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1.
Br J Dermatol ; 178(2): 520-526, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28963775

RESUMEN

BACKGROUND: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. OBJECTIVES: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. METHODS: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2-12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. RESULTS: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. CONCLUSIONS: ABF measured by Duplex ultrasonography is a simple, low-cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated.


Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Capilares/anomalías , Diferencia de Longitud de las Piernas/fisiopatología , Pierna/irrigación sanguínea , Malformaciones Vasculares/fisiopatología , Capilares/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Ultrasonografía Doppler Dúplex
3.
Br J Dermatol ; 174(1): 146-51, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26343230

RESUMEN

BACKGROUND: There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). OBJECTIVES: Our aim was to determine whether NLR measured before the first infusion was associated with OS. PATIENTS AND METHODS: Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. RESULTS: High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06). CONCLUSIONS: High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Linfocitos/efectos de los fármacos , Melanoma/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Neoplasias Cutáneas/tratamiento farmacológico , Femenino , Humanos , Ipilimumab , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Cutáneas/mortalidad
4.
Andrologia ; 47(8): 861-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25233794

RESUMEN

The aim of this study was to investigate the oxidative process associated with sperm capacitation and its impact on DNA fragmentation and sperm function. Redox activity and lipid peroxidation were analysed in human spermatozoa after 3, 6 and 22 h of incubation in Ham's F10 medium plus bovine albumin at 37° and 5% CO2 for capacitation. DNA status, tyrosine phosphorylation pattern and induced acrosome reaction were evaluated after capacitating conditions. At 22 h of incubation, there was a significant (P < 0.05) increase in oxygen-free radicals and lipid peroxidation, with no effect on sperm viability. There also was a significant (P < 0.001) increase in fragmented DNA in capacitated spermatozoa compared to semen values with higher rates being found after the occurrence of the induced acrosome reaction. Protein tyrosine phosphorylation pattern confirms that capacitation took place in parallel with the occurrence of DNA fragmentation. These results indicate that when spermatozoa are incubated for several hours (22 h), a common practice in assisted reproductive techniques, an increase in oxidative sperm metabolism and in the proportion of fragmented DNA should be expected. However, there was no effect on any of the other functional parameters associated with sperm fertilising capacity.


Asunto(s)
Fragmentación del ADN , Especies Reactivas de Oxígeno/análisis , Espermatozoides/metabolismo , Reacción Acrosómica , Humanos , Técnicas In Vitro , Peroxidación de Lípido , Masculino , Oxidación-Reducción , Técnicas Reproductivas Asistidas/efectos adversos , Capacitación Espermática , Espermatozoides/química , Espermatozoides/fisiología
5.
Rev Epidemiol Sante Publique ; 68 Suppl 3: S97, 2020 09.
Artículo en Francés | MEDLINE | ID: mdl-32951634
6.
Skin Res Technol ; 20(3): 274-81, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24283509

RESUMEN

BACKGROUND: Complex decongestive physiotherapy (CDP) is used to treat patients with severe lymphoedema. The efficacy of CDP is usually quantified by calculating limb volume from repeated measurements of circumference at least 10 points before and after treatment of an affected limb. Measurement is time-consuming and operator-dependent. OBJECTIVES: To determine whether decreased dermal thickness is correlated with decreased volume after intensive CDP. METHODS: A consecutive series of patients admitted for intensive CDP were studied over a 6-month period. Before and after CDP, we measured circumference, dermal thickness elasticity and finally improvement in quality of life using a visual analogue scale (VAS). RESULTS: Thirty patients were included in the study. Only three patients were previously untreated. The average relative reduction in limb volume was 4% and the reduction in the dermal thickness was 15% (correlation: r = 0.37, P = 0.05). Viscoelasticity was decreased by 13%. VAS quality of life score was improved by 30%. CONCLUSION: Changes in dermal thickness are slightly correlated with volume changes before and after 5-day intensive CDP in a selected series of patients previously treated at home.


