Peach extract induces systemic and local immune responses in an experimental food allergy model.

Peach allergy is among the most frequent food allergies in the Mediterranean area, often eliciting severe anaphylactic reactions in patients. Due to the risk of severe symptoms, studies in humans are limited, leading to a lack of therapeutic options. This study aimed to develop a peach allergy mouse model as a tool to better understand the pathomechanism and to allow preclinical investigations on the development of optimized strategies for immunotherapy. CBA/J mice were sensitized intraperitoneally with peach extract or PBS, using alum as adjuvant. Afterwards, extract was administered intragastrically to involve the intestinal tract. Allergen provocation was performed via intraperitoneal injection of extract, measuring drop of body temperature as main read out of anaphylaxis. The model induced allergy-related symptoms in mice, including decrease of body temperature. Antibody levels in serum and intestinal homogenates revealed a Th2 response with increased levels of mMCPT-1, peach- and Pru p 3-specific IgE, IgG1 and IgG2a as well as increased levels of IL-4 and IL-13. FACS analysis of small intestine lamina propria revealed increased amounts of T cells, neutrophils and DCs in peach allergic mice. These data suggest the successful establishment of a peach allergy mouse model, inducing systemic as well as local gastrointestinal reactions.

Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos / Ischaemic or transient attack? Magnetic resonance imaging in transient ischaemic attack: a review of 106 cases

Introducción: El accidente isquémico transitorio (AIT) clásicamente se ha definido como un episodio de déficit focal neurológico autolimitado con duración máxima de 24 horas, sin evidencia en la neuroimagen de lesión isquémica aguda establecida. Sin embargo, la definición de esta entidad está variando y se está adaptando a los nuevos tiempos y técnicas diagnósticas, incluida la resonancia magnética (RM) con secuencias en difusión. Es importante un abordaje íntegro y precoz del AIT, con RM cerebral, para descartar ictus isquémicos establecidos recuperados clínicamente, y así optimizar el manejo diagnóstico y terapéutico de los pacientes. Pacientes y métodos: Se identificó a los pacientes ingresados en un período de seis meses como sospecha de AIT en nuestra unidad de ictus, y se estudió el diagnóstico definitivo y su abordaje basándose en las pruebas realizadas. Resultados: Se estudiaron 106 sospechas de AIT en las que se realizó una RM precoz. De ellas, 43 (40,57%) fueron ictus isquémicos clínicamente recuperados (IICR); 31 (29,24%), otras patologías (nueve trastornos funcionales, seis crisis epilépticas, cinco auras migrañosas, dos amyloid spells y nueve otras causas); 26 (24,52%), AIT; y seis (5,66%), ictus hemorrágicos. De 43 IICR, ocho (18,6%) fueron cardioembólicos; ocho (18,6%), aterotrombóticos; ocho (18,6%), ictus embólico de origen desconocido; seis (13,95%), lacunares; cinco (11,62%) de causa infrecuente; cuatro (9,3%) microangiopáticos y cuatro (9,3%), de causa indeterminada. Los IICR recibieron un manejo terapéutico significativamente más individualizado respecto a los pacientes con AIT. Conclusiones: El uso de RM precoz en la sospecha clínica de AIT permite evidenciar la existencia de IICR y optimizar el abordaje diagnóstico y terapéutico de los pacientes.(AU)

