D-methionine (D-met) has demonstrated otoprotection from noise-, aminoglycoside-, and cisplatin-induced hearing loss in animal studies. As a result, D-met is currently progressing through translational "bench to bedside" research. However, D-met's exact otoprotective mechanisms have not been fully elucidated. This study investigated relationships between dose- and time-dependent D-met otoprotection from noise- and aminoglycoside-induced hearing loss. Further, the study correlated protective D-met dose to endogenous antioxidant enzyme activity and lipid peroxidation. Specific aim 1 tested D-met dose response protection by auditory brainstem response (ABR) threshold shift analysis and outer hair cell (OHC) quantification. D-met doses ranging from 25-200 mg/kg/dose were administered to chinchillas every 12 hours five times each before and after steady state noise exposure totaling 10 D-met doses. Results demonstrated optimal, sub-optimal, and supra-optimal bi-phasic D-met otoprotective dose response. Optimal D-met protection from steady state noise occurred at the 50 mg/kg/dose level. OHC quantification confirmed electrophysiological assessment. Specific aim 2 measured D-met rescue protection from steady state noise exposure by ABR threshold shift analysis and OHC quantification. Five intraperitoneal (ip) D-met injections were administered every 12 hours beginning 3, 5, 7, 9, 12, 18, 24, 36, or 48 hours after steady state noise exposure. Results measured full D-met protection when administration began as late as 24 hours after noise secession. Significant partial protection was also measured for the 36 hour delay. OHC quantification confirmed electrophysiological assessment. Specific aim 3 measured D-met preloading protection from steady state noise exposure by ABR threshold shift analysis and OHC quantification. Five ip D-met injections were administered every 12 hours beginning 2, 2.5, or 3 days prior to steady state noise exposure. Results measured significant D-met protection when administration ended as early as 24 hours prior to noise exposure. OHC quantification confirmed electrophysiological assessment. Specific aim 4 tested dose-dependent D-met influence on antioxidant enzyme activity and oxidative stress in steady state noise-exposed chinchillas. One ip D-met injection, ranging from 25 to 200 mg/kg/dose, was administered every 12 hours beginning 2 days prior to steady state noise exposure for a total of 5 injections. Two hours post-noise exposure, animals were sacrificed and serum, liver, and cochleae were collected for endogenous antioxidant analysis. Glutaredoxin 2 (Grx2) was also analyzed 21 days post-noise exposure. Lower D-met doses (25 and 50 mg/kg/dose) increased superoxide dismutase and catalase activity. Glutathione reductase and glutathione peroxidase activities significantly increased with D-met doses but only at high concentrations (200 mg/kg/dose). At 21 days post-noise, Grx2 activity was significantly decreased in liver but greatly increased in the cochlea with high D-met doses (200 mg/kg/dose). The endogenous enzyme studies suggest optimal protective D-met dose determined in specific aims 1 through 3 may be secondary to increased superoxide dismutase and catalase activity which may result from D-met's free radical scavenging characteristics. Glutathione pathway activity increased only with high D-met doses that resulted in less optimal protection in specific aim 1. Thus, D-met-induced glutathione pathway enhancement may be a compensatory or saturation mechanism rather than the primary protective mechanism. Further, the extended pre-loading and rescue protection may be a result of significantly increased s-glutathionylation activity in the cochlea. Specific aim 5 tested D-met protection from impulse noise exposures. D-met dose response, rescue, and antioxidant enzyme assay protocols, similar to those in specific aims 1, 3, and 4 in steady state animals, were performed on impulse noise-exposed chinchillas. D-met provided dose- and time-dependent optimal protection from impulse noise similar to the steady-state noise studies. Optimal D-met protection was measured at the 100 mg/kg/dose level with complete rescue protection as late as 24 hours post-noise exposure. Endogenous enzyme activity measures demonstrated significant superoxide dismutase, catalase, and glutathione peroxidase activity increases which correlated with optimal D-met protective dose (100 mg/kg/dose) and catalase and superoxide