Asunto(s)
Linfedema/diagnóstico , Linfedema/tratamiento farmacológico , Descongestionantes Nasales/uso terapéutico , Piel/diagnóstico por imagen , Piel/fisiopatología , Ultrasonografía/métodos , Monitoreo de Drogas , Módulo de Elasticidad/efectos de los fármacos , Femenino , Humanos , Linfedema/fisiopatología , Masculino , Persona de Mediana Edad , Examen Físico/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento
7.
Hum Reprod ; 28(5): 1297-308, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23427237

RESUMEN

STUDY QUESTION: Is lactoferrin (LF) (detected in oviductal secretion) able to bind to oocytes and sperm and modulate gamete interaction? SUMMARY ANSWER: LF binds to zona pellucida (ZP) and spermatozoa (depending upon the capacitation stage and acrosome status) and inhibits gamete interaction in vitro. WHAT IS KNOWN ALREADY: Proteins from human oviductal tissue secretion modulate gamete interaction and parameters of sperm function in vitro and some of them bind to sperm, but they remain to be isolated and identified. STUDY DESIGN, SIZE, DURATION: Proteins were isolated from human oviductal tissue secretion using their sperm membrane binding ability. One of the isolated proteins was identified as human LF and immunolocalized in tubal tissues. LF expression was analyzed in native oviductal fluid and oviduct epithelial cells (at different phases of the menstrual cycle: proliferative, periovulatory and secretory). In addition, the LF binding sites on spermatozoa (at different capacitation and acrosome reaction stages) and on ZP and the dose-dependent effect of LF on gamete interaction were investigated. All experiments were performed at least three times. PARTICIPANTS/MATERIALS, SETTING, METHODS: Tubal tissues obtained from premenopausal patients (scheduled for hysterectomy, n = 23) were cultured in DMEM/Ham's F12 medium and conditioned media (CM) were collected. Motile spermatozoa were obtained by swim-up from normozoospermic semen samples from healthy donors (n = 4). An affinity chromatography with sperm membrane extracts was used to isolate proteins from CM. Isolated proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophresis and further identified by nano liquid chromatography tandem mass spectrometry peptide sequencing. The presence of LF in oviductal tissue was investigated by immunohistochemistry and immunofluorescence and was detected in native oviductal fluid and oviduct epithelial cells homogenates by western blot. LF binding sites on gametes were investigated by incubating gametes with the protein coupled to fluorescein isothiocyanate (FITC). The acrosome reaction was assessed with Pisum sativum agglutinin conjugated with rhodamine. The effect of increasing concentrations of LF (0.1-100 µg/ml) on gamete interaction was evaluated by a sperm-ZP binding assay, using human oocytes donated by women undergoing IVF procedures. MAIN RESULTS AND THE ROLE OF CHANCE: A protein isolated by the affinity column was identified as human LF. LF was immunolocalized in human oviductal tissue and detected in oviductal fluid and oviduct epithelial cell homogenates. In the latter case, LF expression was highest at the periovulatory phase of the menstrual cycle (P < 0.01). Different LF binding patterns were observed on spermatozoa depending upon capacitation stage and if the acrosome reaction had occurred. Unstained sperm were most prevalent before capacitation, but after incubation for 6 h under capacitating conditions and in acrosome-reacted sperm LF binding was observed, mainly localized in the equatorial segment and post-acrosomal region of the sperm head. LF binding studies on ZP showed homogenous staining. LF caused a dose-dependent significant inhibition of sperm-ZP interaction, and the effect was already significant (P < 0.01) with the lowest LF concentration used. LIMITATIONS, REASONS FOR CAUTION: This study has investigated the effect of LF only on human gamete interaction in vitro and thus has some limitations. Further investigations of the potential mechanisms involved in LF action both on gamete function in vitro and in vivo in animal models are needed to confirm the role of this protein in the reproductive process. WIDER IMPLICATIONS OF THE FINDINGS: The present data indicate that human oviductal LF expression is cycle dependent and inhibited gamete interaction in vitro. No previous data were available about potential direct effects of LF on gamete interaction. It could be thought that the protein is involved in the regulation of the reproductive process, perhaps contributing to prevent polyspermy. Thus, further research is needed to clarify the potential role of LF in the regulation of the fertilization process. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from FONCYT (PICT 01095, S.A.G., M.J.M) and SECyT UNR (PIDBIO238, S.A.G). The authors have no conflict of interest to declare.


