Significato prognostico dell'ecografia cerebrale nei neonati con infezione congenita da citomegalovirus

Background: Congenital cytomegalovirus (CMV) infection may lead to cerebral injury and neurodevelopmental delay. Cranial computed tomography (CT) is currently the standard imaging technique for predicting the outcome of CMV infected patients. Ultrasound (US) is a safe means to assess the extent of cerebral injury due to CMV infection in neonates, and unlike CT, is readily available at the bedside. Aim: To report the accuracy of US in predicting neurodevelopmental and sensorineural outcome in patients with congenital CMV infection. Study design: 57 newborns with congenital CMV infection underwent brain US and were followed prospectively for motor skills, developmental quotient and hearing function. Results: An abnormal US was found in 12/57 newborns. At least one sequela (Developmental Quotient < 85, motor delay, sensorineural hearing loss) was present in 10/11 surviving children with abnormal US (1 patient died in the neonatal period) vs 3/45 newborns with normal US (OR for death or poor outcome: 154, CI 17.3-1219.6, p<0.001, positive predictive value 91.7%, negative predictive value 93.3%). Conclusion: A good correlation is shown between ultrasound abnormalities and the prediction of outcome, suggesting that US may be used to study and follow CMV infected neonates. Our findings await confirmation in a larger population.

Extraintestinal Crohn's disease mimicking autoimmune inner ear disease: a histopathological approach

Patients with autoimmune inner ear disease develop rapidly progressive sensorineural hearing loss over a period of several weeks or months, often accompanied by vestibular loss. This disease can occur as a distinct clinical entity or in association with an underlying autoimmune disorder. Treatment comprises immunosuppression by corticosteroids, cytostatic drugs or tumor necrosis factor- antagonists. We report histopathological and immunohistochemical findings of the inner ear of a patient with a granulomatous inner ear disease suffering from Crohn's disease that was nonresponsive to treatment and who underwent surgery for bilateral cochlear implants.

Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 microM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

Development of a genotyping microarray for Usher syndrome

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool.

Cochlear implantation in children and adults in Switzerland

The cochlear implant (CI) is one of the most successful neural prostheses developed to date. It offers artificial hearing to individuals with profound sensorineural hearing loss and with insufficient benefit from conventional hearing aids. The first implants available some 30 years ago provided a limited sensation of sound. The benefit for users of these early systems was mostly a facilitation of lip-reading based communication rather than an understanding of speech. Considerable progress has been made since then. Modern, multichannel implant systems feature complex speech processing strategies, high stimulation rates and multiple sites of stimulation in the cochlea. Equipped with such a state-of-the-art system, the majority of recipients today can communicate orally without visual cues and can even use the telephone. The impact of CIs on deaf individuals and on the deaf community has thus been exceptional. To date, more than 300,000 patients worldwide have received CIs. In Switzerland, the first implantation was performed in 1977 and, as of 2012, over 2,000 systems have been implanted with a current rate of around 150 CIs per year. The primary purpose of this article is to provide a contemporary overview of cochlear implantation, emphasising the situation in Switzerland.

Comprehensive measures of sound exposures in cinemas using smart phones

OBJECTIVES Sensorineural hearing loss from sound overexposure has a considerable prevalence. Identification of sound hazards is crucial, as prevention, due to a lack of definitive therapies, is the sole alternative to hearing aids. One subjectively loud, yet little studied, potential sound hazard is movie theaters. This study uses smart phones to evaluate their applicability as a widely available, validated sound pressure level (SPL) meter. Therefore, this study measures sound levels in movie theaters to determine whether sound levels exceed safe occupational noise exposure limits and whether sound levels in movie theaters differ as a function of movie, movie theater, presentation time, and seat location within the theater. DESIGN Six smart phones with an SPL meter software application were calibrated with a precision SPL meter and validated as an SPL meter. Additionally, three different smart phone generations were measured in comparison to an integrating SPL meter. Two different movies, an action movie and a children's movie, were measured six times each in 10 different venues (n = 117). To maximize representativeness, movies were selected focusing on large release productions with probable high attendance. Movie theaters were selected in the San Francisco, CA, area based on whether they screened both chosen movies and to represent the largest variety of theater proprietors. Measurements were analyzed in regard to differences between theaters, location within the theater, movie, as well as presentation time and day as indirect indicator of film attendance. RESULTS The smart phone measurements demonstrated high accuracy and reliability. Overall, sound levels in movie theaters do not exceed safe exposure limits by occupational standards. Sound levels vary significantly across theaters and demonstrated statistically significant higher sound levels and exposures in the action movie compared to the children's movie. Sound levels decrease with distance from the screen. However, no influence on time of day or day of the week as indirect indicator of film attendance could be found. CONCLUSIONS Calibrated smart phones with an appropriate software application as used in this study can be utilized as a validated SPL meter. Because of the wide availability, smart phones in combination with the software application can provide high quantity recreational sound exposure measurements, which can facilitate the identification of potential noise hazards. Sound levels in movie theaters decrease with distance to the screen, but do not exceed safe occupational noise exposure limits. Additionally, there are significant differences in sound levels across movie theaters and movies, but not in presentation time.

