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1.
Environ Monit Assess ; 196(7): 672, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940996

RESUMEN

The disaggregated inorganic grain size (DIGS) of bottom sediment analyzed with a Coulter Counter (CC) has been used to show that the fraction of sediment deposited in flocs (floc fraction) increased in both the near and far field after the introduction of open cage salmon aquaculture, altering benthic habitat and species composition. As a result, DIGS was identified as a potential indicator of regional environmental changes due to aquaculture. Laser diffraction is an attractive alternative to the CC because of its greater efficiency and larger size range. To determine if a laser diffraction instrument, Beckman-Coulter LS 13 320 (LS), could replace the CC within a Canadian national aquaculture monitoring program, the DIGS of 581 samples from five different regions in eastern Canada were analyzed with an LS and a CC. Results show that the LS could not be used to calculate floc fraction. Instead, % sortable silt and the volume % of inorganic particles < 16 µm were evaluated as alternative proxies for fine sediment properties. LS and CC values for these parameters were correlated, but they were significantly different and the relationship between the instruments was dependent on the area sampled. The LS did not capture variations between areas seen in the CC DIGS data. Where the DIGS from the CC found no sorting in the finest size classes, all the LS samples had similar size distributions characterized by smooth modal peaks. The LS and CC both return values that can be used to monitor changes in the deposition of fine-grained sediment, but the LS cannot determine changes in floc deposition and caution is required if comparing different sedimentary environments.


Asunto(s)
Acuicultura , Monitoreo del Ambiente , Sedimentos Geológicos , Tamaño de la Partícula , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Canadá , Animales , Rayos Láser
2.
Heliyon ; 10(10): e31491, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38831818

RESUMEN

Whole lung torsion following bilateral lung transplant is a rare complication. This case report describes the diagnostic difficulties and consequences in a 59 year old patient. This study also includes a brief description of other cases in the literature.

3.
Mar Pollut Bull ; 188: 114654, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36736258

RESUMEN

The presence of in-feed anti-sea lice drugs and their relationship with organic enrichment is poorly understood in sediment surrounding salmon farms. Using data from an aquaculture monitoring program (2018-2020), we describe this relationship at ten sites in four Canadian provinces. Three anti-sea lice pesticides (lufenuron, teflubenzuron, emamectin benzoate and metabolite desmethyl emamectin benzoate), and one antibiotic (oxytetracycline) were detected. Concentrations were often below limits of quantification. Values are also lower than those reported in other aquaculture salmon-producing countries. Highest concentrations, along with organic enrichment, were observed ~200 m of cages with lower concentrations detected up to 1.5 km away. Most samples had at least two drugs present: 75.2 % (British Columbia), 91.4 % (Newfoundland), and 54.8 % (New Brunswick/Nova Scotia) highlighting the potential for cumulative effects. Emamectin benzoate and oxytetracycline were detected four and three years respectively after last known treatments, demonstrating the need for research on overall persistence of compounds.


Asunto(s)
Copépodos , Enfermedades de los Peces , Oxitetraciclina , Salmo salar , Animales , Antibacterianos/farmacología , Oxitetraciclina/farmacología , Acuicultura , Sedimentos Geológicos , Colombia Británica
4.
Br J Dermatol ; 185(6): 1232-1239, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34173243

RESUMEN

BACKGROUND: European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients. METHODS: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score. RESULTS: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively. CONCLUSIONS: A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.


