Ein neuer Ansatz zur Linderung von chronisch-dekompensiertem Tinnitus mit monotonalem Charakter wird vorgestellt. Mithilfe von transponierter Musik wird der monotonale Tinnitus gezielt in ein wohlklingendes (harmonisches) Klangerlebnis eingebettet und damit dem Betroffenen das Defokussieren des Dauertons erleichtert. Das Verfahren wurde softwarebasiert umgesetzt und in einer Untersuchungsreihe mit Patienten auf seine Wirksamkeit überprüft. Dabei konnte insbesondere ein Sofort-Effekt unter der angepassten Musik herausgestellt werden, welcher das Intensitätsempfinden des Tinnitus drastisch senkt.

Dans le cadre de la recherche d'antagonistes du NMDA, nous avons synthétisé une librairie de nouveaux composés dérivés du Selfotel (CGS 19755). Ces phosphonates aromatiques ont été obtenus par réaction de couplage croisé utilisant une catalyse au palladium (couplage d'Hirao). Leur hydrolyse a conduit aux acides phosphoniques correspondants. Dans une second temps, la série pipéridine a été obtenue par hydrogénation complète des motifs pyridiniques en utilisant de l'oxyde de platine comme catalyseur.Lors de l'analyse de ces composés, des propriétés spectroscopiques intéressantes en RMN ont été mises en évidence. Des monocristaux ont été obtenus sur certains des acides, ce qui a permis de confirmer leurs structures par diffraction des rayons X. Ces experiences ont clairement montré que l'hydrogénation du cycle aromatique est un processus de cis-hydrogénation.Les études biologiques préliminaires effectuées sur des cultures de neurones ont indiqué une activité certaine sur les récepteurs NMDA. Une partie d'entre eux agissait comme antagonistes du NMDA tandis que l'autre montrait des activités de neuroprotection. Des expériences complémentaires par un test de fluorescence, ont été mises en place. Dans ce contexte, les outils de génie génétique ont été utilisés pour créer une lignée cellulaire de mammifère exprimant de façon stable le récepteur NMDA. Toutefois, ces expériences n'ont pas conduit à des résultats permettant d'expliquer les résultats biologiques obtenus. / The library of novel compounds being derivatives of NMDA antagonists Selfotel (CGS 19755) was synthesized. The series of aromatic esters were obtained in palladium catalyzed cross-coupling reaction (Hirao coupling), followed by their hydrolysis and then the series of aliphatic acids was obtained upon their hydrogenation over PtO2. Majority of designed compounds have not been synthesized before. What is worth emphasizing, none of this compound was studied as potential NMDA receptor antagonist. During the analysis of compounds, interesting spectroscopic properties were observed as well as few of compounds were obtained as monocrystals, which enabled to obtain their crystal structures. Crystal structures of aliphatic acids unequivocally identified that hydrogenation of aromatic ring is a cis process and yields predominantly only one diastereomeric mixture.Initial biological studies performed on cultures of neurons indicated that the compounds posses activity towards NMDA receptors – part of them acting as antagonists and part as protectants or facilitators.More advanced investigation of biological activity by means of fluorescence screening assay, was planned to be performed. Consequently, genetic engineering tools were used in order to create mammalian cell line stably expressing NMDA receptor what would allow to perform these studies. However, these experiments were not successful. Therefore, further investigation should be performed in order to confirm the obtained biological results.

Sammanfattning Tinnitus är idag ett folkhälsoproblem i Sverige som drabbar allt fler. Det finns i dagsläget inget definitivt botemedel men det finns behandlingsmetoder som syftar till att på olika sätt lindra tinnitus. En av dessa metoder är Tinnitus Retraining Therapy (TRT) som grundar sig i den neurofysiologiska modellen. TRT består av två delar; rådgivning och ljudterapi. I ljudterapin tillämpas vanligtvis en ljudstimulator som tillför ett bredbandigt brus på svag nivå i patientens öra. Syftet Syftet med uppsatsen är att redogöra för effekten av behandlingsmetoden Tinnitus Retraining Therapy. Metod Metoden har omfattat granskning av artiklar som sökts via Örebro Universitets databaser samt via relevanta referenslistor i arbeten, böcker och artiklar. Urvalet har innefattat tre steg. Första steget var att välja ut artiklar publicerade i vetenskapliga tidskrifter genom att granska artiklarnas titel. Andra steget var att granska de artiklar som valdes ut i steg ett genom att läsa deras sammanfattningssida för att se om innehållet var relevant för arbetets syfte. Tredje steget var att utförligt läsa de artiklar som valts ut i steg två. Resultat och diskussion Resultatet och diskussionen visar att det är svårt att säga huruvida TRT är effektivt. För detta skulle en mer omfattande liknande studie vara nödvändig.

