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1.
BJOG ; 128(9): 1503-1510, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33982870

RESUMO

OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.


Assuntos
COVID-19/prevenção & controle , Colposcopia/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Idoso , Bases de Dados Factuais , Atenção à Saúde/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Ontário , SARS-CoV-2 , Adulto Jovem
2.
Gynecol Oncol ; 130(2): 329-33, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23707676

RESUMO

OBJECTIVE: In the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. METHODS: All women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. RESULTS: Of 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p=0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p=0.032) while the time to genetic counseling decreased (p=0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. CONCLUSIONS: Despite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.


Assuntos
Cistadenocarcinoma Seroso/genética , Aconselhamento Genético , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Encaminhamento e Consulta
3.
Gynecol Oncol ; 119(1): 22-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20591472

RESUMO

OBJECTIVE: There are no evidence based guidelines for the diagnosis of epithelial ovarian cancer (EOC) prior to the initiation of neoadjuvant chemotherapy. The aim of this study was to review our diagnostic practice, provide guidelines for clinical practice, and suggest a diagnostic strategy for validation in future prospective trials. PATIENTS AND METHODS: A retrospective chart review of patients undergoing neoadjuvant chemotherapy followed by debulking surgery was performed. Final diagnoses were based on expert pathology review of surgical specimens. Diagnostic strategies were defined as histologic, cytologic and clinical. Performance of these strategies in predicting final pathology was compared. RESULTS: Between 1994 and 2007, 149 patients were identified. Initial diagnosis was made on the basis of: cytology (paracentesis, thoracentesis, or fine needle aspirate) 72% (108 patients); histology (core biopsy, surgery) 18% (26), clinical (Radiology and CA-125) 10% (15). The final diagnosis was consistent with invasive EOC in 96% of patients. The diagnostic accuracies of the 3 strategies were: cytology 98%, histology 92%, and clinical 87%, (p=0.04). Specific EOC subtype was identified in 59% of patients (histology 77% and cytology 55%). When available, the initial subtype corresponded to the final subtype in 85% of cases: histology 80%, cytology 86%. CONCLUSION: Diagnosis of epithelial ovarian cancer based on cytology and histology are superior to clinical factors alone. In a centre with trained gynecologic cytopathologists, a diagnosis of EOC by cytology is not significantly inferior to a diagnosis made by histology. These data are important for clinical practice and the design of future clinical trials.


Assuntos
Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Quimioterapia Adjuvante , Células Epiteliais/patologia , Medicina Baseada em Evidências , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
4.
Clin Nutr ; 38(6): 2607-2615, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30522848

RESUMO

BACKGROUND & AIMS: Given the enormous health, economic and societal consequences of the obesity pandemic, identifying effective primary prevention strategies represents a global priority. The aim of this study was to provide evidence on the association between adherence to a food-based score reflecting a set of targeted, well-informed, simple dietary recommendations and the incidence of overweight/obesity. METHODS: A total of 11,349 initially free of overweight/obesity young adults (mean [SD] age: 34.7 y [10.7]), were followed up biennially during a median of 9.3 years. The Dietary Obesity-Prevention Score (DOS) was created based on a priori evidence of foods associated with weight changes. The DOS positively weighted the consumption of vegetables, fruits, legumes, yogurt, nuts, fish, and a ratio of vegetable to animal protein; whereas the consumption of red meat, processed meat, saturated animal fat, refined grains, ultra-processed food, sugary beverages, beer and spirits were inversely weighted. Energy-adjusted tertiles of each item were used to build the DOS, ranging from 14 (lowest adherence) to 42 points (highest adherence). Adherence to the DOS was calculated at baseline and after 10 years of follow-up. We assessed both incident overweight/obesity (BMI ≥25 kg/m2) and average yearly weight changes in grams per year (g/y). RESULTS: During 104,887 person-years, 2153 incident cases of overweight/obesity were identified. A higher adherence to the DOS at baseline was significantly associated with lower risk of future development of overweight/obesity [multivariable-adjusted HR (95% CI) for the highest vs. lowest quintile = 0.63 (0.54-0.74)], with a significant linear dose-response relationship (p for trend < 0.001). When the analyses were updated with repeated measures, the results were similar and remained statistically significant. Consistently, increases in average yearly weight gain were significantly lower with better adherence to the DOS. CONCLUSIONS: In this Mediterranean cohort of university graduates, a higher adherence to a food-based score was significantly associated with lower risk of overweight/obesity and lower average annual weight gain. These findings may help counsel patients regarding dietary risks and raise awareness of weight gain before the onset of overweight/obesity.