dismutase activity decreases at the higher doses (200 mg/kg/dose). Specific aim 6 tested dose-dependent D-met protection from tobramycin, amikacin, kanamycin, and gentamicin aminoglycoside antibiotics. Guinea pig animal models were normalized to achieve a 30-40 dB ABR threshold shift with the lowest possible aminoglycoside dose. D-met and the aforementioned single aminoglycoside were administered for 21, 28, 23, or 14 days, respectively. ABRs were collected and assessed at baseline, 2, 4, and 6 weeks after drug administration initiation. After the 6-week ABR data collection, cochleae were collected and prepared for OHC quantification. ABR threshold shifts and OHC quantifications demonstrate significant bi-phasic D-met-induced protection from each aminoglycoside type with different D-met doses. OHC quantification confirmed electrophysiological assessment. This study identified optimal protective D-met dose for aminoglycoside- and noise- induced ototoxicity. It also identified optimal protective D-met dose timing for steady state and impulse noise-induced hearing loss. Further, this study has identified dose-dependent D-met-induced endogenous antioxidant changes and Grx2 enhancement, and therefore s-glutathionylation, as a potential mechanism for D-met protection. Thus, dose- and time-dependent D-met protection influences endogenous antioxidant activity, but exact optimal D-met protection will continue to warrant further investigation.

The dose-response ototoxic effects of cisplatin were studied in guinea pigs. Loss of Preyer reflex and suppression of the N1 amplitude occurred in cisplatin-treated animals and was described as dose-related. Drug-induced hair cell damage, as observed with scanning electron microscopy, occurred sporadically throughout the turns of the cochlea and the incidence increased with dose. Na, K-ATPase activity in the lateral wall tissues was not significantly different between treatment groups. The results reported here indicate that cisplatin ototoxicity was dose-dependent, but was not directly related to Na,K-ATPase activity in the lateral wall.

Background: Disabling hearing loss is a global burden. This burden is worsened by the emergence of multi-drug resistant tuberculosis (MDR-TB). Some of the medications used to treat MDR-TB are damaging to the cochlea and auditory nerve (ototoxic) and can lead to permanent hearing loss and/or balance disorders. Ototoxicity monitoring aims to reduce this burden by preventing or minimising the damage caused by ototoxic treatment as it can progress and worsen speech perception difficulties. However, the proposed test battery for ototoxicity monitoring is lengthy and demands active participation which is not ideal for ill patients (such as those on MDR-TB treatment). The Sensitive Range of Ototoxicity (SRO) technique is recommended to shorten the test time. The SRO consists of seven consecutive relatively high frequencies determined from the highest frequency the participant responded to. The SRO technique is time efficient. Although the SRO technique provides the prospect of a shortened test battery, there is still a global lack of audiologists. Automated audiometry is a vital application for testing especially when audiologists are not available to physically do the test. Automated audiometry has been previously validated. Clinically, automated audiometry is objective and allows for standardisation. Even though automated audiometry helps improve access to monitoring more patients, patient preference is an important factor when using automated audiometry to ensure patient-centred care is not compromised. Aims and Objectives: This study aimed to investigate the specificity and sensitivity of the SRO technique with automated audiometry compared to the gold standard (manual audiometry). This comparison was made by firstly, determining the testing time efficiency and the correlation of thresholds obtained with the different test methods and, secondly, testing the diagnostic value of automated audiometry using the SRO technique. The incidence of an ototoxicity-induced hearing loss was described by determining the time interval between starting ototoxic MDR-TB treatment and the onset of a significant threshold shift (STS) according to ASHA's criteria. Lastly, the test method preference of the participants with MDR-TB was described and compared using a short exit survey. Study Design: A prospective repeated-measures study design was used. Participants