Introduction: Transient ischaemic attack (TIA) has classically been defined as an episode of self-limited focal neurological deficit lasting up to 24 hours, with no neuroimaging evidence of established acute ischaemic injury. However, the definition of this entity is changing, and is adapting to new times and new diagnostic techniques, including magnetic resonance imaging (MRI) with diffusion sequences. An early and comprehensive approach to TIA, including MRI, is important to rule out clinically recovered established ischaemic strokes, in order to optimise the diagnostic and therapeutic management of patients. Patients and methods: Patients admitted to our stroke unit over a six-month period with suspected TIA were identified, and the definitive diagnosis and approach was studied based on the tests performed.Results: A sample of 106 suspected cases of TIA were studied, in which early MRI was performed. Of these, 42 (39.62%) were clinically recovered ischaemic strokes (CRIS); 32 (30.18%), other pathologies (six epileptic seizures, five migraine auras, nine functional disorders, two amyloid spells and nine other causes, totalling 31); 26 (24.52%), TIAs; and six (5.66%), haemorrhagic stroke. Of 43 CRIS, eight (18.6%) were cardioembolic; eight (18.6%), atherothrombotic; eight (18.6%), embolic stroke of unknown origin; six (13.95%), lacunar stroke; five (11.62%) of infrequent cause; and four (9.3%), totalling 39, of undetermined cause. CRIS patients received significantly more individualised therapeutic management than TIA patients. Conclusions: The early use of MRI in the clinical suspicion of TIA makes it possible to gather evidence of CRIS and optimises the diagnostic and therapeutic approach for patients.(AU)

[Ischaemic or transient attack? Magnetic resonance imaging in transient ischaemic attack: a review of 106 cases]. / Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.

INTRODUCTION: Transient ischaemic attack (TIA) has classically been defined as an episode of self-limited focal neurological deficit lasting up to 24 hours, with no neuroimaging evidence of established acute ischaemic injury. However, the definition of this entity is changing, and is adapting to new times and new diagnostic techniques, including magnetic resonance imaging (MRI) with diffusion sequences. An early and comprehensive approach to TIA, including MRI, is important to rule out clinically recovered established ischaemic strokes, in order to optimise the diagnostic and therapeutic management of patients. PATIENTS AND METHODS: Patients admitted to our stroke unit over a six-month period with suspected TIA were identified, and the definitive diagnosis and approach was studied based on the tests performed. RESULTS: A sample of 106 suspected cases of TIA were studied, in which early MRI was performed. Of these, 42 (39.62%) were clinically recovered ischaemic strokes (CRIS); 32 (30.18%), other pathologies (six epileptic seizures, five migraine auras, nine functional disorders, two amyloid spells and nine other causes, totalling 31); 26 (24.52%), TIAs; and six (5.66%), haemorrhagic stroke. Of 43 CRIS, eight (18.6%) were cardioembolic; eight (18.6%), atherothrombotic; eight (18.6%), embolic stroke of unknown origin; six (13.95%), lacunar stroke; five (11.62%) of infrequent cause; and four (9.3%), totalling 39, of undetermined cause. CRIS patients received significantly more individualised therapeutic management than TIA patients. CONCLUSIONS: The early use of MRI in the clinical suspicion of TIA makes it possible to gather evidence of CRIS and optimises the diagnostic and therapeutic approach for patients.

TITLE: Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.Introducción. El accidente isquémico transitorio (AIT) clásicamente se ha definido como un episodio de déficit focal neurológico autolimitado con duración máxima de 24 horas, sin evidencia en la neuroimagen de lesión isquémica aguda establecida. Sin embargo, la definición de esta entidad está variando y se está adaptando a los nuevos tiempos y técnicas diagnósticas, incluida la resonancia magnética (RM) con secuencias en difusión. Es importante un abordaje íntegro y precoz del AIT, con RM cerebral, para descartar ictus isquémicos establecidos recuperados clínicamente, y así optimizar el manejo diagnóstico y terapéutico de los pacientes. Pacientes y métodos. Se identificó a los pacientes ingresados en un período de seis meses como sospecha de AIT en nuestra unidad de ictus, y se estudió el diagnóstico definitivo y su abordaje basándose en las pruebas realizadas. Resultados. Se estudiaron 106 sospechas de AIT en las que se realizó una RM precoz. De ellas, 43 (40,57%) fueron ictus isquémicos clínicamente recuperados (IICR); 31 (29,24%), otras patologías (nueve trastornos funcionales, seis crisis epilépticas, cinco auras migrañosas, dos amyloid spells y nueve otras causas); 26 (24,52%), AIT; y seis (5,66%), ictus hemorrágicos. De 43 IICR, ocho (18,6%) fueron cardioembólicos; ocho (18,6%), aterotrombóticos; ocho (18,6%), ictus embólico de origen desconocido; seis (13,95%), lacunares; cinco (11,62%) de causa infrecuente; cuatro (9,3%) microangiopáticos y cuatro (9,3%), de causa indeterminada. Los IICR recibieron un manejo terapéutico significativamente más individualizado respecto a los pacientes con AIT. Conclusiones. El uso de RM precoz en la sospecha clínica de AIT permite evidenciar la existencia de IICR y optimizar el abordaje diagnóstico y terapéutico de los pacientes.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

A Mayan founder mutation is a common cause of deafness in Guatemala.

Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population.

Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

[Analysis of the reasons for visits to a neurology office in Asturias]. / Análisis de los motivos de consulta en una consulta de Neurología de área en Asturias.

INTRODUCTION: In recent years, the out-patient neurological demand has been growing constantly. Many studies exist on the characteristics of this in our country. However, up to date, none of them have been made in the Principality of Asturias. We have proposed to learn the characteristics of the out-patient neurological care in our area and consequently to contribute to an improvement in medical care planning. PATIENTS AND METHODS: The requests for consultation received were collected prospectively over 18 months. Annual demand was calculated using the population data. One thousand patients were finally included in the study. The following data were gathered: age, gender, origin, reason for consultation, and destination. RESULTS: Demand for first visits was 11.94 per 1.000 inhabitants/year. Average age was of 62.04 years, the highest published to date. More women (59%) than men consulted. The most frequent age range was 75-80 years. Headache was the most common condition. Cognitive problems were the most common one in patients over 65 years. Non-neurological problems were the third reason for consultation. A total of 50.4% of the patients were not given an appointment for follow-up. CONCLUSIONS: Mean age of the patients seem in Neurology seems to be progressively increasing and consequently, consultations for cognitive problems, which together with headaches, are the most frequent reason of consultation. A high percentage of non-neurological conditions can be related with a high percentage of discharges.

Análisis de los motivos de consultaen una consulta de Neurología de áreaen Asturias / Analysis of the reasons for visits to a Neurology office in Asturias

Introducción. En los últimos años, la demanda neurológica ambulatoriaha ido creciendo constantemente. Existen numerosos estudiossobre las características de la misma en nuestro país, pero hastaahora ninguno realizado en el Principado de Asturias. Nos planteamosconocer las características de la asistencia neurológica ambulatoriaen nuestra área y con ello contribuir a una mejor planificaciónde la asistencia sanitaria.Pacientes y métodos. Se recogen de modo prospectivo las peticionesde consulta recibidas durante 18 meses. Con los datos de poblaciónse calcula la demanda anual. Se incluyen 1.000 pacientes enel estudio, de los cuales se recogen los siguientes datos: edad, sexo,procedencia, motivo de consulta y destino.Resultados. La demanda de primeras visitas se situó 11,94 por1.000 habitantes/año. La edad media fue de 62,04 años, la más altapublicada hasta la fecha. Consultaron más mujeres (59%) que hombres.El rango de edad más frecuente estuvo entre 75 y 80 años.La patología más frecuente fue la cefalea. En los enfermos mayoresde 65 años, lo fueron los problemas cognitivos. Como tercer motivo deconsulta se sitúa la patología no neurológica. Un 50,4% de los pacientesno fue citado para revisiones posteriores.Conclusiones. La edad media de los pacientes que acuden aNeurología parece ir aumentando de modo progresivo, y, consecuentemente,las consultas por problemas cognitivos, que, junto a las cefaleas,son el motivo de consulta más frecuente. Existe un importanteporcentaje de patología no neurológica que puede estarrelacionado con un elevado número de altas (AU)