Assuntos
Dieta/estatística & dados numéricos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adulto , Inquéritos sobre Dietas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Estudos Prospectivos , Adulto Jovem
5.
Nat Commun ; 10(1): 5485, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792208

RESUMO

Band inversions are key to stabilising a variety of novel electronic states in solids, from topological surface states to the formation of symmetry-protected three-dimensional Dirac and Weyl points and nodal-line semimetals. Here, we create a band inversion not of bulk states, but rather between manifolds of surface states. We realise this by aliovalent substitution of Nb for Zr and Sb for S in the ZrSiS family of nonsymmorphic semimetals. Using angle-resolved photoemission and density-functional theory, we show how two pairs of surface states, known from ZrSiS, are driven to intersect each other near the Fermi level in NbGeSb, and to develop pronounced spin splittings. We demonstrate how mirror symmetry leads to protected crossing points in the resulting spin-orbital entangled surface band structure, thereby stabilising surface state analogues of three-dimensional Weyl points. More generally, our observations suggest new opportunities for engineering topologically and symmetry-protected states via band inversions of surface states.

6.
Trials ; 20(1): 282, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118095

RESUMO

BACKGROUND: Leisure activities can be both enjoyable and cognitively stimulating, and participation in such activities has been associated with reduced age-related cognitive decline. Thus, integrating stimulating leisure activities in cognitive training programs may represent a powerful and innovative approach to promote cognition in older adults at risk of dementia. The ENGAGE study is a randomized controlled, double-blind preference trial with a comprehensive cohort design that will test the efficacy and long-term impact of an intervention that combines cognitive training and cognitively stimulating leisure activities. METHODS: One hundred and forty-four older adults with a memory complaint will be recruited in Montreal and Toronto. A particular effort will be made to reach persons with low cognitive reserve. Participants will be randomly assigned to one of two conditions: cognitive + leisure training (ENGAGE-MUSIC/SPANISH) or active control (ENGAGE-DISCOVERY). The ENGAGE-MUSIC/SPANISH training will include teaching of mnemonic and attentional control strategies, casual videogames selected to train attention, and classes in music or Spanish as a second language. The ENGAGE-DISCOVERY condition will comprise psychoeducation on cognition and the brain, low-stimulating casual videogames and documentary viewing with discussions. To retain the leisure aspect of the activities, participants will be allowed to exclude either music or Spanish at study entry if they strongly dislike one of these activities. Participants randomized to ENGAGE-MUSIC/SPANISH who did not exclude any activity will be assigned to music or Spanish based on a second random assignment. Training will be provided in 24 2-h sessions over 4 months. Outcomes will be measured at baseline, at 4-month follow-up, and at 24-month follow-up. The primary outcome will be cognitive performance on a composite measure of episodic memory (delayed recall scores for words and face-name associations) measured at baseline and at the 4-month follow-up. Secondary outcomes will include a composite measure of attention (speed of processing, inhibition, dual tasking, and shifting), psychological health, activities of daily living, and brain structure and function and long-term maintenance measured at the 24-month follow-up. Information on cognitive reserve proxies (education and lifestyle questionnaires), sex and genotype (apolipoprotein (Apo)E4, brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT)) will be collected and considered as moderators of training efficacy. DISCUSSION: This study will test whether a program combining cognitive training with stimulating leisure activities can increase cognition and reduce cognitive decline in persons at risk of dementia. TRIAL REGISTRATION: NCT03271190 . Registered on 5 September 2017.


Assuntos
Cognição , Atividades de Lazer , Transtornos da Memória/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Atenção , Encéfalo/patologia , Encéfalo/fisiopatologia , Estudos de Coortes , Método Duplo-Cego , Humanos , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa
7.
Oncogene ; 26(2): 198-214, 2007 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-16832351

RESUMO

Epidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.


