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1.
Public Health ; 201: 19-25, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742113

RESUMO

OBJECTIVES: To assess the diagnostic performance of the EPICES score for identifying social deprivation during pregnancy in a population of women in the immediate postpartum period. STUDY DESIGN: This cross-sectional survey took place between 5th June and 5th August 2017, among women who had just given birth in either of the maternity units in Clermont-Ferrand, France. METHODS: A self-administered questionnaire was completed by women. The questionnaire came in two parts: the EPICES index and the criteria for social deprivation defined by French law. These criteria were chosen to define the reference standard. The women were classified into two groups, living in precarious circumstances or not, according to the criteria defined by the French law (reference standard). To determine the most relevant threshold of the EPICES score, the precision associated with the threshold (the fraction of those predicted positive who are true positives: positive predictive value) was balanced with its sensitivity. EPICES scores above the threshold were classified as deprived, those below as non-deprived. RESULTS: Of the 947 women who gave birth during the study period, 700 (73.9%) completed the self-administered questionnaire. The best trade-off between precision and sensitivity was obtained with a threshold of 22. For this threshold value, the positive predictive value was 42.3% and the sensitivity 70.3%. CONCLUSIONS: The EPICES score with a threshold validated in the population of pregnant women is a useful, rapid, and easy-to-use tool that makes it possible to identify maternal deprivation at an individual level.


Assuntos
Privação Social , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Gravidez , Fatores Socioeconômicos , Inquéritos e Questionários
2.
Ann Phys Rehabil Med ; 63(3): 202-208, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31541704

RESUMO

BACKGROUND: The physical activity (PA) level of individuals with knee osteoarthritis is lower than in the general population. International recommendations recommend a non-pharmacological intervention including a self-management education program, weight loss and an adapted exercise program. However, we have no scale assessing the perceived barriers to and facilitators of PA in this population. OBJECTIVE: We constructed and validated a self-administered questionnaire assessing perceived barriers to and facilitators of regular practice of PA in people with knee osteoarthritis. METHODS: Semi-structured interviews identified 24 barriers and facilitators. We developed a 24-item questionnaire, Evaluation of the Perception of Physical Activity (EPPA) that was completed by 548 individuals with knee osteoarthritis, to assess acceptability, construct validity, internal consistency and convergent validity. Participants also completed the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Physical Activity Questionnaire (IPAQ). Reliability and sensitivity to change were evaluated in a second group of 168 people with knee osteoarthritis at a 3-week spa therapy resort. RESULTS: Factorial analysis identified 17 items grouped into 4 subscales (Barriers, Facilitators, Motivation and Beliefs). The internal consistency was good for Barriers, Facilitators and Motivation subscales (Cronbach α>0.70) and intermediate for the Beliefs subscale (Cronbach α=0.64). The EPPA subscale scores were significantly correlated with KOFBeQ and WOMAC scores but not associated with IPAQ physical activity level. Reliability was good for all subscales, with intraclass correlation coefficients>0.60. A sensitivity to change was found for only the Beliefs subscale, with a moderate effect size. CONCLUSIONS: The EPPA questionnaire has good psychometric properties and can help guide the management of knee osteoarthritis. It can be used in research for evaluating the perception of physical activity.


Assuntos
Exercício Físico/psicologia , Osteoartrite do Joelho/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Modalidades de Fisioterapia/psicologia , Inquéritos e Questionários/normas , Idoso , Estudos Transversais , Análise Fatorial , Medo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Osteoartrite do Joelho/reabilitação , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes
4.
Ultrasound Obstet Gynecol ; 52(6): 769-775, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29363850