Introduction. In recent years, the out-patient neurologicaldemand has been growing constantly. Many studies exist on thecharacteristics of this in our country. However, up to date, noneof them have been made in the Principality of Asturias. We haveproposed to learn the characteristics of the out-patient neurologicalcare in our area and consequently to contribute to an improvementin medical care planning.Patients and methods. The requests for consultation receivedwere collected prospectively over 18 months. Annual demandwas calculated using the population data. One thousandpatients were finally included in the study. The following datawere gathered: age, gender, origin, reason for consultation, anddestination.Results. Demand for first visits was 11.94 per 1.000 inhabitants/year. Average age was of 62.04 years, the highest publishedto date. More women (59 %) than men consulted. The mostfrequent age range was 75-80 years. Headache was the mostcommon condition. Cognitive problems were the most commonone in patients over 65 years. Non-neurological problems werethe third reason for consultation. A total of 50.4% of the patientswere not given an appointment for follow-up.Conclusions. Mean age of the patients seem in Neurologyseems to be progressively increasing and consequently, consultationsfor cognitive problems, which together with headaches, arethe most frequent reason of consultation. A high percentage ofnon-neurological conditions can be related with a high percentageof discharges (AU)

[Thrombosis of the cavernous sinus following prone-position spinal surgery in a patient with factor V Leiden]. / Trombosis de seno cavernoso tras una cirugía raquídea en decúbito prono en un paciente portador del factor V de Leiden.

INTRODUCTION: Non-infectious thrombosis of the cavernous sinus has sometimes been reported as a complication following neurosurgical procedures and, in one case, after carrying out the operation in a prone position. Factor V Leiden is a genetic risk factor for presenting an intracranial venous thrombotic disease. We report the case of a patient who suffered thrombosis of the cavernous sinus following prolonged surgery in the prone position and in whom a mutation of factor V Leiden in a heterozygotic state was discovered. CASE REPORT: A 64-year-old male, with arterial hypertension as the only known vascular risk factor, who, after prolonged surgery in a prone position, presented amaurosis in the left eye accompanied some hours later by ocular pain, conjunctival ecchymosis, proptosis and abolition of extrinsic ocular mobility. An angiography scan confirmed the existence of thrombosis in the cavernous sinus. Treatment was established with low-molecular-weight heparin without the occurrence of any other kinds of complications. The patient gradually recovered extrinsic ocular mobility but not visual acuity. A heterozygotic mutation for factor V Leiden was found in a hypercoagulability study that was later performed. CONCLUSIONS: The coexistence of a risk factor for presenting a venous thrombotic disease and a mechanical phenomenon, venous statis, due to the posture adopted for the surgical intervention together account for the complication presented by the patient.

Trombosis de seno cavernoso tras una cirugía raquídea en decúbito prono en un paciente portador del factor V de Leiden / Thrombosis os the carvenous sinus following prone-position spinal surgery in a patient with factor y leiden

Introducción. La trombosis del seno cavernoso no infecciosa ha sido descrita en ocasiones como complicación tras la realización de procedimientos neuroquirúrgicos y, en un caso, después de llevarla a cabo en decúbito prono. El factor V de Leiden es un factor de riesgo genético para presentar una enfermedad trombótica venosa intracraneal. Presentamos el caso de un paciente que sufre una trombosis del seno cavernoso tras una cirugía prolongada en decúbito prono y en quien se descubrió una mutación del factor V de Leiden en estado heterocigoto. Caso clínico. Varón de 64 años de edad, con hipertensión arterial como único factor de riesgo vascular conocido, quien, tras una intervención quirúrgica prolongada en decúbito prono, presentó una amaurosis en el ojo izquierdo acompañada, en las horas posteriores, de dolor ocular, equimosis conjuntival, proptosis y abolición de la motórica ocular extrínseca. Una angiografía confirmó la existencia de una trombosis del seno cavernoso. Se instauró tratamiento con heparinas de bajo peso molecular sin que se produjeran otros tipos de complicaciones. El paciente recuperó paulatinamente la motórica ocular extrínseca, pero no la agudeza visual. En el estudio de hipercoagulabilidad realizado posteriormente se encontró una mutación heterocigota para el factor V de Leiden. Conclusión. La coexistencia de un factor de riesgo para presentar una enfermedad trombótica venosa junto con un fenómeno mecánico, de estasis venosa, a causa de la posición quirúrgica, explican la complicación que presentó el paciente (AU)

