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2.
Qual Manag Health Care ; 28(4): 209-221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31567844

RESUMO

BACKGROUND AND OBJECTIVES: Currently, management of patients presenting with chronic rotator cuff tears in Alberta is in need of quality improvements. This article explores the potential impact of a proposed care pathway whereby all patients presenting with chronic rotator cuff tears in Alberta would adopt an early, conservative management plan as the first stage of care; ultrasound investigation would be the preferred tool for diagnosing a rotator cuff tear; and only patients are referred for surgery once conservative measures have been exhausted. METHODS: We evaluate evidence in support of surgery and conservative management, compare care in the current state with the proposed care pathway, and identify potential solutions in moving toward optimal care. RESULTS: A literature search resulted in an absence of indications for either surgical or conservative management. Conservative management has the potential to reduce utilization of public health care resources and may be preferable to surgery. The proposed care pathway has the potential to avoid nearly Can $87 000 in public health care costs in the current system for every 100 patients treated successfully with conservative management. CONCLUSION: The proposed care pathway is a low-cost, first-stage treatment that is cost-effective and has the potential to reduce unnecessary, costly surgical procedures.


Assuntos
Protocolos Clínicos/normas , Melhoria de Qualidade/organização & administração , Lesões do Manguito Rotador/economia , Lesões do Manguito Rotador/terapia , Canadá , Doença Crônica , Terapias Complementares/organização & administração , Tratamento Conservador/economia , Tratamento Conservador/métodos , Análise Custo-Benefício , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Procedimentos Ortopédicos/economia , Procedimentos Ortopédicos/normas , Equipe de Assistência ao Paciente/organização & administração , Atenção Primária à Saúde/organização & administração , Melhoria de Qualidade/economia , Melhoria de Qualidade/normas , Lesões do Manguito Rotador/cirurgia
3.
J Clin Transl Endocrinol ; 10: 28-35, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29204369

RESUMO

AIMS: Diet is a major risk factor for type 2 diabetes mellitus. As cofactors necessary for enzyme function of all metabolic pathways, vitamins and minerals have the potential to improve glucose metabolism. We investigated the effects of a nutrient intervention program on glycemic status. METHODS: We used a form of natural experiment to compare Pure North program participants (n = 1018) that received vitamin D alone (Vital 1) or vitamin D in combination with other nutrients (Vital 2) during two different time periods. Changes in 25-hydroxyvitamin D [25(OH)D], high-sensitivity C reactive protein (hs-CRP), glycated hemoglobin (HbA1c) and glycemic status were characterized over one and two years. RESULTS: Serum 25(OH)D concentrations increased significantly in both Vital 1 (to 111  ±â€¯â€¯49 nmol/L) and Vital 2 (to 119  ±â€¯â€¯52 nmol/L) over one year. HbA1c and hs-CRP were significantly reduced over time in Vital 2. Higher 25(OH)D levels after one year were associated with larger decreases in HbA1c and hs-CRP in Vital 2. At one year, 8% of Vital 2 and 16% of Vital 1 participants progressed from normoglycemia to prediabetes/diabetes, whereas 44% of Vital 2 and 8% of Vital prediabetes/diabetes subjects regressed to normoglycemia. CONCLUSIONS: Vitamin D combined with other nutrients was associated with a reduced risk of progression to diabetes and with an increased rate of reversion to normoglycemia in high risk participants. The results suggest that nutrient supplementation regimes may provide a safe, economical and effective means for lowering diabetes risk. Further examination of this potential via randomized controlled trials is warranted.

4.
Healthc Manage Forum ; 30(4): 197-199, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28929867

RESUMO

For new technology and innovation such as precision medicine to become part of the solution for the fiscal sustainability of Canadian Medicare, decision-makers need to change how services are priced rather than trying to restrain emerging technologies like precision medicine for short-term cost savings. If provincial public payers shift their thinking to be public purchasers, value considerations would direct reform of the reimbursement system to have prices that adjust with technologically driven productivity gains. This strategic shift in thinking is necessary if Canadians are to benefit from the promised benefits of innovations like precision medicine.