were chosen based on a risk factor (i.e. exposure to ototoxic medication) for an outcome of interest (i.e. the presence or absence of an STS). With a repeated measures study, multiple tests using different test methods can be compared with the same sample. Participants: Twenty-seven in-patients at Brooklyn Chest Hospital and DP Marais TB Hospital with normal hearing and on MDR-TB medication were included in the study. Their age range was from 19 to 51 years old with an average age of 33 years old. Non-probability convenience sampling was used as it was cost-effective, reduced data collection time and was relatively easy to execute. Data collection materials and procedures: The procedure for data collection included weekly follow-up testing for a maximum of four weeks. The test battery was as follows: an auditory symptom questionnaire, otoscopy examination, and manual and automated audiometry using the SRO technique with a fifteen-minute break in between. Participants were tested with the KUDUwave ™ in a non-sound treated room. The frequency range was determined with the SRO technique. If an STS was obtained, the patient was discharged from the study after completing an exit survey. Statistics: Analysis included descriptive statistics and inferential statistics. A Bonferroni corrected p-value (initially p ≤ 0.05) was used. Manual and automated audiometry thresholds were compared using the Pearson's Correlation Coefficient test. Manual and automated audiometry testing time and threshold means were compared using paired sample's t-tests. The diagnostic value of automated audiometry with the SRO technique was assessed with Receiver Operating Characteristics (ROC) Curves. Results: Manual audiometry was statistically more time-efficient compared to automated audiometry by an average of one minute and ten seconds (t (94) = -5.44; p< 0.003). There was a strong positive correlation for both left and right ears between the thresholds' obtained from manual and automated audiometry at 8kHz to 16 kHz (df> 28 = r > 0.70, p< 0.003). Automated audiometry was found to be a fair diagnostic test (area under the curve was 0.75; p= 0.002). Also, the ROC curve revealed that automated audiometry had a sensitivity of 61% and specificity of 90% when compared to manual audiometry (gold standard). Only participants that started data collection within 31 days after starting their MDR-TB treatment were included in the analysis of determining the incidence of an ototoxicity-induced hearing loss (n= 24 ears). This study found that 41.67% of ears (n= 10) had an ototoxicity-induced hearing loss. A box and whisker plot revealed that data was skewed to the right (i.e. more variation in data between the median and the maximum values) and that the median number of days for an ototoxicity-induced hearing loss to appear was 33 days. Secondly, 55.55% of participants (n=15 out of 27) reported auditory symptoms before data collection commencement. Aural fullness was the most reported symptom (n= eight out of 15). Ten out of 15 (66.66%) participants that reported auditory symptoms obtained an ototoxicity-induced hearing loss. Lastly, most participants (i.e. 13 out of 19; 68.42%) that completed the exit survey had no preference between manual or automated audiometry. The common rationale among these participants was “No difference noted.” Conclusion: This research study has revealed that manual audiometry was more time-efficient compared to automated audiometry in patients with MDR-TB. Also, automated audiometry was a fair diagnostic test. It may aid in reducing the disproportionate audiologist to patient ratio, especially in a developing country. However, manual audiometry (with the SRO technique) is more clinically appropriate in patients that are difficult-to-test. Secondly, audiometric settings can be changed to accommodate testing frequencies in 1/6 octaves so that the SRO technique can be clinically adopted. An ototoxicity-induced hearing loss seems to appear 33 days after ototoxic MDR-TB treatment commencement. Aural fullness was a commonly reported symptom among participants with MDRTB. Aural fullness is omnipresent in peripheral auditory pathologies. Therefore, auditory symptoms reported by patients' needs a comprehensive audiological investigation. Lastly, more research is needed on how patients (and clinicians) experience the advances in technology innovation especially in audiology where technology innovation is continuously evolving.