Asunto(s)
Trompas Uterinas/metabolismo , Lactoferrina/metabolismo , Oocitos/metabolismo , Espermatozoides/metabolismo , Reacción Acrosómica , Adulto , Sitios de Unión , Membrana Celular/metabolismo , Femenino , Fertilización , Fluoresceína-5-Isotiocianato/farmacología , Humanos , Técnicas In Vitro , Masculino , Unión Proteica , Interacciones Espermatozoide-Óvulo , Zona Pelúcida/metabolismo
8.
Phys Rev Lett ; 110(4): 048102, 2013 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-25166203

RESUMEN

In this Letter, we show how the grooved helical structure of actin microfilaments (F-actin) interacting with mixed fluid lipid bilayers leads to handedness-independent 1D lipid bilayer undulations coupled to longitudinal in-plane ordering of the microfilaments. This longitudinal ordering is forced by the emerging in-plane compression and curvature energy terms of the straight 1D bilayer undulation wave fronts. Thereby, adjacent helices are set into registry along their long axis in their monolayer and π shifted between adjacent monolayers. An ordered composite multilamellar structure emerges by alternate stacking of these lipid bilayers and monolayers of F-actin. This two-dimensionally ordered system has the symmetries of a centered rectangular columnar liquid crystal, the straight 1D wave fronts playing the role of the classical molecular columns.


Asunto(s)
Actinas/química , Membrana Dobles de Lípidos/química , Cristales Líquidos/química , Citoesqueleto de Actina/química , Cinética , Modelos Moleculares , Estructura Secundaria de Proteína , Termodinámica
10.
Br J Dermatol ; 169(2): 298-305, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23551168

RESUMEN

BACKGROUND: Despite the increasing use of medical photography by dermatologists, no study on patients' perceptions of photography in dermatology has been performed to date. OBJECTIVES: Firstly, to evaluate patients' perceptions of medical photography. Secondly, to assess whether perceptions differed between patients in our adult department and parents accompanying a child in our paediatric department. METHODS: An opinion survey was conducted at the Hospital of Tours (France) among adult patients (adult department) and accompanying parents (paediatric department) by completion of a questionnaire after any medical photography had been performed. RESULTS: We collected 272 questionnaires regarding 158 adults and 114 children. A camera used only in the department, and storage of the images in the department's records were the most accepted modalities (> 90%), especially in the paediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (> 85%) rather than distribution via publications (58·3%), e-mails (45·5%), health magazines (44·3%) and websites (32·0%). Most (78·8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the paediatric than the adult survey (44·5% vs. 24·5%, P = 0·001). More than 95% of respondents considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching. CONCLUSIONS: These findings could be used to improve practice, to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.


Asunto(s)
Padres/psicología , Satisfacción del Paciente , Fotograbar/estadística & datos numéricos , Enfermedades de la Piel/psicología , Adulto , Preescolar , Femenino , Francia , Departamentos de Hospitales , Humanos , Lactante , Masculino , Persona de Mediana Edad , Percepción , Fotograbar/economía , Fotograbar/legislación & jurisprudencia , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/economía , Encuestas y Cuestionarios
11.
Stat Med ; 32(19): 3357-72, 2013 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-23553813

RESUMEN

Cluster randomized trials (CRTs) are often prone to selection bias despite randomization. Using a simulation study, we investigated the use of propensity score (PS) based methods in estimating treatment effects in CRTs with selection bias when the outcome is quantitative. Of four PS-based methods (adjustment on PS, inverse weighting, stratification, and optimal full matching method), three successfully corrected the bias, as did an approach using classical multivariable regression. However, they showed poorer statistical efficiency than classical methods, with higher standard error for the treatment effect, and type I error much smaller than the 5% nominal level.


Asunto(s)
Análisis por Conglomerados , Puntaje de Propensión , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Sesgo de Selección , Anciano , Simulación por Computador , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Femenino , Humanos , Masculino , Osteoartritis/fisiopatología , Osteoartritis/terapia , Dolor/prevención & control
12.
Trials ; 23(1): 557, 2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35804404

RESUMEN

BACKGROUND: Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a "watchful waiting" approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment). METHODS: This is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters. DISCUSSION: Given the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04128722 . Registered on 24 September 2019. EudraCT: EUCTR2019-001530-33-FR Sponsor (University Hospital Center of Tours - CHRU Tours): DR190041-TOPGUN French regulatory authorities: ID RCB: 2019-001530-33.


Asunto(s)
Quistes , Anomalías Linfáticas , Adulto , Niño , Quistes/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Anomalías Linfáticas/diagnóstico , Anomalías Linfáticas/tratamiento farmacológico , Anomalías Linfáticas/patología , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia , Dolor/tratamiento farmacológico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Sirolimus , Resultado del Tratamiento
13.
Acta Psychiatr Scand ; 123(1): 62-70, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20958272

