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1.
J Environ Manage ; 333: 117447, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36764179

RESUMEN

BACKGROUND: Sustainability concerns as well as recent increases in fertilizer prices exacerbates the need to optimise the use of biowastes as fertilizers. For this reason, we investigated how different pretreatments affect the P dynamics when biofertilizers are placed in the soil. METHODS: Sewage sludge (SS), sewage sludge ash (SS-ash), meat and bone meal (MBM), and the solid fraction of biogas digestate (BGF) were pretreated with H2SO4, NaOH, and Ca(OH)2 and incubated for 2 and 12 days, respectively, in a one-dimensional reaction system for detailed studies of the interactions in the biomaterial-soil interface and the soil adjacent to the placement zone. RESULTS: Our results showed that acidification and treatment with NaOH increased the P solubility of the biomaterials. The P loss from the biomaterial layer to the soil was correlated with water-extractable P in the biomaterials (0.659) and water-extractable P in the soil (0.809). Acidification significantly increased the total amount of P depleted from the biomaterial to the soil whereas NaOH pre-treatment did not. However, for NaOH-treated SS and SS-ash, the apparent recoveries were significantly higher compared to the acidification due to a decrease in soil P sorption capacity as the soil pH increased due to residual alkalinity in the biomaterials. CONCLUSIONS: Acidification showed promising results by increasing the P solubility of all the biomaterials, and the alkalinization of SS and SS-ash with NaOH by increasing the apparent recovery in the soil. However, further studies are needed to assess the effects of these treatments on plant growth and P uptake.


Asunto(s)
Aguas del Alcantarillado , Suelo , Solubilidad , Ceniza del Carbón , Hidróxido de Sodio , Concentración de Iones de Hidrógeno , Fertilizantes/análisis
2.
Lupus ; 26(4): 396-402, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27587460

RESUMEN

Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.


Asunto(s)
Lupus Eritematoso Sistémico/psicología , Adolescente , Adulto , Anciano , Canadá , Femenino , Humanos , Estudios Longitudinales , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del Tratamiento , Estados Unidos , Adulto Joven
3.
Eur J Neurol ; 24(5): 694-702, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28236340

RESUMEN

BACKGROUND AND PURPOSE: Although there is growing and convincing evidence that socially deprived patients are at higher risk of stroke and worse outcomes, it remains controversial whether or not they suffer more severe stroke. This study aimed to evaluate the influence of social deprivation on initial clinical severity in patients with stroke. METHODS: A total of 1536 consecutive patients with an acute first-ever stroke (both ischaemic stroke and intracerebral hemorrhage) were prospectively enrolled from six French study centers. Stroke severity on admission was measured by the National Institutes of Health Stroke Scale score. Social deprivation was assessed at the individual level by the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé (EPICES) score, a validated multidimensional questionnaire, and several additional single socioeconomic indicators. Polytomous logistic regression analyses were performed to evaluate the association between social deprivation and stroke severity. RESULTS: In univariate analysis, the EPICES score (P = 0.039) and level of education (P = 0.018) were the only two socioeconomic variables associated with stroke severity. Multivariate analysis of the association between EPICES and National Institutes of Health Stroke Scale scores showed that more deprived patients presented a significantly higher risk of both mild and moderate/severe stroke (odds ratio for mild versus minor stroke, 1.39; 95% confidence interval, 1.06-1.84; odds ratio for moderate/severe versus minor stroke, 1.44; 95% confidence interval, 1.09-1.92). A non-significant trend towards a higher risk of both mild and moderate/severe stroke in less educated patients was observed. CONCLUSIONS: Social deprivation was associated with a more severe clinical presentation in patients with stroke. These findings may contribute to the worse outcome after stroke in deprived patients, and underline the need for strategies to reduce social inequalities for stroke.


Asunto(s)
Carencia Psicosocial , Accidente Cerebrovascular/etnología , Accidente Cerebrovascular/fisiopatología , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Hemorragia Cerebral/etiología , Estudios de Cohortes , Femenino , Francia/etnología , Guyana Francesa/etnología , Humanos , Masculino , Persona de Mediana Edad , Indias Occidentales/etnología
4.
Opt Express ; 24(6): 6265-70, 2016 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-27136819

RESUMEN

We propose a procedure for characterizing fabrication deviations within a chip and among different chips in a wafer in silicon photonics technology. In particular, independent measurements of SOI thickness and waveguide width deviations can be mapped through the wafer, allowing a precise and non-destructive characterization of how these variations are distributed along the surface of the wafer. These deviations are critical for most wavelength-dependent integrated devices, like microring resonators, filters, etc. We also show that the technique allows for the characterization of proximity effects.