Dans nos sociétés modernes, la presbyacousie, perte de l'audition liée au vieillissement, prend une place de plus en plus importante. Outre le vieillissement de la population, la prévalence de la presbyacousie est accentuée par l'exposition à des bruits toujours plus forts (concerts, baladeurs, environnement de travail, ...) et la prise de médicaments ototoxiques (cisplatine, aminoglycosides, ...). À ce jour, le lien entre l'endommagement de l'ADN, le stress oxydant et l'inflammation avec l'apparition précoce de certaines maladies liées au vieillissement (Alzheimer, démence, Parkinson, …) a été démontré. Cependant, il n'existe aucune donnée concernant le rôle des dommages de l'ADN dans la dégénérescence des cellules cochléaires et trop peu d'études témoignent de l'existence d'un stress oxydant dans la presbyacousie.Le premier objet de ce travail a donc été d'élucider le rôle des dommages de l'ADN dans la dégénérescence des cellules cochléaires. Pour ce faire, nous avons utilisé des approches de biologie moléculaire et cellulaire pour identifier des voies de signalisation associées aux lésions de l'ADN dans des explants cochléaires issus de souris âgées de 3 jours traités au cisplatine (CDDP). Cet antinéoplasique tire sa cytotoxicité de sa capacité à causer directement des dommages dans l'ADN et est connu pour ses effets nocifs sur l'audition en induisant la dégénérescence des cellules cochléaires. Enfin, nous avons étudié l'implication de p53, un des effecteurs clés de signalisation des dommages de l'ADN, in vivo en traitant avec le CDDP des souris dont le gène codant pour ce facteur de transcription a été invalidé. Nos résultats montrent que le CDDP induit des cassures double brin dans l'ADN des cellules ciliées qui sont à l'origine de l'activation de la voie ATM/DNA¬PK-Chk2-p53, de la formation de foyers βH2AX et 53BP1 et, in fine, de la mort de ces cellules par apoptose. Les cellules ciliées internes, plus résistantes au CDDP que les cellules ciliées externes, présentent une signalisation moins intense et un nombre inférieur de cassures double brin, un phénomène qui pourrait expliquer leur plus faible sensibilité. Nous avons également montré que l'absence de p53 in vivo prévient les pertes d'audition et la dégénérescence des cellules ciliées externes après injection intrapéritonéale de CDDP. Le second objectif a porté sur l'étude des effets délétères du vieillissement sur l'audition et les mécanismes moléculaires associés à cette pathologie. Pour ce faire, nous avons choisi les souris SAMP8 (senescence accelerated mice prone 8), un modèle bien établi de sénescence précoce et des maladies liées au vieillissement. Nous avons combiné des approches fonctionnelles, morphologiques, moléculaires et cellulaires pour phénotyper ces souris et identifier l'origine de l'atteinte de leur audition au cours du vieillissement. L'étude des souris SAMP8 nous a permis de montrer qu'elles sont un excellent modèle de presbyacousie mixte (atteinte de la strie vasculaire, de l'organe de Corti et du ganglion spiral), résumant la pathologie humaine. La dégénérescence des structures cochléaires que nous avons observée chez ces souris provient d'une profonde dysfonction mitochondriale, de l'augmentation du stress oxydant et des processus inflammatoires, d'un stress autophagique et de l'endommagement de l'ADN. Les mécanismes moléculaires aboutissant à la perte des cellules cochléaires constituent autant de cibles thérapeutiques à explorer dans l'avenir afin de tenter de prévenir les troubles de l'audition imputables à l'exposition au bruit ou aux médicaments ototoxiques et au vieillissement. / Our modern society is confronted with a dramatic increase in the number of patients suffering from presbycusis or age related hearing loss. Besides aging, presbycusis prevalence increases with exposition to loud noise (concerts, Walkman, work environment …) and ototoxic drugs (cisplatin, aminoglycosides …). It was reported that the early onset of some aging related diseases (Alzheimer, dementia, Parkinson …) are linked mechanistically to DNA damage, oxidative stress and inflammation. However, the role of DNA damages in cochlear cells degeneration is totally unknown and only few studies have investigated the implication of oxidative stress in presbycusis.The first goal of this study consisted in clarifying the role of DNA damage in cochlear cell degeneration. For this purpose, we used molecular and cellular biology approaches to identify the activation of DNA damage response pathways in cisplatin (CDDP) treated 3 days postnatal mouse cochlear explants