A pesquisa dos potenciais evocados auditivos de tronco encefálico (PEATE) foi indicada para os casos onde há suspeita ou presença de síndromes genéticas pelo Joint Committee on Infant Hearing em 2007. O comitê fornece as diretrizes para a detecção das perdas auditivas na infância, para as quais as síndromes são fator de risco. A alta prevalência da SD e de alterações auditivas nesta população reforça a importância da identificação das perdas auditivas até os três meses de idade, como forma de minimizar os decorrentes prejuízos na comunicação. Este estudo, aprovado pela Comissão de Ética para análise de projetos de pesquisa do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), teve como objetivo descrever as avaliações da audição de 30 crianças com SD, sem queixas otológicas, das quais 25 bebês (idade média de 2,47 meses) compuseram a amostra. Método: Foram pesquisados os PEATE durante o sono natural. A amostra foi analisada por bebês e por orelhas. Os bebês e as orelhas foram agrupados por intensidade de limiar eletrofisiológico: G1 (<= 30 dBNA), G2 (30 | 40 dBNA), G3 (> 40 dBNA) e registradas as latências absolutas I, III e V e as inter-latências I-III, III-V e I-V. Resultado: Dos 25 bebês, 3 apresentaram alteração neurossensorial ao menos unilateral (12%), 5 alteração condutiva (20%) e 17 (68%) indicaram resultados normais ao PEATE. Limiares eletrofisiológicos foram encontrados em 76% (n=38) das orelhas estavam abaixo, e em 24% (n=12), acima de 40 dBNA. Os grupos G1 e G2 apresentaram respostas equivalentes exceto para a latência absoluta da onda V e inter-latência III-V, que estiveram encurtadas no G2 em relação ao G1 (p<0,02;p=0,04) Discussão: Vários autores sugerem maior ocorrência de alterações condutivas entre portadores de SD. A prevalência de alterações auditivas condutivas e neurossensoriais encontradas nos bebês neste estudo apontam para a importância da investigação da via auditiva até os três meses de idade. Conclusão: A perda auditiva é uma alteração frequente em bebês com SD. Ocorreram alterações tanto condutivas quanto neurossensoriais nas orelhas com limiar alterado. As alterações neurossensoriais encontradas neste estudo reforçam a importância da adoção de procedimentos preventivos de avaliação da audição em bebês com SD e consequente intervenção / Introduction: The study of evoked auditory brainstem response (ABR) was indicated for cases of genetic syndromes by the Joint Committee on Infant Hearing in 2007. These guidelines indicate the detection of hearing loss in the childhood, for which genetic syndromes are a risk factor. The high prevalence of DS and of hearing disorders in this population reinforces the importance of identifying hearing loss by 3 months of age, to minimize the losses arising in communication. The main objective of this study, approved by the Ethics Committee of University of São Paulo, School of Medicine, Clinical Hospital (HCFMUSP) was to characterize the hearing ability of 30 children with Down syndrome, of which 25 babies (mean age 2.47 months), with no history of ear disease, comprised the sample. Method: ABR test has been performed during natural sleep. The babies and the ears were put together in groups by threshold level: G1 (<= 30 dB HL), G2 (30 |40 dB HL), G3 (over 40 dB HL). Results: Out of 25 babies, 3 (12%) had sensory neural hearing disorder in at least one ear; 5 (20%) had conductive hearing disorder in at least one ear and 17 (68%) had normal results on the ABR. Electrophysiological thresholds under 40 dB HL have been obtained in 76% (n = 38) of tested ears under, and in 24% (n = 12) over 40 dB HL. Groups G1 and G2 have had similar response, except for III-V interval shortened in G2 when compared to G1. Discussion: Many authors suggest conductive losses are more frequent than sensory neural losses in this population. The prevalence of sensory neural hearing disorder found in these babies point to the importance of investigating the auditory pathway. The group with thresholds between 30 and 40 dB HL was similar to the normal group, except for shortening of interval III-V. Statistically significant differences were found between normal and abnormal in the ABR. Conclusion: Sensory neural losses found in this study reinforce the importance of adopting preventive procedures for evaluating the hearing and subsequent intervention

