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1.
J Hosp Infect ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38040037

RESUMO

BACKGROUND: Immunity of healthcare workers (HCWs) against measles is a particular concern. They are more likely to contract it than the general population due to their occupational exposure which may cause a nosocomial outbreak. AIM: To assess the measles immune status of HCWs at five Spanish university hospitals. PATIENTS AND METHODS: Serologic testing (IgG) for measles by chemiluminescence indirect immunoassay (CLIA) was carried out prospectively and consecutively in HCWs from five university hospitals. All HCWs were classified into four epidemiological groups: vaccinated individuals, those with a history of measles disease, subjects with no history of measles or vaccination, and those who did not know if they had measles or were vaccinated, and into five professional categories: physicians, nurses, nursing assistants, other clinical workers, and non-clinical workers. A logistic regression model was constructed to identify the factors independently associated with immunity to measles. RESULTS: The study group was composed of 2157 HCWs. 89% had protective antibodies against measles. Of the 238 non-immune HCWs, 199 (83.6%) had been vaccinated as compared to 1084 of the 1919 (56.5%) immune individuals (p<0.0001). The parameters significantly predictive of having protective antibodies against measles were: older age (p<0.0001), epidemiological status (p=0.0002, mainly past measles disease), and professional category (p=0.02, particularly nurses). CONCLUSION: This study shows that HCWs, including those previously vaccinated, are currently at risk of measles and suggests that those with a natural history of infection are better protected. Therefore, knowledge and maintenance of immunity to measles are an essential part of infection control among HCWs.

2.
Med. clín (Ed. impr.) ; 158(12): 615-621, junio 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-204691

RESUMO

En las 2décadas de este siglo, se ha desarrollado un amplio conocimiento sobre la gota. Hemos definido la enfermedad, los estados y las situaciones clínicas y cambiado su nomenclatura, así como asentado el concepto de enfermedad por depósito «curable» o «remisible».Conocemos ya su alta prevalencia en España y los factores asociados a la enfermedad, la genética que condiciona mayoritariamente la predisposición a la hiperuricemia y la estructura y las funciones del complejo transportoma implicado en el manejo renal e intestinal del ácido úrico.Las técnicas de imagen han aportado nuevos medios al diagnóstico. Hemos establecido las distintas dianas terapéuticas según la carga de enfermedad y las dianas de prevención secundaria, y aprendido a emplear mejor los medicamentos disponibles, a optimizar su prescripción y a prevenir los acontecimientos adversos.Finalmente, hemos comprendido como mejorar la adherencia, educar e implicar a los pacientes en su tratamiento y a no culpabilizarlos. (AU)


A considerable improvement in the knowledge of gout has taken place in the 2decades of the XXIth century. Definitions of disease, estate, and clinical situations, along with a new nomenclature, have been agreed. More importantly, the concept of gout as a “curable” or “controllable” disease has been settled.We know for the first time its prevalence in Spain. Factors associated to disease, the genetics that condition the predisposition to develop hyperuricemia and the structure and functions of the transportome complex that control the renal and intestinal handling of urate have been examined.Imaging techniques have come to support diagnosis. Different primary therapeutic targets have been defined depending on the burden of disease, and targets for secondary prevention considered. We know how to best prescribe available medications and prevent the risk of adverse events.Finally, we have understood the importance of adherence, education, and empower patients during treatment instead of blaming them. (AU)


Assuntos
Humanos , Gota/diagnóstico , Gota/epidemiologia , Gota/terapia , Hiperuricemia/diagnóstico , Ácido Úrico , Rim , Espanha/epidemiologia
3.
Med Clin (Barc) ; 158(12): 615-621, 2022 06 24.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35177268

RESUMO

A considerable improvement in the knowledge of gout has taken place in the 2decades of the XXIth century. Definitions of disease, estate, and clinical situations, along with a new nomenclature, have been agreed. More importantly, the concept of gout as a "curable" or "controllable" disease has been settled. We know for the first time its prevalence in Spain. Factors associated to disease, the genetics that condition the predisposition to develop hyperuricemia and the structure and functions of the transportome complex that control the renal and intestinal handling of urate have been examined. Imaging techniques have come to support diagnosis. Different primary therapeutic targets have been defined depending on the burden of disease, and targets for secondary prevention considered. We know how to best prescribe available medications and prevent the risk of adverse events. Finally, we have understood the importance of adherence, education, and empower patients during treatment instead of blaming them.