The objective of this study was to describe the influence of tinnitus distress on quality of life (QoL) outcomes in adult cochlear implant (CI) recipients who experience tinnitus, and to investigate the prognostic significance of tinnitus distress over time. A retrospective, longitudinal study of 210 adult (_18 years) CI recipients implanted between 2001 and 2017 was conducted. Data on hearing-related QoL, using the Abbreviated Profile of Hearing Aid Benefit (APHAB) and tinnitus distress, using the Tinnitus Reaction Questionnaire (TRQ) were captured preoperatively as well as at 6-months, 12-months and >24-month postoperatively. The effect of tinnitus distress on hearing-related QoL outcomes over time was determined. Furthermore, 13 potential predictive factors were identified from the retrospective dataset, including demographic, hearing loss, CI, speech perception and tinnitus related factors. Multiple regression analyses were performed to identify variables that influence hearing-related QoL outcomes over time. Lower tinnitus distress and younger age at implantation were the only two out of 13 possible predictor variables that were identified as significant predictors of better hearing-related QoL in adult CI recipients. A general trend of statistically significant (p<0.01) tinnitus relief was evident from the preoperative interval to the 6-months, 12-months and >24-months postoperative intervals, confirming significant relief in tinnitus distress up to more than two years post-implantation. Within this dataset, higher levels of tinnitus distress were associated with poorer hearing-related QoL outcomes, as confirmed by the negative correlation between tinnitus distress and hearing-related QoL. This study contributes to a better understanding of the complex influence that multifactorial variables has upon the hearing-related QoL outcomes of adult CI recipients. This enables clinicians to provide evidence-based preoperative counselling combined with postoperative rehabilitation to adult CI recipients and their families. Not only was tinnitus distress confirmed as a predictive factor for hearing-related QoL in this study, but also the association between residual tinnitus distress and hearing-related QoL. These results emphasize the importance of identification, counselling and timely monitoring of adult CI recipients who experience tinnitus. / Dissertation (MA)--University of Pretoria, 2019. / Speech-Language Pathology and Audiology / MA / Unrestricted