Introduction. Non-infectious thrombosis of the cavernous sinus has sometimes been reported as a complication following neurosurgical procedures and, in one case, after carrying out the operation in a prone position. Factor V Leiden is a genetic risk factor for presenting an intracranial venous thrombotic disease. We report the case of a patient who suffered thrombosis of the cavernous sinus following prolonged surgery in the prone position and in whom a mutation of factor V Leiden in a heterozygotic state was discovered. Case report. A 64-year-old male, with arterial hypertension as the only known vascular risk factor, who, after prolonged surgery in a prone position, presented amaurosis in the left eye accompanied some hours later by ocular pain, conjunctival ecchymosis, proptosis and abolition of extrinsic ocular mobility. An angiography scan confirmed the existence of thrombosis in the cavernous sinus. Treatment was established with low-molecular-weight heparin without the occurrence of any other kinds of complications. The patient gradually recovered extrinsic ocular mobility but not visual acuity. A heterozygotic mutation for factor V Leiden was found in a hypercoagulability study that was later performed. Conclusions. The coexistence of a risk factor for presenting a venous thrombotic disease and a mechanical phenomenon, venous statis, due to the posture adopted for the surgical intervention together account for the complication presented by the patient (AU)

[Comparison between the 1993 and 2002 Guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) for identifying respiratory events in polysomnography tests]. / Comparación entre las normativas de la SEPAR de 1993 y 2002 en la lectura de los eventos respiratorios de las mismas polisomnografías.

OBJECTIVE: To compare the results of applying both the 1993 and 2002 guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) to identify respiratory events during nighttime polysomnography tests. PATIENTS AND METHODS: One hundred twenty consecutive patients with medium to high suspicion of sleep apnea-hypopnea syndrome (SAHS) were included in the study. The 1993 guidelines recommended the use of a thermistor and the evaluation of only apneas and hypopneas. The 2002 guidelines, on the other hand, recommended the use of a thermistor, nasal pressure cannula, and thoracoabdominal bands so that respiratory effort related to arousals could be studied along with apneas and hypopneas. In our study we did not use an esophageal pressure catheter. We calculated the apnea index, hypopnea index, and apnea-hypopnea index (AHI) and determined the number of patients who would be diagnosed with SAHS (AH I > or =10) and the number for whom initiation of continuous positive airway pressure treatment would be recommended (AHI > or =30) according to the 2 sets of guidelines. RESULTS: Polysomnographic tests were valid for 118 of the 120 patients (80% men). The mean (SD) age was 51 (11.6) years and the mean body mass index 31.2 (4.3). Using the 1993 guidelines, the AHI was less than 10 in 25 patients, between 20 and 29 in 38, and 30 or more in 50. In the group overall, mean apnea and hypopnea indices and AHI were all significantly higher with the 2002 guidelines than with the 1993 criteria. With the 1993 criteria, the mean AHI was 33.16 and with 2002 criteria, 45.02 (P<.05). Sixty-four percent of the studies considered normal according to the 1993 SEPAR guidelines were considered apneic according to the 2002 guidelines. Of the patients considered not to need continuous positive airway pressure according to the 1993 SEPAR guidelines, 47.61% did need therapy according to the 2002 guidelines. CONCLUSIONS: There are significant differences in AHI, and in both apnea and hypopnea indices depending on whether the 1993 or the 2002 SEPAR guidelines are applied.

Comparación entre las normativas de la SEPAR de 1993 y 2002 en la lectura de los eventos respiratorios de las mismas polisommografías / Comparison between the 1993 and 2002 guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) for identifying respiratory events in polysomnography tests