Asunto(s)
Penfigoide Ampolloso , Administración Oral , Corticoesteroides/uso terapéutico , Anciano de 80 o más Años , Humanos , Penfigoide Ampolloso/diagnóstico , Prednisona/uso terapéutico , Estudios Prospectivos
5.
Mar Pollut Bull ; 169: 112557, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34089964

RESUMEN

Several trace-elements have been identified as indicators of finfish aquaculture organic enrichment. In this study, sediment sampling at finfish farms was completed as part of an Aquaculture Monitoring Program in three distinct Canadian regions. Despite diverse datasets, multivariate analyses show a consistent clustering of known direct (Cu and Zn) and indirect (Cd, Mo and U) tracers of aquaculture activities with sediment organic matter (OM) and/or total dissolved sulfides concentrations. OM content was also a predictor of Cu, Zn, Mo and U concentrations according to decision tree analyses. Distance from cages did not emerge as a strong driver of differences among sampling points; however, a tendency towards negative associations is clear especially for Zn. Enriched stations as determined after geochemical normalization were mostly localized within 150 m of net-pens. Selected trace-elements (in particular Zn) can be useful indicators of aquaculture organic enrichment in different ecosystems and valuable tools for monitoring programs.


Asunto(s)
Metales Pesados , Oligoelementos , Contaminantes Químicos del Agua , Acuicultura , Canadá , Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados/análisis , Oligoelementos/análisis , Contaminantes Químicos del Agua/análisis
6.
Rev Mal Respir ; 37(10): 769-775, 2020 Dec.
Artículo en Francés | MEDLINE | ID: mdl-33158640

RESUMEN

INTRODUCTION: The number of lung transplantations performed is increasing worldwide. With an improved experience and outcomes, the age of the recipient on its own has ceased to be an absolute contra-indication. We report our first experience with lung transplantation in patients aged 65 years or older. METHODS: From January 2014 to March 2019, the files of patients aged 65 years or older undergoing lung transplantation were retrospectively reviewed. RESULTS: During the study period, 241 patients underwent lung transplantation in Bichat hospital (Paris, France), including 25 recipients aged 65 years or older. Underlying diagnoses were interstitial (72%) and obstructive (28%) disease. The rate of single lung transplantation was 80%. Sixteen patients required ECMO assistance during the procedure. Early complications were mostly grade III primary graft dysfunction (12%) and cellular rejection (20%). Overall one-year survival rate was 76%. CONCLUSION: After a careful selection of the recipients, the early results of our retrospective single center series are encouraging. We continue to consider lung transplantation in rigorously selected recipients of aged 65 years and more.


Asunto(s)
Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Pulmonares Obstructivas/epidemiología , Enfermedades Pulmonares Obstructivas/terapia , Trasplante de Pulmón , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Supervivencia de Injerto , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Obstructivas/mortalidad , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/métodos , Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/estadística & datos numéricos , Masculino , Paris/epidemiología , Periodo Posoperatorio , Disfunción Primaria del Injerto/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
7.
Nutr Res ; 79: 23-34, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32610255

RESUMEN

Studies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress.


Asunto(s)
Encéfalo/metabolismo , Dieta Alta en Grasa , Dieta Occidental , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Distrés Psicológico , Animales , Antioxidantes/metabolismo , Azúcares de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Regulación de la Expresión Génica , Masculino , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/genética , Oxidación-Reducción , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Ácido Úrico/metabolismo
8.
Rev Epidemiol Sante Publique ; 68(2): 75-82, 2020 Apr.
Artículo en Francés | MEDLINE | ID: mdl-32145923

RESUMEN

INTRODUCTION: In France, the management of pediatric cancers is carried out in reference hospitals that can delegate care to local health centres (LHC), forming "care networks". There is no LHC in Corsica, forcing children and their families to leave the island for all care in the reference centre. The aim of this study was to describe the situation in Corsica and to consider this organisation. METHODS: This is a descriptive preliminary study based on databases from the National Childhood Cancer Registry, "RHeOP" network and a patient questionnaire. We included over a period of 10 years all children with onco-hematological disease who resided in Corsica. RESULTS: The incidence of pediatric cancers since 2005 ranged from 5 to 12 new cases per year. The hospital centre of Timone (Marseille) was the reference centre for 73% of patients, followed by Nice University Hospital for 14%. Almost all the parents interviewed (90%) were in favour of creating an LHC and all of them highlighted many difficulties that, according to them, could be improved by the presence of a LHC in Corsica (organisation of travel, delay and distance from home…). However, there currently appears to be a lack of training for medical and paramedical staff to provide quality second-line care. CONCLUSION: The rates of pediatric onco-hematological diseases in Corsica may warrant the creation of an LHC on the island. Additional cost studies on the feasibility of an LHC in Corsica are needed to optimise the care and quality of life of these children and their families.