Tinnitus, ringing in the ears, is a phantom sound percept affecting roughly 10-20% of the total world population. Tinnitus severely impacts the quality of life of 10% of tinnitus sufferers, affecting their sleep, concentration, emotion, social enjoyment, and sometimes leading to depression and suicidal tendencies. In humans, most forms of tinnitus are associated with noise-exposure, leading to compensatory maladaptive plasticity of central auditory neurons. Human and animal studies suggest that tinnitus alters normal adult attentional resources. Human studies by McKenna, Hallam and Surlock 1996, suggested tinnitus-related impairment in sustained attention, vigilance, visual conceptualization and visuo-motor memory. Additionally, tinnitus may impact aspects of selective or divided attention as well as working and long-term memory. The involvement of primary auditory cortex and nicotinic signaling in selective attention, working and long-term memory has been well established. Neuronal nicotinic acetylcholine receptors (nAChRs) are present on presynaptic and postsynaptic inputs that innervate neurons across layers of primary auditory cortex (A1). Layer 5 pyramidal neurons (PNs) in the A1 are major output neurons, conveying auditory information to corticocortical and subcortical nuclei. The excitation of PNs is regulated by a complex microcircuitory of inhibitory neurons with vasointestinal peptide positive (VIP) neurons playing a key role in regulating the excitation. The focus of present studies was to: 1) Characterize tinnitus-related changes in the physiology and nAChR signaling of layer 5 PNs and VIP neurons in the A1 and 2) Determine the ability of nAChR partial/desensitizing agonists to ameliorate tinnitus pathology in subcellular studies. Wild-type, ChAT-Cre and VIP-Cre:Rosa26-loxP-stop-loxP-tdTomato (VIP-Cre:Rosa-tdTomato Long-Evans rats were used in the present study. CHAT-Cre rats allowed us to selectively express cre-inducible AAV-EF1a-DIO-hChR2(H134R)-EYFP and stimulate the cholinergic neurons of basal forebrain (BF). VIP-Cre:Rosa-tdTomato express fluorescent tdTomato protein in the VIP positive neurons allowing us to identify them under fluorescence microscopy using 550 nm wavelength. An established noise-exposure (one hour of 116 dB narrowband noise centered at 16 kHz) was used to induce behavioral tinnitus in a rat model. Approximately 50-60% noise-exposed animals (53/92) exhibited behavioral evidence of tinnitus with significant shifts in hearing threshold contiguous to the exposure frequency. Animals were classified as control, exposed tinnitus and non-tinnitus. In vitro whole-cell patch clamp recordings were performed in control and tinnitus animals. Results: Numerous tinnitus-related changes in the physiology of layer 5 PNs and VIP neurons, and changes in the activity of excitatory and inhibitory input neurons were observed. The resting membrane potential of A1 layer 5 PNs from tinnitus animals was significantly depolarized compared to PNs from unexposed controls. PNs from the A1 of animals with behavioral evidence of tinnitus showed increases in the frequency of excitatory and decreases in frequency of inhibitory spontaneous postsynaptic currents, which directly correlated with the rat’s tinnitus score. Optical stimulation of thalamocortical terminals from PNs in tinnitus animals evoked significantly larger excitatory/inward currents than in currents evoked in PNs from controls. A1 layer 5 PNs showed tinnitus-related decreases in postsynaptic gamma-amino butyric acid (GABA) signaling suggestive of GABA-A receptors (GABA-ARs) subunit switches or loss of GABA-ARs. VIP neurons favoring excitation of layer 5 PNs via disinhibition, were depolarized with significantly lower current to evoke action potentials (rheobase current). The excitability of VIP neurons was significantly increased, with this increase being strongly correlated to the rat’s tinnitus score. Tinnitus-related changes in nAChR signaling were then tested in layer 5 PNs and VIP neurons. Both PNs and VIP neurons receive cholinergic input from basal forebrain and were highly sensitive to nicotinic stimulation. Optical stimulation of basal forebrain (BF) terminals evoked a depolarizing current from VIP neurons. In tinnitus animals, layer 5 PNs showed a significant loss of nAChR signaling, while, VIP neurons showed tinnitus-related increase in responses to nicotinic stimulation. Most of the nAChR responses in auditory cortex are believed to be mediated via volume transmission of acetylcholine (ACh). Continuous voltage clamped recordings were used to examine the activity of excitatory and inhibitory neurons impacting PNs in the presence of bath applied ACh. We observed significant tinnitus-related changes in nAChR signaling with layer 5 PNs showing significantly larger GABAergic input after prolonged bath application of ACh. This led us to hypothesize that desensitization of nAChRs could increase/normalize the activity of GABAergic input neurons. To test this hypothesis, nAChR partial desensitizing agonists sazetidine-A and varenicline were used in cellular and behavioral studies. Immediately after bath application of sazetidine-A or varenicline, a dramatic increase in the activity of inhibitory input neurons onto PNs was observed. In a behavioral tinnitus test, both sazetidine-A and varenicline were effective in lowering the tinnitus-like behavior. In conclusion, we identified a significant tinnitus-related disruption in intrinsic physiology of layer 5 PNs and VIP neurons, with strong evidence of dysregulated cholinergic signaling. Partial/desensitizing agonists sazetidine-A and varenicline increased the activity of inhibitory input neurons, showing therapeutic potential in both subcellular and behavioral studies.

No description available.

No description available.