Caracterização do perfil audiológico de escolares de escola pública do município de Bauru/SP

Muitos dos problemas auditivos não são notados por pais e professores. Este fato prejudica a aprendizagem da criança principalmente no ambiente escolar. Por isso, programas de triagem auditiva podem ser utilizados com o intuito de detectar e, posteriormente, diagnosticar escolares a fim de que se possa prevenir ou minimizar o impacto a que possíveis sequelas auditivas venham prejudicar o rendimento escolar da criança. Hoje em dia podemos contar com programas que permitem o melhor acompanhamento de populações que necessitam de cuidados preventivos e curativos, e a audição é um aspecto muito importante que pode ser avaliado quando estes programas são colocados em prática. O Programa Nacional de Reorientação da Formação Profissional em Saúde (Pró-Saúde), que visou reorientar a formação profissional, teve como objetivo integrar ensino-serviço e promover atenção básica por meio da abordagem integral do processo saúde-doença. Ambientes externos podem ser utilizados por alunos e professores universitários para que possam colocadas em prática ações que possibilitem a humanização das práticas de atenção a saúde e a integralidade das mesmas, por meio da articulação de ações e serviços de saúde, preventivos e curativos, individuais e coletivos. A escola é considerada um dos ambientes que este trabalho pode ser realizado. O Programa Saúde na Escola (PSE) abre o ambiente escolar com a finalidade de contribuir para a formação integral dos estudantes da rede pública de educação básica por meio de ações de prevenção, promoção e atenção à saúde. Sendo um estudo do tipo retrospectivo transversal, como objetivo principal caracterizar o perfil audiológico de escolares de escola pública do município de Bauru SP, contando com a integração de profissionais da área da saúde e educação no ambiente escolar, o que teve como base os programas citados acima. A triagem auditiva foi realizada com a aplicação dos seguintes procedimentos: imitanciometria, inspeção visual do meato acústico externo, emissões otoacústicas por produto de distorção e audiometria tonal liminar. Observou-se que do total de 652 estudantes, a grande maioria (97,1%) dos participantes com faixa etária entre 10 e 18 anos, apresentaram audição normal. Em 2,9% desta população foi encontrada alguma alteração auditiva temporária. Com a exceção de um único participante, portador de perda auditiva sensorioneural. Apesar de encontrarmos muitas crianças e adolescentes com audição normal, o que mais ressalta a importância deste trabalho é a necessidade da triagem auditiva em ambientes escolares e, essencialmente, o acompanhamento das mesmas nesta faixa etária, já que são escassos os estudos referentes a ela. Apesar das poucas alterações auditivas encontradas serem passageiras, são exatamente estas que interferem no bom rendimento escolar e outros fatores.

Reconhecimento de monossílabos em idosos: análise do nível de apresentação da fala

A perda auditiva no idoso acarreta em dificuldade na percepção da fala. O teste comumente utilizado na logoaudiometria é a pesquisa do índice de reconhecimento de fala máximo (IR-Max) em uma única intensidade de apresentação da fala. Entretanto, o procedimento mais adequado seria a realização do teste em diversas intensidades, visto que o índice de acerto depende da intensidade da fala no momento do teste e está relacionado com o grau e configuração da perda auditiva. A imprecisão na obtenção do IR-Max poderá gerar uma hipótese diagnóstica errônea e o insucesso no processo de intervenção na perda auditiva. Objetivo: Verificar a interferência do nível de apresentação da fala, no teste de reconhecimento de fala, em idosos com perda auditiva sensorioneural com diferentes configurações audiométricas. Métodos: Participaram 64 idosos, 120 orelhas (61 do gênero feminino e 59 do gênero masculino), idade entre 60 e 88 anos, divididos em grupos: G1- composto por 23 orelhas com configuração horizontal, G2- 55 orelhas com configuração descendente, G3- 42 orelhas com configuração abrupta. Os critérios de inclusão foram: perda auditiva sensorioneural de grau leve a severo, não usuário de aparelho de amplificação sonora individual (AASI), ou com tempo de uso inferior a dois meses, e ausência de alterações cognitivas. Foram realizados os seguintes procedimentos: pesquisas do limiar de reconhecimento de fala (LRF), do índice de reconhecimento de fala (IRF) em diversas intensidades e do nível de máximo conforto (MCL) e desconforto (UCL) para a fala. Para tal, foram utilizadas listas com 11 monossílabos, para diminuir a duração do teste. A análise estatística foi composta pelo teste Análise de Variância (ANOVA) e teste de Tukey. Resultados: A configuração descendente foi a de maior ocorrência. Indivíduos com configuração horizontal apresentaram índice médio de acerto mais elevado de reconhecimento de fala. Ao considerar o total avaliado, 27,27% dos indivíduos com configuração horizontal revelaram o IR-Max no MCL, assim como 38,18% com configuração descendente e 26,19% com configuração abrupta. O IR-Max foi encontrado no UCL, em 40,90% dos indivíduos com configuração horizontal, 45,45% com configuração descendente e 28,20% com configuração abrupta. Respectivamente, o maior e o menor índice médio de acerto foram encontrados em: G1- 30 e 40 dBNS; G2- 50 e 10 dBNS; G3- 45 e 10 dBNS. Não há uma única intensidade de fala a ser utilizada em todos os tipos de configurações audiométricas, entretanto, os níveis de sensação que identificaram os maiores índices médios de acerto foram: G1- 20 a 30 dBNS, G2- 20 a 50 dBNS; G3- 45 dBNS. O MCL e o UCL-5 dB para a fala não foram eficazes para determinar o IR-Max. Conclusões: O nível de apresentação teve influência no desempenho no reconhecimento de fala para monossílabos em idosos com perda auditiva sensorioneural em todas as configurações audiométricas. A perda auditiva de grau moderado e a configuração audiométrica descendente foram mais frequentes nessa população, seguida da abrupta e horizontal.

