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1.
Artigo em Inglês | MEDLINE | ID: mdl-38883231

RESUMO

Tics and tic disorders can significantly impact children, but limited screening tools and diagnostic challenges may delay access to care. The current study attempted to address these gaps by evaluating sensitivity and specificity of the Motor or Vocal Inventory of Tics (MOVeIT), a tic symptom screener, and the Description of Tic Symptoms (DoTS), a brief diagnostic assessment for tic disorders. Children (n=100, age 6-17 years old) with tic disorders attending a Tourette specialty clinic and a community-recruited sample without tics completed a gold-standard assessment by a tic expert; these evaluations were compared to child self-report and parent and teacher report versions of the MOVeIT, and child and parent versions of the DoTS. The parent and child MOVeIT met or exceeded pre-specified 85% sensitivity and specificity criteria for detecting the presence of tics when compared to a gold-standard tic expert diagnosis. The Teacher MOVeIT had lower sensitivity (71.4%) but good specificity (95.7%) for identifying any tic symptoms compared to gold standard. For determination of the presence or absence of any tic disorder, sensitivity of both parent and child DoTS was 100%; specificity of the parent DoTS was 92.7% and child DoTS specificity was 75.9%. More work may be needed to refine the teacher MOVeIT, but it is also recognized that tic expression may vary by setting. While the MOVeIT and DoTS parent and child questionnaires demonstrated adequate sensitivity and specificity for determining the presence of tics and tic disorders in this well-defined sample, additional testing in a general population is warranted.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30792803

RESUMO

BACKGROUND: There is a strong call for clinically useful standardized assessment tools in everyday child and adolescent psychiatric practice. The attitudes of clinicians have been raised as a key-facilitating factor when implementing new methods. An explorative study was conducted aimed to investigate the clinicians' attitudes regarding standardized assessments and usefulness of diagnoses in treatment planning. METHODS: 411 mental health service personnel working with outpatient and inpatient assessment and treatment within the specialist child and adolescent mental health services, Stockholm County Council were asked to participate in the study, of which 345 (84%) agreed answer a questionnaire. The questionnaire included questions regarding Attitudes toward Standardized Assessment and Utility of Diagnosis. Descriptive analyses were performed and four subscales were compared with information from a similar study in US using the same instruments. The demographic and professional characteristics (age, working years, gender, education, profession, management position, involvement in assessment, level of service) in terms of prediction of attitudes were studied by univariate and multivariate linear regressions. RESULTS: Overall, the clinicians had quite positive attitudes and were more positive compared to a similar study conducted in the US earlier. There were differences in attitudes due to several characteristics but the only characteristic predicting all subscales was type of profession (counselor, nurse, psychiatrist, psychologist, other), with counselors being less positive than other groups. CONCLUSION: The overall positive attitudes toward standard assessment are of importance in the development of evidence-based practice and our study implies that clinicians in general value and are willing to use standardized assessment. Nevertheless, there are specific issues such as adequate training and available translated assessment instrument that need to be addressed. When implementing new methods in practice, there are general as well as specific resistances that need to be overcome. Studies in different cultural settings are of importance to further extend the knowledge of what is general and what is specific barriers.

3.
Pediatr Neurol ; 68: 49-58.e3, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28254245

RESUMO

BACKGROUND: Tic disorders, including Tourette syndrome, are complex, multisymptom diseases, yet the impact of these disorders on affected children, families, and communities is not well understood. METHODS: To improve the understanding of the impacts of Tourette syndrome, two research groups conducted independent cross-sectional studies using qualitative and quantitative measures. They focused on similar themes, but distinct scientific objectives, and the sites collaborated to align methods of independent research proposals with the aim of increasing the analyzable sample size. RESULTS: Site 1 (University of Rochester) was a Pediatric Neurology referral center. Site 2 (University of South Florida) was a Child Psychiatry referral center. A total of 205 children with tic disorders were enrolled from both studies. The University of Rochester also enrolled 100 control children in order to clearly isolate impacts of Tourette syndrome distinct from those occurring in the general population. The majority of children with tic disorders (n = 191, 93.1%) had Tourette syndrome, the primary population targeted for these studies. Children with Tourette syndrome were similar across sites in terms of tic severity and the occurrence of comorbid conditions. The occurrence of psychiatric comorbidities in the control group was comparable with that in the general pediatric population of the United States, making this a well-justified comparison group. CONCLUSIONS: Through collaboration, two sites conducting independent research developed convergent research methods to enable pooling of data, and by extension increased power, for future analyses. This method of collaboration is a novel model for future epidemiological research of tic disorders.