Introdução: O Acidente Vascular Cerebral do tipo isquêmico é um quadro clínico que afeta milhares de pessoas no mundo. Como resultado dessa injúria observamos morte neuronal, e no decorrer natural de recuperação, o indivíduo pode desenvolver a sepse. A sepse é uma resposta inflamatória sistêmica que pode levar o indivíduo a morte. No seu desenvolvimento há a produção de diversas citocinas que caracterizam o processo inflamatório no organismo. Para avaliar as condições clínicas de um paciente com esse quadro o Potencial Evocado Auditivo de Tronco Encefálico (PEATE) pode ser útil,uma vez que ele não é um procedimento invasivo, sua técnica é rápida e pode ser feita à beira do leito. Porém, por outro lado, o PEATE pode ser sensível ao uso de alguns anestésicos. Objetivos: Fazer análise das citocinas IL-6, IL-10 e TNF- no decorrer da sepse; verificar os valores de latência do PEATE em gerbils submetidos à isquemia e sepse; e verificar a influência do anestésico ketamina associado à xilazina nos valores do PEATE desses animais. Método: Foram coletados os PEATEs de 72 gerbils machos adultos que foram divididos em 6 grupos, a saber: controle, sepse, isquemia, sham, isquemia com sepse e sham com sepse. Para a indução de sepse foi aplicado Lipopolissacarídeo (LPS) intraperitoneal nos gerbils. Os animais foram anestesiados antes das coletas com ketamina associada à xilazina, seus PEATEs foram coletados antes de qualquer procedimento (coleta base), após isquemia e 2, 4, 8 e 24 horas após a aplicação de LPS. Foi avaliada a latência absoluta da onda V, e os valores foram comparados intra e intergrupos. As citocinas IL-6, IL-10 e TNF- foram analisadas e comparadas em cada grupo estudado. Resultados: Foi observado aumento das citocinas IL-6, IL-10 e TNF- no decorrer da sepse. Houve diferença estatisticamente significante nos grupos submetidos à sepse no valor da latência da onda V em relação aos demais grupos. Observou-se, também, aumento da latência da onda V após a aplicação sucessiva do anestésico ketamina/xilazina em todos os grupos estudados. Conclusão: Houve aumento dos níveis das citocinas IL-6, IL-10 e TNF- nos animais que sofreram aplicação de LPS, revelando uma alteração de expressão gênica de moléculas pró (IL-6 e TNF-) e anti-inflamatória (IL-10) no decorrer da sepse.O PEATE se mostrou sensível a sepse com aumento de latência da onda V no desenvolver da doença no modelo experimental utilizado. O uso de Ketamina associada à xilazina influenciou o resultado do PEATE, aumentando o valor de latência absoluta da onda V do PEATE / Introduction: The Cerebrovascular Accident of ischemic type is a clinical condition affecting thousands of people around the world. As a result of this injury we observe neuronal death, and along the natural course of recovery individuals may develop sepsis. Sepsis is a systemic inflammatory response that may lead to death. Along its development, several cytokines are produced that characterize the inflammatory process on the body. To assess the clinical conditions of a patient with this condition the Auditory Brainstem Response (ABR) may be useful, as it is not an invasive procedure, it is fast to perform, and may be done at the patients bedside. On the other hand, the ABR may be sensitive to the use of some anesthetics. Objectives: To perform an analysis of the IL-6, IL-10 and TNF- cytokines in the course of sepsis; to verify the ABR latency values in gerbils submitted to ischemia and sepsis; and to verify the influence of the ketamine/xylazine anesthetic on the ABR values in these animals. Method: ABRs were collected for 72 adult male gerbils divided into 6 groups, namely: control, sepsis, ischemia, sham, ischemia with sepsis and sham with sepsis. For induction