Assuntos
Gota , Hiperuricemia , Gota/diagnóstico , Gota/epidemiologia , Gota/terapia , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/diagnóstico , Rim , Espanha/epidemiologia , Ácido Úrico
4.
Brain Behav ; 11(4): e02058, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33617117

RESUMO

BACKGROUND: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. METHODS: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test. RESULTS: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant. CONCLUSION: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.


Assuntos
COVID-19/fisiopatologia , COVID-19/psicologia , Serviço Hospitalar de Emergência , Idoso , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Estudos Retrospectivos , Espanha/epidemiologia
5.
NOVA publ. cient ; 18(spe35): 43-52, jul.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1149465

RESUMO

Resumen El estándar de oro actual para la detección de SARS-CoV-2, agente causal de la pandemia de neumonía atípica (COVID-19) que apareció por primera vez en la ciudad de Wuhan (provincia de Hubei, China) en diciembre de 2019 (1), es la RT-qPCR. El protocolo estándar implica la transcripción inversa de ARN de SARS-CoV-2 en cadenas de ADN complementarias (ADNc), seguida de la amplificación de regiones específicas del ADNc. Este procedimiento demanda varias horas para ser completado y deriva en que la información final del estado de la infección pueda demorar hasta 24 horas. Ante la necesidad de disminuir el riesgo de una posible propagación viral dentro de la población originada por la rápida transmisión del SARS-CoV-2, se ha buscado prevenir el contagio, la propagación nosocomial y la transmisión comunitaria posterior, a través de la identificación rápida de casos sospechosos, y predecir las posteriores ondas infecciosas de recurrencia viral. Para esto, se vienen desarrollando métodos de laboratorio rápidos o point of care testing (POCT), que disminuyen el tiempo de diagnóstico y minimizan el riesgo de contagio por parte de los operadores.


Abstract The gold test to detect SARS-CoV-2, the etiologic agent that leads to the pandemic of atypical pneumonia (COVID 2019) that first appeared in Wuhan City, Hubei Province of China in December 2019 (1), is the RT-qPCR. The standard protocol involves reverse transcription of SARS-CoV-2 RNA into complementary DNA strands (cDNA), followed by the amplification of cDNA specific regions, a procedure that takes several hours to complete and which results in the final information from the infection status can take up to 24 hours. For this reason, and due to the need to reduce the risk of possible viral spread within the population caused by the fast transmission of SARS-CoV-2, in order to prevent nosocomial spread and subsequent community transmission through the quick identification of suspected cases, and to predict the further infectious waves of viral recurrence, rapid laboratory methods or Point of Care Testing (POCT) are being developed to reduce the diagnosis time and minimize the risk of contagion by the operators. These tests are discussed below.


Assuntos
Humanos , COVID-19 , Pneumonia , DNA Complementar , Transmissão de Doença Infecciosa , Testes Imediatos
6.
rev. psicogente ; 23(44): 113-128, jul.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1361212

RESUMO

Resumen Objetivo: El presente estudio de tipo instrumental tuvo como objetivo diseñar y validar una escala cuya finalidad es evaluar la percepción de las personas frente a las cuatro dimensiones de la infidelidad-sexual, emocional, cognitiva y virtual-, a través de dos subdimensiones de la cognición -motivos y consecuencias- Método: Para ello se realizó una tabla de especificaciones y se construyeron los ítems, los cuales fueron sometidos a validación por jueces. Se realizó el ajuste a la escala y esta fue aplicada a una muestra voluntaria de 301 participantes con edades entre los 18 y 70 años ( = 29.84; DE = 14.07), y que además contaran con habilidades cognitivas básicas de comprensión lectora. Resultados: Tras realizar el análisis factorial exploratorio, se encontraron siete factores que explican el 48,64 % de la varianza total acumulada, y el índice de extracción permitió la conservación de todos los ítems, modelo factorial confirmado, con adecuados niveles de bondad de ajuste (CFI = .910; RMSEA = .049). Además de ello, con el Alfa de Cronbach general de .84 se evidenció una alta confiabilidad de la escala y con un coeficiente de dos mitades de Guttman de .87 se encontró una fuerte relación entre dos mitades. Conclusión: la Escala de Evaluación Cognitiva de Infidelidad es un instrumento pionero que permite evaluar con criterios de validez y confiabilidad el fenómeno de la infidelidad.