Assuntos
Androgênios/farmacologia , Proteína BRCA1/genética , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Ovário/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Células Cultivadas , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Progressão da Doença , Células Epiteliais/metabolismo , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Zíper de Leucina , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/metabolismo , Ovário/patologia , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Análise Serial de Tecidos
8.
Neuroimage ; 42(1): 272-84, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18515149

RESUMO

We describe a Bayesian inference scheme for quantifying the active physiology of neuronal ensembles using local field recordings of synaptic potentials. This entails the inversion of a generative neural mass model of steady-state spectral activity. The inversion uses Expectation Maximization (EM) to furnish the posterior probability of key synaptic parameters and the marginal likelihood of the model itself. The neural mass model embeds prior knowledge pertaining to both the anatomical [synaptic] circuitry and plausible trajectories of neuronal dynamics. This model comprises a population of excitatory pyramidal cells, under local interneuron inhibition and driving excitation from layer IV stellate cells. Under quasi-stationary assumptions, the model can predict the spectral profile of local field potentials (LFP). This means model parameters can be optimised given real electrophysiological observations. The validity of inferences about synaptic parameters is demonstrated using simulated data and experimental recordings from the medial prefrontal cortex of control and isolation-reared Wistar rats. Specifically, we examined the maximum a posteriori estimates of parameters describing synaptic function in the two groups and tested predictions derived from concomitant microdialysis measures. The modelling of the LFP recordings revealed (i) a sensitization of post-synaptic excitatory responses, particularly marked in pyramidal cells, in the medial prefrontal cortex of socially isolated rats and (ii) increased neuronal adaptation. These inferences were consistent with predictions derived from experimental microdialysis measures of extracellular glutamate levels.


Assuntos
Potenciais de Ação/fisiologia , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Modelos Neurológicos , Rede Nervosa/fisiologia , Transmissão Sináptica/fisiologia , Animais , Teorema de Bayes , Simulação por Computador , Humanos
9.
Neuroscience ; 157(4): 813-20, 2008 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-18948173

RESUMO

Processing of information for long-term storage requires specific patterns of activity that lead to modification of synapse structure and eventual change in neural connectivity pattern. Morphological change associated with memory consolidation is reliant on neural cell adhesion molecule (NCAM) function and that of its polysialylated variant (NCAM PSA). Across species and paradigms, a transient frequency increase of polysialylated neurons in the hippocampal dentate has been found necessary for memory consolidation, however, recent studies suggest that NCAM PSA may serve to suppress memory formation in certain paradigms. As intraventricular infusions of NCAM blocking antibodies have been used successfully to demonstrate its time-dependent role at the 6 h post-training period of memory consolidation, we employed the same procedure to demonstrate a functional requirement for NCAM PSA in the consolidation of two commonly used behavioral paradigms: avoidance conditioning and spatial learning in Wistar rats. Anti-PSA was found to significantly induce amnesia of the passive avoidance response when infused at the 10 h post-training time, a period coincident with the learning-associated increase in dentate polysialylated cell frequency. Moreover, the amnesia became apparent at the 48 h recall time and was not apparent at the 24 h post-training time, suggesting a possible role in memory reconsolidation. A similar anti-PSA action was observed following water maze training in aged animals but was not apparent in young animals, an effect suggested to be due to inadequate antibody saturation of the polysialylated cell population. These studies confirm the requirement for NCAM PSA in memory consolidation and separate it from that of NCAM.


Assuntos
Anticorpos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/fisiopatologia , Molécula L1 de Adesão de Célula Nervosa/imunologia , Ácidos Siálicos/imunologia , Comportamento Espacial/efeitos dos fármacos , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Hipocampo/citologia , Injeções Intraventriculares/métodos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos
11.
Curr Biol ; 4(7): 604-10, 1994 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-7953534