of sepsis, intraperitoneal lipopolysaccharide (LPS) was injected into the gerbils. The animals were anesthetized prior to the collections with ketamine/xylazine, theirs ABRs were collected before any procedure (base collection), after ischemia and 2, 4, 8 and 24 hours after the LPS injection. The absolute latency of the V wave was assessed, and values were compared within and among groups. The IL-6, IL-10 and TNF- cytokines were analyzed and compared in each study group. Results: An increase was observed in IL-6, IL-10 and TNF- cytokines in the course of sepsis. There was a statistically significant difference in the groups submitted to sepsis in the value of the V wave latency compared to the other groups. An increase in the V wave latency was also observed after successive injection of the ketamine/xylazine anesthetic in all study groups. Conclusion: There was an increase in the levels of IL-6, IL-10 and TNF- cytokines in the animals injected with LPS, revealing a change of the gene expression of the pro- (IL-6 and TNF-) and anti-inflammatory (IL-10) molecules in the course of sepsis. The ABR proved to be sensitive to sepsis with an increase of the V wave latency in the course of the disease on the experimental model used. The use of ketamine/xylazine influenced the results of the ABR, increasing the absolute latency value for the V wave of the ABR

Made available in DSpace on 2016-04-27T18:11:55Z (GMT). No. of bitstreams: 1 Daniela Veronese Bento.pdf: 1507917 bytes, checksum: 505321b79ebbf90c862cd111179b4352 (MD5) Previous issue date: 2012-02-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / INTRPDUCTION: Many different rates for ABR can be used to sensitize the exam. However, due to possible differences that can occur in the latencies and amplitudes when using ABR, it is necessary to carry out research to support the audiological diagnosis and help the clinical decision-making process. AIM: To study the influences at the two different repetition stimulus rates in the ABR in adults, neonates and premature infants. METHOD: ten normal-hearing neonates (GI), adults (GII) and premature infants (GIII) were subjected to ABR registration by air with repetition rates from 27.7 to 61.1 clicks per second (intensities: 80, 60, 40 and 20 dBHL). RESULTS: The arithmetic means and medians showed adjacent values for each combination of repetition rate and groups, which suggests that the distribution of the variables shows symmetry. Nevertheless, at 80 dBHL, the repetition rate of 61.1 clicks per second attained an absolute latency in waves I, II and V augmented in the groups GI and GIII (P=0.003, P=0* and P=0, respectively) and the amplitude in waves III and V reduced in the GI and GII (P=0.014 and P=0*). Wave III had the most reduced amplitude with a rarefied polarity (P=0.014). Moreover, the latency time during interpeak intervals I-III were higher for GI and GIII (P=0.0035); during III-V were higher for GIII (P=0*) and during I-V were higher for GI (P=0*). At 60 dBHL, the latency was higher for GI and GIII, -at 61.1 clicks per second in the three groups (P=0+)-, and the amplitude was more reduced for GI and GII (P=0,001). At 40 dBHL, two repetition rates attained a higher latency and reduced amplitude for GI and GII (P=0,005 and P=0,001, respectively); however, the three groups presented a higher latency time at 61.1 clicks per second (P=0,005). At 20 dBHL, the latency was higher for GII and GIII - 61.1 clicks per second (p=0,020)-, and the amplitude was smaller for GI and GIII (P=0,002). The exam length was higher - 27.7 click per second (P=0*)- in the three groups. CONCLUSION: Despite the latency increase and amplitude reduction, the method of raising the repetition rate of the acoustic stimuli to register electrophysiological hearing responses can be incorporated to sensitize the exam and decrease its duration / INTRODUÇÃO: O estímulo clique é utilizado para avaliar a integridade do sistema auditivo e verificar a sincronia neural. No registro do Potencial Evocado Auditivo de Tronco