Assuntos
Custos de Cuidados de Saúde , Invenções , Inovação Organizacional , Medicina de Precisão , Canadá , Redução de Custos , Reforma dos Serviços de Saúde/economia , Reforma dos Serviços de Saúde/organização & administração , Humanos , Invenções/economia , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/organização & administração , Inovação Organizacional/economia , Medicina de Precisão/economia , Medicina de Precisão/instrumentação , Medicina de Precisão/métodos
5.
Can J Public Health ; 108(2): e135-e144, 2017 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-28621649

RESUMO

OBJECTIVES: Home ownership as opposed to renting is associated with lower rates of food insecurity, the latter being a marker of household economic deprivation associated with adverse health outcomes. It is unclear whether this relationship persists during a major economic decline, or whether different subgroups of home owners are equally protected. The 2008-2009 recession in Canada was tied to events in the United States related to inappropriate mortgage financing; the impact of the recession on food insecurity among home owners may identify policies to mitigate recessionary outcomes. METHODS: We used a before-and-after natural experimental design using data from the Canadian Community Health Survey (CCHS) cycles 2007/2008 (pre-recession) and 2009/2010 (post-recession) with information on household food insecurity, home ownership versus renting, and socio-demographics. Applying multivariable logistic regression, we examined changes in household food insecurity by housing tenure and sex over the period. RESULTS: Pre-recession, food insecurity affected 3.3% of home owners and 17.1% of renter households. Among home owners, the risk of food insecurity increased post-recession by 10%, which was not statistically significant. Post-recession, and with adjustment, although renters' higher absolute risk of food insecurity persisted, male-respondent home owners experienced the highest rate of increase in food insecurity prevalence by subgroup (OR = 1.26, 95% CI: 1.06-1.50) versus renters (OR = 1.17, 95% CI: 1.05-1.29). CONCLUSION: Housing policies in Canada protected most home owners from precarity during the 2008-2009 economic recession; however, male-respondent home owners exhibited a unique economic vulnerability during this time. Implications of Canadian home ownership policies are discussed in light of differential vulnerability of home owner groups.


Assuntos
Recessão Econômica , Características da Família , Abastecimento de Alimentos/estatística & dados numéricos , Habitação/estatística & dados numéricos , Propriedade/estatística & dados numéricos , Adolescente , Adulto , Idoso , Canadá , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Res Dev Disabil ; 65: 1-11, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28412577

RESUMO

BACKGROUND: As a signatory to the UN Convention on the Rights of Persons with Disabilities, Canada has committed to protect the rights and dignity of persons with developmental disabilities (DD), which means that labour markets, education, and training opportunities should be inclusive and accessible. PURPOSE: Describe the unmet employment, education and daily needs of adults with DD, with a sub analysis of persons with autism spectrum disorder (ASD) and cerebral palsy (CP) in Canada, to inform efficient and equitable policy development. METHODS AND PROCEDURES: Secondary analysis of 2012 Canadian Survey on Disability was used to study a sample including working age (15-64 years old) individuals with self-reported DD, CP and ASD. Persons with DD reported on their met and unmet needs in term of activities of daily living, education and employment. OUTCOMES AND RESULTS: Labour force participation is the lowest for those with DD compared to any other disability. Individuals with CP and ASD report a high level of unmet needs that differ in terms of educational, vocational and daily living supports. CONCLUSIONS AND IMPLICATIONS: Improving labour force participation to be inclusive and accessible requires policy that considers the range of unmet needs that exist for persons with DD.


