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1.
Bull Cancer ; 110(12): 1251-1259, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37696744

RESUMEN

INTRODUCTION: Therapeutic approaches in Multiple Myeloma (MM) have considerably changed over the last few years, with effective oral chemotherapy and continuous treatment. In this context, the objective of this study was to examine the circuitry of an advanced practitioner nurse (APN)-led intervention that provided supportive care for MM patients treated with oral chemotherapy. METHODS: This population-based study was conducted at the hematology department - Institut de Cancérologie Lucien Neuwirth (ICLN, Saint-Priest-en-Jarez), from April 2017 to September 2020. A follow-up program was established with a specialized APN in oncology. RESULTS: All APN interventions were recorded, representing 1240 phone calls and 162 consultations for 42 MM patients. Eighty-two calls were referred to the physician with 45 consultations triggered. Most of the calls were frequent within the few first months, with a high request for information and reassurance, especially for treatment-naive or relapsed patients. In our study, the APN was able to manage multiple side effects through care organization (i.e., hospitalizations, transfusions) and a careful coordination between the primary care team and the hospital. DISCUSSION: In order to respond to the high need for care pathway and safety improvement, especially in elderly population, we have initiated an original follow-up by an APN for MM patients treated with oral chemotherapy. While the role of APN has become prominent in the oncology field in recent years, its holistic approach has to be emphasized in further studies to bring a comprehensive perspective to health care coordination in the future.


Asunto(s)
Mieloma Múltiple , Humanos , Anciano , Mieloma Múltiple/tratamiento farmacológico , Atención a la Salud
2.
J Thromb Haemost ; 20(8): 1859-1867, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35557490

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) is a concern for patients with newly diagnosed multiple myeloma. OBJECTIVES: We aimed to evaluate VTE incidence, risk factors, and risk score. PATIENTS/METHODS: We performed a substudy of the "Intergroupe Francophone du Myelome 2009" randomized controlled trial. RESULTS: We assessed 700 patients receiving lenalidomide/bortezomib/dexamethasone, followed or not by autologous hematopoietic stem cell transplantation. VTE incidence at 6 months was 4.8% (95% confidence interval [CI]: 3.3-6.9%) and 1.5% (95% CI: 0.8-2.9%) from 6 to 12 months. Using multivariate analysis we confirmed history of VTE (odds ratio 5.1 [1.6-16.7], P = .007) as a strong VTE-related risk factor, invalidated erythropoietin exposure (0.6 [0.2-1.7], P = .3) as risk factor, and added two new risk factors: fracture at diagnosis (2.6 [1.3-5.5], P = .01), and serum gamma globulin level > 27 g/L (2.8 [1.2-6.8,] P = .02). Moreover, we noticed that VTE occurred earlier in patients with gamma globulin levels >27 g/L, suggesting a need to revisit the thromboprophylaxis timeframe. Heparin administration was associated with a decreased risk (0.3 [0.1-0.7], P = .005) but failed to erase the risk regardless of dose. The area under the receiver operating characteristic curve of the IMPEDE VTE score was 0.67, as previously reported, confirming our cohort was well representative. CONCLUSIONS: Prospective studies are warranted in light of these results to improve VTE risk stratification and to design adapted thromboprophylaxis in terms of timing and dose.


Asunto(s)
Mieloma Múltiple , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Bortezomib/efectos adversos , Dexametasona/efectos adversos , Humanos , Lenalidomida/efectos adversos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , gammaglobulinas/uso terapéutico
3.
Res Pract Thromb Haemost ; 3(1): 89-98, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30656281

RESUMEN

BACKGROUND: Multiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients. OBJECTIVE: To determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles. METHODS: This prospective and longitudinal observational study included patients newly diagnosed with MM. TG was determined in platelet-rich and platelet-poor plasma using calibrated automated thrombography with a low tissue factor (TF) concentration. RESULTS: Seventy-one patients were enrolled, allowing TG analysis during 213 chemotherapy cycles. TG remained unchanged throughout follow-up irrespective of treatment regimen, but values determined before cycles 2 and 3 were significantly higher in patients receiving iMiDs-containing regimens. No association was found between TG and its changes and thrombosis occurrence during follow-up: venous thrombosis in eight patients; no cardiovascular event. A significantly (87%) lower risk of venous thrombosis was observed in patients receiving prophylaxis with a low-molecular-weight heparin (LMWH; OR: 0.13 (95% CI: 0.02-0.76). Neither bortezomib- nor dexamethasone-containing regimens were associated with thrombotic risk. Changes in TG, as studied, were not associated with thrombotic events. CONCLUSIONS: The only factor associated with a reduction in early thrombotic risk was prophylaxis with LMWH. The issue of how to identify patients requiring prophylactic anticoagulation remains unresolved.