RESUMO

OBJECTIVE: The quality of ultrasound images is impaired in obese patients. All ultrasound scanners are calibrated for an ultrasound propagation velocity of 1540 m/s, but the propagation in fatty tissue is slower (in the order of 1450 m/s). The main objective of this study was to evaluate the quality of images obtained with different ultrasound propagation velocity settings during the mid-trimester fetal ultrasound examination in obese patients. METHODS: This was a cross-sectional study using image sets of four recommended scanning planes collected from 32 obese pregnant women during their mid-trimester fetal scan. Each image set comprised three images obtained successively at three different propagation velocity settings (1540 m/s, 1480 m/s and 1420 m/s). A panel of 114 experts assessed the quality of 100 image sets, grading them from A (most acceptable) to C (least acceptable). Scanning-plane-specific indicators of adiposity (fatty layer thickness, probe-to-organ distance) were analyzed for each scanning plane. RESULTS: The experts had a mean of 18.1 ± 10.2 years of experience. The grade distribution (A, B, C) differed significantly (P < 0.0001) between the three propagation velocity settings tested; at the lower speed of 1480 m/s, images were most often graded A, while at the conventional speed of 1540 m/s, they were most often graded C. Regardless of the scanning plane, the thicker the fatty layer of the abdominal wall in a given plane, the lower the preferred speed (P < 0.0001). CONCLUSION: The construction of images taking into account ultrasound propagation velocities lower than 1540 m/s can improve significantly the quality of images obtained during mid-trimester fetal ultrasonography in obese women. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Aumento da Imagem/normas , Obesidade/complicações , Ultrassonografia Pré-Natal/métodos , Estudos Transversais , Feminino , Humanos , Aumento da Imagem/métodos , Obesidade/diagnóstico por imagem , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Trimestres da Gravidez
5.
J Gynecol Obstet Hum Reprod ; 46(3): 235-242, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28403920

RESUMO

INTRODUCTION: The objectives were to evaluate the acceptability, reliability and validity of the cross-cultural adaptation of the Endometriosis Health Profile-30 instrument into French. METHODS: This cross-sectional study was conducted between July and October 2015. We created an online link (REDCap platform) with the questionnaires. An endometriosis patients association spread the link on its website and with social networks. The translation and cultural adaptation of the EHP-30 was performed according to guidelines. Psychometric evaluation included data completeness, score distributions, floor and ceiling effects, factor analysis, internal consistency, item-total correlations corrected for overlap, convergent validity and test-retest reliability. RESULTS: The study included 913 women with endometriosis. In our results, data completeness was excellent. No floor effects were found and one ceiling effect was observed for the 'Infertility' scale. The highest means scores were found for 'Control and powerlessness' and 'Infertility' scales. Factor analysis confirmed the structure of the original EHP-30 questionnaire. Internal consistency was good (Cronbach's α range=0.72-0.96). The correlations of similar scale scores between EHP-30 and SF-36 were all significant (Spearman correlation coefficients ranging from -0.52 to -0.75). Test-retest reliability was good (intraclass correlation coefficients range=0.51-0.98). CONCLUSION: The French version of the EHP-30 is an acceptable, reliable and valid instrument for measuring health-related quality of life in women with endometriosis.


Assuntos
Endometriose/psicologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Estudos Transversais , Endometriose/complicações , Análise Fatorial , Feminino , França , Humanos , Psicometria , Reprodutibilidade dos Testes , Traduções
6.
Encephale ; 42(2): 124-9, 2016 Apr.
Artigo em Francês | MEDLINE | ID: mdl-26796558

