Mediators and Cytokines in Persistent Allergic Rhinitis and Nonallergic Rhinitis with Eosinophilia Syndrome

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1 beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1 beta was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL-5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES. Copyright (C) 2012 S. Karger AG, Base

A common language to assess allergic rhinitis control : results from a survey conducted during EAACI 2013 Congress

Peer reviewedPublisher PD

CT-Scans of Cochlear Implant Patients with Characteristics of Pendred Syndrome

Background: Sensorineural hearing loss (SNHL) in newborns is estimated with an incidence around 1:10,000 per year and is divided into syndromic and non-syndromic forms. In case of present retrocochlear function‚ cochlear implantation allows speech and cognitive development in affected children, comparable to that of normal hearing children. Pathogenesis of SNHL remains unclear in many cases. Imaging of the temporal bone, such as computed tomography (CT) and magnetic resonance imaging (MRI), can reveal conspicuous findings, e.g. enlarged vestibular aqueduct (EVA) and Mondini malformation (MM) of the cochlea. These malformations can be a clinical sign for Pendred syndrome. Methods: We screened CT scans of 75 cochlear implant patients for EVA and MM. Results: Six patients were observed to have either EVA alone (n=3), or MM alone (n=2), or a combination of both (n=1). Further malformations of the temporal bone could be found within the whole group, as well. Conclusion: Our results confirm the general opinion on EVA and MM, being commonly found in patients with SNHL. A possible association with Pendred syndrome needs to be confirmed by genetic investigations with search for mutations in the SLC26A4 gene and further clinical tests, such as Perchlorate test for surveillance of thyroid function

Genetic Determinants of Non-Syndromic Enlarged Vestibular Aqueduct: A Review

Hearing loss is the most common sensorial deficit in humans and one of the most common birth defects. In developed countries, at least 60% of cases of hearing loss are of genetic origin and may arise from pathogenic sequence alterations in one of more than 300 genes known to be involved in the hearing function. Hearing loss of genetic origin is frequently associated with inner ear malformations; of these, the most commonly detected is the enlarged vestibular aqueduct (EVA). EVA may be associated to other cochleovestibular malformations, such as cochlear incomplete partitions, and can be found in syndromic as well as non-syndromic forms of hearing loss. Genes that have been linked to non-syndromic EVA are SLC26A4, GJB2, FOXI1, KCNJ10, and POU3F4. SLC26A4 and FOXI1 are also involved in determining syndromic forms of hearing loss with EVA, which are Pendred syndrome and distal renal tubular acidosis with deafness, respectively. In Caucasian cohorts, approximately 50% of cases of non-syndromic EVA are linked to SLC26A4 and a large fraction of patients remain undiagnosed, thus providing a strong imperative to further explore the etiology of this condition

Twofold spontaneous otogenic pneumocephalus - Case report

Introduction: Occurrence of spontaneous pneumocephalus, without any determined cause like trauma, infection or surgery, is rare. Case report: A 67-year old female patient was admitted to the outpatient clinic due to acute change in personality and occurrence of expressive aphasia. Imaging showed an intracranial pneumocephalus located in the left temporal lobe. High-resolution CT scan of the temporal bone demonstrated an osteo-dural defect of the floor of the middle cranial fossa. The defect was sealed with a duraplasty via a transmastoid approach following a quick postoperative recovery. Discharge was 10 days after surgery. Six weeks later the patient presented with acute emesis, reported clear rhinorrhea and confusion. CT scan showed recurrence of the pneumocephalus on the left side. MRI scan demonstrated another defect in the left lateral temporal bone. A second surgery was performed in which a new osteo-dural leakage was found. The former duraplasty was unremarkable with no sign of liquorrhea. Another duraplasty was carried out. After operation the patient's clinical condition improved again rapidly. She was discharged on the 7th postoperative day. There has been no recurrence ever since. Discussion: Etiology of these two consecutive osteo-dural defects remains unclear. An arachnoidal cyst as possible cause is under debate. However, a review of the radiological images could not confirm this theory. Conclusion: Occurrence of spontaneous pneumocephalus is a rare event and should be considered in case of acute unspecific neurological symptoms. A diverse range of symptoms is described. Mostly surgical intervention is needed