Asunto(s)
Atención a la Salud/organización & administración , Accesibilidad a los Servicios de Salud/organización & administración , Neoplasias/epidemiología , Neoplasias/terapia , Adolescente , Edad de Inicio , Niño , Preescolar , Redes Comunitarias/organización & administración , Redes Comunitarias/normas , Redes Comunitarias/estadística & datos numéricos , Atención a la Salud/normas , Atención a la Salud/estadística & datos numéricos , Femenino , Francia/epidemiología , Accesibilidad a los Servicios de Salud/normas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Islas del Mediterráneo/epidemiología , Padres/psicología , Calidad de Vida , Derivación y Consulta/organización & administración , Derivación y Consulta/normas , Derivación y Consulta/estadística & datos numéricos , Sistema de Registros , Encuestas y Cuestionarios , Tiempo de Tratamiento/estadística & datos numéricos , Viaje
9.
Arch Pediatr ; 25(6): 359-364, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30041884

RESUMEN

BACKGROUND: Adult deprived patients consume more healthcare resources than others, particularly in terms of increased length of stay (LOS) and costs. Very few pediatric studies have focused on LOS, although the effect of deprivation could be greater in children due to the vulnerability of this population. Our objective was to compare LOS between deprived and nondeprived children hospitalized for acute infectious diseases in two university-affiliated pediatric departments located in a low-income area of northern Paris. METHODS: We performed a prospective observational multicenter study in two university-affiliated hospitals, Hôpital Robert-Debré and Hôpital Jean-Verdier. All the patients under 15 years of age admitted to the general pediatric department for pneumonia, bronchiolitis, gastroenteritis, or pyelonephritis between 20 October 2016 and 20 March 2017 were included. Deprivation was assessed with an individual questionnaire and score (EPICES). Endpoints included length of stay, costs, and readmission rates at 15 days in each quintile of deprivation. Multivariate regression assessed the association between deprivation and each endpoint. RESULTS: A total of 556 patients were included in the study and 540 were analyzed. Sixty percent were boys and the mean age was 9 months±18. Bronchiolitis was the most frequent diagnosis (67.8%). Fifty-six percent of patients were considered to be deprived based on the EPICES questionnaire. Mean LOS was 4.6±3.5 days and we found no significant difference in LOS between the different deprivation quintiles (P=0.83). Multivariate regression did not show an association between LOS and deprivation. CONCLUSION: There was no difference between deprived and nondeprived patients in terms of LOS. Deprivation may therefore impact hospitals in other ways such as admission rates. The impact of deprivation during hospitalization for chronic diseases should also be investigated.


Asunto(s)
Enfermedades Transmisibles/epidemiología , Tiempo de Internación/estadística & datos numéricos , Carencia Psicosocial , Adolescente , Niño , Preescolar , Femenino , Hospitalización/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Paris/epidemiología , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Encuestas y Cuestionarios
10.
Oxid Med Cell Longev ; 2018: 5895439, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29682159