Encefálico (PEATE) podem ser utilizadas diferentes taxas de apresentação do clique para sensibilizar o exame. Entretanto, devido a possíveis diferenças que podem ocorrer nas latências e amplitudes no PEATE, faz-se necessária a realização de um estudo que forneça dados normativos, para fundamentar o diagnóstico audiológico e auxiliar na tomada de decisões quanto aos protocolos utilizados na prática clínica. OBJETIVO: Estudar a influência de duas taxas diferentes de repetição do estímulo clique no PEATE, em adultos, neonatos-termo e prematuros. MÉTODO: Dez neonatos-termo (GI), dez adultos (GII) e dez neonatos prétermos (GIII) com audição normal foram submetidos ao registro do PEATE por via aérea nas taxas de repetição de 27.7 e 61.1 cliques/segundo nas intensidades de 80, 60 40 e 20 dBnNA. RESULTADOS: As médias e medianas apresentaram valores próximos para cada combinação de taxa de repetição e grupos, sugerindo que a distribuição das variáveis estudadas apresenta simetria. Entretanto, na intensidade de 80 dBnNA, a taxa de repetição de 61.1 cliques/segundo obteve a latência absoluta das ondas I, III e V aumentada nos grupos GI e GIII (valor P=0,003, valor P=0+ e valor P=0+, respectivamente) e amplitude das ondas III e V reduzida no GI e GII (valor P=0,014 e valor P=0+), sendo que a onda III teve amplitude mais reduzida com a polaridade rarefeita (valor P=0,014). Além disso, o tempo de latência dos intervalos interpicos I-III foi maior para o GI e GIII (valor P=0,035); em III-V foi maior para o GIII (valor P=0+) e em I-V foi maior para o GI (valor P=0+). Em 60 dBnNA, a latência foi maior para GI e GIII, e em 61.1 cliques/segundo nos três grupos (valor P=0+), e a amplitude foi menor para GI e GIII (P=0,001). Em 40 dBnNA, as duas taxas de repetição obtiveram latência maior e amplitude menor em GI e GIII (valor P=0,005 e valor P=0,001, respectivamente); entretanto, os três grupos apresentaram tempo de latência maior em 61.1 cliques/segundo (valor P=0,005). Em 20 dBnNA, a latência foi maior para GII e GIII em 61.1 cliques/segundo (valor P=0,020), e a amplitude foi menor para GI e GIII (valor P=0,002). A média de duração do exame foi maior em 27.7 cliques/segundo (valor P=0+) nos três grupos. CONCLUSÃO: Apesar do aumento da latência e da diminuição da amplitude, o método de elevar a taxa de repetição do estímulo acústico para registrar respostas eletrofisiológicas da audição pode ser incorporado para sensibilizar o exame, investigando a integridade do sistema auditivo e a sincronia neural, com tempo de realização do exame diminuído

Made available in DSpace on 2016-04-27T18:11:56Z (GMT). No. of bitstreams: 1 Taise Argolo Sena.pdf: 595972 bytes, checksum: 7693a80adc39a593cccdae56ded0102f (MD5) Previous issue date: 2012-02-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Introduction: The Automated Auditory Brainstem Response (AABR) is an important tool to make Newborn Hearing Screening. However, some aspects that make it more difficult to exam, like time and intensity of acoustic stimulus, must be taken into consideration. Aim: Analyze the results of Newborn Hearing Screening with Automated Auditory Brainstem Response with new technologies that use the detection method in the frequency domain and stimulus repetition rate at 93Hz. Methodology: The Automated Auditory Brainstem Response was made at 200 newborns (93 female and 107 male), at 30 and 35dBnHL. Subsequently all newborns were submitted to the Auditory Brainstem Response (ABR) Diagnostic Mode, as golden standard test. Results: The sensibility and specificity were calculated through Fisher Exact Test taken into consideration the ABR Diagnostic Mode. The sensibility found at AABR at 35dBnNA was 100% and the specificity was 100%, at the intensity of 30dBnNA the sensibility found was 100% and the specificity was 97.23%. The average time to make the automated exam was 28.3 seconds in the 35 dBnHL and 32.9 seconds in the 30 dBnHL. The time was analyzed considering the state of consciousness of the newborn, based on the Brazelton Scale