5.
Rev Neurol (Paris) ; 170(6-7): 432-9, 2014.
Artículo en Francés | MEDLINE | ID: mdl-24856285

RESUMEN

Multiple sclerosis (MS) is one of the 30 chronic conditions specifically listed by the French healthcare system as a long-term disease (affections de longue durée [ALD]) for which the main health insurance fund (Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]) provides full (100%) coverage of healthcare costs. The CNAMTS insures 87% of the French population (52,359,912 of the 60,028,292 inhabitants). The objectives of this study were to evaluate the direct and indirect medical costs of MS among the entire population insured by the CNAMTS in France in 2004. The CNAMTS provided us with access to the ALD database of patients with MS that contains different MS-related expenditures made in 2004. We calculated the overall direct and indirect cost of MS and the cost per patient and per item of expenditure. In 2004, 49,413 patients were registered on the ALD list for MS. Direct cost for MS patients was 469,719,967 €. The direct cost per patient and per year was 9,506 € with variations between regions (French administrative divisions) ranging from 10,800 € in northeastern France (Champagne-Ardenne) to 8,217 € in western France (Pays de la Loire). The different items of expenditure were treatments (44.5%), hospitalization (27.9%), nursing care (5.8%), physiotherapy (5.7%), transport (4%), biology (1.1%), and other (1.5%). During the course of the disease, the overall cost of MS increased slowly during the first 15 years (from 8,000 to 11,000 €), but dramatically the last year of life (23,410 €). The costs of immunomodulator treatments were higher during the first six years after registration on the ALD list. Conversely, physiotherapy costs increased linearly with time during the course of MS. Indirect costs were an estimated 116 million euros in 2004. A disability pension (8,918 € per patient) was perceived by 9,430 patients (19.1%) and a daily allowance (3,317 € per patient) by 9,894 patients (20%). In France, MS has an important economic impact, comparable to human immunodeficiency virus infection.


Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Esclerosis Múltiple/economía , Programas Nacionales de Salud/economía , Adulto , Técnicas de Laboratorio Clínico/economía , Costos de los Medicamentos , Economía de la Enfermería , Equipos y Suministros/economía , Femenino , Francia/epidemiología , Gastos en Salud , Hospitalización/economía , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Pensiones/estadística & datos numéricos , Modalidades de Fisioterapia/economía , Sistema de Registros , Transportes/economía
6.
Clin Infect Dis ; 56(9): 1223-31, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23362291

RESUMEN

BACKGROUND: Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. METHODS: We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. RESULTS: Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P = .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were <10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and then continued increasing to 52.3% and almost 70% at 28 and 39 GA weeks, respectively. Because of a significant reduction in risk of clinical signs of congenital toxoplasmosis in infected children born from mothers diagnosed after 1995 when polymerase chain reaction testing on amniotic fluid was initiated (87/794 vs 46/1150; P = .012), probabilities of clinical signs at 3 years were estimated based on 1015 maternal infections diagnosed after 1995 including 207 infected children, with symptoms in 46 (22.2%). CONCLUSIONS: These analyses demonstrated that introduction of monthly prenatal screening and improvement in antenatal diagnosis were associated with a significant reduction in the rate of congenital infection and a better outcome at 3 years of age in infected children. Our updated estimates will improve individual management and counseling in areas where genotype II Toxoplasma is predominant.


Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Diagnóstico Prenatal/métodos , Toxoplasmosis Congénita/prevención & control , Toxoplasmosis/diagnóstico , Adolescente , Adulto , Preescolar , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Embarazo , Adulto Joven
7.
Strahlenther Onkol ; 189(11): 932-7, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24013528

RESUMEN

PURPOSE: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. PATIENTS AND METHODS: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 × 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. RESULTS: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). CONCLUSION: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.