Assuntos
Família , Projetos de Pesquisa , Transtornos de Tique/epidemiologia , Transtornos de Tique/psicologia , Adolescente , Criança , Pré-Escolar , Comorbidade , Comportamento Cooperativo , Estudos Transversais , Família/psicologia , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Transtornos de Tique/complicações , Estados Unidos/epidemiologia
4.
Osteoporos Int ; 24(9): 2471-81, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23436075

RESUMO

UNLABELLED: The purpose of this study was to describe the evolution of femoral neck strength relative to load across the menopause transition. It declined significantly over the 10 years bracketing the final menstrual period, and the rate of decline was modified by body mass index, race/ethnicity, and smoking status. INTRODUCTION: Composite indices of femoral neck strength, which integrate dual energy X-ray absorptiometry (DXA)-derived bone mineral density and bone size with body size, are inversely associated with hip fracture risk. Our objective was to describe longitudinal trajectories of the strength indices across the menopausal transition. METHODS: Data came from the Study of Women's Health Across the Nation; participants were pre- or early peri-menopausal, ages 42-53 at baseline, and were followed up for 9.1 ± 1.8 years. Composite indices of femoral neck strength in different failure modes (compression, bending, and impact) were created in 921 women who had three or more hip DXA scans and had definable final menstrual period (FMP) dates. We used mixed effects models to fit piecewise linear growth curves to the baseline-normalized strength indices as a function of time to/after the FMP. RESULTS: Compression and impact strength indices did not decline until 1 year prior to the FMP, and declined rapidly thereafter, with some slowing of decline 1 year after the FMP. Bending strength index increased slightly until 2 years prior to the FMP, then plateaued, and began to decline at the FMP. Mean decline in strength indices over 10 years was 6.9 % (compression), 2.5 % (bending), and 6.8 % (impact). Women with higher body mass index had larger declines in two of the three indices. Other major modifiers of rates of decline were race/ethnicity and smoking status. CONCLUSIONS: Femoral neck strength relative to load declines significantly during the menopausal transition, with declines commencing 1 to 2 years prior to the FMP.


Assuntos
Densidade Óssea/fisiologia , Colo do Fêmur/fisiologia , Menopausa/fisiologia , Absorciometria de Fóton , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Envelhecimento/etnologia , Envelhecimento/fisiologia , Asiático/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Coortes , Força Compressiva/fisiologia , Feminino , Seguimentos , Humanos , Menopausa/etnologia , Pessoa de Meia-Idade , Fumar/fisiopatologia , Estresse Mecânico
5.
Osteoporos Int ; 24(4): 1379-88, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22810918

RESUMO

UNLABELLED: The study goal was to compare simple two-dimensional (2D) analyses of bone strength using dual energy x-ray absorptiometry (DXA) data to more sophisticated three-dimensional (3D) finite element analyses using quantitative computed tomography (QCT) data. DXA- and QCT-derived femoral neck geometry, simple strength indices, and strength estimates were well correlated. INTRODUCTION: Simple 2D analyses of bone strength can be done with DXA data and applied to large data sets. We compared 2D analyses to 3D finite element analyses (FEA) based on QCT data. METHODS: Two hundred thirteen women participating in the Study of Women's Health Across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact. RESULTS: DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R=0.92 and 0.70) and with QCT-derived indices (R=0.83-0.85 and 0.65-0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56). CONCLUSIONS: Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data.