classification. It was possible to notice that when the newborn was quieter the examination time was quicker. Conclusion: The AABR made at frequency domain with stimulus repetition rate at 93Hz shows high sensibility and specificity, with relative short time to get the results. The state of consciousness influences the execution time of the exam. / Introdução: O Potencial Evocado Auditivo de Tronco Encefálico Automático (PEATE-A) é uma ferramenta importante para realização da Triagem Auditiva Neonatal. Entretanto, alguns aspectos que dificultam a realização do exame, como o tempo e a intensidade do estímulo acústico, devem ser levados em consideração. Objetivos: Analisar os resultados da Triagem Auditiva Neonatal com Potencial Evocado Auditivo de Tronco Encefálico Automático, com novas tecnologias que utilizam método de detecção no domínio da frequência e taxa de repetição do estímulo a 93Hz. Metodologia: O Potencial Evocado Auditivo de Tronco Encefálico Automático foi realizado em 200 neonatos (93 do sexo feminino e 107 do masculino), nas intensidades de 30 e 35dBnNA. Em seguida, todos os neonatos foram submetidos ao exame de Potencial Evocado Auditivo de Tronco Encefálico (PEATE) Modo Diagnóstico, como teste padrão ouro. Resultados: A sensibilidade e especificidade foram calculadas por meio do Teste Exato de Fisher, levando em consideração o resultado do PEATE Modo Diagnóstico. A sensibilidade encontrada para o PEATE-A na intensidade de 35dBnNA foi de 100% e a especificidade de 100%; para a intensidade de 30dBnNA a sensibilidade encontrada foi de 100% e a especificidade, de 97,23%. O tempo médio de realização do exame automático foi de 28,3 segundos para a intensidade de 35 dBnNA e de 32,9 segundos para a intensidade de 30dBnNA. O tempo também foi analisado de acordo com o estado de consciência do neonato, conforme a classificação da Escala de Brazelton. Foi possível observar que quanto mais quieto o neonato, mais rápido o tempo de realização do exame. Conclusão: O PEATE-A realizado no domínio da frequência com taxa de repetição em 93Hz apresenta alta sensibilidade e especificidade, com tempo consideravelmente curto para a determinação da resposta. O estado de consciência influencia no tempo de execução do exame

Made available in DSpace on 2016-04-27T18:12:05Z (GMT). No. of bitstreams: 1 Raquel Alves Nobre.pdf: 1069573 bytes, checksum: b8d1295a1b5de37c7e8a3aac4652d769 (MD5) Previous issue date: 2014-09-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Universal Newborn Hearing Screening (UNSH) aims to provide early diagnosis in newborns. The procedure uses objective measures such as the Transient Evoked Otoacustic Emissions (TEOAEs) and the Auditory Brainstem Response (ABR). Different stages and protocols are broadly used in TANU, and that may change the values of passes and fails of each program. Purpose: To study the rate of passes and fails in the protocols and stages that are used at TANU, which were performed using electroacoustic (TEOAEs) and electrophysiological (ABR) procedures through an integrative review. Methods: Type of study: An integrative review. Search strategy: The following databases were examined: PubMed, SciELO and SCOPUS.Criteria for selecting the readings: Articles that have evaluated at least a minimum of 1,000 newborns; specifying the time (hours of life of the newborn) in which the test was accomplished; articles specifying how many days later the retest was performed after the hospital discharge, if the infant failed the test; in the article´s methodology the tests that were used and its stages must be included. The method of choice should be: TEOAEs test and retest in newborns with no risk; TEOAEs in conjunction with ABR and ABR in the retest in newborns with no risk and ABR on the test and retest in newborns with a risk factor; the results should present the pass and fail results of each step, such as the diagnosis result. Results: A total of 3950 references were found in English, Portuguese and Spanish. After removing duplicated studies (300), 