Asunto(s)
Adenoma/diagnóstico , Adenoma/cirugía , Fraccionamiento de la Dosis de Radiación , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/cirugía , Radiocirugia/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Resultado del Tratamiento , Adulto Joven
8.
J Dairy Sci ; 96(11): 6944-6954, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24054302

RESUMEN

Serum amyloid A3 (SAA3) is the predominant SAA isoform secreted by mammary epithelial cells in dairy cows; it is also expressed in bovine adipose tissue (AT). The adipokine SAA3 is linked to obesity and insulin resistance of AT and the respective inflammatory response, at least in mice. Dietary treatment with conjugated linoleic acids (CLA) reportedly also affects insulin sensitivity and inflammatory status in monogastrics. Both SAA3 and CLA thus seem to alter similar functions. Based on changes in insulin sensitivity and the inflammatory status throughout lactation, we hypothesized that the mRNA abundance of SAA3 in various tissues might be regulated as well and that CLA could be a modulator of SAA3 mRNA expression. In 2 trials, 21 pluriparous and 25 primiparous Holstein cows were fed 100g/d of a CLA or a control fat supplement from d 1 to 182 or 105 postpartum, respectively. Biopsies from liver and subcutaneous (s.c.) AT from pluriparous cows and samples from 3 different visceral AT and 3 s.c. AT, muscle, mammary gland, and liver tissue from slaughtered primiparous cows were obtained. In an adipocyte cell culture system, cell samples were collected during differentiation of bovine preadipocytes at d 0, 2, 6, 8, 10, 12, and 13 relative to the onset of differentiation. The SAA3 mRNA abundance in tissues and in differentiating bovine preadipocytes was measured by real-time PCR. The presence of the SAA protein was confirmed by Western blotting. Treatment with CLA yielded only few and inconsistent effects on SAA3 mRNA abundance. In both trials, SAA3 mRNA peaked at d 1 postpartum in all tissues except in mesenteric AT, in which the change was not significant. The highest SAA3 mRNA expression was observed in the mammary gland, followed by omental AT. The SAA protein was present in the visceral and s.c. AT depots investigated. Adipocytes as one source of SAA3 were confirmed by the SAA3 mRNA profile in differentiating adipocytes. The longitudinal changes observed point to SAA3 being involved in the inflammatory situation around parturition.


Asunto(s)
Bovinos/fisiología , Lactancia/fisiología , Ácidos Linoleicos Conjugados/metabolismo , Metabolismo de los Lípidos , Proteína Amiloide A Sérica/genética , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Inflamación , Resistencia a la Insulina , Grasa Intraabdominal/metabolismo , Hígado/metabolismo , Estudios Longitudinales , Paridad , Parto , Periodo Posparto , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína Amiloide A Sérica/metabolismo
9.
Birth Defects Res ; 115(12): 1109-1119, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37243321

RESUMEN

BACKGROUND: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies. METHODS: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123-246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM). RESULTS: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123-246). CONCLUSION: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data).


Asunto(s)
Feto , Atención Prenatal , Ratas , Animales , Humanos , Embarazo , Femenino , Ratas Sprague-Dawley , Feto/anomalías , Europa (Continente)
10.
Clin Genet ; 81(5): 433-42, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21564093

RESUMEN

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.


Asunto(s)
Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Mutación , Adolescente , Adulto , Niño , Fibrilina-1 , Fibrilinas , Estudios de Seguimiento , Humanos , Masculino , Adulto Joven
11.
Mult Scler ; 18(8): 1108-15, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22298591

RESUMEN

BACKGROUND: In France, the incidence of multiple sclerosis (MS) is not well known, and MS is one of the 30 long-term illnesses for which patients are covered for 100% of their health care costs. OBJECTIVE: To estimate the incidence of MS in France and its geographic variations. METHODS: We estimated the national rate for notification of MS to the main French health insurance system, and its confidence interval (CI), between November 2000 and October 2007, which covers 87% of the population. We analysed geographic variations using a Bayesian approach. RESULTS: Between November 2000 and October 2007, among a covered population of 52,449,871, some 28,682 individuals were registered as having MS. After age standardization according to the European population, the notification rate for MS was 6.8 per 100,000 (6.7-6.9), 9.8 (9.7-10.0) in women and 3.7 (3.6-3.8) in men. When the under-notification rate (11.5% and 29%) was taken into account, the notification rate per 100,000 inhabitants was estimated between 7.6 and 8.8. The notification rate was higher in north-eastern France, and lower on the Atlantic coast and in the Alps as well as on both sides of the Rhône River. CONCLUSIONS: This study, conducted on a representative French population, provides for the first time national estimates of MS incidence between November 2000 and October 2007.