Assuntos
Colo do Fêmur/fisiologia , Pós-Menopausa/fisiologia , Absorciometria de Fóton/métodos , Adulto , Densidade Óssea/fisiologia , Força Compressiva/fisiologia , Feminino , Colo do Fêmur/anatomia & histologia , Colo do Fêmur/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Estudos Longitudinais , Pessoa de Meia-Idade , Estresse Mecânico , Tomografia Computadorizada por Raios X/métodos , Suporte de Carga/fisiologia
6.
Osteoporos Int ; 23(3): 887-99, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21625880

RESUMO

UNLABELLED: To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION: The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS: A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS: Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION: Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.


Assuntos
Fraturas Ósseas/etiologia , Insuficiência Renal Crônica/complicações , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Cistatina C/sangue , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/etnologia , Taxa de Filtração Glomerular , Humanos , Mediadores da Inflamação/sangue , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/etnologia , Pós-Menopausa/fisiologia , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Medição de Risco/métodos , Estados Unidos/epidemiologia
7.
Osteoporos Int ; 23(4): 1381-90, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21927926

RESUMO

UNLABELLED: Bone mineral density does not explain race/ethnicity differences in hip fracture risk. In this study, we demonstrated that race/ethnicity differences in composite hip strength indices were consistent with documented race/ethnicity differences in hip fracture risk, suggesting that unlike bone density, the composite indices may represent ethnicity-independent measures of bone strength. INTRODUCTION: African-American and Asian women have lower risks of hip fracture than Caucasian women, but such racial/ethnic variation in hip fracture risk cannot be explained by bone mineral density (BMD). The composite indices of femoral neck strength integrate femoral neck and body size with BMD and predict hip fracture risk in Caucasian women. We hypothesize that unlike race/ethnic differences in BMD, race/ethnic differences in the composite strength indices would be consistent with race/ethnic differences in hip fracture risk. METHODS: We studied a community-based sample of Caucasian (n = 968), African-American (n = 512), Chinese (n = 221), and Japanese (n = 239) women, premenopausal or in early perimenopause, from the Study of Women's Health Across the Nation. RESULTS: Unadjusted indices were similar in Caucasian and African-American women but higher in Asian women. After adjusting for age, body mass index, and menopause status, all three minority groups had higher composite strength indices than Caucasian women. Foreign-born Japanese women had higher unadjusted and adjusted composite strength indices than US-born Japanese women, but such differences by nativity were not observed in Chinese women. CONCLUSION: We concluded that composite strength indices have the potential to explain racial/ethnic differences in hip fracture risk, suggesting that composite strength indices may represent ethnicity-independent measures of bone strength. This contention needs to be verified by further research on the fracture predictive ability of composite strength indices in multi-ethnic longitudinal cohorts.


Assuntos
Colo do Fêmur/fisiopatologia , Fraturas do Quadril/etnologia , Fraturas por Osteoporose/etnologia , Absorciometria de Fóton/métodos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Antropometria/métodos , Povo Asiático/estatística & dados numéricos , Densidade Óssea/fisiologia , Feminino , Fraturas do Quadril/fisiopatologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fraturas por Osteoporose/fisiopatologia , Perimenopausa/etnologia , Perimenopausa/fisiologia , Pré-Menopausa/etnologia , Pré-Menopausa/fisiologia , População Branca/estatística & dados numéricos
8.
Int J Clin Pract ; 64(9): 1190-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20497262

RESUMO

BACKGROUND: Available screening tools for mild cognitive impairment (MCI), often a precursor to Alzheimer's disease, are insensitive or not feasible for administration in a busy primary care setting. Display Enhanced TEsting for Cognitive impairment and Traumatic brain injury (DETECT) addresses these issues by creating an immersive environment for the brief administration of neuropsychological (NP) measures. OBJECTIVE: The aim of this study was to determine if the DETECT cognitive subtests can identify MCI patients as accurately as standard pen and paper NP tests. METHODS: Twenty patients with MCI recruited from a memory disorders clinic and 20 age-matched controls were given both a full battery of NP tests (standard NP) and the DETECT screen. Logistic regression models were used to determine whether individual tests were predictive of group membership (MCI or control). Demographic variables including age, race, education and gender were adjusted as covariates. Selection methods were used to identify subset models that exhibited maximum discrimination between MCI patients and controls for both testing methods. RESULTS: Both the standard NP model (C-index = 0.836) and the DETECT model (C-index = 0.865) showed very good discrimination and were not significantly different (p = 0.7323). CONCLUSION: The DETECT system shows good agreement with standard NP tests and is capable of identifying elderly patients with cognitive impairment.