Assuntos
Atividades Cotidianas , Transtorno do Espectro Autista , Paralisia Cerebral , Deficiências do Desenvolvimento , Educação Inclusiva , Readaptação ao Emprego , Adolescente , Adulto , Transtorno do Espectro Autista/economia , Transtorno do Espectro Autista/epidemiologia , Canadá/epidemiologia , Paralisia Cerebral/economia , Paralisia Cerebral/epidemiologia , Deficiências do Desenvolvimento/economia , Deficiências do Desenvolvimento/epidemiologia , Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Educação Inclusiva/organização & administração , Educação Inclusiva/estatística & dados numéricos , Readaptação ao Emprego/organização & administração , Readaptação ao Emprego/estatística & dados numéricos , Feminino , Direitos Humanos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades/estatística & dados numéricos , Formulação de Políticas , Inquéritos e Questionários
7.
J Shoulder Elbow Surg ; 26(2): 314-322, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27727062

RESUMO

BACKGROUND: The Rotator Cuff Quality of Life Index (RC-QOL) was developed to evaluate quality of life in patients with rotator cuff disorders (RCD). The purpose of this study was to provide additional reliability, validity, and responsiveness testing in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. METHODS: Preliminary patient interviews included 15 patients. Seventy patients (mean age, 58; standard deviation, 9 years) with RCD were evaluated. Methodology testing included internal consistency, test-retest reliability, measurement error, content validity, and construct validity. Responsiveness, interpretability, and generalizability were also analyzed. RESULTS: The Cronbach α was 0.96 (95% confidence interval, 0.89-0.99; range, 0.72-0.94). The intraclass correlation coefficient for the RC-QOL was 0.87 (95% confidence interval, 0.79-0.85; range, 0.77-0.88). The standard error of measurement was 8 (range, 7-13). The smallest detectable change was 3 (range, 2-4). Content validity was confirmed through standardized patient interviews. All a priori hypotheses were confirmed. No floor or ceiling effects were present. The minimally clinical important difference ranged between 7 and 14 points. The study met the COSMIN criteria for interpretability and generalizability. CONCLUSION: The RC-QOL is a reliable and valid measure of health-related quality of life in patients with chronic RCD. The results of this study added to the methodologic quality assessment of the RC-QOL, completing 7 of 10 COSMIN criteria.


Assuntos
Psicometria , Qualidade de Vida , Lesões do Manguito Rotador/psicologia , Adulto , Idoso , Alberta , Traumatismos em Atletas/psicologia , Benchmarking , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários
8.
Can J Public Health ; 107(2): e176-e182, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27526215

RESUMO

OBJECTIVE: Although there is widespread recognition that poverty is a key determinant of health, there has been less research on the impact of poverty reduction on health. Recent calls for a guaranteed annual income (GAI), defined as regular income provided to citizens by the state regardless of work status, raise questions about the impact, relative to the costs, of such a population health intervention. The objective of this study was to determine the impact of Canadian seniors' benefits (Old Age Security/Guaranteed Income Supplement, analogous to a GAI program) on the self-reported health, self-reported mental health and functional health of age-eligible, low-income seniors. METHODS: We used the 2009-2010 Canadian Community Health Survey to examine unattached adult respondents with an annual income of $20,000 or less, stratified by seniors' benefits/GAI eligibility (55-64 years: ineligible; 65-74 years: eligible). Using regression, we assessed self-reported health, selfreported mental health and functional health as measured by the Health Utilities Index, as outcomes for seniors' benefits/GAI-eligible and -ineligible groups. RESULTS: We found that individuals age-eligible for seniors' benefits/GAI had better health outcomes than recipients of conditional income assistance programs. Eligibility for seniors' benefits/GAI after age 64 was associated with better self-reported health, functional health and self-reported mental health outcomes, and these effects were observed until age 74. CONCLUSION: Using seniors' benefits as an example, a GAI leads to significantly better mental health and improved health overall. These improvements are likely to yield reduced health care costs, which may offset the costs associated with program expansion.