4.
J Clin Oncol ; 37(19): 1657-1665, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31091136

RESUMEN

PURPOSE: The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM. METHODS: Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients. RESULTS: In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell's concordance index greater than 70%). CONCLUSION: The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.


Asunto(s)
Análisis Citogenético/métodos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Pronóstico , Análisis de Supervivencia , Anciano , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 5/genética , Supervivencia sin Enfermedad , Femenino , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Análisis Multivariante , Medición de Riesgo , Translocación Genética , Trisomía
6.
Int J Mol Med ; 22(6): 825-32, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19020782

RESUMEN

Peroxisome proliferator-activated receptor-gamma (PPARgamma) belongs to the nuclear hormone receptor family. This receptor is implicated in colon cell differentiation and in colon cancer. Receptor activation by specific agonists has been shown to protect against colon cancer progression. PPARgamma protein content within cells is modulated by several mechanisms, including proteasome degradation, activation of Wnt signalling pathways and presence of fermentation products such as butyrate. Herein, we investigated the impact of L-glutamine on PPARgamma expression during the differentiation of Caco-2 cells grown in medium containing dialyzed fetal calf serum supplemented or not with L-glutamine. Using RT-PCR and Western blotting, we demonstrated that PPARgamma expression was decreased when L-glutamine was added to the medium. Using immunohistochemistry, we demonstrated that PPARgamma immunostaining was mainly found in cytoplasm when cells were cultured with L-glutamine while it was found in nuclei and cytoplasm when cells were grown without the addition of L-glutamine. Supershift retardation assays demonstrated a decrease of PPARgamma binding onto consensus peroxisome proliferator response element. We concluded that L-glutamine modulated PPARgamma expression in Caco-2 cells.


Asunto(s)
Diferenciación Celular , Colon/citología , Glutamina/farmacología , PPAR gamma/metabolismo , Western Blotting , Células CACO-2 , Colon/metabolismo , Medios de Cultivo , Citoplasma/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Glutaminasa/genética , Glutaminasa/metabolismo , Glutamina/metabolismo , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
7.
Stud Health Technol Inform ; 138: 49-58, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18560107

RESUMEN

The NeuroLOG project designs an ambitious neurosciences middleware, gaining from many existing components and learning from past project experiences. It is targeting a focused application area and adopting a user-centric perspective to meet the neuroscientists expectations. It aims at fostering the adoption of HealthGrids in a pre-clinical community. This paper details the project's design study and methodology which were proposed to achieve the integration of heterogeneous site data schemas and the definition of a site-centric policy. The NeuroLOG middleware will bridge HealthGrid and local resources to match user desires to control their resources and provide a transitional model towards HealthGrids.


Asunto(s)
Seguridad Computacional , Sistemas de Computación , Procesamiento de Imagen Asistido por Computador/instrumentación , Neurociencias/organización & administración , Diseño de Software , Programas Informáticos , Interfaz Usuario-Computador , Francia , Humanos
8.
Joint Bone Spine ; 85(5): 569-572, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29198886