RESUMO

OBJECTIVE: Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients. The aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio-professional psychiatrists' characteristics are related to their practices. METHODS: We contacted by mail 190 psychiatrists to take part in an observational survey of their AP prescribing practices for elderly (aged over 65) schizophrenia patients. RESULTS: The response rate was 44.2%, and of the psychiatrists who replied 75% were treating elderly schizophrenia patients. A second-generation AP (SGAP) was prescribed as first-line of treatment by 87.7% of the psychiatrists. The most frequently used SGAPs were risperidone and olanzapine (respectively preferred by 54.4% and 19.3% of the psychiatrists taking part). At the beginning of treatment, 91.1% of the psychiatrists prescribed a lower dose than for middle-aged patients. Of the psychiatrists taking part, 64.9% prescribed monotherapy; and among these psychiatrists, 65% cited insufficient control of the disease as the reason for their choice, while 48.7% of those who elected not to prescribe combined AP did so in order to limit the side-effects. Of the psychiatrists taking part, 54.4% prescribed long-acting injectable AP (LAAP); better therapeutic compliance and alliance was the main argument in the choice of LAAP given by the psychiatrists taking part who prescribed the drug, whereas the absence of indications and problems of tolerance were arguments against for those who did not. "Personal experience" emerged as the governing factor in the choice of AP. The AP side-effect profile was the main criterion of choice of the AP agent for 3.5% of the psychiatrists taking part, and the most frequently chosen secondary criterion (29.8%). Monitoring of treatment was partly performed according to professional recommendations: pre-treatment and post-prescription assessments of waist circumference and ophthalmological monitoring were very infrequent (8.8 to 18.5%) as were pre-treatment and early post-prescription assessments of prolactinaemia (14.8 to 20.4%); long-term cardiac monitoring was infrequent (43.9%). The psychiatrists taking part whose first-line drug was SGAP were more familiar with professional recommendations than those who prescribed first generation antipsychotic (FGA) drugs (72% as against 14.3%, P=0.006). Of the psychiatrists taking part in the study, 64.9% reported they commonly use professional recommendations. Psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long-term than those who did not (74.3% as against 41.2%, P=0.0315). They also measured waist circumference over the long-term significantly more often than psychiatrists who did not commonly use professional recommendations (22.9% as against 0%, P=0.0420). Psychiatrists treating more than ten of these patients yearly measured significantly more often over the long-term pulse rate and blood pressure than those treating fewer patients (80% as against 50%, P=0.0399). Over the long-term monitoring, psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test, lipid profile and referral for cardiac consultation with ECG (respectively, 95.5% as against 70.8%, P=0.0489; 90.9% as against 58.3%, P=0.0182; 81.8% as against 29.2%, P<0.0001). CONCLUSIONS: The results of this survey need to be confirmed in a larger population sample. The antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the AP agent. Some clinical and paraclinical medical examinations were carried out infrequently, in particular cardiac monitoring over the long-term, which is essential in this elderly patient population. One important element to emerge from our results was that common use of professional recommendations is associated with better monitoring.


Assuntos
Antipsicóticos/uso terapêutico , Psiquiatria , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Glicemia/análise , Monitoramento de Medicamentos , Prescrições de Medicamentos/estatística & dados numéricos , Eletrocardiografia/efeitos dos fármacos , Feminino , Pesquisas sobre Atenção à Saúde , Hemodinâmica/efeitos dos fármacos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Psicologia do Esquizofrênico
7.
Rev Epidemiol Sante Publique ; 63(3): 183-90, 2015 Jun.
Artigo em Francês | MEDLINE | ID: mdl-25982226

RESUMO

BACKGROUND: To assess health-related quality of life in French adults aged 65 years and over, living at home, with a specific self-administered questionnaire, the LEIPAD, cross-culturally adapted in French. METHODS: Elderly completed socio-demographic and medical questionnaires, a questionnaire about negative life events during the last 12 months and the LEIPAD. RESULTS: Data of 195 subjects (mean age: 72.6 years, men: 56.5%) were analyzed. The response rates to the LEIPAD scales were superior to 90%. Elderly reported on the whole a good health-related quality of life. Age had a negative effect on quality on life, which deteriorates over years. Age was correlated to the scales "Physical function", "Self-care", "Cognitive functioning" and "Sexual functioning". Elderly hospitalized in the last year had worse quality of life with a significant difference for "Physical function" scale. The number of health problems was positively correlated to "Physical function" scale. Elderly declaring at least one health problem had worse quality of life for this scale. Problems in couple, materials and financial problems had also negative effects on health-related quality of life. CONCLUSION: Our study highlights a good health-related quality of life for the majority of these adults aged 65 years and over, as well as the negative effect of age, health, couple, materials and financial problems on their quality of life.


Assuntos
Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Idioma , Masculino , Características de Residência , Inquéritos e Questionários
8.
Gynecol Obstet Fertil ; 43(3): 187-90, 2015 Mar.
Artigo em Francês | MEDLINE | ID: mdl-25708848