RESUMEN

Few studies have focused on the protective role of selenium (Se) against skin aging and photoaging even though selenoproteins are essential for keratinocyte function and skin development. To the best of our knowledge, the impact of Se supplementation on skin cells from elderly and young donors has not been reported. Therefore, the main objective of our study was to evaluate the effects of Se supplementation on skin keratinocytes at baseline and after exposure to ultraviolet A (UVA) irradiation. Low doses of Se (30 nM) were very potently protective against UVA-induced cytotoxicity in young keratinocytes, whereas the protection efficiency of Se in old keratinocytes required higher concentrations (240 nM). Additionally, the DNA repair ability of the old keratinocytes drastically decreased compared with that of the young keratinocytes at baseline and after the UVA exposure. The Se supplementation significantly enhanced the DNA repair of 8-oxoguanine (8oxoG) only in the keratinocytes isolated from young donors. Therefore, aged keratinocytes have an increased vulnerability to oxidative DNA damage, and the Se needs in the elderly should be considered. Strengthening DNA repair activities with Se supplementation may represent a new strategy to combat aging and skin photoaging.


Asunto(s)
Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Selenio/uso terapéutico , Rayos Ultravioleta , Adulto , Factores de Edad , Anciano , Células Cultivadas , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Humanos , Queratinocitos/efectos de la radiación , Persona de Mediana Edad , Adulto Joven
11.
Arch Pediatr ; 25(1): 63-71, 2018 Jan.
Artículo en Francés | MEDLINE | ID: mdl-29254735

RESUMEN

Cerebral vasculopathy is a common and severe complication of sickle cell disease in children. The pathophysiology consists of progressive damage to the basal intracranial arteries and cerebral microcirculation, while chronic anemia worsens exposure to cerebral hypoxia. It results in stroke and subclinical or poorly symptomatic ischemic lesions. Many clinical, biological, and radiological risk factors have been identified. The prevention strategy through systematic transcranial Doppler screening of large-vessel vasculopathy has revolutionized the management of this disease and has greatly decreased the risk of developing stroke. MRI-MRA is a complementary diagnostic tool for anatomical analysis of parenchymal and vascular lesions, which is used for chronic disease monitoring or in the context of an acute neurological event. New exploration opportunities are offered by submandibular Doppler sonography and indirect evaluation methods of cerebral oxygenation and perfusion. If chronic blood transfusion therapy is used to prevent the occurrence and recurrence of cerebral complications of sickle cell disease, only allogeneic hematopoietic stem cell transplantation can safely and definitively stop the transfusion program. It should therefore be proposed early, before irreversible cerebral or vascular lesions occur. Hydroxycarbamide treatment has recently emerged as a potential substitute for chronic transfusions for the maintenance of transcranial Doppler velocities, but only after an initial treatment by transfusions and provided there is close follow-up. In the long run, cerebral vascular damage can cause progressive cognitive impairment and disability, even in children without radiologically identified lesions, indicating the importance of systematic and repeated neuropsychological testing.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Encéfalo/diagnóstico por imagen , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/etiología , Humanos , Imagen por Resonancia Magnética , Factores de Riesgo , Ultrasonografía Doppler Transcraneal
12.
Arch Pediatr ; 24(12): 1188-1196, 2017 Dec.
Artículo en Francés | MEDLINE | ID: mdl-29153908

RESUMEN

INTRODUCTION: Regionalization of perinatal care has been developed to improve the survival of preterm babies. The mortality rate is higher among very premature infants born outside level-3 maternity units. The objective of this study was to evaluate the preventability of these very premature births occurring outside recommendations within level-2B maternity units. The secondary objective was to describe the care of premature infants between 23 and 24 weeks. METHODS: This is a single-center retrospective qualitative study of the care delivery pathways. Thirty-one deliveries in which the fetus was alive between 23 and 30 weeks+6 days occurred in a level-2B maternity unit in Thionville, France, between 1 January 2013 and 31 December 2015. After oral presentation of the cases, a level 2-3 multidisciplinary committee of experts in Lorraine evaluated the preventability criteria and reasons, and divided the deliveries into three groups: (i) birth in level-2B institutions avoidable, (ii) inevitable with factors related to the mother or the organization of care, (iii) with no inevitable factors. RESULTS: Out of the 31 deliveries included, the committee classified six deliveries as preventable, 14 as inevitable with factors, and 11 as inevitable with no factors. The criteria for preventability of birth in a level-2B unit were underestimation of maternal and fetal risk, an erroneous initial estimate of term or preterm labor, and two births in the upper limits of the French recommendations for in utero transfer. Nineteen of the 35 premature infants before 31 weeks' gestation died, 16 children were transferred to a level-3 maternity ward, and 16 children were allowed to go home. CONCLUSION: Analysis of the obstetrical-pediatric care course by an expert committee determined the preventability of the average birth and prematurity in level-2B maternity units in Lorraine for a small but significant number of cases. The local regionalization of neonatal care could be improved by the application of this method of analysis to other maternity wards in the Lorraine network.