Assuntos
Transtornos Cognitivos/diagnóstico , Diagnóstico por Computador/instrumentação , Avaliação Geriátrica/métodos , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Software
9.
Gene Ther ; 17(3): 419-23, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19956270

RESUMO

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.


Assuntos
Doença da Artéria Coronariana/terapia , DNA/administração & dosagem , Eletroporação/métodos , Técnicas de Transferência de Genes , Terapia Genética/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Animais , DNA/genética , Vetores Genéticos , Coração , Plasmídeos/administração & dosagem , Plasmídeos/genética , Biossíntese de Proteínas/genética , Suínos , Fator A de Crescimento do Endotélio Vascular/biossíntese
10.
AJNR Am J Neuroradiol ; 30(1): 91-4, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19001536

RESUMO

BACKGROUND AND PURPOSE: Elastase-induced aneurysms in rabbits have been proposed as a useful preclinical tool for device development. The object of this study was to report rates of morbidity and mortality associated with the creation and embolization of elastase-induced rabbit aneurysms and to assess the impact of operator experience on these rates. MATERIALS AND METHODS: Elastase-induced model aneurysms were created in New Zealand white rabbits (n = 700). One neuroradiologist/investigator, naive to the aneurysm-creation procedure at the outset of the experiments, performed all surgeries. All morbidity and deaths related to aneurysm creation (n = 700) and embolization procedures (n = 529) were categorized into acute and chronic deaths. Data were analyzed with single-regression analysis and analysis of variance. To assess the impact of increasing operator experience, we broke the number of animals into 50-animal increments. RESULTS: There were 121 (17%) deaths among 700 subjects. Among 700 aneurysm-creation procedures, 59 deaths (8.4%) were noted. Among 529 aneurysm-embolization procedures, 43 deaths (8.1%) were noted. Nineteen additional deaths (2.7% of 700 subjects) were unrelated to the procedures. Simple regression-indicated mortality associated with procedures diminished with increasing operator experience (R(2) = 0.38, P = .0180), and that for each 50-rabbit increment mortality was reduced, on average, by 0.6%. CONCLUSIONS: Mortality rates of approximately 8% are associated with both experimental aneurysm creation and with embolization in the rabbit elastase-induced aneurysm model. Increasing operator experience is inversely correlated with mortality, and the age of the rabbit is positively associated with morbidity.


Assuntos
Modelos Animais de Doenças , Aneurisma Intracraniano/induzido quimicamente , Aneurisma Intracraniano/mortalidade , Elastase Pancreática , Medição de Risco/métodos , Análise de Sobrevida , Taxa de Sobrevida , Animais , Humanos , Incidência , Coelhos , Fatores de Risco
11.
AJNR Am J Neuroradiol ; 29(4): 739-44, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18184848