RESUMEN

OBJECTIVE: Little is known concerning mortality and predictive factors for anorexia nervosa in-patients. This study aimed to establish mortality rates and identify predictors in a large sample of adults through a 10-year post in-patient treatment follow-up. METHOD: Vital status was established for 601 anorexia nervosa (DSM-IV) consecutive in-patients with initial evaluation at admission. Standardized mortality ratio (SMR) was calculated. Cox analyses for hypothesized predictors of mortality were performed. RESULTS: Forty deaths were recorded. SMR was 10.6 [CI 95% (7.6-14.4)]. Six factors at admission were associated with death: older age, longer eating disorder duration, history of suicide attempt, diuretic use, intensity of eating disorder symptoms, and desired body mass index at admission. CONCLUSION: Anorexia nervosa in-patients are at high risk of death. This risk can be predicted by both chronicity and seriousness of illness at hospitalization. These elements should be considered as warnings to adapt care provision and could be targeted by treatment.


Asunto(s)
Anorexia Nerviosa , Adulto , Factores de Edad , Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/mortalidad , Anorexia Nerviosa/psicología , Índice de Masa Corporal , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Admisión del Paciente , Modelos de Riesgos Proporcionales , Factores de Riesgo , Índice de Severidad de la Enfermedad , Intento de Suicidio/psicología , Tiempo , Adulto Joven
14.
Hum Reprod ; 25(6): 1504-12, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20338958

RESUMEN

BACKGROUND: Spermatozoa acquire the ability to fertilize an oocyte when they become capacitated. Capacitation takes place when sperm pass through the female reproductive tract, interacting with female fluids. Both tyrosine phosphorylation of sperm proteins and the ability to respond to acrosome reaction (AR) inducers have been associated with sperm capacitation. Recent data indicate that conditioned media (CM) from human oviductal tissue culture decrease sperm affinity for the zona pellucida in vitro. Since capacitation enables the sperm-oocyte interaction, the aim of the present study was to investigate the effect of CM on events related to sperm capacitation and to assess whether these effects were permanent. METHODS: Oviductal tissue was obtained from premenopausal patients (scheduled for hysterectomies because of uterine fibromyoma). The tissues were cultured as explants and CM were collected. Explant viability was assessed as tissue DNA integrity. Normozoospermic semen samples were obtained from healthy donors. Motile spermatozoa were incubated under capacitating conditions with or without increasing protein concentrations of CM for 6 or 22 h. Human follicular fluid-induced AR was detected by the Pisum sativum technique. Tyrosine phosphorylated proteins were detected with a monoclonal anti-phosphotyrosine antibody. RESULTS: The incubation of spermatozoa in the presence of increasing concentrations of conditioned medium (CM) proteins caused a dose-dependent decrease in both tyrosine phosphorylation of sperm proteins and in the level of AR induction. When CM was removed from the sperm incubation media, the effects were reversed. Heat-inactivated CM did not affect either tyrosine phosphorylation or the induction of AR. CONCLUSIONS: The present data suggest that proteins secreted from human oviductal tissue are able to inhibit events associated with sperm capacitation in vitro.


Asunto(s)
Reacción Acrosómica/efectos de los fármacos , Trompas Uterinas/metabolismo , Capacitación Espermática/efectos de los fármacos , Espermatozoides/metabolismo , Análisis de Varianza , Supervivencia Celular , Medios de Cultivo Condicionados/metabolismo , Medios de Cultivo Condicionados/farmacología , Daño del ADN , Femenino , Líquido Folicular/metabolismo , Humanos , Masculino , Fosforilación , Proteínas/metabolismo , Proteínas/farmacología , Motilidad Espermática , Espermatozoides/efectos de los fármacos , Técnicas de Cultivo de Tejidos
15.
Respir Med Res ; 78: 100770, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32777737

RESUMEN

INTRODUCTION: Nonspecific interstitial pneumonia (NSIP) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Classic immunosuppressants are used as first-line treatment, with only one third of patients being responders and no clear recommendations exist for the choice of the second-line therapy. The EvER-ILD study is the first one to prospectively evaluate the efficacy and safety of rituximab and mycophenolate mofetil (MMF) versus placebo and MMF in a broad range of NSIP patients that did not respond to a first-line therapy. A pharmacokinetic-pharmacodynamic analysis based on rituximab serum concentrations will allow identification of potential factors associated with therapeutic response and/or adverse effects. METHODS: EvER-ILD study is a French multicenter, prospective, randomized, double blind, placebo-controlled, superiority trial. Patients with severe and progressive NSIP non-responding to a first line immunosuppressive treatment will be randomized in 2 groups of treatment: one course of rituximab plus 6 months MMF (RTX-MMF group) and one course of placebo plus 6 months MMF (Placebo-MMF group). The primary outcome is the change in Forced Vital Capacity (FVC, % of predicted) from baseline to 6 months. Several clinical, biological, and quality of life secondary outcomes will be measured at 3, 6 and 12 months. A sample size of 122 patients (61 patients per group) would allow to show a point difference between groups in the change of FVC at 6 months, based on a common standard deviation for FVC change of 8% with a power of 90%, alpha 5% two-sided, and anticipating an extreme 10% drop-out rate. ETHICS AND DISSEMINATION: The protocol was approved by the French Research Ethics Committee (CPP Tours Ouest 1 2016-R28) on November 10, 2016, and by the French competent authority (ANSM, reference 160771A-22) on December 1st, 2016. This article refers to protocol V2, dated November 18, 2016. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. Results will be disseminated via peer reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER: NCT02990286 (clinicaltrials.gov), EudraCT 2016-003026-16 (European Medicines agency).