Asunto(s)
Atención Perinatal , Nacimiento Prematuro/prevención & control , Atención Prenatal , Adulto , Vías Clínicas , Femenino , Edad Gestacional , Maternidades , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Embarazo , Tercer Trimestre del Embarazo , Estudios Retrospectivos , Centros de Atención Secundaria
13.
J Vet Intern Med ; 31(4): 1202-1208, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28556535

RESUMEN

BACKGROUND: Knowledge of the mineral composition of the causative urolith is important to develop preventative strategies. Advances in analytic techniques have led to detection of urolith components not previously recognized. HYPOTHESIS/OBJECTIVES: The objectives of this study were to characterize uroliths in sheep and goats structurally and clinically. We hypothesized that amorphous magnesium calcium phosphate (AMCP) would be a naturally occurring urolith type in sheep and goats. ANIMALS: Forty-nine sheep and goats presenting for obstructive urolithiasis from June 15, 2014 through June 14, 2016 were reviewed along with the demographic data of all small ruminants admitted during that same period. METHODS: Medical records were reviewed for demographic and historical data, and 36 uroliths obtained from these cases during diagnostic or therapeutic procedures were analyzed by infrared spectroscopy to determine chemical composition. RESULTS: AMCP is a naturally occurring urolith type in obstructed male sheep and goats and was the most common urolith type in this study, where it occurred as a majority component with struvite (39% of uroliths) or as a pure component (11%). Pure struvite was found in 1 urolith (2%). Calcium carbonate was the second most frequent urolith with 31% of uroliths being pure calcium carbonate. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates that uroliths, which appear consistent with struvite, could actually be calcium-containing AMCP. Urolith analysis is critical in determining mineral content of uroliths to guide dietary recommendations for prevention.


Asunto(s)
Enfermedades de las Cabras/metabolismo , Enfermedades de las Ovejas/metabolismo , Cálculos Urinarios/veterinaria , Urolitiasis/veterinaria , Animales , Fosfatos de Calcio/análisis , Enfermedades de las Cabras/diagnóstico por imagen , Cabras , Magnesio/análisis , Masculino , Radiografía/veterinaria , Ovinos , Enfermedades de las Ovejas/diagnóstico por imagen , Cálculos Urinarios/química , Cálculos Urinarios/diagnóstico por imagen , Urolitiasis/diagnóstico por imagen , Urolitiasis/metabolismo
14.
Methods Enzymol ; 583: 279-307, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28063495

RESUMEN

Structural studies on lipases by X-ray crystallography have revealed conformational changes occurring in the presence of surfactants/inhibitors and the pivotal role played by a molecular "lid" of variable size and structure depending on the enzyme. Besides controlling the access to the enzyme active site, the lid is involved in lipase activation, formation of the interfacial recognition site (IRS), and substrate docking within the active site. The combined use of surfactants and inhibitors has been critical for a better understanding of lipase structure-function relationships. An overview of crystal structures of lipases in complex with surfactants and inhibitors reveals common structural features and shows how surfactants monomers interact with the lid in its open conformation. The location of surfactants, inhibitors, and hydrophobic residues exposed upon lid opening provides insights into the IRS of lipases. The mechanism by which surfactants promote the lid opening can be further investigated in solution by site-directed spin labeling of lipase coupled to electron paramagnetic resonance spectroscopy. These experimental approaches are illustrated here by results obtained with mammalian digestive lipases, fungal lipases, and cutinases.