Assuntos
Nível de Saúde , Renda/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Assistência a Idosos , Idoso , Canadá , Definição da Elegibilidade , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Pobreza , Avaliação de Programas e Projetos de Saúde
9.
Healthc Pap ; 15(4): 41-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27230718

RESUMO

Needs for non-medical residential care services, long-term care (LTC), will increase over the next 30 years as Canada's population ages. Adams and Vanin (2016) explore four options for raising the public and private monies required to meet LTC needs. In this commentary, I raise a fifth option for finding the resources to meet emerging LTC needs. An alternative approach is to divert resources from Canada's well-resourced, but inefficient, medical treatment system. The dividend of provinces pursuing long overdue reforms to medicare is the liberation of public funds to finance emerging priorities for Canadians like LTC.


Assuntos
Seguro de Assistência de Longo Prazo , Assistência de Longa Duração , Canadá , Recursos em Saúde , Humanos , Pensões
10.
Autism Res ; 7(6): 704-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25288440

RESUMO

There is a concern that the allocation of autism spectrum disorder (ASD) research funding may be misallocating resources, overemphasizing basic science at the expense of translational and clinical research. Anthony Bailey has proposed that an economic evaluation of autism research funding allocations could be beneficial for funding agencies by identifying under- or overfunded areas of research. In response to Bailey, we illustrate why economics cannot provide an objective, technical solution for identifying the "best" allocation of research resources. Economic evaluation has its greatest power as a late-stage research tool for interventions with identified objectives, outcomes, and data. This is not the case for evaluating whether research areas are over- or underfunded. Without an understanding of how research funding influences the likelihood and value of a discovery, or without a statement of the societal objectives for ASD research and level of risk aversion, economic analysis cannot provide a useful normative evaluation of ASD research.


Assuntos
Transtorno Autístico/economia , Pesquisa/economia , Alocação de Recursos/economia , Pesquisa Biomédica/economia , Humanos , Projetos de Pesquisa , Reino Unido , Estados Unidos
11.
Public Health Nutr ; 17(1): 49-57, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22958521

RESUMO

OBJECTIVE: Food insecurity, lack of access to food due to financial constraints, is highly associated with poor health outcomes. Households dependent on social assistance are at increased risk of experiencing food insecurity, but food insecurity has also been reported in households reporting their main source of income from employment/wages (working households). The objective of the present study was to examine the correlates of food insecurity among households reliant on employment income. DESIGN: Working households reporting food insecurity were studied through analysis of the Canadian Community Health Survey, 2007-2008, employing descriptive statistics and logistic regression. Food insecurity was measured using the Household Food Security Survey Module; all provinces participated. SETTING: Canada. SUBJECTS: Canadian households where main income was derived through labour force participation. Social assistance recipients were excluded. RESULTS: For the period 2007-2008, 4% of working households reported food insecurity. Canadian households reliant on primary earners with less education and lower incomes were significantly more likely to experience food insecurity; these differences were accentuated across some industry sectors. Residence in Quebec was protective. Working households experiencing food insecurity were more likely to include earners reporting multiples jobs and higher job stress. Visible minority workers with comparable education levels experienced higher rates of food insecurity than European-origin workers. CONCLUSIONS: Reliance on employment income does not eliminate food insecurity for a significant proportion of households, and disproportionately so for households with racialized minority workers. Increases in work stress may increase the susceptibility to poor health outcomes of workers residing in households reporting food insecurity.