3650 references were obtained, that were analyzed through titles and summaries. Of this total, 3500 were excluded for being researches with different topics. Hereby, 15 filled all the inclusion criteria. The final rates of pass and fail found in the studied protocols were the following: for the TEOAEs test/retest protocol the pass rate varied from 99,53% to 97,39% and the fail rate from 2,41% to 0,44%. In the TEOAEs and ABR test protocol and in the ABR retest the pass results ranged from 99,84% to 98% and fail from 0,35% to 0,16%. And in the ABR test/retest protocol in newborns with risk factors the pass rate was reached from 98,62% to 92,74% and the fail rate from 1,7% to 1,38%. All the pass and fail rates are within of what is recommended by literature. Conclusion: The protocol that presented the smaller number of false positives was the TEOAEs combined with the ABR in the test and ABR in retest. The findings indicate that the probability of fail for the TEOAEs in the test and retest is larger than the TEOAEs and ABR in the test and ABR in retest, both for the newborns screened until 24 hours of life and for the newborns screened between 25 and 72 hours of life / A Triagem Auditiva Neonatal Universal (TANU) tem como objetivo realizar o diagnóstico precoce em neonatos. A sua realização utiliza medidas, como as emissões otoacústicas evocadas por estímulo transiente (EOAET) e o potencial evocado auditivo de tronco encefálico (PEATE). Diferentes etapas e protocolos são utilizados na TANU, o que pode alterar os índices de passa e falha de cada programa. Objetivo: Estudar os resultados de índice de passa-falha dos protocolos e etapas utilizados na TANU, realizada com procedimentos eletroacústicos (EOAET) e eletrofisiolóficos (PEATE) por meio de uma revisão integrativa. Método: Tipo de estudo: Revisão integrativa Estratégia de busca: Foram pesquisadas as seguintes bases de dados: PUBMED, SCieLO e SCOPUS. Critério para a seleção dos estudos: artigos que avaliaram um número mínimo de 1000 neonatos; artigos que especificaram as horas de vida do neonato em que foi realizado o teste; artigos que especificaram quantos dias depois da alta hospitalar foi realizado o reteste, caso o neonato falhasse no teste; no método, deveriam constar quais os testes utilizados e suas etapas. Neste caso, os testes utilizados deveriam ser: EOAET no teste e no reteste em neonatos sem risco; EOAET combinado com PEATE no teste e PEATE no reteste em neonatos sem risco e PEATE no teste e no reteste em neonatos com risco; os estudos deveriam apresentar o resultado de passa e falha de cada etapa, assim como o resultado do diagnóstico. Resultados: Foi identificado um total de 3950 referências no idioma inglês, português e espanhol. Após a remoção dos estudos duplicados (300), foram obtidas 3650 referências, que foram analisadas por meio dos títulos e dos resumos. Deste total, 3500 foram excluídos por se tratarem de pesquisas com outro tema. Desta forma, 150 estudos foram selecionados, na íntegra. Deste total, 15 preencheram todos os critérios de inclusão. Os índices de passa e falha final encontrados nos protocolos estudados foi de: para o protocolo EOAET no teste e reteste, o índice de passa variou de 99,53 a 97,39% e falha de 2,41% a 0,44%. No protocolo de EOAET combinado com PEATE no teste, e PEATE no reteste foi de passa em 99,84% a 98%, e falha de 0,35% a 0,16%. No protocolo PEATE no teste e reteste em neonatos com risco o índice de passa foi de 98,62% e 92,74% e falha de 1,7% e 1,38%. Todos os índices de passa e falha estão dentro do que é recomendado pela literatura. Conclusão: O protocolo que apresentou menor número de falso-positivo foi o EOAET combinado com PEATE no teste, e PEATE no reteste. Os resultados mostram que a probabilidade de falha para protocolo- EOAET no teste e reteste é maior do que para o protocolo- EOAET combinado com PEATE no teste, e PEATE no reteste, tanto para o neonatos triados até 24 horas de vida, quanto para o grupo de neonatos triados entre 25 e 72 horas

No description available.