O zumbido é um sintoma relatado frequentemente na rotina clínica fonoaudiológica, a qual está inserida desde a avaliação e diagnóstico até a intervenção deste sintoma. Diversos estudos são desenvolvidos com objetivos direcionados à promoção de saúde auditiva, sendo a Telessaúde uma alternativa para este cenário. O objetivo deste estudo foi desenvolver e avaliar uma plataforma virtual de transmissão de informações sobre o gerenciamento do zumbido para fonoaudiólogos utilizando a Teleducação. Visando oferecer atualização e conhecimento aos profissionais de todas as regiões do país, foi proposta a realização do curso à distância, por meio do Portal do Zumbido, disponibilizado no endereço eletrônico zumbido.fob.usp.br/. A plataforma é composta por módulos que contemplam a introdução ao sintoma, avaliação e intervenção do zumbido, sendo que todos os materiais elaborados são em forma de Infográficos disponibilizados para download. Foram convidados a avaliar a plataforma, fonoaudiólogos das diferentes regiões do Brasil por meio de correio eletrônico, havendo cadastramento de 46 profissionais. Deste total, 38 responderam a avaliação da plataforma virtual de aprendizagem, por meio de um questionário sobre o conteúdo teórico e uma Ficha de Pesquisa Motivacional. Os profissionais responderam corretamente entre 90% e 100% das questões, demonstrando que o conteúdo foi absorvido de forma positiva, além disto, o material foi considerado impressionante após a realização da análise dos dados da Ficha de Pesquisa Motivacional. O Portal do Zumbido foi elaborado e disponibilizado no endereço eletrônico zumbido.fob.usp.br/, com avaliação satisfatória pelos profissionais participantes do estudo. / Tinnitus is a prevalent symptom in the audiological clinics and the speech therapist participate in the assessment, diagnose and intervention of tinnitus. A range of studies are developed with the aim to promote auditory health, thus telemedicine is an option for this purpose. According to the purpose of telemedicine, the aim of the present study was to develop and to evaluate a virtual platform on tinnitus management for speech therapists. The purpose was to offer distance learning course, by means of Portal do Zumbido, available in the following eletronic address: zumbido.fob.usp.br/. The platform was composed for modules and comprised the introduction to the symptom, assessment and intervention for tinnitus and the elaborated information is presented by means of infographics, available to download. Speech therapists of different regions of Brazil, receveid an e-mail invitation to participate and avaluate the study and 46 were registered. From all the 46 speech therapists registered, 38 evaluated the virtual platform, by means of a questionnaire about the theoric content and a Motivational Research. The professionals correctly answered 90% and 100% of the questions, which means the content was learned, in addittion, the content was considered to be impressive when the Motivational Research was analysed. The Portal do Zumbido was elaborated and provided in the following eletronic address: zumbido.fob.usp.br/, furthermore, the speech therapists made satisfactory evaluation.

Introdução: o zumbido é uma desordem que acomete 10 a 15% da população mundial e por se tratar de um sintoma subjetivo que apresenta grande repercussão na vida do indivíduo, pesquisas científicas na área são de grande importância. A terapia sonora realizada por meio do aparelho de amplificação sonora individual (AASI) com gerador de som (GS) associado é uma das formas de tratamento do zumbido e vem ganhando espaço nos serviços de saúde auditiva. Proposição: analisar a eficácia de quatro ruídos mascaradores no alívio do zumbido de indivíduos com perda auditiva sensorioneural bilateral de grau leve e moderado e a influência dos mesmos na percepção da fala. Casuística e Métodos: o estudo foi desenvolvido na Clínica de Fonoaudiologia da Faculdade de Odontologia de Bauru (FOB) - USP após a aprovação do Comitê de Ética e anuência do paciente. Participaram 35 indivíduos com zumbido e perda auditiva sensorioneural leve e moderada bilateral, divididos em quatro grupos, sendo três grupos compostos por nove indivíduos e um grupo por oito. Todos os grupos passaram pela adaptação do AASI com GS, sendo regulados no modo combinado (GS + amplificação). No grupo 1 (G1) foi aplicado o estímulo White Noise, no grupo 2 (G2) o Pink Noise, o grupo 3 (G3), o Speech Noise e o grupo 4 (G4) o High Tone Noise. Todos os pacientes passaram pelos seguintes procedimentos: anamnese, diagnóstico audiológico composto por audiometria de alta frequência, imitanciometria e acufenometria. Foram aplicados os questionários Tinnitus Handicap Inventory (THI), a Escala Análoga Visual (EAV) e avaliação da percepção da fala por meio do Hearing in Noise Test (HINT) na situação de fala no silêncio (FS) e ruído frontal (RF). Os procedimentos foram realizados pré e pós-intervenção auditiva, após três meses de uso do AASI. Os resultados foram tabulados e descritos de acordo com a análise estatística descritiva de todas as variáveis estudadas. Resultados: todos os grupos apresentaram diferença estatisticamente significativa para o questionário THI, EAV e HINT na situação de FS, pré e pós-intervenção auditiva. Na situação de RF, somente o G2 apresentou diferença significativa. Porém, na comparação entre grupos não houve diferença significativa. Conclusão: os quatro ruídos mascaradores demonstraram ser igualmente eficazes na melhora do zumbido e na percepção de fala na situação de silêncio, porém no RF, o G2 apresentou melhora significativa. / Introduction: tinnitus is a disorder that affects 10 to 15% of the world\'s population and since it is a subjective symptom which presents great impact on the individual\'s life, all scientific contribution becomes significant and important. The sound therapy performed through the individual sound amplification apparatus (AASI) with associated sound generator (GS) is one of the forms of tinnitus treatment and has been obtaining space in the hearing health services. Proposition: analyzing the effectiveness of four masking noises in relieving tinnitus of individuals with mild and moderate bilateral sensorineural hearing loss and influence thereof on speech perception. Casuistry and Methods: the study was developed at the Speech Therapy Clinic of the Faculty of Dentistry of Bauru (FOB) - USP after approval by the Ethics Committee and patient consent. Participants were 35 individuals with tinnitus and bilateral mild and moderate sensorineural hearing loss, divided into four groups, three groups composed of nine subjects and one group comprising eight subjects. All groups underwent hearing loss adaptation with GS, being regulated in the combined mode (GS + Amplification). In Group 1 (G1) the White Noise stimulus was applied, in group 2 (G2) Pink Noise was applied, in group 3 (G3), Speech Noise and in group 4 (G4) the High Tone Noise was applied. All patients were subjected to the following procedures: anamnesis, audiological diagnosis composed of high frequency audiometry, immittanciometry and acuphenometry. The Tinnitus Handicap Inventory (THI), Visual Analogue Scale (EAV) and Speech Perception Assessment questionnaires were applied through the Hearing in Noise Test (HINT) in the speech silence (FS) and frontal noise (RF) situation. The procedures were performed prior to and after hearing intervention, after three months of use of AASI. The results were tabulated and described according to the descriptive statistical analysis of all variables studied. Results: all groups presented a statistically significant difference for the THI, EAV and HINT questionnaires in the FS, pre- and post-hearing intervention. In the RF situation, only G2 presented a significant difference. However, in the comparison among groups there was no significant difference. Conclusion: the four masking noises proved to be equally effective in improving tinnitus and in speech perception in the silent situation, but in RF situation, G2 presented significant improvement.