Asunto(s)
Esclerosis Múltiple/epidemiología , Adolescente , Adulto , Anciano , Teorema de Bayes , Niño , Preescolar , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Sistema de Registros , Características de la Residencia , Factores de Tiempo , Adulto Joven
12.
World J Surg ; 35(7): 1621-5, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21562868

RESUMEN

BACKGROUND: The frequency, characteristics, and effect on outcome of abdominal and pelvic injuries (API) caused by road traffic accidents are not well known. We studied them in a well-defined geographical area in France. METHODS: The medical data of all hospitalized victims of road traffic accidents that occurred over a 3-year period were recorded. Injuries were coded according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Continuous and qualitative variables were described by means and standard deviations or medians and percentages, respectively. Proportions and means were compared using the χ2 and Student tests, respectively. RESULTS: Of 6,977 victims of road traffic accidents, 2,009 were hospitalized (mean ISS=7.9). API were present in 9.3% (n=186) of all hospitalized victims and in 32.2% (n=82) of the most severely injured (ISS≥16, n=255) hospitalized victims. The most frequently seriously injured abdominopelvic organs (AIS≥3) were the spleen, the retroperitoneal organs, and the liver. The mean ISS and the mortality rate were significantly higher for victims with API than those without API (17.5 vs. 6.9, P<0.001; 9.7% vs. 1.9%, P<0.001). In multivariate analysis, the presence of severe API increased the mortality rate by a factor of 2.5. CONCLUSIONS: In this study, API were present in one third of the most severely injured victims of road traffic accidents and were a significant factor of gravity and mortality. This study, conducted in France where there is no National Trauma Registry, underlined the need for establishing such registry.


Asunto(s)
Traumatismos Abdominales/epidemiología , Accidentes de Tránsito/estadística & datos numéricos , Pelvis/lesiones , Adulto , Femenino , Francia/epidemiología , Humanos , Masculino
13.
J Med Genet ; 46(11): 752-8, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19880712

RESUMEN

BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Asesoramiento Genético , Heterocigoto , Tamizaje Neonatal , Penetrancia , Estudios Transversales , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Humanos , Recién Nacido , Estimación de Kaplan-Meier , Mutación , Fenotipo
14.
Cytogenet Genome Res ; 126(1-2): 202-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20016171

RESUMEN

Spermatozoa from 2 dairy AI (artificial insemination) bulls (A and B), identified by their abnormal spermiogram with cells depicting frequent macrocephaly, double tails and nuclear vacuoles, were case-investigated and compared to normal spermatozoa from a control AI sire (C). Head sizes were measured and morphological abnormalities scored using brightfield and differential interference contrast microscopy. The degree of sperm maturation and of resistance to acid-induced DNA denaturation in situ were determined after uploading of acridine orange using flow cytometry of 5,000 cells/sample. Nuclear fragmentation, i.e. the ratio of red to total (red + green) fluorescence, reached 7.1% and 31% in bulls A and B, compared to 2% in bull C. The proportion of immature spermatozoa, i.e. those with incomplete histone-protamine exchange and depicting higher green fluorescence compared to the main population of the control bull, reached 9.54% in A and 7.75% in B, compared to only 0.47% in the control. In the second part of this study the previously unknown chromosomal constitution of large-headed spermatozoa of bull A was investigated by fluorescence in situ hybridization using an X-Y painting probe set. The 7.5% XY-bearing cells and the presence of diploid spermatozoa detected by flow cytometry indicate a meiotic arrest in the first division in bull A, becoming the first proven case of association of macrocephaly and M1 diploidy. The diverse approaches used for the investigation of spermatozoal DNA provide insights into the etiology of macrocephaly.


Asunto(s)
Encéfalo/citología , Cromatina/metabolismo , Diploidia , Espermatozoides/citología , Animales , Encéfalo/metabolismo , Bovinos , Hibridación Fluorescente in Situ , Masculino , Espermatozoides/metabolismo
15.
Am J Med Genet A ; 149A(5): 854-60, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19353630

RESUMEN

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.