<p>Topical treatment of several inner ear diseases through the round window membrane (RWM) might be feasible in the near future. Bacteria toxins, ototoxic drugs and noise trauma seem to harm the inner ear by a common pathway which involves, excessive outflow of the afferent neurotransmitter glutamate and formation of nitric oxide (NO), which can severely damage cells/nerve endings and lead to cell death.</p><p>In this study we used 98 Sprague-Dawley rats and seven human temporal bones. Various substances were instilled into the middle ear of the rat, such as Pseudomonas Aeruginosa Exotoxin (PaExoA), gentamicin, NO-inhibitor N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME), and glucocorticoids. The effects of the substances were studied by morphological analysis of RWM and the endolymphatic sac (ES) by light and electron microscopic. Hearing level was measured in the rats by ABR technique. The human temporal bones were studied immunomorphologically to search for glutamate.</p><p>In the human inner ear, glutamate receptors and glutamine synthetase, were identified. In the rat, we found, following PaExoA exposure, reversible and permanent hearing loss and morphological changes in the RWM. The ES showed increased numbers of macrophages and thickening of the epithelia. When L-NAME was used as an otoprotector from gentamicin ototoxicity a therapeutic effect in the high frequency area was found. Hydrocortisone (but not dexamethasone) exposure of the RWM resulted in membrane thickening, and adjacent to the membrane, inflammatory cells.</p><p>The importance of the RWM as a portal for toxic substances and topical treatment of inner ear diseases was highlighted in this study. The difficulties of applying drugs in the round window niche were exposed. The results of this study add important knowledge concerning certain mechanisms of inner ear injury and help us to understand possibilities and problems of local treatment of inner ear diseases in patients.</p>

Topical treatment of several inner ear diseases through the round window membrane (RWM) might be feasible in the near future. Bacteria toxins, ototoxic drugs and noise trauma seem to harm the inner ear by a common pathway which involves, excessive outflow of the afferent neurotransmitter glutamate and formation of nitric oxide (NO), which can severely damage cells/nerve endings and lead to cell death. In this study we used 98 Sprague-Dawley rats and seven human temporal bones. Various substances were instilled into the middle ear of the rat, such as Pseudomonas Aeruginosa Exotoxin (PaExoA), gentamicin, NO-inhibitor N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME), and glucocorticoids. The effects of the substances were studied by morphological analysis of RWM and the endolymphatic sac (ES) by light and electron microscopic. Hearing level was measured in the rats by ABR technique. The human temporal bones were studied immunomorphologically to search for glutamate. In the human inner ear, glutamate receptors and glutamine synthetase, were identified. In the rat, we found, following PaExoA exposure, reversible and permanent hearing loss and morphological changes in the RWM. The ES showed increased numbers of macrophages and thickening of the epithelia. When L-NAME was used as an otoprotector from gentamicin ototoxicity a therapeutic effect in the high frequency area was found. Hydrocortisone (but not dexamethasone) exposure of the RWM resulted in membrane thickening, and adjacent to the membrane, inflammatory cells. The importance of the RWM as a portal for toxic substances and topical treatment of inner ear diseases was highlighted in this study. The difficulties of applying drugs in the round window niche were exposed. The results of this study add important knowledge concerning certain mechanisms of inner ear injury and help us to understand possibilities and problems of local treatment of inner ear diseases in patients.