RESUMEN

OBJECTIVES: Bone alterations at the subchondral level during rheumatoid arthritis (RA) remain under investigation. It remains unknown whether subchondral bone damage might still occur in RA patients in clinical remission, which could then infer suggesting that even minor subclinical inflammatory changes in the joint can induce local bone loss. METHODS: Thirty-two RA patients treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) with low disease activity since at least 6 months and having erosion on the second or third metacarpeal head were enrolled in this pilot cross-sectional study. They were divided in two groups according to local inflammation assessed by Doppler-ultrasound exam surrounding the site of erosion. Cortical and trabecular parameters of the metacarpeal head were then assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) and compared in both groups. RESULTS: Twenty and twelve RA patients were enrolled in the "Doppler positive erosion" (DE+) group and Doppler negative erosion (DE-) group, respectively. No difference was observed in their clinical or biological RA characteristics. Both cortical density and thickness were similar among groups. Within the trabecular network, while no difference in bone volume was observed, trabecular density as well as trabecular number were decreased (P<0.001 and P<0.05 respectively), whereas trabecular separation and distribution of trabecular separation were increased in DE+ compared to DE- (P<0.05). CONCLUSION: In RA patients in low disease activity under bDMARDs, persistence of local inflammation was associated with alteration of the trabecular compartment. Trabecular density was the most strongly altered parameter and could be a candidate to assess drug effect on periarticular bone damage.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Productos Biológicos/uso terapéutico , Progresión de la Enfermedad , Huesos del Metacarpo/patología , Anciano , Antirreumáticos/uso terapéutico , Estudios Transversales , Femenino , Francia , Humanos , Inflamación/patología , Inflamación/fisiopatología , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
9.
Joint Bone Spine ; 85(6): 727-731, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29631069

RESUMEN

OBJECTIVE: Many patients with spondyloarthritis (SpA) are at risk of fracture due to bone fragility, whereas their bone mineral density (BMD) is not significantly diminished. Other tools, such as trabecular bone score (TBS), evaluating other characteristics of bone tissue are therefore necessary in order to evaluate bone changes in these patients. Therefore we evaluated TBS as a bone quality marker, in a cohort of patients with SpA and investigated which clinical and biological factors were correlated with TBS values. METHODS: Patients fulfilling ASAS criteria of SpA with a BMD assessment and visiting our department for initiation or switch of a biologic treatment were selected. The clinical and biological data were collected at the time of BMD measurement. RESULTS: Ninety-five patients were included in the study, with a mean age of 40.2 and a mean disease duration of 8.2 years. Lumbar BMD T-score was <-1 and <-2.5 in 17% and 3% of patients, respectively. On average, TBS value was 1.34±0.12. Lumbar BMD was positively correlated with TBS (r=0.61), while disease duration, disease activity score and serum PTH levels were negatively correlated with TBS (r=-0.24, r=-0.33, and r=-0.27, respectively). These correlations persisted in a multivariate analysis. Furthermore, more than half of the patients with a BMD level above -2.5 T-score had a low TBS value. CONCLUSION: Our results show that TBS provides information additional to BMD on the bone status of patients with SpA. They suggest that TBS may help in identifying those patients at risk of fracture.


Asunto(s)
Densidad Ósea/fisiología , Hueso Esponjoso/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico , Espondiloartritis/diagnóstico , Absorciometría de Fotón/métodos , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares , Masculino , Fracturas Osteoporóticas/etiología , Estudios Retrospectivos , Espondiloartritis/complicaciones , Espondiloartritis/metabolismo
10.
Biochimie ; 89(3): 329-36, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17070643

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors and belong to the nuclear hormone receptor superfamily. They form heterodimers with retinoid X receptor (RXR) and bind to specific PPAR-response elements. To identify novel PPAR target genes, we developed an affinity method to isolate human genomic fragments containing binding sites for PPARs. For this, an antibody raised against all PPAR subtypes was used. Immunoselected fragments were amplified and sequenced. One of them, ISF1029, was mapped by BLAT and BLAST searches on different human chromosomes, downstream of several POTE genes. ISF1029 contained three hexamers strongly related to the AGGTCA motif organized according to a DR0/3 motif. The latter was found to bind to PPARalpha in gel mobility shift and supershift assays and to exhibit a downregulation potentiality in transfection experiments under clofibrate treatment. POTE genes were shown to be highly expressed in human Caco-2 colorectal adenocarcinoma cells and downregulated by fenofibrate and 9-cis-retinoic acid, as attested by RT-PCR assays. Microarray analysis confirmed and extended to the human T98-G glioblastoma cells, the downregulation of several POTE genes expression by Wy-14,643, a potent PPARalpha activator. Our data provide new insights about the pleiotropic action of PPARs.