Asunto(s)
Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Adulto , Estudios de Cohortes , Desplazamiento del Cristalino/diagnóstico , Desplazamiento del Cristalino/genética , Desplazamiento del Cristalino/patología , Fibrilina-1 , Fibrilinas , Humanos , Masculino , Síndrome de Marfan/clasificación , Síndrome de Marfan/patología , Mutación , Fenotipo
16.
J Med Genet ; 45(6): 384-90, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18310266

RESUMEN

BACKGROUND: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening. METHODS: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling "clinical" criteria. In patients with unfulfilled "clinical" criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the "clinical" international criteria. RESULTS: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled "clinical criteria" when compared to the Marfan syndrome group (44% vs 73% at 40 years, p<0.001), but the lifelong risk for ascending aortic dissection or surgery was not significantly different in both groups. CONCLUSIONS: Because of its implications for aortic follow-up, FBN1 molecular analysis is recommended in newly suspected MFS when two systems are involved with at least one major system affected. This is of utmost importance in patients without aortic dilatation and in children.


Asunto(s)
Cooperación Internacional , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Adolescente , Adulto , Anciano , Aorta/patología , Niño , Femenino , Fibrilina-1 , Fibrilinas , Humanos , Masculino , Mutación/genética
17.
Cytogenet Genome Res ; 121(3-4): 245-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18758165

RESUMEN

An AI Ayrshire bull was subjected to cytogenetic examination due to lowered fertility. Preliminary Giemsa staining revealed a normal chromosome complement (60,XY) and G-banding did not allow us to draw a clear conclusion concerning an occurrence of chromosome rearrangement. Testicles were collected at slaughter and synaptonemal complex (SC) analysis revealed a large cross-shaped tetravalent configuration in pachytene spreads. No association between the tetravalent and XY bivalent was observed. Chromosome painting, with the use of bovine whole chromosome painting probes, conjugated with DAPI staining, facilitated a detailed description of the translocation rcp(2;4)(q45;q34). This study shows that post mortem analysis of synaptonemal complexes is a simple and useful tool for the preliminary detection of reciprocal translocation carriers.


Asunto(s)
Pintura Cromosómica , Complejo Sinaptonémico/metabolismo , Translocación Genética , Animales , Bovinos , Masculino , Microscopía Electrónica , Complejo Sinaptonémico/ultraestructura
18.
Theriogenology ; 70(7): 1129-35, 2008 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-18640712

RESUMEN

In 1996-2005, ejaculates of 2048 boars were collected. All boars were intended for use in artificial insemination or natural breeding and had two descended testes. Azoospermia was present in 16 of the 1097 Yorkshire boars (1.5%) and in 2 of the 951 Landrace boars (0.2%). The two most frequent diagnoses of azoospermia were arrested spermatogenesis at the pachytene spermatocyte stage (n=8) and segmental aplasia of the Wolffian ducts (n=7). Morphometric evaluations of testicular tissues of azoospermic boars were performed using an image analyzer. The morphometric evaluations revealed decreased portions and diameter of seminiferous tubule in tissue slides from the studied azoospermic boars compared with normal boars. The use of an image analyzer for morphometric evaluations of testicular tissues proved to be a good tool to characterize findings in testicular slides of azoospermic boars.


Asunto(s)
Azoospermia/veterinaria , Enfermedades de los Porcinos/patología , Porcinos/genética , Porcinos/fisiología , Testículo/patología , Animales , Masculino
19.
Reprod Domest Anim ; 43(6): 690-5, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18397189