Asunto(s)
Hidrolasas de Éster Carboxílico/química , Inhibidores Enzimáticos/química , Proteínas Fúngicas/química , Lipasa/química , Tensoactivos/química , Animales , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Dominio Catalítico , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Proteínas Fúngicas/antagonistas & inhibidores , Fusarium/química , Fusarium/enzimología , Interacciones Hidrofóbicas e Hidrofílicas , Lipasa/antagonistas & inhibidores , Mamíferos , Modelos Moleculares , Unión Proteica , Estructura Secundaria de Proteína , Especificidad por Sustrato
15.
Br J Dermatol ; 175(4): 776-81, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27037896

RESUMEN

BACKGROUND: Anti-p200 pemphigoid is a rare autoimmune blistering disease (AIBD) of the dermoepidermal junction, characterized by autoantibodies to laminin γ1. The clinical course of anti-p200 pemphigoid in patients remains poorly investigated. OBJECTIVES: We aimed to describe the clinical and immunological features and the course of a series of patients with anti-p200 pemphigoid. METHODS: We conducted a retrospective study by immunoblotting detection of sera on 200-kDa dermal protein extracts from the register of the French reference centre for AIBD. We recorded the clinical and immunological features and the course of patients. RESULTS: A total of 14 patients with a mean age 81·6 ± 6·5 years were included. Only one patient had an associated neurological condition and one had psoriasis. Twelve patients had atypical clinical presentation, including eczematous, urticarial, prurigo-like, dyshydrosis-like and rosette-like skin lesions. Eight patients (57%) had mucosal involvement. Immunoblot analysis of sera on dermal and epidermal extracts showed a 200-kDa band in 14 and 10 cases, respectively. All eight of the sera tested by enzyme-linked immunosorbent assay detected recombinant human laminin γ1. Disease control was obtained in six of nine patients treated with topical corticosteroids, and four of five patients who received systemic treatment. Seven patients relapsed (50%) and five patients (36%) died during the median follow-up time of 12·6 months. At the end of the study, only one of the nine living patients was in complete remission off therapy. CONCLUSIONS: Many patients with anti-p200 pemphigoid had heterogeneous clinical presentation and a more severe prognosis than previously suspected.


Asunto(s)
Laminina/inmunología , Penfigoide Ampolloso/patología , Anciano , Anciano de 80 o más Años , Fármacos Dermatológicos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/inmunología , Pronóstico , Recurrencia , Estudios Retrospectivos
16.
Ann Dermatol Venereol ; 142(11): 646-52, 2015 Nov.
Artículo en Francés | MEDLINE | ID: mdl-26383619

RESUMEN

BACKGROUND: Clinical differential diagnosis between incipient nodular basal carcinoma (NBC) and sebaceous hyperplasia (SH) of the face is difficult in some cases. A comparative histological analysis of these two entities led us to the hypothesis that 20MHz high-resolution ultrasonography (HRUS) may enable differentiation between NBC and SH. PATIENTS AND METHODS: Seventy-seven facial tumours requiring histological confirmation to distinguish between NBC and SH were scanned using HRUS before excision. No other imaging technique was used. The ultrasound scans were submitted to two blinded reviewers who were asked to classify the ultrasound pictures of the tumours as either hypoechoic or isoechoic/hyperechoic. Hypoechogenicity was defined as a diagnostic criterion for NBC. RESULTS: Reviewer response reproducibility for 2 images of the same tumour was 90%. Both reviewers agreed regarding the echogenicity classification of an image in 87.4% of cases. The sensitivity of the procedure was 90.9% for detection of NBC and 89.4% for detection of malignant lesions. Specificity was 69.6% for detection of basal cell carcinomas and 78.8% for detection of malignant lesions. DISCUSSION: HRUS is a non-invasive examination technique with excellent sensitivity for the detection of NBC in differential diagnosis with SH. Hypoechogenicity is not specific to NBC. The sensitivity of HRUS in our study suffered as a result of ultrasonography difficulties regarding unexpected differential diagnoses of NBC as well as tumour localisation in seborrhoeic areas.