RESUMO

OBJECTIVE: To compare peripartum management of anticoagulated patients concerning locoregional analgesia, post-partum hemorrhage and thrombotic events according to planified interruption or not of antithrombotic therapy. PATIENTS AND METHODS: We conducted a single tertiary care center retrospective study of all deliveries associated with antithrombotic therapy from January 2005 to September 2011. RESULTS: We identified 120 cases with prophylactic (71%) or curative (29%) anticoagulation. Two thrombotic events occurred. In case of curative therapy, the use of locoregional analgesia was lower (P<0.0001) and post-partum hemorrhage occurred more frequently (P=0.07) compared to prophylactic therapy. According to planified interruption or not of antithrombotic therapy, we observed a more prolonged duration of therapeutic interruption before delivery (55.6h±63.3 vs 26.4 h±11.6, P<0.0001), higher use of locoregional analgesia (83% vs 71%, P=0.02) but no difference concerning cesarean rate (35% vs 39%, P=0.8) or post-partum hemorrhage (13% vs 14%, P=0.9). CONCLUSION: In case of curative anticoagulation, plannified interruption favours the use of perimedullar analgesia after 24hour delay. In case of preventive anticoagulation, plannified interruption appears unnecessary as the 12hour delay is easier to reach.


Assuntos
Anticoagulantes/uso terapêutico , Período Periparto , Adulto , Analgesia/estatística & dados numéricos , Anticoagulantes/efeitos adversos , Cesárea/estatística & dados numéricos , Feminino , Humanos , Hemorragia Pós-Parto/epidemiologia , Gravidez , Estudos Retrospectivos , Centros de Atenção Terciária
9.
Infection ; 41(6): 1157-61, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23765511

RESUMO

In 2009-2011, 113 adult in- and outpatients with measles were referred to the University Hospital of Clermont-Ferrand (centre of France): 71 (62.8 %) needed hospitalisation, 31 had pneumonia, 29 diarrhoea, 47 liver enzymes elevation, 38 thrombopaenia, one encephalitis and there were no deaths. Nineteen cases occurred among healthcare workers and five of them were hospital-acquired. There were 92 unvaccinated patients. The 2011 peak of that measles re-emerging epidemic occurred when non-immunised adults were affected.


Assuntos
Surtos de Doenças , Sarampo/epidemiologia , Adolescente , Adulto , Criança , Feminino , França/epidemiologia , Hospitais Universitários , Humanos , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Pessoa de Meia-Idade , Adulto Jovem
10.
Qual Life Res ; 22(3): 509-20, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22476573

RESUMO

PURPOSE: To cross-culturally adapt a French version of the LEIPAD, a self-administered questionnaire assessing the health-related quality of life (HRQoL) in adults aged 65 years and over living at home, and to evaluate its psychometric properties. METHODS: After having translated LEIPAD in accordance with guidelines, we studied psychometric properties: reliability and construct validity-factor analysis, relationships between items and scales, internal consistency, concurrent validity with the Medical Outcome Study Short-Form 36 and known-groups validity. RESULTS: The results obtained in a sample of 195 elderly from the general population showed very good acceptability, with response rates superior to 93 %. Exploratory factor analysis extracted eight factors providing a multidimensionality structure with five misclassifications of items in the seven theoretical scales. Good internal consistency (Cronbach's alpha ranging from 0.73 and 0.86) and strong test-retest reliability (ICCs higher than 0.80 for six scales and 0.70 for one) were demonstrated. Concurrent validity with the SF-36 showed small to strong expected correlations. CONCLUSION: This first evaluation of the French version of LEIPAD's psychometric properties provides evidence in construct validity and reliability. It would allow HRQoL assessment in clinical and common practice, and investigators would be able to take part in national and international research projects.


Assuntos
Nível de Saúde , Avaliação de Resultados em Cuidados de Saúde , Psicometria/instrumentação , Qualidade de Vida , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Comparação Transcultural , Cultura , Análise Fatorial , Feminino , Humanos , Idioma , Masculino , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Tradução
11.
Diabetes Metab ; 38(1): 82-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22172401