RESUMEN

In the period 1996-2006 two specific sperm defects, the knobbed acrosome (KA) defect and the immotile short-tail sperm (ISTS) defect, showed a strong negative association with fertility in Finnish breeding boars. In this study, we examined the incidence of these two sperm defects in two pig breeds, their effects on fertility and their associations with sperm morphology and testicular histology. Semen samples from 2048 (1097 Yorkshire, 951 Landrace) boars were collected. None of the Landrace boars revealed either the KA defect or the ISTS defect. Of the Yorkshire boars, 0.8% were afflicted with the KA defect and 7.6% with the ISTS defect. Boars diagnosed with the ISTS defect produced no litters. Fertility data were available from two artificially inseminated (AI) boars and six farm breeding boars affected with the KA defect. Breeding boars with 45-81% knobbed spermatozoa (n = 6) did not produce any litters out of 71 sows bred. AI boars with 25-30% knobbed spermatozoa had a poor non-return rate (on average 47% compared with 85% for normal control boars) and produced small litters, on average 2.5 piglets less than other boars of the same breed. Morphometry of testicular tissue and distribution of different cells in the seminiferous tubules were examined in nine boars. Boars with the KA defect had a smaller diameter of the seminiferous tubules (p < 0.05) and a lower number of Sertoli cells (p < 0.05) than controls. ISTS boars, in turn, had a significantly lower number of elongated spermatids (p < 0.05), and they also produced on average only 12% of the spermatozoa of normal boars. The ISTS defect is a manifestation of an autosomal recessive disease caused by an insertion in the KPL2 gene in porcine chromosome 16. Although we tried to map the KA defect, its aetiology remains unclear.


Asunto(s)
Infertilidad Masculina/veterinaria , Reproducción/fisiología , Espermatozoides/anomalías , Enfermedades de los Porcinos/genética , Porcinos/fisiología , Acrosoma/patología , Animales , Cruzamiento , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Infertilidad Masculina/fisiopatología , Tamaño de la Camada , Masculino , Oligospermia/veterinaria , Reproducción/genética , Túbulos Seminíferos/anatomía & histología , Túbulos Seminíferos/patología , Motilidad Espermática/genética , Motilidad Espermática/fisiología , Cola del Espermatozoide/patología , Porcinos/genética , Enfermedades de los Porcinos/patología , Enfermedades de los Porcinos/fisiopatología , Testículo/anatomía & histología , Testículo/patología
20.
Circulation ; 111(15): 1938-45, 2005 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-15837947

RESUMEN

BACKGROUND: Adipose tissue is a prominent source of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of plasminogen activation. Increased PAI-1 expression acts as a cardiovascular risk factor, and plasma levels of PAI-1 strongly correlate with body mass index (BMI). Elevated serum levels of interleukin-6 (IL-6), an inflammatory cytokine and a member of the glycoprotein 130 (gp130) ligand family, are found in obese patients and might indicate low-grade systemic inflammation. Another gp130 ligand, oncostatin M (OSM), upregulates PAI-1 in cardiac myocytes, astrocytes, and endothelial cells. We used tissue explants and primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether IL-6 and OSM affect PAI-1 expression in fat. METHODS AND RESULTS: Human subcutaneous and visceral adipose tissue responded to treatment with IL-6 and OSM with a significant increase in PAI-1 production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocyte differentiation was induced by hormone supplementation. All cell types expressed receptors for IL-6 and OSM and produced up to 12-fold increased levels of PAI-1 protein and up to 9-fold increased levels of PAI-1 mRNA on stimulation with IL-6 and OSM. AG-490, a janus kinase/signal transducer and activator of transcription inhibitor, abolished the OSM-dependent PAI-1 induction almost completely. CONCLUSIONS: We have for the first time established a link between the gp130 ligands, the proinflammatory mediators IL-6 and OSM, and the expression of PAI-1 in human adipose tissue. Thus, we speculate that IL-6 and OSM, by upregulating PAI-1 in adipose tissue, can contribute to the increased cardiovascular risk of obese patients.


Asunto(s)
Tejido Adiposo/metabolismo , Inflamación/inmunología , Interleucina-6/farmacología , Péptidos/farmacología , Inhibidor 1 de Activador Plasminogénico/genética , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Adulto , Anciano , Antígenos CD , Células Cultivadas , Receptor gp130 de Citocinas , Inhibidores Enzimáticos/farmacología , Humanos , Ligandos , Glicoproteínas de Membrana , Persona de Mediana Edad , Oncostatina M , Inhibidor 1 de Activador Plasminogénico/análisis , ARN Mensajero/análisis , Receptores de Citocinas/análisis , Receptores de Interleucina-6/análisis , Receptores de Oncostatina M , Tirfostinos/farmacología , Regulación hacia Arriba/efectos de los fármacos
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