Asunto(s)
ADN/metabolismo , Genoma Humano , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Elementos de Respuesta/genética , Secuencia de Bases , Sitios de Unión/genética , Southern Blotting , Células CACO-2 , Línea Celular Tumoral , ADN/inmunología , ADN/aislamiento & purificación , Ensayo de Cambio de Movilidad Electroforética , Regulación de la Expresión Génica , Células HCT116 , Humanos , Inmunoprecipitación , Modelos Genéticos , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptores Activados del Proliferador del Peroxisoma/agonistas , Receptores Activados del Proliferador del Peroxisoma/inmunología , Unión Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Joint Bone Spine ; 84(5): 611-614, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27697401

RESUMEN

INTRODUCTION: Alzheimer's disease or other Dementias (ADD) and postmenopausal osteoporosis are two major public health problems with a huge impact on mortality. Here, we examined the prevalence of ADD in postmenopausal women with osteoporosis, monitored within a dedicated fracture liaison service. METHODS: We conducted a cross-sectional observational study in a population of 2041 women, visiting the university hospital of Saint-Etienne for a peripheral fragility fracture. We assessed the prevalence of ADD among these patients and compared to French population. We also compared the characteristics of women with ADD and without ADD. RESULTS: ADD prevalence was on average 13.5% in the population of interest with a mean age of 85years. As women with ADD were older than women without ADD, the prevalence of the disease significantly increased with age as 0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups, respectively. Proximal femoral fracture was the most frequent fracture (77%) followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD prevalence observed in our study was 3 to 4 times the ADD prevalence in France. Despite the overall increase of the ADD prevalence with age, it was still 2.2 and 1.9 times that of the French female population in the 80-84 and 85-89 age groups respectively. CONCLUSION: ADD prevalence was higher in postmenopausal women with severe osteoporosis, especially those with femoral fractures. Thus, our results incite to a more efficient care of this population with a high risk of fracture and mortality.


Asunto(s)
Demencia/epidemiología , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Densidad Ósea , Distribución de Chi-Cuadrado , Comorbilidad , Estudios Transversales , Demencia/diagnóstico , Femenino , Francia/epidemiología , Hospitales Universitarios , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/diagnóstico , Fracturas Osteoporóticas/diagnóstico por imagen , Prevalencia , Pronóstico , Medición de Riesgo
12.
Int J Oncol ; 28(4): 977-84, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16525649

RESUMEN

This study tests the hypothesis that the activators of peroxisome proliferator-activated receptors (PPARs) and 9-cis-retinoic acid receptor (RXR) regulate human semaphorin 6B (Sema6B) gene expression. The human MCF-7 breast adenocarcinoma cell line was chosen because it expresses Sema6B at a high level. The Sema6B mRNA level was analyzed by RT-PCR and the semaphorin 6B protein content was determined using a polyclonal antibody that we have produced and characterized. Treatments with fenofibrate (a PPARalpha activator) and troglitazone (a PPARgamma ligand) strongly decreased the Sema6B mRNA. The drop in Sema6B mRNA level and in protein content was more important when the treatment combined the action of fenofibrate or troglitazone and 9-cis-retinoic acid. On the other hand, no significant change was observed in the Sema6B mRNA and protein levels when the cells were exposed to the combined action of GW610742 (a PPARbeta activator) and 9-cis-retinoic acid. These data suggest that PPARalpha/RXR and PPARgamma/RXR heterodimers are involved in the regulation of Sema6B gene expression and open new perspectives concerning the participation of these nuclear receptors in cell recognition and migration.


Asunto(s)
Cromanos , Fenofibrato , Semaforinas , Tiazolidinedionas , Humanos , Alitretinoína , Western Blotting , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular , Línea Celular Tumoral , Cromanos/farmacología , Dimerización , Fenofibrato/farmacología , Expresión Génica/efectos de los fármacos , Células HT29 , Células K562 , PPAR alfa/agonistas , PPAR alfa/química , PPAR gamma/agonistas , PPAR gamma/química , Receptores X Retinoide/agonistas , Receptores X Retinoide/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ARN Mensajero/genética , ARN Mensajero/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Tiazoles/farmacología , Tiazolidinedionas/farmacología , Tretinoina/farmacología , Troglitazona
13.
Sleep Med ; 22: 25-32, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27544832