RESUMO

BACKGROUND AND PURPOSE: Modified coils have failed to improve long-term recanalization of aneurysms. This study examined whether ex vivo transduction of replication-deficient adenovirus containing the bone morphogenetic protein-13 gene (Ad-BMP-13) in fibroblast allografts would improve angiographic results via increased collagen synthesis, compared with fibroblast-coated platinum coils (FBC) and bare platinum coils (PA). MATERIALS AND METHODS: Aneurysms were embolized with Ad-BMP-13-coated coils (n = 20). Rabbits were sacrificed at 14 days and at 1, 3, and 6 months after implantation. Digital subtraction angiography (DSA) evaluated stability after embolization. Histologic specimens were examined with a qualitative grading system. Masson trichrome evaluated collagen deposition. Findings were compared with previously reported controls for PA and FBC in the same model and time points. RESULTS: The grading system showed a greater total score (P = .0002) in Ad-BMP-13 (6.8 +/- 1.6) and FBC (6.3 +/- 2.4) compared with PA (4.7 +/- 2.4). A group main effects test showed that aneurysm neck tissue coverage in Ad-BMP-13 (2.5 +/- 1.1) was higher (P = .0007) than both FBC (1.6 +/- 1.4) and PA (0.9 +/- 1.1). Ad-BMP-13 had more (P < .0001) collagen deposition than the FBC and PA. One- and 3-month Ad-BMP-13 collagen depositions increased (P < .05) over the FBC and PA. Finally, Ad-BMP-13 showed radiographic stability in 15 (75%) cases, coil compaction in 4 (20%) cases, and progressive occlusion in 1 (5%) case. There were no differences in angiographic results (P = .6522). CONCLUSION: The Ad-BMP-13-coated coils can improve neck coverage and dome fibrosis in the rabbit model, even in the absence of observed differences in angiographic outcome.


Assuntos
Adenoviridae/genética , Proteínas Morfogenéticas Ósseas , Materiais Revestidos Biocompatíveis , Embolização Terapêutica/instrumentação , Fibroblastos/transplante , Aneurisma Intracraniano/terapia , Transfecção , Adenoviridae/metabolismo , Angiografia Digital , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Angiografia Cerebral , Colágeno/biossíntese , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/metabolismo , Platina , Coelhos
12.
J Environ Manage ; 86(3): 465-80, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17292530

RESUMO

The resulting impact of disasters on society depends on the affected country's economic strength prior to the disaster. The larger the disaster and the smaller the economy, the more significant is the impact. This is clearest seen in developing countries, where weak economies become even weaker afterwards. Deliberate strategies for the sharing of losses from hazardous events may aid a country or a community in efficiently using scarce prevention and mitigation resources, thus being better prepared for the effects of a disaster. Nevertheless, many governments lack an adequate institutional system for applying cost effective and reliable technologies for disaster prevention, early warnings, and mitigation. Modelling by event analyses and strategy models is one way of planning ahead, but these models have so far not been linked together. An approach to this problem was taken during a large study in Hungary, the Tisza case study, where a number of policy strategies for spreading of flood loss were formulated. In these strategies, a set of parameters of particular interest were extracted from interviews with stakeholders in the region. However, the study was focused on emerging economies, and, in particular, on insurance strategies. The scope is now extended to become a functional framework also for developing countries. In general, they have a higher degree of vulnerability. The paper takes northern Vietnam as an example of a developing region. We identify important parameters and discuss their importance for flood strategy formulations. Based on the policy strategies in the Tisza case, we extract data from the strategies and propose a framework for loss spread in developing and emerging economies. The parameter set can straightforwardly be included in a simulation and decision model for policy formulation and evaluation, taking multiple stakeholders into account.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Política Pública , Alocação de Recursos , Países em Desenvolvimento , Humanos , Medição de Risco , Gestão de Riscos , Vietnã , Populações Vulneráveis
13.
AJNR Am J Neuroradiol ; 28(5): 849-56, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17494655

RESUMO

BACKGROUND AND PURPOSE: The mechanism of aneurysm healing after coiling remains poorly understood. The purpose of the study was to obtain a better understanding of the cellular and molecular events that are associated with aneurysm healing after endovascular coiling in a swine aneurysm model. MATERIALS AND METHODS: Twenty sidewall aneurysms were created surgically in common carotid arteries in 10 swine. These aneurysms were embolized immediately after creation by using platinum coils by endovascular means. Two and 12 weeks after implantation, aneurysm samples were collected for histologic and biochemical analysis. RESULTS: All aneurysms were completely or nearly completely occluded angiographically at the time of embolization and at follow-up. At 2 weeks, aneurysm cavities were filled with inflammatory cells and myofibroblasts. At 12 weeks, aneurysm cavities were filled with richly vascularized fibrous tissue and disorganized collagen bundles. The expression of matrix metalloproteinase (MMP)-2 and -9 was found to be elevated at 2 weeks. Expression remained greater than that in control tissue at 12 weeks but was significantly decreased compared with the earlier time point. Expression of tissue inhibitors of MMPs (TIMPs) was diminished at both time points. Expression of vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) was elevated at both 2 weeks and 12 weeks. Endothelial nitric oxide synthase expression was not different from that in controls. Transforming growth factor-beta expression was elevated at 2 weeks only. CONCLUSION: The coil occlusion in this model that is prone to heal is associated with increased expression of MMP-2, MMP-9, VCAM-1, and VEGF, and decreased expression of TIMPs.