Asunto(s)
Neumonías Intersticiales Idiopáticas/tratamiento farmacológico , Ácido Micofenólico/administración & dosificación , Rituximab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Resistencia a Medicamentos/efectos de los fármacos , Quimioterapia Combinada , Femenino , Francia , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Rituximab/efectos adversos , Resultado del Tratamiento
16.
Clin Nutr ESPEN ; 40: 392-400, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33183568

RESUMEN

CONTEXT: Following bariatric surgery, protein deficiency intakes are reported in morbidly obese patients, whereas post-bariatric protein requirements are not specifically defined with validated method in this population. OBJECTIVE: To assess average protein requirement (APR) in obese subjects, before, 3 months and 12 months after bariatric surgery using the validated method of nitrogen balance. DESIGN AND SETTING: Prospective longitudinal study conducted in 21 morbidly obese patients (BMI 43.9 ± 1.4 kg/m2) before (M0), 3 months (M3) and 12 months (M12) after sleeve gastrectomy or Roux-en-Y gastric by-pass. An additional larger cross-sectional study was performed to validate APR before surgery in non-operated matched obese patients (n = 106). APR was evaluated at M0, M3, M12 by measuring 3 days dietary intakes together with losses of nitrogen in urine and stools. MAIN OUTCOME MEASURE: APR was defined as the mean value of protein intake required to achieve balance nitrogen equilibrium. RESULTS: Before surgery, APR in morbidly obese patients was 0.76 [95%CI, 0.66-0.92] g/kg Body Weight (BW)/d in the experimental group, and 0.74 [0.70-0.80] g/kg BW/d in the validation group. APR was 0.62 [0.51-0.75] g/kg/d at M3 and 0.87 [0.75-0.98] g/kg/d at M12, with no difference between surgical procedures. Spontaneous protein intakes were respectively 0.80 ± 0.05, 0.43 ± 0.03 and 0.71 ± 0.04 g/kg BW/d respectively at M0, M3 and M12. CONCLUSION: This study demonstrates a temporal change in protein requirement after bariatric surgery whatever the type of surgery. Spontaneous protein intakes following bariatric surgery does not cover protein requirements for most patients, suggesting that specific dietary protein recommandations have to be adapted in obese patients with bariatric surgery. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01249326.


Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Estudios Transversales , Humanos , Estudios Longitudinales , Obesidad Mórbida/cirugía , Estudios Prospectivos
18.
Gynecol Obstet Fertil Senol ; 47(5): 471-477, 2019 05.
Artículo en Francés | MEDLINE | ID: mdl-30872189

RESUMEN

OBJECTIVES: Triples negative breast cancer defined by the absence of expression of the hormone receptors and HER2 protein, are considered as aggressive tumours with bad outcome in comparison to the hormone sensitive tumours. The aim of the study was to evaluate the link between hormone factors and prognostic factors of triple-negative tumours. METHODS: All patients managed for a triple-negative breast cancer between January, 2009 and December, 2013 were included. For every patient, collected data were the clinical, histological, adjuvant or neoadjuvant treatments, as well as survival data. RESULTS AND CONCLUSION: During the study period, 1682 patients were operated for a breast cancer, among which 1444 presented at least an invasive tumour. One hundred and fifty-five women (10.7%) had a negative triple tumour. The average age of diagnosis was 56.4years, is significantly younger than for patients with other types of tumours, P=0.0001. For women with a triple-negative tumour, the parity was the only hormonal factor identified as an independent factor for axillary lymph node involvement (OR=1.53; 95% CI [1.10-2.25] P=0.02) and previous hormone replacement therapy as an independent factor of locoregional recurrence (OR=0.13 [0.005-0.64] P=0.001). We did not find any hormonal factor predictive of distant metastasis. We did not find any difference in overall survival according to the parity (P=0.72), the Body mass index (P=0.62) or the use of HRT (P=0.49). CONCLUSION: Hormone factors seem to have a prognostic implication for triple-negative despite the absence of hormone receptors expression.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/terapia , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Paridad , Embarazo , Pronóstico , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/terapia
19.
Andrology ; 3(6): 1068-75, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26445132