RESUMEN

OBJECTIVE: Several studies suggest a relationship between bone mineral density (BMD) anthropometric and metabolic variables, and obstructive sleep apnea (OSA); all of these factors have an effect on osteoporosis (OS) risk. This cross-sectional study explores these associations in a large sample of older subjects with and without OSA. METHODS: Volunteers were recruited from the PROgnostic indicator OF cardiovascular and cerebrovascular events survey. A total of 461 subjects, aged 68.7 ± 0.8 years, were examined, blood samples were taken, and they were subjected to home polygraphy, assessment of daily energy expenditure (DEE), and dual-energy X-ray absorptiometry. RESULTS: Osteopenia (OP) was detected in 44% of subjects at the femoral and 39% at the vertebral level, while the prevalence of OS was lower at the femoral (4%) and vertebral (12%) levels. As expected, women had a higher prevalence of OP and OS. Subjects with OP and OS had a tendency to have lower DEE and values of obesity, apnea-hypopnea index (AHI), and indices of hypoxemia (ODI). At the correlation analyses, anthropometric factors and DEE were significantly related to BMD with a slight effect of indices of OSA severity. After adjustment for confounding variables, univariate and multivariate regression analyses showed a strong significant association between femoral and lumbar BMD and T-score and DEE without contribution of metabolic data and with a slight negative effect of respiratory factors. CONCLUSIONS: In this sample of the elderly, physical activity was the best predictor of OS with a slight effect of body mass index. The indices of OSA confirm their protective effect on bone mineral density.


Asunto(s)
Ejercicio Físico/fisiología , Osteoporosis/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Absorciometría de Fotón , Anciano , Antropometría , Densidad Ósea/fisiología , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Prevalencia , Factores de Riesgo , Factores Sexuales , Encuestas y Cuestionarios
14.
J Clin Sleep Med ; 12(11): 1461-1469, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27655463

RESUMEN

STUDY OBJECTIVES: Clinical and epidemiological studies suggest a relation between bone mineral density (BMD) and self-assessment of sleep with an effect on bone formation and osteoporosis (OS) risk in short and long sleepers. This study explores this association in a large sample of older subjects. METHODS: We examined 500 participants without insomnia complaints aged 65.7 ± 0.8 y. Each participant had a full evaluation including anthropometric measurement, clinical examination and measurements of BMD at the lumbar spine and femoral sites by dual-energy X-ray absorptiometry. The daily energy expenditure (DEE) was measured by the Population Physical Activity Questionnaire. Sleep duration and quality were evaluated by the Pittsburgh Sleep Quality Index. The subjects were stratified into three groups according to sleep duration, i.e., short (< 6 h), normal (6-8 h), and long (≥ 8 h) sleepers. RESULTS: Osteopenia was found in 40% of the subjects at the femoral level and 43% at the vertebral level. The prevalence of OS was lower both at femoral (8%) and vertebral (12%) levels. Short, normal, and long sleepers accounted for 29%, 40%, and 31% of subjects, respectively. After adjustments for metabolic, anthropometric, and DEE, multinomial logistic regression analysis indicated that long sleepers were more likely to have femoral neck OS with a slight effect of DEE at vertebral spine. CONCLUSIONS: In a sample of older subjects, self-reported long sleep was the best predictor of OS risk at the femoral level. This finding suggests an association between OS and self-reported sleep duration in older subjects. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.


Asunto(s)
Densidad Ósea/fisiología , Evaluación Geriátrica/métodos , Estado de Salud , Osteoporosis/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Sueño/fisiología , Absorciometría de Fotón , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Factores de Riesgo , Factores de Tiempo
16.
Obesity (Silver Spring) ; 23(7): 1511-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26054548