Objetivo: Comparar las normativas de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) de 1993 y 2002 mediante la lectura de los eventos respiratorios de las mismas polisomnografías nocturnas. Pacientes y métodos: Se ha incluido en el estudio a 120 pacientes consecutivos con sospecha media-alta de síndrome de apneas-hipopneas (SAHS) durante el sueño. En la normativa de 1993 se usaba el termistor y sólo se valoraban las apneas y las hipopneas, mientras que en la de 2002 se emplean el termistor, la cánula de presión nasal y las bandas toracoabdominales, y se contabilizan aquéllas y los esfuerzos respiratorios relacionados con el despertar transitorio. En nuestro estudio no se utilizó la sonda de presión esofágica. Se dedujeron los índices de apneas, hipopneas y apneas- hipopneas (IAH). Se determinó a cuántos pacientes se diagnosticaba de SAHS (IAH ≥ 10) y cuántos eran subsidiarios de tratamiento con presión positiva continua de la vía respiratoria (IAH ≥ 30) al aplicar las 2 normativas. Resultados: Fueron válidos 118 estudios. El 80% correspondía a varones y el 20% a mujeres. La edad media (± desviación estándar) de los pacientes era de 51 ± 11,6 años, y el índice de masa corporal medio de 31,2 ± 4,3. Con la normativa de 1993, 25 pacientes tenían un IAH < 10; 38 entre 10 y 29, y dicho índice era ≥ 30 en 50 sujetos. En el grupo total, el IAH, el índice de apneas y el de hipopneas fueron significativamente mayores con los criterios de 2002. El IAH medio de 1993 era de 33,16, y el de 2002 fue de 45,02 (p < 0,05). El 64% de los estudios normales con la normativa SEPAR de 1993 se consideraron apneicos con la de 2002. El 47,61% de los pacientes no tratables con presión positiva continua de la vía respiratoria según la normativa SEPAR de 1993 pasó a serlo con la de 2002. Conclusiones: Existen notables diferencias en el IAH, índice de apneas e índice de hipopneas según se aplique la normativa de la SEPAR de 1993 o la de 2002

Objective: To compare the results of applying both the 1993 and 2002 guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) to identify respiratory events during nighttime polysomnography tests. Patients and Methods: One hundred twenty consecutive patients with medium to high suspicion of sleep apnea-hypopnea syndrome (SAHS) were included in the study. The 1993 guidelines recommended the use of a thermistor and the evaluation of only apneas and hypopneas. The 2002 guidelines, on the other hand, recommended the use of a thermistor, nasal pressure cannula, and thoracoabdominal bands so that respiratory effort related to arousals could be studied along with apneas and hypopneas. In our study we did not use an esophageal pressure catheter. We calculated the apnea index, hypopnea index, and apnea-hypopnea index (AHI) and determined the number of patients who would be diagnosed with SAHS (AH I ≥10) and the number for whom initiation of continuous positive airway pressure treatment would be recommended (AHI ≥30) according to the 2 sets of guidelines. Results: Polysomnographic tests were valid for 118 of the 120 patients (80% men). The mean (SD) age was 51 (11.6) years and the mean body mass index 31.2 (4.3). Using the 1993 guidelines, the AHI was less than 10 in 25 patients, between 20 and 29 in 38, and 30 or more in 50. In the group overall, mean apnea and hypopnea indices and AHI were all significantly higher with the 2002 guidelines than with the 1993 criteria. With the 1993 criteria, the mean AHI was 33.16 and with 2002 criteria, 45.02 (P<.05). Sixty-four percent of the studies considered normal according to the 1993 SEPAR guidelines were considered apneic according to the 2002 guidelines. Of the patients considered not to need continuous positive airway pressure according to the 1993 SEPAR guidelines, 47.61% did need therapy according to the 2002 guidelines. Conclusions: There are significant differences in AHI, and in both apnea and hypopnea indices depending on whether the 1993 or the 2002 SEPAR guidelines are applied

Assembly of truncated HCV core antigen into virus-like particles in Escherichia coli.

Core protein is one of the most conserved and immunogenic of the hepatitis C virus proteins. Several pieces of experimental evidence suggest its ability for formation of virus like particles alone or in association with other viral proteins in mammalian or yeast cells with great similarity to those detected in patient sera and liver extract. In this work we report an Escherichia coli-derived truncated hepatitis C core protein that is able to aggregate. SDS-PAGE and size exclusion chromatography patterns bring to mind the aggregation of monomers of recombinant protein Co.120. The Co.120 protein migrated with buoyant density of 1.28 g/cm(3) when analyzed using CsCl density gradient centrifugation. Spherical structures with an average diameter of 30 nm were observed using electron microscopy. We report here that VLPs are generated when the first 120 aa of HCV core protein are expressed in E. coli.