Introdução: O saco endolinfático tem sido apontado como o alvo das reações imuno-alérgicas da orelha interna. A prevalência de alergia em pacientes com Doença de Ménière foi estabelecida em torno de 41,6% para inalantes e 26,6% para alimentos, por Derebery em 2000, dados aumentados em relação à prevalência de alergia na população em geral, que, no Brasil, varia de 9% a 30% para inalantes e de 1% a 3% para alimentos. Objetivos: Avaliar a prevalência de reações de hipersensibilidade tipo I a inalantes e alimentos na população do setor de Otoneurologia do Hospital das Clínicas da Faculdade de Medicina de São Paulo e descrever os sintomas vestibulares dos pacientes. Casuística e método: Setenta e cinco pacientes com distúrbios do equilíbrio de origem periférica foram submetidos a questionário de caracterização clínica de sintomas cócleo-vestibulares e teste cutâneo (prick test) para 13 inalantes e 5 alimentos. Resultados: Vinte e cinco (33,3%) pacientes apresentaram prick test positivo a pelo menos um alérgeno inalante e 6 (8%) a pelo menos um alérgeno alimentar. Quatro pacientes apresentaram prick test positivo na ausência de sintomas alérgicos. Prevaleceu a queixa de tontura de caráter rotatório em proporções semelhantes entre os pacientes com prick test positivo e negativo. Conclusão: A prevalência de reações de hipersensibilidade tipo I a inalantes e a alimentos na população avaliada foi maior do que na população em geral. Os sintomas vestibulares não diferiram entre os pacientes da amostra, com prick test positivo ou negativo. No entanto, deve-se obter maior número de amostra para que os dados sejam confiáveis. / Introduction: The endolymphatic sac has been pointed out as the target of immuno-allergic reactions in the inner ear. The prevalence of allergy in patients with Ménières disease was established as approximately 41,6% for inhalants and 26,6% for food by Derebery in 2000, an increase in the data in relation to that of the prevalence of allergy in the general population, which in Brazil varies from 9% to 30% for inhalants and from 1% to 3% for food. Objectives: To evaluate the prevalence of reactions to type I hypersensitivity to inhalants and food in the population of the Otoneurological Section of the Clinics Hospital of the University of São Paulo Medicine School and to describe the vestibular symptoms of the patients. Method: Seventy-five patients with peripheral equilibrium disturbances who had answered a questionnaire of clinical characterization regarding cochlear-vestibular symptoms and undergone prick test for 13 inhalants and 5 types of food. Results: Twenty-five (33,3%) of the patients were positive for the prick test and for at least one allergen inhalant and 6 (8%) for at least one food allergen. Four patients were positive for the prick test in the absence of allergy symptoms. There was a prevalence of the complaint of rotatory dizziness in similar proportions among the patients with positive and negative prick test. Conclusion: The presence of type I hypersensitivity reactions to inhalants and food in the population evaluated was greater than in the general population. The vestibular symptoms did not differ among the patients in the sample, neither with positive or negative prick test results. However, a sample of greater number should be obtained for a higher confidence level of data results.