Assuntos
Aneurisma/metabolismo , Aneurisma/terapia , Embolização Terapêutica , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Aneurisma/patologia , Animais , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/terapia , Feminino , Sus scrofa , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/fisiologia
14.
AJNR Am J Neuroradiol ; 28(5): 857-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17494656

RESUMO

BACKGROUND AND PURPOSE: Animal models with appropriate volume are crucial for preclinical assessment of aneurysm therapies. Our purpose was to control the aneurysm volume by adjusting the position of ligation during creation of elastase-induced aneurysms in rabbits. MATERIALS AND METHODS: Sixty elastase-induced aneurysms in rabbits were created. Two different methods were used for creation, including group 1 (n=30) by using a lower ligation (from the origin of the right common carotid artery [RCCA] to the ligation point, 10 mm) and group 2 (n=30) by using a higher ligation (from the origin of the RCCA to the ligation point, 15 mm). Aneurysm sizes (neck diameter, width, and height) and volumes in the 2 groups were measured and calculated, and they were compared by using the Student t test. RESULTS: The mean aneurysm neck diameter, width, and height for group 2 were significantly larger than those of group 1 (3.3 +/- 0.8 versus 2.7 +/- 0.6 mm, P<.001; 3.7 +/- 0.7 versus 2.5 +/- 0.7 mm, P<.001; 9.0 +/- 1.7 versus 7.3 +/- 1.9 mm, P<.001, respectively). The aneurysm volume in group 2 was significantly larger than that in group 1 (102.4 +/- 54.8 mm(3) versus 36.6 +/- 26.8 mm(3), P<.001). CONCLUSION: The aneurysm volume of elastase-induced models in rabbits can be controlled by adjusting the position of the ligation. Using a higher ligation can create relatively more voluminous aneurysms, compared with using a lower ligation.


Assuntos
Modelos Animais de Doenças , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Coelhos , Angiografia Digital , Animais , Angiografia Cerebral , Aneurisma Intracraniano/induzido quimicamente , Ligadura , Elastase Pancreática
15.
AJNR Am J Neuroradiol ; 27(8): 1681-4, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16971614

RESUMO

BACKGROUND AND PURPOSE: Reproducible animal models with appropriate neck size are crucial for preclinical assessment of aneurysm therapies. Our purpose was to determine whether the neck size of elastase-induced aneurysms could be controlled by adjusting the position of the temporary occlusion balloon. METHODS: Seventy-two elastase-induced aneurysms in rabbits were retrospectively analyzed. Three groups (group 1, n = 35; group 2, n = 32; group 3, n = 5) were defined according to different balloon position (lowest, intermediate, and highest, respectively) related to the origin of right common carotid artery (CCA). Aneurysm sizes in different groups were measured and compared; parent artery dilation was assessed as present or absent. The Wilcoxon rank sum test, the Fisher exact test, and the chi(2) test were used for statistics process. RESULTS: The mean aneurysm neck diameter in group 1 was significantly wider than that in group 2 (P = .0001). The proportion of wide-necked (diameter of neck >4 mm) aneurysms in group 1 was significantly higher than that in group 2 (P = .0011). The mean dome/neck ratio in group 1 was smaller than that of group 2 (P = .0031). Aneurysm width and height and the frequency of parent artery dilation were not different in groups 1 and 2 (P = .43, P = .10, and P = .25). No aneurysms formed in group 3. CONCLUSION: The neck size of elastase-induced aneurysms can be controlled by adjusting the position of the inflated balloon, with balloon positioning that bridges from the CCA to the subclavian/brachiocephalic arteries yielding narrow-necked aneurysms.