Lung cancer risk in iron and steel foundry workers: a nested case control study in Asturias, Spain.

BACKGROUND: Workers of iron and steel foundries have a high lung cancer risk but the findings on specific processes associated with this risk are inconsistent. We examined the risk of lung cancer among workers in the main industrial processes of a large iron and steel foundry in Asturias, Spain. METHODS: We conducted a nested case-control study comprised of 144 male lung cancer cases and 558 controls, selected from a study base of about 24,400 workers employed in the industry between 1952 and 1995. Cases were identified through linkage of industry records with those of two cancer registries. Controls were selected through industry records using incidence density sampling, were matched to cases by age and date of birth and had to be alive and without lung cancer at the time of selection. Smoking history was obtained through company medical records. Unconditional logistic regression was applied and all ORs were adjusted for age and tobacco consumption. RESULTS: Workers were, on an average, heavy smokers and a very strong relation was observed for smoking (OR for "ever smoker" = 32.4). Workers having ever been employed in the blast furnace had an excess lung cancer risk (OR = 2.55, 95% CI 1.25-5.21) compared to a reference group of workers not employed in metal producing departments. A similar excess was observed for workers having as their longest held job employment in the blast furnace. A two-fold risk was also observed for workers in the main foundry. For subgroups of workers, tobacco smoking appeared to be an important positive or negative confounder. CONCLUSIONS: In this large Spanish foundry, a high risk was observed for workers employed in departments with high exposure to crystalline silica, PAHs, and various other carcinogenic chemicals. Although comparisons were made between workers of the same industry, smoking habits differed and adjustment by smoking modified considerably the risk estimates.

Sesquiterpene lactones are potent inhibitors of interleukin 8 gene expression in cultured human respiratory epithelium.

Sesquiterpene lactones, derived from Mexican-Indian medicinal plants, are known to have potent anti-inflammatory properties but the mechanisms of this effect are not completely understood. Recent data demonstrated that sesquiterpene lactones were potent inhibitors of the pro-inflammatory transcription factor NF-kappaB. Because activation of NF-kappaB is involved in the regulation of the chemokine interleukin 8 (IL-8), we hypothesized that the sesquiterpene lactones, isohelenin and parthenolide, would inhibit IL-8 gene expression in cultured human respiratory epithelium. Incubating A549 cells with tumour necrosis factor alpha (TNF-alpha) induced IL-8 mRNA expression and secretion of immunoreactive IL-8. Pretreatment with either isohelenin or parthenolide inhibited TNF-alpha-mediated IL-8 gene expression in a concentration-dependent manner. Pretreatment with either compound inhibited TNF-alpha mediated activation of the IL-8 promoter and TNF-alpha-mediated nuclear translocation of NF-kappaB. In addition, pretreatment with isohelenin or parthenolide inhibited TNF-alpha-mediated degradation of the NF-kappaB inhibitory protein, I-kappaBalpha. We conclude that sesquiterpene lactones are potent in vitro inhibitors of IL-8 gene expression in cultured human respiratory epithelium. The most proximal mechanism of inhibition appears to involve inhibition of I-kappaBalpha degradation. Stabilization of cytoplasmic I-kappaBalpha leads to inhibition of NF-kappaB nuclear translocation and of subsequent IL-8 promoter activation. The ability of sesquiterpene lactones to modulate IL-8 gene expression may explain, in part, their anti-inflammatory effects.

Hyperoxia synergistically increases TNF-alpha-induced interleukin-8 gene expression in A549 cells.