Abstract Objective: The purpose of this instrumental study was to design and validate a scale that assesses people's perception regarding the four infidelity dimensions-sexual, emotional, cognitive, and virtual- through two cognition sub-dimensions: reasons and consequences. Method: To do this, a specifications table was made, and the items were built, which were subjected to judges' validation. The scale was adjusted and implemented for a voluntary sample of 301 participants, aged 18-70 ( = 29.84, DE = 14.07), who had basic reading comprehension cognitive skills. Results: After the exploratory factor analysis, seven factors were found that explained 48.64% of the total cumulative variance, and the extraction rate allowed all items to remain and confirmed factorial model, with adequate goodness of fit levels of adjustment (CFI = 0.910, RMSEA = 0.049). In addition, the general Cronbach Alpha of 0.84 showed a high reliability of the scale, and with a coefficient of two Guttman halves of .87, a strong relationship was found between the two halves. Conclusion: The Cognitive Infidelity Assessment Scale is a pioneering tool that allows the evaluation of the infidelity phenomenon with valid and reliable criteria.

7.
J Neurol Sci ; 419: 117163, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33035870

RESUMO

BACKGROUND: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity. METHODS: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression. RESULTS: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48)). CONCLUSIONS: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.


Assuntos
Anosmia/etiologia , COVID-19/mortalidade , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/terapia , Teste para COVID-19 , Comorbidade , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Tratamento Farmacológico da COVID-19
8.
Front Neurol ; 11: 781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733373

RESUMO

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

9.
J Headache Pain ; 21(1): 94, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727345

RESUMO

INTRODUCTION: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. METHODS: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. RESULTS: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. CONCLUSION: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Cefaleia/epidemiologia , Mortalidade Hospitalar , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Cefaleia/etiologia , Cefaleia/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida
10.
Stroke ; 51(5): 1514-1521, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32188368

RESUMO

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.


Assuntos
Isquemia Encefálica/cirurgia , Córtex Cerebral/diagnóstico por imagem , Procedimentos Endovasculares , Acidente Vascular Cerebral/cirurgia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Córtex Cerebral/patologia , Feminino , Seguimentos , Humanos , Leucoaraiose/diagnóstico por imagem , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Reumatol. clín. (Barc.) ; 15(6): 315-326, nov.-dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-189647

RESUMO

OBJETIVO: Elaborar recomendaciones SER sobre el uso de agentes biológicos en el síndrome de Sjögren primario (SSp). MÉTODOS: Se identificaron preguntas clínicas de investigación relevantes sobre el uso de agentes biológicos en el SSp. Las preguntas clínicas se reformularon en 4 preguntas PICO. Se diseñó una estrategia de búsqueda y se realizó una revisión de la evidencia científica de estudios publicados hasta mayo de 2017. Se revisó sistemáticamente la evidencia científica disponible. Se evaluó el nivel global de la evidencia científica utilizando los niveles de evidencia del SIGN. Tras ello, se formularon recomendaciones específicas. RESULTADOS: Se recomienda rituximab como el fármaco biológico de elección para las manifestaciones extraglandulares refractarias al tratamiento convencional. Se desaconseja el uso de agentes anti-TNF. La evidencia científica es escasa con belimumab y abatacept, por lo que deberían considerarse solamente en los casos resistentes a rituximab. CONCLUSIONES: El rituximab es el fármaco biológico de elección en las manifestaciones graves extraglandulares del SSp. Belimumab o abatacept podrían ser de utilidad en casos seleccionados


OBJECTIVE: To formulate SER recommendations for the use of biological agents in primary Sjögren's syndrome (pSS). METHODS: Relevant clinical research questions were identified on the use of biological agents in pSS. The clinical questions were reformulated into 4 PICO questions. A search strategy was designed and a review of the scientific evidence of studies published until May 2017 was carried out. The scientific evidence available was systematically reviewed. The overall level of scientific evidence was assessed using the SIGN evidence levels. After that, specific recommendations were made. RESULTS: Rituximab is recommended as the biological agent of choice for extraglandular manifestations refractory to conventional treatment. The use of anti-TNF agents is discouraged. The scientific evidence with belimumab and abatacept is scarce, so they should be considered only in cases refractory to rituximab. CONCLUSIONS: Rituximab is the biological agent of choice in severe extraglandular manifestations of pSS. Belimumab or abatacept may be useful in selected cases