The role of fissula ante fenestram in unilateral sudden hearing loss

El objetivo de este trabajo es la modelización del proceso de reconstrucción del sistema inmune de un paciente. El sistema inmune del paciente ha sido eliminado tras recibir radio o químioterapia, a continuación se procede a re- alizar transplante de células blancas. Con el objetivo de modelizar el proceso, se consideran cuatro ecuaciones diferenciales del modelo propuesto en Szymanska [R.4] y una quinta ecuación del modelo propuesto en de Colijn et al [R.2]. Ésta última ecuación contiene seis parámetros desconocidos, para esti- marlos se ha implementado el método de los mínimos cuadrados utilizando un algoritmo de optimización, conocido como Algoritmo de la colonia de hormi- gas (Ant colony Optimization). El método de los mínimos cuadrados se utiliza para hallar una combinación de parámetros que minimice el error cometido entre los datos reales y los obtenidos mediante la simulación numérica. La simulaciones numéricas son obtenidas por el método de Runge-Kutta y se compara con los datos clónicos proporcionados por el Servicio de Inmunología del Hospital La Paz. La optimización de la colonia de hormigas es un método basado en el comportamiento de las hormigas cuando éstas buscan el camino más corto a la fuente de comida.---ABSTRACT---The main goal of this paper is to model the reconstruction process of the immune system of a patient. Due to the chemotherapy, the immune system of the patient has been destroyed; in order to reconstruct it the patient receives a white cells transplant. Having this objective in mind, 4 di erential equations from the Szymanska's model [ R.4 ] and a fth equation from Colijn's model [ R.5 ] have been studied. The latter has 6 unknown parameters, in order to es- timate them the least squares method has been applied using an optimization algorithm known as the ant colony optimization. The least square method has been used to compute a parameter combination that minimize the distance between the real data and the approximated data. The numerical simulations have been obtained through the Runge-Kutta method and are compared to clinical data provided by the Hospital La Paz. The ant colony optimization is a method based on the ant's behavior when they are looking for the shortest path to the food sourc

Functional Testing of SLC26A4 Variants—Clinical and Molecular Analysis of a Cohort with Enlarged Vestibular Aqueduct from Austria

The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype

Novel POU3F4 variants identified in patients with inner ear malformations exhibit aberrant cellular distribution and lack of SLC6A20 transcriptional upregulation

Hearing loss (HL) is the most common sensory defect and affects 450 million people worldwide in a disabling form. Pathogenic sequence alterations in the POU3F4 gene, which encodes a transcription factor, are causative of the most common type of X-linked deafness (X-linked deafness type 3, DFN3, DFNX2). POU3F4-related deafness is characterized by a typical inner ear malformation, namely an incomplete partition of the cochlea type 3 (IP3), with or without an enlargement of the vestibular aqueduct (EVA). The pathomechanism underlying POU3F4-related deafness and the corresponding transcriptional targets are largely uncharacterized. Two male patients belonging to a Caucasian cohort with HL and EVA who presented with an IP3 were submitted to genetic analysis. Two novel sequence variants in POU3F4 were identified by Sanger sequencing. In cell-based assays, the corresponding protein variants (p.S74Afs*8 and p.C327*) showed an aberrant expression and subcellular distribution and lack of transcriptional activity. These two protein variants failed to upregulate the transcript levels of the amino acid transporter gene SLC6A20, which was identified as a novel transcriptional target of POU3F4 by RNA sequencing and RT-qPCR. Accordingly, POU3F4 silencing by siRNA resulted in downregulation of SLC6A20 in mouse embryonic fibroblasts. Moreover, we showed for the first time that SLC6A20 is expressed in the mouse cochlea, and co-localized with POU3F4 in the spiral ligament. The findings presented here point to a novel role of amino acid transporters in the inner ear and pave the way for mechanistic studies of POU3F4-related H

Data_Sheet_2_Novel POU3F4 variants identified in patients with inner ear malformations exhibit aberrant cellular distribution and lack of SLC6A20 transcriptional upregulation.xlsx

Hearing loss (HL) is the most common sensory defect and affects 450 million people worldwide in a disabling form. Pathogenic sequence alterations in the POU3F4 gene, which encodes a transcription factor, are causative of the most common type of X-linked deafness (X-linked deafness type 3, DFN3, DFNX2). POU3F4-related deafness is characterized by a typical inner ear malformation, namely an incomplete partition of the cochlea type 3 (IP3), with or without an enlargement of the vestibular aqueduct (EVA). The pathomechanism underlying POU3F4-related deafness and the corresponding transcriptional targets are largely uncharacterized. Two male patients belonging to a Caucasian cohort with HL and EVA who presented with an IP3 were submitted to genetic analysis. Two novel sequence variants in POU3F4 were identified by Sanger sequencing. In cell-based assays, the corresponding protein variants (p.S74Afs*8 and p.C327*) showed an aberrant expression and subcellular distribution and lack of transcriptional activity. These two protein variants failed to upregulate the transcript levels of the amino acid transporter gene SLC6A20, which was identified as a novel transcriptional target of POU3F4 by RNA sequencing and RT-qPCR. Accordingly, POU3F4 silencing by siRNA resulted in downregulation of SLC6A20 in mouse embryonic fibroblasts. Moreover, we showed for the first time that SLC6A20 is expressed in the mouse cochlea, and co-localized with POU3F4 in the spiral ligament. The findings presented here point to a novel role of amino acid transporters in the inner ear and pave the way for mechanistic studies of POU3F4-related HL.</p