Asunto(s)
Carcinoma/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Diagnóstico Diferencial , Cara/patología , Femenino , Humanos , Hiperplasia/diagnóstico por imagen , Aumento de la Imagen/métodos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias Cutáneas/patología , Ultrasonografía
17.
Allergy ; 70(7): 795-804, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25846209

RESUMEN

BACKGROUND: Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch pollen (BP)-allergic patients. METHODS: Following expression in Escherichia coli and purification, rBet v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed in a multicentre, double-blind, placebo-controlled study conducted in 483 patients with BP-induced rhinoconjunctivitis. RESULTS: In-depth characterization confirmed the intact product structure and high purity of GMP-grade rBet v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of rBet v 1 did not induce the production of any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v 1 tablets were well tolerated by patients, consistent with the known safety profile of SLIT. The average adjusted symptom scores were significantly decreased relative to placebo in patients receiving once daily for 5 months rBet v 1 tablets, with a mean difference of 17.0-17.7% relative to the group treated with placebo (P < 0.025), without any influence of the dose in the range (12.5-50 µg) tested. CONCLUSION: Recombinant Bet v 1 has been produced as a well-characterized pharmaceutical-grade biological drug. Sublingual administration of rBet v 1 tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.


Asunto(s)
Alérgenos/inmunología , Antígenos de Plantas/inmunología , Polen/inmunología , Proteínas Recombinantes , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/terapia , Inmunoterapia Sublingual , Adolescente , Adulto , Alérgenos/química , Alérgenos/genética , Alérgenos/aislamiento & purificación , Antígenos de Plantas/química , Antígenos de Plantas/genética , Antígenos de Plantas/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , Conformación Proteica , Pruebas de Función Respiratoria , Rinitis Alérgica Estacional/diagnóstico , Factores de Riesgo , Inmunoterapia Sublingual/efectos adversos , Adulto Joven
18.
J Eur Acad Dermatol Venereol ; 29(4): 801-4, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24628777

RESUMEN

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) may relapse following introduction of drugs structurally unrelated to the initial culprit drug. OBJECTIVE: To assess the frequency and characteristics of recurrent drug eruptions in patients with history of DRESS. METHODS: Patients who had developed adverse cutaneous reaction after DRESS occurrence were recruited from the regional database of Upper Normandy in France. Rate of recurrences were compared with patients with Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson syndrome (SJS) patients during the same time frame. RESULTS: Of the 60 cases of DRESS collected, 15 (25%) with recurrences were retained for analysis. Seven patients had a single recurrence, whereas eight patients had several relapses. In the patients with pre-existing DRESS, recurrences were incomplete, corresponding to cutaneous rash in 13 cases and associated with eosinophilia in seven cases. Internal organ involvement was observed in two cases. In contrast, a single recurrence was found out of 61 patients with TEN/SJS. CONCLUSION: Incomplete recurrences with structurally unrelated culprit drugs are a frequent phenomenon in DRESS patients.


Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/epidemiología , Síndrome de Hipersensibilidad a Medicamentos/etiología , Francia/epidemiología , Humanos , Recurrencia , Estudios Retrospectivos , Síndrome de Stevens-Johnson/epidemiología
19.
J Comp Pathol ; 150(1): 35-46, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24016781

RESUMEN

Epidermal tight junctions (TJs) have been well characterized in human medicine. Abnormality of these structures is involved in skin diseases such as atopic dermatitis. There is little information about the expression and distribution of TJ proteins in the canine skin. The aim of this study was to develop an optimal immunohistochemical method for assessment of the expression of TJ proteins in the skin of healthy dogs. Formalin-fixed and paraffin wax-embedded skin biopsy samples from healthy human and canine patients were used. Canine skin samples were from the inguinal region and the nasal planum. Immunohistochemistry was used to study the expression of zonula occludens-1 (ZO-1), occludin and claudin-1, -4 and -7. Heat-induced antigen retrieval with EDTA (pH 9.0) yielded the best labelling of TJ proteins. ZO-1 and occludin were expressed in the cytoplasm and along the keratinocyte membrane, while claudin-1 and -4 were mainly membrane in distribution. ZO-1, occludin and claudin-1 were detected in all epidermal layers with the exception of the stratum corneum, while claudin-4 expression was restricted to the stratum granulosum. Expression of claudin-7 was difficult to evaluate. There was no difference in labelling pattern between inguinal and nasal planum skin.


Asunto(s)
Claudinas/metabolismo , Epidermis/metabolismo , Inmunohistoquímica/métodos , Ocludina/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Animales , Perros , Femenino , Humanos
20.
Ann Dermatol Venereol ; 140(12): 784-7, 2013 Dec.
Artículo en Francés | MEDLINE | ID: mdl-24315224

RESUMEN

BACKGROUND: Anti-p200 pemphigoid is a recently described autoimmune subepidermal bullous dermatosis characterized by its target antigen and the associated anatomoclinical picture. The treatment is not as yet well defined. PATIENT AND METHODS: A 73-year-old man consulted for a pruritic bullous eruption with buccal involvement. Direct immunofluorescence revealed linear deposits of IgG and C3 at the dermal-epidermal junction. Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. A diagnosis of bullous pemphigoid was suspected. After an unfavourable clinical outcome under clobetasol and then prednisolone and methotrexate, other immunological tests were performed. Indirect immunofluorescence on NaCl-cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting showed antibodies directed against a 200-kDa antigen on a dermal extract. A diagnosis of anti-p200 pemphigoid was made. The patient was treated with dapsone combined with prednisolone. Seventy-two hours later, treatment was stopped due to hepatic cytolysis related to immunoallergic hepatitis. Treatment with mycophenolate mofetil was then initiated and resulted in complete remission, which persisted at seven months. DISCUSSION: The diagnosis of anti-p200 pemphigoid was made on the basis of a set of clinical and immunological factors. Anti-p200 pemphigoid differs from standard bullous pemphigoid in terms of more frequent cephalic, acral and mucous membrane involvement, as well as a greater degree of miliary scarring. There was no eosinophilia. Elisa screening for anti-BP180 and anti-BP230 antibodies was negative. Immunoblotting showed antibodies directed against a 200kDa protein on dermal extract. The treatment is not well defined, even if dapsone appears to be the most effective therapy. To our knowledge, our patient is the first to be successfully treated with mycophenolate mofetil. CONCLUSION: Treatment of anti-p200 pemphigoid is difficult. In our case, treatment by mycophenolate mofetil was effective and could offer an alternative to dapsone.


Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Inmunoglobulina G/inmunología , Inmunosupresores/uso terapéutico , Laminina/inmunología , Ácido Micofenólico/análogos & derivados , Penfigoide Ampolloso/tratamiento farmacológico , Anciano , Autoanticuerpos/análisis , Clobetasol/uso terapéutico , Dapsona/uso terapéutico , Resistencia a Medicamentos , Humanos , Inmunoglobulina G/análisis , Masculino , Metotrexato/uso terapéutico , Ácido Micofenólico/uso terapéutico , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Penfigoide Benigno de la Membrana Mucosa/inmunología , Penfigoide Ampolloso/inmunología , Prednisolona/uso terapéutico , Inducción de Remisión , Piel/inmunología
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