RESUMO

BACKGROUND: Earlier work with neurological patients has shown that the visual perception of object size and orientation depends on visual pathways in the cerebral cortex that are separate from those mediating the use of these same object properties in the control of goal-directed grasping. We present evidence suggesting that the same dissociation between perception and action is evident in the visual processing of object shape. In other words, discrimination between objects on the basis of their shape appears to be mediated by visual mechanisms that are functionally and neurally distinct from those controlling the pre-shaping of the hand during grasping movements directed at those same objects. RESULTS: We studied two patients with lesions in different parts of the cerebral visual pathways. One patient (RV), who had sustained bilateral lesions of the occipitoparietal cortex, was unable to use visual information to place her fingers correctly on the circumference of irregularly shaped objects when asked to pick them up, even though she had no difficulty in visually discriminating one such object from another. Conversely, a second patient (DF), who had bilateral damage in the ventrolateral occipital region, had no difficulty in placing her fingers on appropriate opposition points during grasping, even though she was unable to discriminate visually amongst such objects. CONCLUSIONS: This double dissociation lends strong support to the idea that the visual mechanisms mediating the perception of objects are functionally and neurally distinct from those mediating the control of skilled actions directed at those objects. It also supports the recent proposal of Goodale and Milner that visual perception depends on a ventral stream of projections from the primary visual cortex to the inferotemporal cortex, whereas the visual control of skilled actions depends on a dorsal stream from the primary visual cortex to the posterior parietal cortex.


Assuntos
Vias Neurais/fisiologia , Lobo Occipital/fisiologia , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adulto , Agnosia/fisiopatologia , Mapeamento Encefálico , Intoxicação por Monóxido de Carbono/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Discriminação Psicológica/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/anatomia & histologia , Tato/fisiologia , Vias Visuais/anatomia & histologia , Vias Visuais/fisiologia
12.
J Neuropathol Exp Neurol ; 60(2): 132-40, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11273001

RESUMO

To investigate the role of polysialylated neural cell adhesion molecule (NCAM PSA)-mediated plasticity after injury, we examined the temporal and spatial expression of NCAM PSA immunoreactivity in the medial temporal lobe following global ischemia. Male Mongolian gerbils were subjected to bilateral common carotid artery occlusion for 5 min and killed at increasing times post-occlusion. The well-characterized delayed CAl pyramidal cell death was observed 5-7 days post-occlusion. At post-occlusion days 1-2 there was a small but significant increase of NCAM PSA-positive hippocampal granule cells followed by an equally significant decrease at post-occlusion day 5. In contrast, a substantial increase in glial PSA expression was observed in all hippocampal regions at 1-7 days post-occlusion that was associated generally with stellate astroglia and specifically with the radial processes of glia traversing the granule cell layer of the dentate gyrus. Administration of the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-ben-zo(F)quinoxaline significantly blocked the ischemia-induced modulation of neuronal and glial NCAM PSA expression. Astroglial NCAM polysialylation became attenuated by 35 days post-occlusion except in the CAI area of cell death. The temporal and regional pattern of polysialylated NCAM expression in the ischemic gerbil hippocampus implicates this neuroplastic marker in mechanisms of neurotrophic-dependent repair/remodeling that ensue following transient interruption of blood flow.


Assuntos
Hipocampo/patologia , Ataque Isquêmico Transitório/patologia , Molécula L1 de Adesão de Célula Nervosa , Moléculas de Adesão de Célula Nervosa/metabolismo , Neuroglia/patologia , Neurônios/patologia , Ácidos Siálicos/metabolismo , Animais , Contagem de Células , Morte Celular , Modelos Animais de Doenças , Gerbillinae , Masculino , Células Piramidais/patologia
13.
Stroke ; 32(2): 479-84, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11157186

RESUMO

BACKGROUND AND PURPOSE: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. METHODS: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. RESULTS: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017). CONCLUSIONS: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.


Assuntos
Angioplastia com Balão/métodos , Aterectomia/efeitos adversos , Estenose das Carótidas/cirurgia , Embolia Intracraniana/prevenção & controle , Stents/efeitos adversos , Arteriosclerose/complicações , Arteriosclerose/patologia , Arteriosclerose/cirurgia , Artéria Carótida Interna/patologia , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Embolia de Colesterol/sangue , Embolia de Colesterol/patologia , Embolia de Colesterol/prevenção & controle , Embolia Gordurosa/sangue , Embolia Gordurosa/patologia , Embolia Gordurosa/prevenção & controle , Humanos , Embolia Intracraniana/etiologia , Nimodipina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos
14.
FEBS Lett ; 467(2-3): 263-7, 2000 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-10675551