Assuntos
Aneurisma/diagnóstico por imagem , Angiografia Digital , Oclusão com Balão , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Modelos Animais de Doenças , Aneurisma/induzido quimicamente , Animais , Tronco Braquiocefálico/diagnóstico por imagem , Doenças das Artérias Carótidas/induzido quimicamente , Artéria Carótida Primitiva/efeitos dos fármacos , Elastase Pancreática , Coelhos , Artéria Subclávia/diagnóstico por imagem
16.
AJNR Am J Neuroradiol ; 27(8): 1700-2, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16971617

RESUMO

Digital subtraction angiography through the central artery of the ear was performed to show elastase-induced aneurysms in 34 rabbits. Twenty-eight (82%) aneurysms in which common origins of the bilateral common carotid artery (CCA) were found were well shown. All 6 other aneurysms not well shown had separate origins of the CCAs from the aortic arch (P < .001). This method can be used for angiographic follow-up when there is a common origin of the CCAs.


Assuntos
Angiografia Digital/métodos , Angiografia Cerebral/métodos , Modelos Animais de Doenças , Orelha/irrigação sanguínea , Aneurisma Intracraniano/diagnóstico por imagem , Animais , Artérias , Meios de Contraste/administração & dosagem , Aneurisma Intracraniano/induzido quimicamente , Iohexol , Variações Dependentes do Observador , Elastase Pancreática , Coelhos , Sensibilidade e Especificidade
17.
AJNR Am J Neuroradiol ; 27(4): 736-41, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16611755

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to probe the cellular mechanism of healing in aneurysms after platinum coil embolization, by using multiple special stains and immunolabels. METHODS: Elastase-induced aneurysms were created and embolized in 28 rabbits. Aneurysms were excised between 2 and 24 weeks after embolization. Specimens were embedded in paraffin, sectioned, and stained with hematoxylin-eosin, Masson trichrome, and multiple immunostains. RESULTS: At 2 weeks, peripheral sparse spindle-nucleated cells were positive for alpha-smooth muscle actin (SMA), myosin, and vimentin, indicating myofibroblastic differentiation. At 4 weeks, all spindle-nucleated cells in the aneurysm were positive for SMA, myosin, desmin, and vimentin. Ten weeks after embolization, positive immunohistochemical staining in the cells populating the aneurysm significantly decreased. Mean positive SMA cells, per high-powered field were 5 +/- 3, 45 +/- 9, 10 +/- 5, 0 +/- 0, and 0 +/- 0 at 2, 4, 10, 16, and 24 weeks, respectively. Findings of a Kruskal-Wallis test showed these data to be significantly different (P =.0001). Post hoc tests revealed significantly greater amounts of SMA-positive staining in the cells at 4 weeks compared with those at 2, 10, 16, and 24 weeks (P < .05). In addition, the 10-week group had significantly more positive cells than the 16- and 24-week groups (P < .05). There was a 78% decrease in apoptotic cells between 4 (37 +/- 11) and 10 weeks (8 +/- 4) after implantation. Apoptotic cells were completely absent beyond 10 weeks. CONCLUSION: Aneurysm healing, in response to platinum coil embolization, appeared to progress through the stages of thrombus formation, granulated tissue organization, and loose connective tissue formation. Myofibroblasts, the key cellular component involved in healing, appeared within the aneurysm early. They progressively reduced in number with time and finally disappeared through the mechanism of apoptosis.