RESUMO

AIM: Deprivation has been linked to more complicated and uncontrolled diabetes. The validated Évaluation de la précarité et des inégalités de santé dans les centres d'examens de santé (EPICES; Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres) score could help to identify such deprived patients. The present study evaluated the relationships between deprivation and prevalence of complications, uncontrolled diabetes and quality of life. METHODS: This prospective study was conducted in the diabetology department of a tertiary university hospital from November 2006 to July 2007. Patients with diabetes were divided into two groups, according to their deprivation status [non-deprived: EPICES score<30.17; deprived: EPICES score≥30.17 (56.5%)]. Diabetes control, complications and quality of life [Short Form Health Survey (SF-36)] were compared in the two groups. RESULTS: Of a total of 102 patients, 97 completed all of the questionnaires: 18 had type 1 diabetes and 79 had type 2 diabetes, in a geographical area moderately affected by deprivation. No statistical relationship could be demonstrated between deprivation and HbA(1c). Deprived patients with diabetes presented with higher levels of fasting blood glucose, lower levels of LDL cholesterol and a significantly higher risk of obesity (P=0.0020). As for complications, microalbuminuria was linked to deprivation (P=0.03), but no associations with other complications were found. Quality of life was poorer for all physical, mental and social dimensions in deprived patients. CONCLUSION: In this diabetic population, deprivation and glycaemic control were not associated. However, more deprived subjects with diabetes were at higher risk of renal disease. A deprived state was related to an altered quality of life as assessed by the SF-36 score.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Programas de Rastreamento/métodos , Pobreza , Qualidade de Vida , Algoritmos , Glicemia/metabolismo , Pressão Sanguínea , Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Feminino , França/epidemiologia , Hemoglobinas Glicadas/metabolismo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Inquéritos e Questionários
12.
J Dent ; 37(11): 827-34, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19628326

RESUMO

OBJECTIVES: Little is known about how dentists implement caries management and provide restorative dental services in everyday practice. This study explored whether or not recent concepts in caries management were implemented in practice by private practitioners. The influence of patient and practitioner characteristics on the provision of restorative dental services was also investigated through multidimensional analyses. METHODS: A sample of French general private dental practitioners was asked to record the characteristics of 35 preventive or restorative treatments made on vital permanent teeth. The data collection form was designed to explore dentists' attitudes towards caries management and their use of minimally invasive therapies. RESULTS: Twenty-six practitioners recorded the characteristics of 921 treatments performed on 457 patients. Results indicate that participants rarely performed non-invasive treatments. They used an inappropriate detection tool, as most of decisions to treat were based on visual inspection frequently associated with probing. Multidimensional analysis showed that dentists provided different restorative treatments depending on patient characteristics, with minimally invasive, esthetic restorations preferentially performed for healthy, young and well-insured patients. Restorative treatments and detection tools also varied markedly among practitioners. These variations in service patterns were not related to a specific patient profile in each dental practice. CONCLUSIONS: Results indicate that recent concepts in caries management have not yet been adopted in everyday practice. Patient and dentist characteristics influence the provision of restorative dental services. Decision-making in caries management not only depends on pathophysiology but also seems to be influenced by many other factors.


Assuntos
Tomada de Decisões , Tratamento Dentário Restaurador sem Trauma/estatística & dados numéricos , Cárie Dentária/terapia , Participação do Paciente/estatística & dados numéricos , Padrões de Prática Odontológica/estatística & dados numéricos , Adulto , Análise por Conglomerados , Cárie Dentária/diagnóstico , Cárie Dentária/patologia , Feminino , França , Humanos , Seguro Odontológico , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Prática Privada , Adulto Jovem
14.
Arch Pediatr ; 16(7): 991-8, 2009 Jul.
Artigo em Francês | MEDLINE | ID: mdl-19428227

RESUMO

PURPOSE: The aim of this retrospective study was to describe the prevalence of metabolic abnormalities among obese children. PATIENTS AND METHODS: Two hundred and forty-four obese children were referred in our center between 2003 and 2007. The frequency of metabolic syndrome (MS) was assessed with the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria. Insulin resistance was defined as a Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) greater than the 75th percentile. RESULTS: Around 95.9% of the children had abdominal obesity, 38.1% had systolic hypertension, 19.3% diastolic hypertension, 12.3% hypertriglyceridemia, and 4.1% hypoHDLemia. Insulin resistance was present in 69.6% of children; 11.5% of children met the criteria for MS. Both the Z-score of the body mass index and the prevalence of metabolic abnormalities were higher in the group of the youngest children. CONCLUSION: The prevalence of metabolic abnormalities is high among overweight children, particularly in the youngest children. However, the management of obesity but not metabolic-specific intervention remains the priority.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Fatores Etários , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Criança , HDL-Colesterol/sangue , Estudos Transversais , Feminino , França , Inquéritos Epidemiológicos , Humanos , Hipertensão/epidemiologia , Hipertrigliceridemia/epidemiologia , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/sangue , Fatores de Risco , Circunferência da Cintura
15.
Rev Neurol (Paris) ; 165 Suppl 4: S123-8, 2009 Mar.
Artigo em Francês | MEDLINE | ID: mdl-19361676