RESUMEN

OBJECTIVE: Obesity and aging are considered risk factors for developing sleep apnea syndrome (OSA). The aim of this study was to determine the association between body fat composition and OSA in healthy elderly subjects examined in a 7-year longitudinal study. METHODS: A total of 209 elderly with unrecognized OSA aged 68.3 ± 0.8 years underwent a clinical, ambulatory nocturnal respiratory recording, and anthropometric as well as body fat composition assessment by dual-energy X-ray absorptiometry (DEXA) at baseline and follow-up. RESULTS: At study entry, 50.3% of the population showed an apnea+hypopnea index (AHI) <15 with a mean AHI of 16.8 ± 11. At follow-up, a reduction of OSA cases (42%) was evident with a mean AHI of 14.6 ± 10.2. The DEXA data demonstrated that body mass and total lean mass were reduced at follow-up, while central and peripheral fat mass showed a slight increase. Correlation analysis between the changes in DEXA measurements versus the changes in AHI and the indices of nocturnal hypoxemia showed an absence of a statistical correlation. CONCLUSIONS: The lack of correlation between the DEXA measurement changes and the changes in the AHI confirm our previous data on the absence of a central fat mass effect on OSA in the elderly.


Asunto(s)
Tejido Adiposo/fisiopatología , Composición Corporal , Evaluación Geriátrica/métodos , Obesidad/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Absorciometría de Fotón , Anciano , Antropometría , Índice de Masa Corporal , Comorbilidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Polisomnografía , Factores de Riesgo , Apnea Obstructiva del Sueño/diagnóstico
17.
Biochem Pharmacol ; 63(2): 237-45, 2002 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-11841798

RESUMEN

Among the different hypotheses advanced to explain the peroxisome proliferator (PP)-induced hepatocarcinogenicity in rodents, one is based on the development of an oxidative stress due to an imbalance in the production of reactive oxygen species that leads to DNA damages and lipid peroxidation. On the other hand, human cells appear to be nonresponsive to PPs. As metallothionein proteins play an important antioxidant role, the aim of the present study was to investigate the expression of metallothionein IA (MTIA) and IIA (MTIIA) in HepG2 human hepatoma cells exposed to clofibric acid. When HepG2 cells were treated for 24 hr with 0.50 or 0.75 mM CA, a significant decrease was observed in MT protein-level determined by Western blotting and in the MTIIA mRNA content analyzed by RT-PCR and Northern blotting. No significant change was observed in the MTIA mRNA amount whatever the CA concentration and the duration of treatment. The decrease in MTIIA mRNA-level was not mediated via peroxisome proliferator-activated receptor alpha as attested by our data from gel mobility shift DNA binding assays, Dot blotting and cotransfection experiments with MTIIA promoter-driven luciferase reporter gene and PPARalpha expression vector. These results provide new insights about the pleiotropic effects of PPs on human cells.


Asunto(s)
Ácido Clofíbrico/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Metalotioneína/metabolismo , Carcinoma Hepatocelular , Regulación hacia Abajo/efectos de los fármacos , Humanos , Hipolipemiantes/farmacología , Neoplasias Hepáticas , Metalotioneína/genética , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/fisiología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Células Tumorales Cultivadas
18.
Microsc Res Tech ; 61(2): 185-90, 2003 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-12740825

RESUMEN

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear hormone receptor superfamily that can be activated by natural fatty acids and various xenobiotics, including clofibrate. This transcription factor primarily regulates genes involved in lipid metabolism and homeostasis. We present the expression pattern of the PPARalpha subtype in the adult jerboa Jaculus orientalis, determined by RT-PCR and Western blotting using specific probes and a polyclonal antibody for PPARalpha, respectively. PPARalpha is highly expressed in liver and kidney, and to a lesser extent in duodenum and colon. PPARalpha expression is increased at the mRNA and protein levels in liver and duodenum of jerboa treated for 2 weeks with the peroxisome proliferator (PP) clofibrate. The induction is tissue-specific as no significant changes are observed in kidney and colon. The present data indicate that the PP-induced PPARalpha gene expression is not dependent on the PPARalpha content in target cells.