Assuntos
Embolização Terapêutica/instrumentação , Aneurisma Intracraniano/terapia , Próteses e Implantes , Animais , Imuno-Histoquímica , Aneurisma Intracraniano/patologia , Estudos Longitudinais , Desenho de Prótese , Coelhos , Indução de Remissão
18.
AJNR Am J Neuroradiol ; 27(1): 139-41, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16418373

RESUMO

BACKGROUND AND PURPOSE: Long-term patency in untreated experimental aneurysms represents a critical attribute of any system proposed for the testing of aneurysm occlusion devices. Our purpose was to evaluate the long-term patency in elastase-induced saccular aneurysm models in rabbits. METHODS: Serial intravenous digital subtractive angiography (IVDSA) was performed in 20 elastase-induced saccular aneurysm models in rabbits 1, 3, 6, 9, 12, and 24 months after creation. Aneurysm dimensions, including neck diameter, width, and height, were measured and calculated from IVDSA images. Comparisons of the aneurysm sizes across time were performed by using the paired Wilcoxon signed rank test and the Friedman test. RESULTS: None of the 20 aneurysms showed spontaneous thrombosis at any time point. Mean dimensions did not change over time for any parameter. Mean aneurysm neck, width, and height were not significantly changed at interval evaluations of 1, 3, 6, 9, 12, and 24 months (P = .210; P = .413, and P = .405, respectively). CONCLUSION: Long-term patency in elastase-induced saccular aneurysm models in rabbits is excellent. Aneurysm dimensions remain stable for as long as 2 years following creation.


Assuntos
Modelos Animais de Doenças , Aneurisma Intracraniano/diagnóstico por imagem , Elastase Pancreática , Coelhos , Grau de Desobstrução Vascular , Angiografia Digital , Animais , Aneurisma Intracraniano/induzido quimicamente , Aneurisma Intracraniano/patologia
19.
Am J Clin Pathol ; 121(6): 810-5, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15198352

RESUMO

Terminal deoxynucleotidyl transferase (TdT) is a unique intranuclear DNA polymerase that catalyzes the template-independent addition of deoxynucleotides to the 3'-hydroxyl terminus of oligonucleotide primers. The expression of TdT is restricted to lymphoid precursors. It is a useful marker in distinguishing acute lymphoblastic leukemia (ALL)from mature lymphoid neoplasms. Although TdT- T-cell ALL has been reported in the literature rarely, the frequency and significance of TdT-nonpositive (TdT(np) B-cell ALL have not been examined extensively. We reviewed the immunophenotypes of 186 new cases of pediatric B-cell ALL and found 5 TdT(np) cases (2.7%). They showed significantly higher frequencies of a WBC count of more than 50,000/microL (> 50.0 x 10(9)/L), CD10-, CD34-, and MLL gene rearrangement compared with those in TdT+ cases (3/5 [60%] vs 27/181 [14.9%], P = .03; 3/5 [60%] vs 11/181 [6.1%], P = .003; 4/5 [80%] vs 24/179 [13.4%], P = .002; 3/5 [60%] vs 9/181 [5.0%], P = .0019; respectively). These results indicate that nonpositive TdT does not rule out a diagnosis of ALL and suggest that TdT(np) B-cell ALL might be associated with CD10- and CD34- disease, a high WBC count, and MLL gene rearrangement.


Assuntos
Biomarcadores Tumorais/análise , DNA Nucleotidilexotransferase/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Feminino , Citometria de Fluxo , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Lactente , Masculino , Proteína de Leucina Linfoide-Mieloide , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
J Clin Epidemiol ; 54 Suppl 1: S9-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11750203

RESUMO

The Veterans Aging Cohort Study (VACS) planning meeting was the first of a series of organizational meetings and VA-sponsored conference calls designed to build the scientific foundation and methodological infrastructure for a multisite, longitudinal study of HIV and chronic disease outcomes among aging veterans. More specifically, it served as a consensus conference to determine scientific priorities, develop hypotheses, and to assemble working groups and committees to outline the specific methodological approaches needed. Scientists, physicians from 20 VA clinical facilities in the United States, community members, and experts in the fields of immunology, cancer, sociology, aging, cognition, psychiatry and mental health, epidemiology, large database analysis, and health services research gathered for an intense, 2-day meeting held in Pittsburgh, PA, November 8-9, 2000.


Assuntos
Envelhecimento/fisiologia , Infecções por HIV/epidemiologia , Veteranos , Doença Crônica , Soronegatividade para HIV , Humanos , Estudos Longitudinais , Projetos de Pesquisa , Estados Unidos/epidemiologia
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