Ototoxicidade

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Defining Atoh1 function and regulation in avian supporting cells during auditory hair cell regeneration

Thesis (Ph.D.)--University of Washington, 2016-06

Mutation in mitochondrial DNA as a cause of presbyacusis

Much of the hearing loss that occurs in old age is likely to be due to the long-term deterioration of the mitochondria in the different structures of the cochlea. The current review surveys some of the basic information on mitochondria and mitochondrial DNA, as a background to their possible involvement in presbyacusis. It is likely that oxygen radicals damage mitochondrial DNA and other components of the mitochondria, such as their proteins and lipids. This further compromises both oxidative phosphorylation and the repair processes in mitochondria, setting up a vicious cycle of degradation. Evidence is presented from inherited point mutations on the possibly most critical sites for mutations in mitochondrial DNA associated with hearing loss. It is suggested that random sorting and clonal expansion of mutations both maintain the integrity of the pool of mitochondrial DNA molecules and give rise to the apoptosis that leads to loss of vulnerable cells, and hence to deafness. It is moreover suggested that apoptosis of the vulnerable cells of the inner ear may to some extent be preventable, or at least delayed. Copyright (C) 2004 S. Karger AG, Basel.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

Fratura traumática do osso temporal : diagnóstico, sequelas e tratamento

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Características sociodemográficas del adulto mayor con deterioro auditivo en el centro de atención del IESS. Cuenca 2015

OBJETIVO GENERAL: Establecer las características sociodemográficas del adulto mayor con deterioro auditivo en el centro de atención del IESS. Cuenca 2015. METODOLOGÍA: Estudio de tipo descriptivo transversal. El universo compuesto por 1800 personas que se encontraron inscritos en el centro de atención del adulto mayor, en la ciudad de Cuenca, 2015. Se trabajó con una muestra de 317 adultos mayores. Este proyecto se realizó mediante: encuestas y audiometrías. Los datos que se obtuvieron fueron analizados en SPSS 20.00 y Excel 2010; para el análisis se utilizó la estadística descriptiva; además personal capacitado realizó la audiometría de tipo tonal, en el Centro de diagnóstico de la Universidad de Cuenca. RESULTADOS: Los resultados obtenidos de las encuestas y de las audiometrías realizadas son los siguientes. De los 317 encuestados (248 (78%) femeninos, 69 (22%) masculinos), las audiometrías realizadas a 160 adultos mayores, presentan algún tipo de deterioro auditivo destacando el grado de audición normal 11% (34), hipoacusia conductiva leve 7% (22), hipoacusia conductiva moderada 3% (11), hipoacusia mixta leve 8% (25), hipoacusia mixta moderada 3% (8), hipoacusia sensorioneural leve 9% (29), hipoacusia sensorioneural moderada 9% (27), hipoacusia sensorioneural severa 1% (3). La información obtenida de la investigación permite establecer una evaluación general del estado actual del grado de audición de los adultos mayores, permite evidenciar la importancia de una atención adecuada a partir de los 60 o más años, para evitar la pérdida de audición por envejecimiento

Does cochlear implantation improve speech recognition in children with auditory neuropathy spectrum disorder? A systematic review

OBJECTIVE: Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. DESIGN: Systematic review. STUDY SAMPLE: A total of 27 studies from an initial selection of 237. RESULTS: All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. CONCLUSIONS: Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.