RESUMO

Multiple sclerosis is responsible for impairment and disability, which play a major role in the personal burden of the disease. Health-related quality of life (HRQoL) has been intensively studied in this medical condition, more intensively than in other chronic neurological disorders, perhaps because of the limitations of the conventional disability instruments, which seem less sensitive to change. Moreover, HRQoL measurements can summarize all sources of patient satisfaction and dissatisfaction. Instead of relying on motor limitations, many psychological, social, and neuropsychological factors, such as cognitive impairment and fatigue, are predictors of a reduced quality of life, even in the early stages, more than conventional radiological MRI. The analysis of self-administered HRQoL questionnaires, generic or mixed (specific and generic), can help clinicians advance toward the best therapeutic approach for the patient.


Assuntos
Esclerose Múltipla/psicologia , Qualidade de Vida/psicologia , Efeitos Psicossociais da Doença , Progressão da Doença , Humanos , Esclerose Múltipla/terapia , Prognóstico
16.
Cell Death Differ ; 16(2): 298-311, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19023333

RESUMO

Promyelomonocytic leukemia (PML) is a prominent oncosuppressor whose inactivation is involved in the pathogenesis of hematological and epithelial cancers. Here, we report that PML aggregated in nuclear bodies in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. PML aggregation occurred after the fusion of nuclei (karyogamy) within syncytia but before the apoptotic program was activated. The aggregation of PML was detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Using a range of specific inhibitors of PML (the oncogenic PML/RARalpha fusion product or specific small interfering RNAs), we demonstrated that, in Env-elicited syncytia, PML was required for activating phosphorylation of ataxia telangiectasia mutated (ATM), which colocalized with PML in nuclear bodies, in a molecular complex that also involved topoisomerase IIbeta-binding protein 1. PML knockdown thus inhibited the ATM-dependent DNA damage response that culminates in the activation of p53, p53-dependent transcription of pro-apoptotic genes and cell death. Infection of CD4-expressing cells with HIV-1 also induced syncytial apoptosis, which could be suppressed by inhibiting PML. Altogether, these data indicate that PML activation is a critical early event that participates in the apoptotic demise of HIV-1-elicited syncytia.


Assuntos
Apoptose , HIV-1 , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células Gigantes/virologia , Células HeLa , Humanos , Proteína da Leucemia Promielocítica , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
17.
Nucleic Acids Res ; 31(14): e70, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12853647

RESUMO

A new method for helicase-catalyzed DNA unwinding is described. This assay takes advantage of the substantial change in fluorescence polarization (FP) upon helicase binding and DNA unwinding. The low anisotropy value, due to the fast tumbling of the free oligonucleotide in solution, increases abruptly upon binding of helicase to the fluorescein-labeled oligonucleotide. The high anisotropy of the helicase- DNA complex decreases as the fluorescein-labeled oligonucleotide is released from the complex through helicase-catalyzed DNA unwinding. This FP signal can be measured in real time by fluorescent spectroscopy. This assay can simultaneously monitor DNA binding and helicase-catalyzed DNA unwinding. It can also be used to determine the polarity in DNA unwinding mediated by helicase. This FP assay should facilitate the study of the mechanism by which helicase unwinds duplex DNA, and also aid in screening for helicase inhibitors, which are of growing interest as potential anticancer agents.


Assuntos
DNA Helicases/metabolismo , DNA/química , Polarização de Fluorescência/métodos , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/farmacologia , Ligação Competitiva/efeitos dos fármacos , Catálise , DNA/metabolismo , DNA Helicases/genética , Cinética , Magnésio/farmacologia , Mutagênese Sítio-Dirigida , Mutação , Conformação de Ácido Nucleico/efeitos dos fármacos , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Especificidade por Substrato , Temperatura
18.
Proc Natl Acad Sci U S A ; 98(18): 10090-5, 2001 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-11504911