Asunto(s)
Clofibrato/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Proliferadores de Peroxisomas/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Roedores/metabolismo , Factores de Transcripción/metabolismo , Animales , Mucosa Intestinal/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética
19.
Sleep ; 36(10): 1509-15, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-24082310

RESUMEN

STUDY OBJECTIVES: Chronic intermittent hypoxia (IH) acts as a stimulator of mesenchymal stem cell (MSC) mobilization, intensifying osteoblast formation in animal models. The recurrence of apnea and oxygen desaturation in obstructive sleep apnea (OSA) may mimic experimental models of IH. We hypothesized that in elderly with OSA, apnea-related IH may mobilize MSCs and thereby prevent the age-related decline in osteogenesis. This study explored the relationship between OSA and bone mineral density (BMD), and the effect of IH on BMD, in a large sample of elderly subjects. PARTICIPANTS: There were 833 volunteers age 68.6 ± 0.8 y (59% women). INTERVENTION: Each participant underwent evaluation of BMD at lumbar spine and femoral sites by dual-energy x-ray absorptiometry (DEXA) as well as clinical and polygraphic examinations. OSA was diagnosed on the basis of an apnea-hypopnea index (AHI) ≥ 15. MEASUREMENTS AND RESULTS: There were 55% of the participants who presented with OSA, and these subjects were predominantly male and overweight. Compared with subjects without OSA, those with OSA had a higher femoral and spinal BMD (P < 0.001). Body mass index (BMI), AHI, and oxygen desaturation index (ODI) (P < 0.01) were significantly related to BMD. After adjustment for sex, BMI, metabolic values, and hypertension, multiple regression analysis showed a significant association between femoral and lumbar T scores and both daily energy expenditure (P < 0.001) and ODI (P = 0.007). CONCLUSIONS: In elderly subjects, the presence of obstructive sleep apnea is associated with higher bone mineral density, with oxygen desaturation index being a significant determinant of bone metabolism. These results suggest that apnea-related intermittent hypoxia may stimulate the bone remodeling process in older population. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.


Asunto(s)
Densidad Ósea/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Absorciometría de Fotón , Anciano , Huesos/metabolismo , Estudios de Casos y Controles , Femenino , Fémur/fisiología , Humanos , Vértebras Lumbares/fisiología , Masculino , Polisomnografía , Apnea Obstructiva del Sueño/metabolismo
20.
Sleep ; 36(4): 501-7, 2013 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-23564997

RESUMEN

STUDY OBJECTIVES: Obesity is a recognized risk factor for obstructive sleep apnea syndrome (OSAS). We evaluated whether total trunk and central fat mass (CFM) is associated with OSAS in elderly subjects. DESIGN: Cross-sectional. SETTING: Body composition assessment by dual-energy X-ray absorbsiometry (DEXA). PARTICIPANTS: 749 volunteers aged 67.2 ± 0.8 years (59.4% women). INTERVENTION: All participants underwent evaluation of their body composition by DEXA in parallel with clinical and polygraphic assessments. The presence of OSAS was defined by an apnea plus hypopnea index (AHI) ≥ 15. MEASUREMENTS AND RESULTS: A total of 44.8% of the population had an AHI < 15, and 55.2% presented OSAS. OSAS subjects were more frequently overweight and had a higher total trunk fat mass and central fat mass (CFM). Correlation analyses revealed that body mass index (r = 0.27, P < 0.001), neck circumference (r = 0.35, P < 0.001), and CFM (r = 0.23, P < 0.001) were significantly related to AHI. Logistic regression analysis indicated that in mild OSAS cases (> 15AHI < 30), BMI (OR: 1.10; 95% CI: 1.03-1.18; P = 0.008), and male gender (OR: 1.49; 95% CI: 1.05-2.12, P = 0.03) were key factors explaining an AHI between 15 and 30. In severe cases (AHI > 30), male gender (OR: 3.65; 95% CI: 2.40-5.55; P < 0.001) and CFM (OR: 1.10; 95% CI: 1.03-1.19; P = 0.009) were significant independent predictors of OSAS. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584. CONCLUSIONS: Although central fat mass plays a role in the occurrence of severe OSAS in men older than 65 years of age, its low discriminative sensitivity in mild OSAS cases does not warrant systematic use of DEXA for the diagnosis of OSAS.


Asunto(s)
Grasa Abdominal/diagnóstico por imagen , Sobrepeso/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Absorciometría de Fotón/métodos , Anciano , Análisis de Varianza , Composición Corporal , Índice de Masa Corporal , Estudios Transversales , Femenino , Francia , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Masculino , Oportunidad Relativa , Sobrepeso/fisiopatología , Polisomnografía/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Apnea Obstructiva del Sueño/fisiopatología
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