RESUMO

Fatty acid utilization is initiated by fatty acid-CoA ligase, which converts free fatty acids into fatty acyl-CoA esters. We have cloned previously the human long-chain fatty acid-CoA ligase 4 (FACL4), which is a central enzyme in controlling the free arachidonic acid level in cells and thereby regulating eicosanoid production. We report here the expression of this gene in tissues, particularly in different parts of the brain. We found that FACL4 encoded a 75 kDa enzyme and that there was a modified translation product expressed in the brain. FACL4 was expressed in early stages of development with a significant amount of FACL4 mRNA detected in an E7 mouse embryo. In addition, FACL4 was highly expressed in both adult and newborn mouse brain especially in the granule cells of the dentate gyrus and the pyramidal cell layer of CA1 in hippocampus, and the granular cell layer and Purkinje cells of the cerebellum.


Assuntos
Encéfalo/enzimologia , Coenzima A Ligases/genética , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Animais , Animais Recém-Nascidos , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Coenzima A Ligases/metabolismo , Giro Denteado/embriologia , Giro Denteado/enzimologia , Desenvolvimento Embrionário e Fetal , Hipocampo/embriologia , Hipocampo/enzimologia , Humanos , Camundongos , Células de Purkinje/enzimologia , RNA Mensageiro/análise
15.
Neuropsychologia ; 38(4): 388-402, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10683390

RESUMO

Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.


Assuntos
Lesões Encefálicas/psicologia , Cognição/fisiologia , Lobo Frontal/lesões , Testes Neuropsicológicos , Lesões Encefálicas/patologia , Feminino , Lobo Frontal/patologia , Humanos , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia , Tomografia Computadorizada por Raios X
16.
Int J Radiat Oncol Biol Phys ; 49(5): 1213-7, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11286825

RESUMO

PURPOSE: The purpose of this study was to examine the relationship between overall survival and prognostic factors in carcinoma of the cervix treated with radiation therapy. A clinicopathologic study was performed on 24 patients. METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor biopsies were stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53. Clinical factors such as stage, grade, tumor size, pre- and post-treatment hemoglobin level, and radiotherapy dose were also evaluated. RESULTS: Median follow-up was 75 months for living patients. The only immunohistochemical or clinical factor that was associated with improved survival was decreased COX-2 distribution staining. High COX-2 distribution staining was associated with decreased overall survival (p = 0.021) and decreased disease-free survival (p = 0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall survival rates for tumors with low vs. high COX-2 distribution values were 75% and 35%, respectively. COX-2 staining intensity was found to correlate positively with tumor size (p = 0.022). CONCLUSION: These findings indicate that increased expression of COX-2 portends a diminished survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early-response gene involved in angiogenesis and inducible by different stimuli, these data may indicate opportunity to intervene with specific inhibitors of COX-2 in carcinoma of the cervix.


Assuntos
Adenocarcinoma/enzimologia , Adenocarcinoma/mortalidade , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , Isoenzimas/metabolismo , Proteínas de Neoplasias/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/radioterapia , Ciclo-Oxigenase 2 , Feminino , Humanos , Proteínas de Membrana , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Neoplasias do Colo do Útero/radioterapia
17.
Neuroscience ; 99(2): 229-32, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10938428

RESUMO

In previous studies, we observed a transient increase in dendritic spine frequency in the molecular layer of the dentate gyrus at 6h following passive avoidance training [O'Malley A., O'Connell C. and Regan C. M. (1998) Neuroscience 87, 607-613]. To determine if a similar change is associated with spatial forms of learning, we have estimated time-dependent modulations of spine number in the dentate gyrus of the adult rat following water maze training. All animals exhibited significant reductions in the latency to locate the platform over the five training sessions of the single trial (median and interquartile ranges of 60, 8 versus 8, 3 s for trials 1 and 5, respectively) and this improved performance was retained just prior to killing at the 6h post-training time. The unbiased dissector stereological procedure was used to estimate spine number in serial pairs of ultrathin coronal sections obtained at a point 3.3 mm caudal of Bregma. This analysis revealed a significant learning-associated increase in spine number at the 6h post-training time (1.32+/-0.18 spines/microm(3)) as it was not observed in paired controls exposed to the water maze for a similar swim-time (0.66+/-0.11 spines/microm(3)). The increase was transient as spine number returned to control levels at the 72 h post-training time. These spine frequency changes are proposed to reflect increased synapse turnover rate and concomitant change in connectivity pattern in the processing of information for long-term storage.