RESUMEN

In a recent study, lactoferrin (LF) was detected in human oviductal secretion. The protein was able to bind to oocytes and sperm, and modulated gamete interaction. The aim of the present study was to investigate the effect of LF on parameters related to human sperm capacitation and sperm-zona pellucida interaction. Semen samples were obtained from healthy normozoospermic donors (n = 7). Human follicular fluids and oocytes were collected from patients undergoing in vitro fertilization. Motile sperm obtained by swim-up were incubated for 6 or 22 h under capacitating conditions with LF (0-100 µg/mL). After incubations, viability, motility, presence of α-d-mannose receptors (using a fluorescent probe on mannose coupled to bovine serum albumin), spontaneous and induced acrosome reaction (assessed with Pisum sativum agglutinin conjugated to fluorescein isothiocyanate), and tyrosine phosphorylation of sperm proteins were evaluated. Sperm-zona pellucida interaction in the presence of LF was investigated using the hemizone assay. The presence of LF did not affect sperm viability or motility, but caused a dose-dependent significant decrease in sperm α-d-mannose-binding sites, and the effect was already significant with the lowest concentration of the protein used after 22 h incubation. Dose-dependent significant increases in both induced acrosome reaction and tyrosine phosphorylation of sperm proteins were observed in the presence of LF. The present data indicate that LF modulates parameters of sperm function. The inhibition of gamete interaction by LF could be partially explained by the decrease in sperm d-mannose-binding sites. The presence of the LF promoted sperm capacitation in vitro.


Asunto(s)
Lactoferrina/farmacología , Oocitos/efectos de los fármacos , Capacitación Espermática/efectos de los fármacos , Interacciones Espermatozoide-Óvulo/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Reacción Acrosómica/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactoferrina/metabolismo , Lectinas Tipo C/efectos de los fármacos , Lectinas Tipo C/metabolismo , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/efectos de los fármacos , Lectinas de Unión a Manosa/metabolismo , Oocitos/metabolismo , Fosforilación , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Superficie Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Espermatozoides/metabolismo , Factores de Tiempo , Tirosina , Adulto Joven
20.
Diabetes Metab ; 41(1): 37-44, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25277526

RESUMEN

AIM: Our study assessed the distribution of physical activity during various typical tasks of daily life in adults with type 2 diabetes (T2D), a population typified by low physical activity. METHODS: We investigated the duration and intensity of physical activity in four domains (work, leisure, transportation and domestic), and how individual determinants might influence the repartition. The long-form International Physical Activity Questionnaire (IPAQ) was administered to participants from the échantillon national témoin représentatif des personnes diabétiques (ENTRED), a study of French adults with T2D (n=724, 65% men, age 62±10y, BMI 29±5kg.m(-2), HbA1c 7.1±1.1%), and the associations between sociodemographic/clinical characteristics and categories of physical activity intensity (low, moderate or high) were examined by logistic regression. RESULTS: The median total physical activity was 2079 [Q1=893, Q3=3915]MET-min·week(-1). The main contributors to total physical activity were domestic chores, followed by leisure-time activities and transportation (median: 630, 347 and 198MET-min·week(-1), respectively). Absence of cardiovascular complications (OR=1.87, 95% CI=1.01-3.47), age<65y (OR=2.28, 95% CI=1.30-4.01) and better self-perceived health (OR=2.12, 95% CI=1.18-3.83) were associated with more physical activity. In all patient subgroups (defined by category of physical activity intensity or stratified by determinants of physical activity level), domestic chores were always the main contributor to total physical activity (P<0.0001). CONCLUSION: Domestic chores are the predominant routine whereby adults with T2D engage in physical activity. This emphasizes the vast potential for promoting voluntary leisure-time physical activity in this population.


Asunto(s)
Actividades Cotidianas , Diabetes Mellitus Tipo 2/epidemiología , Actividad Motora/fisiología , Anciano , Índice de Masa Corporal , Estudios Transversales , Ejercicio Físico , Femenino , Francia/epidemiología , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios
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