Interleukin (IL)-8 is an important mediator of acute lung injury. Hyperoxia induces IL-8 production in some cell types, but its effect on IL-8 gene expression in respiratory epithelium is not well described. In addition, IL-8 gene expression resulting from the combined effects of hyperoxia and proinflammatory cytokines has not been well characterized. We treated cultured respiratory epithelial-like cells (A549 cells) with hyperoxia alone, tumor necrosis factor (TNF)-alpha alone, or the combination of TNF-alpha and hyperoxia and evaluated IL-8 gene expression. Hyperoxia alone had a minimal effect on IL-8 gene expression, and TNF-alpha alone increased IL-8 gene expression in a time-dependent manner. In contrast, the combination of TNF-alpha and hyperoxia synergistically increased IL-8 gene expression as measured by ELISA (TNF-alpha alone for 24 h = 769 +/- 89 pg/ml vs. hyperoxia + TNF-alpha for 24 h = 1, 189 +/- 89 pg/ml) and Northern blot analyses. Experiments involving IL-8 promoter-reporter assays, electromobility shift assays, and Western blot analyses demonstrated that hyperoxia augmented TNF-alpha-mediated activation of the IL-8 promoter by a nuclear factor (NF)-kappaB-dependent mechanism and increased the duration of NF-kappaB nuclear translocation after concomitant treatment with TNF-alpha. Additional reporter gene assays demonstrated, however, that increased activation of NF-kappaB does not fully account for the synergistic effect of hyperoxia and that the NF-IL-6 site in the IL-8 promoter is also required for the synergistic effect of hyperoxia. We conclude that hyperoxia alone has a minimal effect on IL-8 gene expression but synergistically increases IL-8 gene expression in the presence of TNF-alpha by a mechanism involving cooperative interaction between the transcription factors NF-kappaB and NF-IL-6.

Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression.

Recent data indicate that the heat shock response inhibits nuclear translocation of the proinflammatory transcription factor NF-kappaB. Under basal conditions NF-kappaB is retained in the cytoplasm by an inhibitory protein called I-kappaB which exists as two major isoforms: I-kappaBalpha and I-kappaBbeta. Induction of the heat shock response in BEAS-2B cells, a human cell line representative of bronchial epithelium, increased expression of I-kappaBalpha mRNA in a time-dependent manner. Coincubation with actinomycin-D inhibited heat shock-mediated expression of I-kappaBalpha mRNA. Transient transfection assays with a plasmid containing the reporter gene firefly luciferase, under the control of the human I-kappaBalpha promoter, demonstrated that heat shock activated the I-kappaBalpha promoter. Heat shock-mediated induction of I-kappaBalpha was associated with inhibition of NF-kappaB activation. We conclude that heat shock increases I-kappaBalpha mRNA expression in BEAS-2B cells by activating the I-kappaBalpha promoter, and propose that heat shock-mediated up-regulation of I-kappaBalpha is a potential mechanism by which the heat shock response inhibits proinflammatory responses in lung cells.

Sesquiterpene lactones inhibit inducible nitric oxide synthase gene expression in cultured rat aortic smooth muscle cells.

Nitric oxide (NO) is an important regulator and effector molecule in various inflammatory disease states. High output of NO during inflammation is generated by the inducible isoform of nitric oxide synthase (iNOS). Sesquiterpene lactones are derived from Mexican-Indian medicinal plants and are known to have potent anti-inflammatory properties. The mechanisms by which sesquiterpene lactones exert their anti-inflammatory effects are not fully understood. In the current studies we determined if the sesquiterpene lactones, parthenolide and isohelenin, modulate iNOS gene expression in cultured rat aortic smooth muscle cells (RASMC) treated with lipopolysaccharide and interferon-gamma. Treatment with parthenolide or isohelenin inhibited NO production and iNOS mRNA expression in a concentration-dependent manner. Transient transfection studies with an iNOS promoter-luciferase reporter plasmid demonstrated that parthenolide and isohelenin also inhibited activation of the iNOS promoter. Inhibition of iNOS promoter activation was associated with inhibition of both I-kappaBalpha degradation and nuclear translocation of NF-kappaB. Neither parthenolide nor isohelenin induced the heat shock response in RASMC. We conclude that sesquiterpene lactones inhibit iNOS gene expression by a mechanism involving stabilization of the I-kappaBalpha/NF-kappaB complex. This effect is not related to induction of the heat shock response. The ability of sesquiterpene lactones to inhibit iNOS gene expression may account, in part, for their anti-inflammatory effects.