Assuntos
Emprego/estatística & dados numéricos , Características da Família , Abastecimento de Alimentos/estatística & dados numéricos , Renda , Pobreza , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Quebeque
12.
Prev Med ; 57(6): 963-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24055151

RESUMO

OBJECTIVE: This study uses a population health intervention modeling approach to project the impact of recent legislated increases in age eligibility for Canadian federally-funded pension benefits on low income seniors' health, using food insecurity as a health indicator. METHOD: Food insecurity prevalence and income source were assessed for unattached low income (<$20,000 CAD) persons aged 60-64 years (population weighted n=151,350) versus seniors aged 65-69 years (population weighted n=151,485) using public use data from the Canadian Community Health Survey Cycle 4.1 (2007-2008). RESULTS: Seniors' benefits through federal public pension plans constituted the main source of income for the majority (79.4%) of low income seniors aged 65-69 years, in contrast to low income seniors aged 60-64 years who reported their main income from employment, employment insurance, Workers' Compensation, or welfare. The increase in income provided by federal pension benefits for low income Canadians 65 and over coincided with a pronounced (50%) decrease in food insecurity prevalence (11.6% for seniors ≥65 years versus 22.8% for seniors <65 years). CONCLUSION: Raising the age of eligibility for public pension seniors' benefits in Canada from 65 to 67 years will negatively impact low income seniors' health, relegating those who are food insecure to continued hardship.


Assuntos
Nível de Saúde , Legislação como Assunto , Pensões , Pobreza/estatística & dados numéricos , Idoso/estatística & dados numéricos , Canadá/epidemiologia , Governo Federal , Abastecimento de Alimentos/economia , Abastecimento de Alimentos/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Renda/estatística & dados numéricos , Legislação como Assunto/economia , Legislação como Assunto/estatística & dados numéricos , Pessoa de Meia-Idade , Pensões/estatística & dados numéricos , Pobreza/economia
13.
Chronic Dis Inj Can ; 33(1): 1-11, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23294916

RESUMO

INTRODUCTION: Over recent decades, two prominent trends have been observed in Canada and elsewhere: increasing prevalence of childhood overweight and obesity, and increasing participation of women (including mothers) in the paid labour force and resulting demand for child care options. While an association between child care and children's body mass index (BMI) is plausible and would have policy relevance, its existence and nature in Canada is not known. METHODS: Using data from the National Longitudinal Survey of Children and Youth, we examined exposure to three types of care at age 2/3 years (care by non-relative, care by relative, care in a daycare centre) in relation to change in BMI percentile (continuous and categorical) between age 2/3 years and age 6/7 years, adjusting for health and sociodemographic correlates. RESULTS: Care by a non-relative was associated with an increase in BMI percentile between age 2/3 years and age 6/7 years for boys, and for girls from households of low income adequacy. CONCLUSION: Considering the potential benefits of high-quality formal child care for an array of health and social outcomes and the potentially adverse effects of certain informal care options demonstrated in this study and others, our findings support calls for ongoing research on the implications of diverse child care experiences for an array of outcomes including those related to weight.


Assuntos
Índice de Massa Corporal , Cuidado da Criança/métodos , Cuidado da Criança/estatística & dados numéricos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Canadá/epidemiologia , Criança , Creches , Pré-Escolar , Família , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Fatores Socioeconômicos
14.
Can J Public Health ; 103(7 Suppl 1): eS49-56, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23618050

RESUMO

OBJECTIVES: One argument made in favour of drinking water fluoridation is that it is equitable in its impact on oral health. We examined the association between exposure to fluoridation and oral health inequities among Canadian children.PARTICIPANTS, SETTING AND INTERVENTION: We analyzed data from 1,017 children aged 6-11 from Cycle 1 of the Canadian Health Measures Survey, a cross-sectional, nationally representative survey that included a clinic oral health examination and a household interview. The outcome measure was a count of the number of decayed, missing (because of caries or periodontal disease) or filled teeth, either deciduous or permanent (dmftDMFT). Data were analyzed using linear (ordinary least squares) and multinomial logistic regression; we also computed the concentration index for education-related inequity in oral health. Water fluoridation status (the intervention) was assigned on the basis of the site location of data collection. OUTCOMES: Fluoridation was associated with better oral health (fewer dmftDMFT), adjusting for socio-economic and behavioural variables, and the effect was particularly strong for more severe oral health problems (three or more dmftDMFT). The effect of fluoridation on dmftDMFT was observed across income and education categories but appeared especially pronounced in lower education and higher income adequacy households. dmftDMFT were found to be disproportionately concentrated in lower-education households, though this did not vary by fluoridation status. CONCLUSIONS: The robust main effect of fluoridation on dmftDMFT and the beneficial effect across socio-economic groups support fluoridation as a beneficial and justifiable population health intervention. Fluoridation was equitable in the sense that its benefits were particularly apparent in those groups with the poorest oral health profiles, though the nature of the findings prompts consideration of the values underlying the judgement of health equity.


