Almudena Trinidad

Point Mutation of an EYA1‐gene Splice Site in a Patient with Oto‐facio‐cervical Syndrome

Mutations of the EYA1 gene (8q13.3) are the most common known cause of the branchio‐oto‐renal dysplasia (BOR), an autosomal dominant disease that includes developmental defects of branchial arch structures, middle and/or inner ear and kidney. The distinction between BOR and other dysplasias, such as oto‐facio‐cervical syndrome (OFC), is challenged by frequent association of the former to other diverse malformations, and by variable expressivity even within the same family. OFC is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Recent characterization of one OFC patient shed some light on the controversy over whether OFC and BOR are the same disease, and led to the hypothesis that OFC is caused by contiguous deletions of EYA1 and adjacent genes. By contrast, we show here that an OFC patient bears a single‐nucleotide substitution in a splice site of EYA1. Our results indicate that not only major rearrangements, but also point mutations altering the EYA1 reading frame, can be found in patients with OFC syndrome.

Adverse Effects of Glucocorticoid Therapy for Inner Ear Disorders

Background: Because of their anti-inflammatory effects and suppression of the immune system, glucocorticoids have been widely used in otolaryngologic disorders and perioperative conditions. Objective: The objective of the present study was to determine the incidence of adverse effects after the administration of glucocorticosteroids in patients affected by diverse inner ear disorders. Methods: One hundred and sixty-three patients affected by sudden sensorineural hearing loss, 39 with progressive sensorineural hearing loss and 16 with fluctuating sensorineural hearing loss were subjected to glucocorticosteroid therapy with 6-methylprednisolone at a starting dose of 1 mg/kg body weight per day; this therapy was tapered during the next 21–28 days. In 20 patients with profound hearing loss (>70 dB), 3 boluses of prednisolone-21-hydrogen-succinate (500 mg per day) were administered. After receiving the boluses, these patients continued with the oral 6-methylprednisolone scheme. Results: Mild adverse effects were observed in 16 patients (7.01%). Only 2 patients (0.9%) with sudden sensorineural hearing loss showed severe complications: peptic ulcer and avascular necrosis of the femoral heads. Conclusions: The low percentage of severe adverse effects observed in the present study validates the use of corticosteroids for the treatment of inner ear disorders although we should not underestimate these rare complications.

Revisión de las terapias biológicas en la enfermedad inmunomediada del oído interno

INTRODUCTION AND OBJECTIVES Immune-mediated inner ear disease (IMIED) is one of the few reversible forms of sensorineural hearing loss. Treatment is based on high-dose corticosteroids, although long-term therapy is associated with serious adverse effects; this has led to the use of other agents or different routes of administration such as transtympanic delivery. This study analyses the role of biological agents in IMIED management. MATERIAL AND METHODS We searched PUBMED for studies that examined the response to treatment with different biological agents in patients with IMIED. The following data were extracted from the selected studies and entered into a standardised database: exclusion and inclusion criteria, characteristics of the patients studied, treatment, outcome measures and response rates achieved. RESULTS Thirteen studies were included in this review. A TNF alpha inhibitor (etanercept, infliximab, adalimumab) was used in 8 studies, an IL-1 antagonist (anakinra) was used in 3 studies and rituximab, an antibody directed against the CD20 surface antigen on B lymphocytes, was evaluated in 2 studies. Most studies achieved a hearing improvement or stabilisation in more than 70% of treated patients. CONCLUSIONS Biological agents can play a role in the management of patients with IMIED, at least in those patients who do not respond to conventional therapy or whose hearing is not stabilised. However, specially-designed randomised controlled clinical trials are needed to assess their effectiveness.

Cisplatin-induced hearing loss does not correlate with intracellular platinum concentration

Conclusion. Inductively coupled plasma mass spectrometry (ICP-MS) can be applied to organic tissues obtained from experimental animals. Hearing loss does not correlate with the platinum (Pt) concentration found in the inner ear. Drug structure and affinity to inner ear proteins could explain ototoxicity caused by cisplatin. Objectives. To analyse Pt affinity for brain and ear tissues (of similar embryologic origin) in the Wistar rat and clearance gradient after a single dose, and to correlate these findings with hearing changes. Materials and methods. Thirty-two Wistar rats were intraperitoneally injected with cisplatin at a dose of 5 mg/kg. Animals were sacrificed after obtaining auditory brain responses (ABRs) at 3, 7, 30 and 90 days (nine, seven, seven and nine animals, respectively). Brain and both temporal bones were extracted from each animal and analysed by ICP-MS to determine the absolute concentrations of the metal. Eight non-treated animals were employed as a control group. Results. The ABR thresholds were significantly elevated in animals from all groups after cisplatin treatment. A maximum accumulation of Pt for inner ear and brain was revealed around the first week: 3.175 (57%) and 0.342 (72%), respectively. Pt significantly accumulated in greater quantities in ear than in brain (p<0.01) and was cleared at a higher rate in brain than in ear (p<0.01) following cochlea/brain ratio analysis. No statistically significant correlation was found between amounts of Pt and hearing loss in the study animals.