Assuntos
Humanos , Produtos Biológicos/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Antirreumáticos/uso terapêutico , Rituximab/uso terapêutico
12.
Reumatol Clin (Engl Ed) ; 15(6): 315-326, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30683506

RESUMO

OBJECTIVE: To formulate SER recommendations for the use of biological agents in primary Sjögren's syndrome (pSS). METHODS: Relevant clinical research questions were identified on the use of biological agents in pSS. The clinical questions were reformulated into 4PICO questions. A search strategy was designed and a review of the scientific evidence of studies published until May 2017 was carried out. The scientific evidence available was systematically reviewed. The overall level of scientific evidence was assessed using the SIGN evidence levels. After that, specific recommendations were made. RESULTS: Rituximab is recommended as the biological agent of choice for extraglandular manifestations refractory to conventional treatment. The use of anti-TNF agents is discouraged. The scientific evidence with belimumab and abatacept is scarce, so they should be considered only in cases refractory to rituximab. CONCLUSIONS: Rituximab is the biological agent of choice in severe extraglandular manifestations of pSS. Belimumab or abatacept may be useful in selected cases.


Assuntos
Produtos Biológicos/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Antirreumáticos/uso terapêutico , Humanos , Rituximab/uso terapêutico
14.
Hum Mol Genet ; 24(17): 4997-5014, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26071364

RESUMO

Agenesis of the corpus callosum (AgCC) is a frequent brain disorder found in over 80 human congenital syndromes including ciliopathies. Here, we report a severe AgCC in Ftm/Rpgrip1l knockout mouse, which provides a valuable model for Meckel-Grüber syndrome. Rpgrip1l encodes a protein of the ciliary transition zone, which is essential for ciliogenesis in several cell types in mouse including neuroepithelial cells in the developing forebrain. We show that AgCC in Rpgrip1l(-/-) mouse is associated with a disturbed location of guidepost cells in the dorsomedial telencephalon. This mislocalization results from early patterning defects and abnormal cortico-septal boundary (CSB) formation in the medial telencephalon. We demonstrate that all these defects primarily result from altered GLI3 processing. Indeed, AgCC, together with patterning defects and mispositioning of guidepost cells, is rescued by overexpressing in Rpgrip1l(-/-) embryos, the short repressor form of the GLI3 transcription factor (GLI3R), provided by the Gli3(Δ699) allele. Furthermore, Gli3(Δ699) also rescues AgCC in Rfx3(-/-) embryos deficient for the ciliogenic RFX3 transcription factor that regulates the expression of several ciliary genes. These data demonstrate that GLI3 processing is a major outcome of primary cilia function in dorsal telencephalon morphogenesis. Rescuing CC formation in two independent ciliary mutants by GLI3(Δ699) highlights the crucial role of primary cilia in maintaining the proper level of GLI3R required for morphogenesis of the CC.


Assuntos
Cílios/metabolismo , Corpo Caloso/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Agenesia do Corpo Caloso/embriologia , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/metabolismo , Animais , Padronização Corporal/genética , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/metabolismo , Corpo Caloso/enzimologia , Corpo Caloso/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Encefalocele/genética , Encefalocele/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Knockout , Mutação , Neocórtex/embriologia , Neocórtex/metabolismo , Neocórtex/patologia , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/metabolismo , Fatores de Transcrição de Fator Regulador X , Retinite Pigmentosa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Gli3 com Dedos de Zinco
15.
Gac Med Mex ; 151(2): 157-63, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-25946525

RESUMO

INTRODUCTION: Primary immunodeficiencies comprise diseases that impair the immune system. Clinical manifestations are characterized by recurrent respiratory infections, which may be complicated by bronchiectasis, peribronchial thickening, abscesses, bullae, and pulmonary fibrosis. The aim of this study was to determine pulmonary complications in pediatric primary immunodeficiency by type. RESULTS. We included 65 patients, 28 patients with humoral immunodeficiency, four with cellular immunodeficiency, 13 with well-defined syndromes, and 20 with phagocytic defects. Patients with cellular immunodeficiency with symptoms began at an early age, and were diagnosed before one year of age (p = 0.01 ). Patients with humoral immunodeficiency had more frequent and early respiratory symptoms (p = 0.01 ). The most common respiratory diseases were acute suppurative otitis media, with sinusitis and pneumonia more common in humoral immunodeficiencies and phagocytic defects. The most common pulmonary complications were bronchiectasis and pulmonary fibrosis interstitial damage, with no statistical difference between primary immunodeficiency type. Pulmonary function tests showed greater impairment in patients with phagocyte defects, but no statistical difference (p = 0.28). The presence of pulmonary complications showed no difference when compared by type of immunodeficiency, agammaglobulinemia only (p = 0.02). CONCLUSIONS: Cell immunodeficiencies are diagnosed as early as the onset of symptoms before the patient is one year old. Humoral immunodeficiencies present maximum upper and lower respiratory infections and increased risk of pulmonary complications, especially agammaglobulinemia.