Assuntos
Água Potável/análise , Fluoretação/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Saúde Bucal/estatística & dados numéricos , Canadá , Criança , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Fatores Socioeconômicos
15.
Health Policy ; 79(2-3): 165-74, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16412528

RESUMO

Governments and physician organizations in Canada have identified current and anticipated future shortages of physicians. The creation of opportunities for licensure for the sizeable population of unlicensed international medical graduates (IMG) residing in Canada can alleviate some of the shortage of medical manpower. We examine whether expenditures on IMG skills assessment, training and licensing are a socially desirable use of resources. We estimate the financial rate of return to Alberta taxpayers from resources allocated to the Alberta International Medical Graduate (AIMG) program, started in 2001. Our estimates show that resources allocated to providing skills assessment and residency training opportunities for IMGs that lead to licensing as a Canadian physician generate real annual rates of return of 9-13%.


Assuntos
Médicos Graduados Estrangeiros/normas , Internato e Residência/economia , Adulto , Alberta , Competência Clínica/normas , Análise Custo-Benefício , Credenciamento , Humanos , Pessoa de Meia-Idade , Médicos/provisão & distribuição
16.
Ann Fr Anesth Reanim ; 21(5): 431-5, 2002 May.
Artigo em Francês | MEDLINE | ID: mdl-12078439

RESUMO

A 28-year-old woman, G3P3, who was otherwise healthy and had taken no medication and had no known allergy, was admitted to our hospital for delivery after a normal pregnancy. An epidural catheter was inserted for analgesia and labour was induced with oxytocin. Two hours later, she suffered a sudden cardiac arrest. She was immediately treated and, since a normal cardiac rhythm and a blood pressure of 90 mmHg has been obtained 30 minutes later, a 3750 g child was delivered by caesarean section. Soon after delivery, a life-threatening uterine haemorrhage appeared, due to DIC. Evolution was favourable, after bilateral uterine arteries embolization had been performed. The diagnosis of amniotic fluid embolism was established by the clinical course, the absence of local cause and the presence of a large number of amniotic cells in the mother's peripheral blood. Tryptase blood concentration was normal in the mother's blood.


Assuntos
Embolia Amniótica/terapia , Embolização Terapêutica , Útero/irrigação sanguínea , Adulto , Cesárea , Embolia Amniótica/complicações , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Humanos , Gravidez , Fluxo Sanguíneo Regional/fisiologia , Serina Endopeptidases/sangue , Triptases , Hemorragia Uterina/complicações
17.
Biochemistry ; 37(13): 4437-50, 1998 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-9521763

