antigen, thyroglobulin (Tg). Immune parameters were examined at 6 and 10 wk of age. In males, anti-BSA immunoglobulin G (IgG) levels were significantly increased at the highest lead treatment level compared to sodium acetate controls, while female antibody production was unaltered. Similarly, after early exposure to lead, males (which were noninducible for anti-thyroglobulin antibodies in sodium acetate controls) were induced to produce autoanti-thyroglobulin IgG. Lead exposure did not markedly alter autoantibody levels in females, although, unlike males, control females could be induced to produce autoantibody to thyroglobulin. Males differed significantly in total leukocyte counts between treatment groups, whereas females did not. No marked differences were observed in males or females in the delayed-type hypersensitivity response, lymphocytic infiltration of thyroids, or in spleen, thymus, or bursa weights following exposure to lead. These results suggest that there is a differential immunotoxic effect based on gender after a single in ovo exposure to lead. Therefore, when examining the developmental immunotoxic effects of a metal such as lead, gender is a potential risk factor.


Assuntos
Galinhas/fisiologia , Imunoglobulina G/análise , Chumbo/toxicidade , Animais , Autoanticorpos , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Feminino , Imunidade Celular/efeitos dos fármacos , Contagem de Leucócitos , Masculino , Fatores de Risco , Fatores Sexuais
20.
Toxicol Sci ; 42(2): 129-35, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9579025

RESUMO

Lead has been shown to exert toxic effects during early development. In these in vivo and ex vivo experiments, the effect of lead on the immune system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water during breeding and pregnancy (exposure was discontinued at parturition). Offspring received no additional lead treatment after birth. Immune function was assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were not different from controls with respect to the immune endpoints used in these experiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effector function properties (tumor necrosis factor-alpha and nitric oxide production) were elevated in the 250 ppm group, while cell-mediated immune function was depressed, as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm group. Interferon-gamma levels were decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate that exposure of mothers to moderate levels of lead produces chronic immune modulation in their F344 rat offspring exposed in utero. Since the mothers were not susceptible to chronic immune alterations, a developmental bias to the immunotoxic effects of lead is indicated. The differences observed are consistent with the possibility that lead may bias T helper subset development and/or function, resulting in alterations in the balance among type 1 and type 2 immune responses.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Chumbo/toxicidade , Animais , Peso Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade Tardia , Imunoglobulina E/sangue , Interferon gama/biossíntese , Interleucina-2/biossíntese , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Chumbo/sangue , Contagem de Leucócitos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Endogâmicos F344 , Superóxidos/metabolismo , Tíbia/química , Fator de Necrose Tumoral alfa/biossíntese
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