RESUMO

Self-assembly of HIV-1 integrase (IN) in solution has been studied previously by time-resolved fluorescence, using tryptophan anisotropy decay. This approach provides information on the size of macromolecules via the determination of rotational correlation times (theta). We have shown that, at submicromolar concentration, IN is characterized by a long rotational correlation time (theta(20 degrees C) = 90-100 ns) corresponding to a high-order oligomeric form, likely a tetramer. In the present work, we investigated the self-assembly properties of the DNA-bound IN by using three independent fluorophores. Under enzymatic assay conditions (10(-7) M IN, 2 x 10(-8) M DNA), using either fluorescein-labeled or fluorescent guanosine analog-containing oligonucleotides that mimic a viral end long terminal repeat sequence, we found that the DNA-IN complex was characterized by shorter theta(20 degrees C) values of 15.5-19.5 and 23-27 ns, calculated from experiments performed at 25 degrees C and 37 degrees C, respectively. These results were confirmed by monitoring the Trp anisotropy decay as a function of the DNA substrate concentration: the theta of IN shifted from 90-100 ns to lower values (<30 ns) upon increasing the DNA concentration. Again, the normalized theta(20 degrees C) values were significantly higher when monitored at 37 degrees C as compared with 25 degrees C. These results indicate that upon binding the viral DNA end, the multimeric enzyme undergoes a dissociation, most likely into a homogeneous monomeric form at 25 degrees C and into a monomer-dimer equilibrium at 37 degrees C.


Assuntos
DNA Viral/metabolismo , Integrase de HIV/química , Integrase de HIV/metabolismo , Sequência de Bases , DNA Viral/genética , Polarização de Fluorescência , HIV-1/genética , HIV-1/metabolismo , Humanos , Técnicas In Vitro , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/metabolismo , Subunidades Proteicas , Triptofano/química
19.
FEBS Lett ; 491(1-2): 30-4, 2001 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-11226413

RESUMO

Upon in vitro myogenesis, the intermediate filament protein vimentin is replaced by desmin, the switch in gene expression occurring essentially at the transcriptional level. Trying to elucidate the molecular mechanisms of this genetic control, we show here that the vimentin promoter is specifically recognized and activated by a protein most probably identical to H4TF-1, and that this factor is present in proliferating myoblasts but disappears upon fusion of these cells into multinucleated myotubes. Our results suggest that H4TF-1 is a differentiation stage-specific factor involved in the downregulation of vimentin gene expression during myogenesis.


Assuntos
Regulação para Baixo , Proteínas Musculares/genética , Músculo Esquelético/citologia , Fatores de Transcrição/metabolismo , Vimentina/genética , Motivos de Aminoácidos , Animais , Diferenciação Celular , Células Cultivadas , Genes Reporter , Humanos , Camundongos , Desenvolvimento Muscular , Proteínas Musculares/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Regiões Promotoras Genéticas , Transfecção , Vimentina/metabolismo
20.
Biochem Biophys Res Commun ; 279(2): 401-6, 2000 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-11118299

RESUMO

EWS Fli-1, a fusion gene resulting from a t(11;22) translocation is found in 90% of both Ewing's sarcoma and primitive neuroectodermal tumor (PNET). In the present study, we show that recently developed polyisobutylcyanoacrylate nanocapsules with an aqueous core were able to encapsulate efficiently high amounts of phosphorothioate oligonucleotides (ODN) directed against EWS Fli-1 chimeric RNA. Release of these ODN in serum medium was shown to be biphasic which was explained by the presence of two types of nanocapsules able to release ODN with different kinetics. In addition, nanocapsules were found to provide protection of these oligonucleotides from the degradation in serum. These ODN nanocapsules permitted to obtain inhibition of Ewing sarcoma-related tumor in mice after intratumoral injection of a cumulative dose as low as 14.4 nanomoles. This new type of non viral vector shows great potential for in vivo administration of oligonucleotides.


Assuntos
Proteínas de Ligação a DNA/genética , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Proteínas Proto-Oncogênicas , Sarcoma de Ewing/genética , Sarcoma de Ewing/terapia , Transativadores/genética , Células 3T3 , Animais , Cápsulas , Portadores de Fármacos , Humanos , Camundongos , Camundongos Nus , Tumores Neuroectodérmicos Primitivos/genética , Oligodesoxirribonucleotídeos Antissenso/administração & dosagem , Oligodesoxirribonucleotídeos Antissenso/sangue , Proteína Proto-Oncogênica c-fli-1 , Tionucleotídeos , Transfecção
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