Assuntos
Dendritos/fisiologia , Giro Denteado/fisiologia , Aprendizagem em Labirinto/fisiologia , Sinapses/fisiologia , Animais , Dendritos/ultraestrutura , Giro Denteado/citologia , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Ratos , Sinapses/ultraestrutura
18.
J Histochem Cytochem ; 49(5): 667-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11304807

RESUMO

As techniques evolve that allow molecular characterization of disease processes such as cancer, definition of "normal" at a molecular level becomes increasingly important. Increasingly large numbers of mutations are found at the genomic level, but whether all of those mutations contribute to the malignant state of a carcinoma cell is not clear. Without knowledge of what constitutes normality on the proteomic level in an organ or cell, we cannot determine what genomic changes are physiologically important. Traditionally, colon cancer is identified and classified by histological criteria. Margins of the colon are defined as "grossly uninvolved" when the histology is indistinguishable from that of normal (free from disease) colon. By using molecular pathology techniques and working backward from colon adenocarcinoma to hypoplastic polyps to presumably normal mucosa, we defined some of those protein differences. Our results may provide a molecular basis for identifying tumor formation and progression in situ.(J Histochem Cytochem 49:667-668, 2001)


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Colo/metabolismo , Neoplasias do Colo/metabolismo , Pólipos do Colo/metabolismo , DNA Topoisomerases Tipo II , Transativadores , Antígenos de Neoplasias , Antígenos Glicosídicos Associados a Tumores/metabolismo , Biomarcadores Tumorais/classificação , Proteínas do Citoesqueleto/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA , Mucinas Gástricas/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Isoenzimas/metabolismo , Proteínas de Membrana/metabolismo , Mucina-1/metabolismo , Fosfoproteínas/metabolismo , Projetos Piloto , Proteína da Zônula de Oclusão-1 , alfa Catenina , beta Catenina
19.
Neuroreport ; 9(12): 2727-31, 1998 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-9760110

RESUMO

The distribution and modulation of neural cell adhesion molecule polysialylation state (NCAM PSA) and the consequence of antisense inactivation of the Kv1.1 potassium channel was investigated following avoidance learning in mice. PSA immunoreactivity was most notable on cells at the inner denate border and in cortical layer II. Task acquisition resulted in a significant 30% transient increase in the frequency of dentate polysialylated neurons at the 12 h post-training time. In contrast, animals pretreated with the Kv1.1 antisense oligonucleotide exhibited both attenuated recall avoidance latencies and polysialylated cell frequency. As Kv1.1 is enriched on the dendrites of these granule-like cells, the attenuated polysialylation response is considered secondary to NCAM-mediated events during their transient synapse production in the 6-8 h post-training period.


Assuntos
Giro Denteado/fisiologia , Aprendizagem/fisiologia , Moléculas de Adesão de Célula Nervosa/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/metabolismo , Animais , Giro Denteado/metabolismo , Imuno-Histoquímica , Ativação do Canal Iônico/fisiologia , Canal de Potássio Kv1.1 , Masculino , Camundongos , Ácido N-Acetilneuramínico/metabolismo , Canais de Potássio/genética
20.
Obstet Gynecol ; 70(6): 930-2, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3479735

RESUMO

Between November 1984 and May 1986, 56 patients presenting with a pelvic mass to the Gynecologic Oncology Service of McMaster University and the Hamilton Regional Oncology Center underwent laparotomy for possible ovarian cancer. All patients had blood drawn for CA 125 three days before operation. Levels above 35 U/mL were considered positive; CA 125 had a positive predictive value of 60%. False positives occurred in patients with nongynecologic malignancies and with benign gynecologic conditions. On the other hand, CA 125 had a negative predictive value of 100%, suggesting that this test may be useful in identifying those patients with pelvic masses at higher risk for malignancy, who may require transfer for surgery at a tertiary care center.


Assuntos
Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Neoplasias Ovarianas/imunologia , Neoplasias Pélvicas/imunologia , Adolescente , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores , Reações Falso-Positivas , Feminino , Humanos , Laparotomia , Pessoa de Meia-Idade , Valor Preditivo dos Testes
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