Myringotomy plays an important role in otological therapy. The procedure requires an efficient anesthesia, which can be obtained without general anesthesia. However, the use of local anesthetics on the tympanic membrane (TM) has been abandoned in many places, as general anesthesia has been readily available. In the present study the effects of some commonly used topical anesthetics on the TM structure and inner ear were tested in an animal model (rat and guinea pig).Four different anesthetic compounds—Xylocaine®, Bonain's liquid, phenol and Emla®—were applied to the TMs of the animals, which were sacrificed 10 minutes to 5 months after application. Morphological effects regarding time after treatment and number of applications were elucidated. At sacrifice the tissue was fixed and the TMs analysed by light microscopy (LM) and transmission electron microscopy (TEM). In nine animals phenol, Xylocaine® Spray or Emla® was applied to the round window niche and ABR recordings were made at 24 h to 6 months after exposure. After the final ABR evaluation the animals were sacrificed and the cochleae prepared for LM and scanning electron microscopy (SEM).On the TM phenol and Bonain's liquid caused instant destruction of the keratinizing stratified squamous epithelium followed by long-lasting hyperplasia of this epithelium and the underlying connective tissue. A pronounced hyperplasia of these two layers was also noted for the Xylocaine® Spray group, but without immediate destruction of the keratinizing epithelium. The extent of structural changes differed in relation to the extent of spreading of the agent. Emla® showed little, if any, sign of epithelial reaction and had no effect on the connective tissue. Regarding the inner ear Emla®, Xylocaine® Spray and phenol induced significantly impaired ABR thresholds mainly affecting the higher frequencies. However, the impaired ABR thresholds were reversible and at the end of the experiment there was no significant impairment compared to the control data. All agents, except Xylocaine®, damaged the hair cells in the basal part of the cochlea as shown by cytocochleogram and SEM analysis.Instant destruction of the epidermis seems to be necessary for an instant anesthetic effect. All agents caused profound connective tissue reactions. The manner of application, depending on the physical properties of the agent, determined the extent of the structural changes. The changes of the connective tissue were concentrated to the submucosal layer, which seems to be the area for reconstruction of the damaged TM. All agents caused functional inner ear changes. With the exception of Xylocaine® they also caused morphological alterations of the cochlea. The functional changes were partly reversible. Topical anesthetics applied to the TM should be used with caution and when used in an appropriate manner they can be considered safe, especially in an inflamed middle ear, with a thickened round window membrane, which should prevent the agents from reaching the inner ear structures. / digitalisering@umu

Intratympanic injection of various otoprotectants through the round window membrane (RWM) might become available in the near future as an alternative to the currently available medical and surgical methods used to treat several inner ear diseases. The most common outcome of such diseases is sensorineural hearing loss (SNHL). Two examples of  these otoprotectants are Edaravone and Brain-Derived Neurotrophic Factor (BDNF), both of which have already proved effective against  noise-induced hair cell loss, barotrauma  and ototoxicity caused by cisplatin. In four different studies we used two electrophysiological methods, auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), to study the effects of tobramycin and Pseudomonas aeruginosa exotoxin A (PaExoA) on the inner ears of 129 male Sprague-Dawley rats. In two investigations, not only the otoprotective effects of Edaravone on tobramycin-induced ABR threshold shifts and PaExoA-induced DPOAE  threshold changes, were studied but even different application times, in order to establish in which interval it was still possible to achieve effective otoprotection.We found that Edaravone gave otoprotection from tobramycin when injected simultaneously or within 7 days, but it had only a limited effect on the changes in DPOAE thresholds caused by PaExoA when injected 1, 2, or 4 hours after the exotoxin. The effect of BDNF on PaExoA-induced ABR threshold shifts was investigated in two studies, where different doses of intratympanically injected PaExoA were used and where BDNF was applied simultaneously, 12 or 72 hours efter exotoxin instillation. We found that BDNF had an otoprotective effect on SNHL induced by different doses PaExoA when injected simultaneously or with no more than 12 hours delay.