RESUMO

The Swi4-Swi6 family of transcription factors confers G1/S specific transcription in budding and fission yeast. These proteins contain four ankyrin repeats, which are present in a large number of functionally diverse proteins and have been shown to be important for protein-protein interaction. However, no specific sequence has been identified that is diagnostic of an ankyrin repeat-interacting protein. To determine the function of the ankyrin repeats of Swi6, we generated both random and site-directed mutations within the ankyrin repeat domain of Swi6 and assayed the transcriptional function of these mutant swi6 alleles. We found six single mutations, scattered within the first and the fourth repeats, that generate a temperature-sensitive Swi6 protein. In addition, we found that alanine substitutions for the most conserved residues in each repeat were highly deleterious and also confer temperature sensitivity. Most of these swi6 alleles are able to form ternary complexes with Swi4 and DNA, but these complexes display reduced mobility in band-shift gels, suggesting a dramatic conformational change. We have modeled the ankyrin repeats of Swi6 using the coordinates derived for 53BP2 and find that, despite its low level of sequence conservation, these modeling studies and our mutation data are consistent with Swi6 having a structure very similar to that of 53BP2. Moreover, all but one of our single mutants and all of the site-directed mutants disrupt critical structural features of the predicted folding pattern of these repeats. We conclude that the ankyrin repeats play a major structural role in Swi6. Ankyrin repeats are unlikely to have inherent protein or DNA binding properties. However, they form a characteristic and stable structure with surfaces that may be tailored for many different macromolecular interactions.


Assuntos
Repetição de Anquirina/genética , Proteínas Fúngicas/genética , Mutação , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Alanina/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Proteínas Reguladoras de Apoptose , Proteínas de Transporte/química , Proteínas de Ligação a DNA , Proteínas Fúngicas/química , Immunoblotting , Modelos Moleculares , Dados de Sequência Molecular , Plasmídeos , Reação em Cadeia da Polimerase , Conformação Proteica , Temperatura , Fatores de Transcrição/química , Transcrição Gênica
18.
Radiother Oncol ; 40(1): 51-4, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8844887

RESUMO

Radiosurgery (RS) was initiated in Lyon in October 1989. The technique was adapted from that described by Lutz and Saunders in Boston (BRW stereotactic frame). Irradiation is delivered with 18-MV photons produced by a LINAC. From December 1989 to December 1992, 41 patients with arteriovenous malformations were treated by RS; the median age was 33 years. The largest lesion diameter was 11.2-38.5 mm. Fifteen to 20 Gy were delivered on the 70% isodose line. Angiography was performed at 2 years post-treatment in 32 patients demonstrating an overall complete thrombosis rate of 81.3%. This incidence was significantly correlated with the Spetzler and Martin grade before RS (P = 0.0055). Two patients (4.9%) experienced haemorrhage after radiosurgical treatment and one died from an intracerebral-intraventricular haemorrhage. Four patients (9.7%) experienced permanent radiation-induced neurological complications.


Assuntos
Malformações Arteriovenosas Intracranianas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Radiocirurgia/instrumentação , Adulto , Angiografia Cerebral , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/epidemiologia , Masculino , Fatores de Tempo , Resultado do Tratamento
19.
Ann Radiol (Paris) ; 37(6): 441-8, 1994.
Artigo em Francês | MEDLINE | ID: mdl-7702337

RESUMO

This double-blind cross-over study was carried out in 16 patients (16 arteriographies). In order to evaluate the intra-arterial infusion of buflomédil during arteriographies with lipiodol for the positive and staging diagnosis of hepatocarcinoma and in arteriolar chemoembolisation during a second period for the treatment of the known hepatocarcinoma. The intra-arterial effect of buflomédil was studied by measuring the up-stream reflux of the catheter during the infusion, the number of lesions and the suppression of arterial spasms. The buflomédil infusion decreased the upstream reflux, the number of spasms in the hepatic artery observed during the reiterated chemoembolisations. On the other hand, the visualisation of the limits and number of nodular lesions was impaired and under-estimated by excessive impregnation of the tissue by the contrast medium. In one case buflomédil permitted to visualize an arterio-portal fistula unrecognized under placebo. The clinical tolerance was good with no side-effects. The systolic and diastolic blood pressure did not change versus placebo. The buflomédil infusion during chemoembolisation makes the technique potentially safer by decreasing the up-stream reflux and spasms of hepatic arteries.


Assuntos
Angiografia/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Pirrolidinas , Vasodilatadores , Idoso , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Feminino , Humanos , Injeções Intra-Arteriais , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinas/administração & dosagem , Pirrolidinas/uso terapêutico , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico
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