[Autoimmune hearing loss: improving diagnostic performance].

OBJECTIVES Due to the lack of specific serological markers for the diagnosis of immune-mediated hearing loss, an exhaustive immunologic work-up study for patients is usually performed. The aim of the present study is to find the most cost-effective laboratory tests used for the diagnosis of this entity. PATIENTS AND METHOD Comparative study between 2 groups of patients with a high suspicion of suffering diverse clinical forms of immune-mediated hearing loss, subjected to different serologic testing designs: the classical immunologic work-up study (125 patients) in comparison with a more restricted examination analysis (57 patients), based on a high risk profile recently reported. RESULTS Diagnostic efficiency was similar. CONCLUSIONS Since financial resources are limited, ANA and immunophenotype of PBL (peripheral blood lymphocytes) are recommended for the evaluation of a patient with suspected immune-mediated hearing loss.

Anti-adhesive properties of polytetrafluoroethylene (Gore-Tex) in middle ear surgery. An experimental study.

Conclusions. Polytetrafluoroethylene (PTFE) may represent a material that prevents adhesions when implanted in the middle ear. This characteristic can be used to improve the design of prostheses. Objective. Prostheses in the middle ear have a relatively high failure rate due to extrusion, deformation and adhesion. Adhesion of prostheses to the walls of the tympanic cavity is the commonest cause of long-term hearing loss. The anti-adhesive properties of PTFE have been previously studied in abdominal and vascular surgery. To the best of our knowledge, this is the first work in which the properties of PTFE have been studied in the context of middle ear pathology. Material and methods. In order to induce otitis media with effusion, 27 Wistar rats underwent a technique based on permanent cauterization of the pharyngeal Eustachian tube. PTFE was subsequently implanted in the middle ear. Rats that underwent cauterization without implantation and cauterization with implantation of hydroxyapatite and Plastipore were included as controls. Results. Histopathological study of the tympanic bullae at 15 and 90 days after implantation demonstrated good biocompatibility of the PTFE implant under the analyzed conditions, with formation of a capsule around the material and no adhesions between the ear tissues and the prosthesis.

Sordera autoinmunitaria: mejorando el rendimiento de su diagnóstico

Objetivos La falta de especificidad de los marcadores serologicos para el diagnostico de la sordera inmunomediada obliga a realizar un exhaustivo estudio inmunologico. El objetivo del presente trabajo consiste en la busqueda de las pruebas de laboratorio mas sensibles para el diagnostico controvertido de esta entidad. Pacientes y metodo Estudio comparativo entre dos grupos de pacientes con un alto indice de sospecha de sordera inmunomediada, sometidos a distintos protocolos de estudio: analisis clasico, que incluia una bateria exploratoria mas amplia y un mayor numero de pacientes (125) frente a un estudio restringido, basado en un perfil de alto riesgo recientemente descrito por nuestro grupo, que incluyo a 57 pacientes. Resultados La eficiencia diagnostica obtenida con ambos protocolos fue similar. Conclusiones Dado que los recursos financieros son limitados, se aconseja aplicar una bateria exploratoria restringida al estudio de los ANA y al inmunofenotipo para el diagnostico de la sordera inmunomediada.

Spontaneous otitis media in Wistar rats: an overlooked pathology in otological research.

The rat is commonly employed in otological research, but spontaneous ear infections can confound the results of experimental procedures—wasting time, money, and animals. The authors focus on the incidence of spontaneous otitis media in Wistar rats. They compare disease incidence in animals housed in standard cages with those housed in barrier units, showing that 20% of their conventionally housed animals developed spontaneous otitis media, whereas only 5% of their animals housed in isolated units were infected. These results underscore the importance of strict control of the shipping, housing conditions, and manipulation of animals to be used in otological research.

Inner Ear Malformations: Mondini’s Dysplasia

Advances in imaging techniques are enabling the detection of increasing numbers of inner ear malformations. Mondini’s dysplasia, whether alone or in association with other malformations, is one of those most frequently encountered. We report 4 cases of Mondini’s dysplasia treated by us, discussing recent embryological and genetic findings.

Estudio ultraestructural de la porción lateral del órgano sensorial auditivo mediante un método sin descalcificación

Objetivo Explicar el desarrollo de una tecnica personal de estudio de la estria vascular y ligamento espiral de la coclea en cobaya mediante la obtencion de la muestra sin necesidad de descalcificacion y valorar su validez para su analisis con microscopio electronico. Material y metodo Se obtuvieron muestras de 5 hembras de cobaya de 200-250 g que se fijaron con glutaraldehido y paraformaldehido, y se analizo la ultraestructura del ligamento espiral y la estria vascular obtenidos mediante microscopio electronico de transmision. Resultados Se pudo observar todos los componentes ultraestructurales del ligamento espiral y la estria vascular sin necesidad de descalcificar. Conclusiones Nuestro metodo de obtencion de las muestras es una forma valida, sencilla y mas rapida que otros metodos para la obtencion y el estudio de la porcion lateral de la coclea.