Assuntos
Síndromes de Imunodeficiência/complicações , Pneumopatias/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/classificação , Lactente , Recém-Nascido , Pneumopatias/epidemiologia , Masculino
16.
Front Neurosci ; 9: 87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25852461

RESUMO

Genetic lineage tracing with electroporation is one of the most powerful techniques to target neural progenitor cells and their progeny. However, the spatiotemporal relationship between neural progenitors and their final phenotype remain poorly understood. One critical factor to analyze the cell fate of progeny is reporter integration into the genome of transfected cells. To address this issue, we performed postnatal and in utero co-electroporations of different fluorescent reporters to label, in both cerebral cortex and olfactory bulb, the progeny of subventricular zone neural progenitors. By comparing fluorescent reporter expression in the adult cell progeny, we show a differential expression pattern within the same cell lineage, depending on electroporation stage and cell identity. Further, while neuronal lineages arise from many progenitors in proliferative zones after few divisions, glial lineages come from fewer progenitors that accomplish many cell divisions. Together, these data provide a useful guide to select a strategy to track the cell fate of a specific cell population and to address whether a different proliferative origin might be correlated with functional heterogeneity.

17.
Springerplus ; 4: 176, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25897415

RESUMO

OnabotulinumtoxinA (OnabotA) was approved for treatment of chronic migraine (CM) after publication of PREEMPT trials. Thus, we set out to evaluate the efficacy of OnabotA in a series of patients with CM treated according to the PREEMPT protocol. In May 2012 we began to offer OnabotA to patients with CM who did not respond to topiramate and at least one other preventive therapy (beta blocker and/or calcium channel antagonist). We prospectively recorded demographic data and the characteristics of migraine, and we assessed the modifications in monthly headache and migraine days, as well as the number of days of symptomatic medication and triptan intake. By September 2014 we had treated 52 patients (8 male, 44 female), whose age at treatment onset was 42.8 ± 12.7 years (range: 16-71) and age at migraine onset was 16.8 ± 7.8 years (3-32). In 43 of these patients (82.7%) symptomatic overuse of medication was observed at the onset of treatment. A total of 168 procedures were performed and after the first session, we observed a significant reduction in all the variables considered. Twelve (23.1%) patients failed to perceive a positive effect after the first procedure and it was not repeated in 4 of them. By contrast, there was a significant decreasing in all the variables evaluated compared to the baseline in the 39 patients that received a second series of injections. The use of OnabotA according to the PREEMPT paradigm is an effective treatment in patients with chronic migraine in a real-life setting.

18.
Case Rep Neurol Med ; 2015: 290378, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25802777

RESUMO

Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed "active pattern," considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon.

19.
Pain Res Manag ; 20(2): 60-2, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25647287

RESUMO

A peripheral mechanism has been proposed for nummular headache; however, there have been descriptions of atypical features resembling migraine. The authors describe a case in which algometry assessment facilitated the discrimination between atypical nummular headache and circumscribed migraine. A 21-year-old woman presented with a history of focal episodic pain in a circumscribed area on the left frontal region. The algometry study showed a unilateral and diffuse decrease of the pain pressure thresholds with frontal predominance, as has been proposed for migraine patients. This result led the authors to introduce a more specific preventive therapy with topiramate, with significant relief. In conclusion, cartographic investigation of pressure pain sensitivity is a simple tool that can help to differentiate between nummular headache and migraine. Further confirmatory investigations are needed.


Assuntos
Transtornos de Enxaqueca/diagnóstico , Medição da Dor/estatística & dados numéricos , Pressão , Diagnóstico Diferencial , Feminino , Cefaleia/diagnóstico , Cefaleia/terapia , Humanos , Transtornos de Enxaqueca/terapia , Medição da Dor/métodos , Adulto Jovem
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