in culture. Indeed, the cytotoxicity of CDDP arises from its capacity to directly damage DNA. It is also well known that one of the major dose limiting side effects of CDDP is its ototoxicity. Finally, we investigated the role of p53, a key effector of the DNA damage response pathway, in vivo by treating p53 knockout mice with CDDP. Our results show that CDDP induces double strand breaks leading to the activation of ATM-/DNA PK¬ Chk2 p53 pathway, βH2AX and 53BP1 foci formation and, in fine, apoptotic cell death. Inner hair cells, which are more resistant to CDDP treatment than outer hair cells, show a less intense signaling and fewer double strand breaks. This phenomenon could explain their weaker sensitivity to CDDP treatment. In vivo, p53 deletion prevents hearing loss and outer hair cells degeneration induced bay intraperitoneal injection of CDDP.The second goal consisted in studying the deleterious effects of aging on hearing and the molecular mechanisms involved in this pathology. Here, we studied the mechanism of presbycusis using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes. Based on complementary approaches combining functional, morphological, biochemistry, cellular and molecular biology, we found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e. strial, sensory and neural degeneration). The molecular mechanisms associated with premature presbycusis in SAMP8 mice involve oxidative stress, mitochondrial dysfunction, chronic inflammation, autophagic stress and DNA damages. Molecular mechanisms leading to cochlear cells loss represent therapeutic targets of interest to explore in the future in order to prevent hearing impairments due to loud sound or ototoxic drugs exposure and due to aging.

Doctor Educationis / Ototoxic induced hearing loss is a common adverse event related to aminoglycosides used in Multi Drug Resistant -Tuberculosis treatment. Exposure to ototoxic drugs damages the structures of the inner ear. Symptomatic hearing loss presents as tinnitus, decreased hearing, a blocked sensation, difficulty understanding speech, and perception of fluctuating hearing, dizziness and hyperacusis/recruitment. The World Health Organization (1995) indicated that most cases of ototoxic hearing loss globally could be attributed to treatment with aminoglycosides. The aim of the study was to determine the proportion of DR-TB patients initiated on treatment at three decentralized sites during a defined period (1st October to 31st December 2015) who developed ototoxic induced hearing loss and the corresponding risk factors, whilst receiving audiological monitoring with an extended high frequency audiometer (KUDUwave). A retrospective cross-sectional study was conducted. Cumulatively across the three decentralized sites, 69 patient records were reviewed that met the inclusion criteria of the study. The mean age of the patients was 36.1, with a standard deviation (SD) of 10.7 years; more than half (37) were female. Ototoxicity , a threshold shift, placing patients at risk of developing a hearing loss was detected in 56.5% (n=39)of patients and not detected in 30.4%(n=21).The remaining 13,1% (n=9)is missing data. As a result, the regimen was adjusted in 36.2% of patients. . From the 53 patients who were tested for hearing loss post completion of the injectable phase of treatment, 22.6% (n=12) had normal hearing, 17.0 % (n=9) had unilateral hearing loss, and 60.4% (n=32) had bilateral hearing loss. Therefore, a total of 41 patients had a degree of hearing loss: over 30% (n=22)had mild to moderate hearing loss, and only about 15% (n=11)had severe to profound hearing loss. Analysis of risk factors showed that having ototoxicity detected and not adjusting regimen significantly increases the risk of patients developing a hearing loss. The key findings of the study have shown that a significant proportion of DR-TB patients receiving an aminoglycoside based regimen are at risk of developing ototoxic induced hearing loss, despite receiving audiological monitoring with an extended high frequency audiometer that allows for early detection of ototoxicity (threshold shift).

Purpose: The main objective of the current study was to investigate and monitor the auditory status in a group of adult patients with AIDS receiving antiretroviral therapy (ART) and other therapies in a hospital outpatient clinic in Gauteng, South Africa. Specific objectives included estimating the prevalence of hearing loss and the presence of other otologic effects over and above hearing impairment (tinnitus, aural fullness, disequilibrium, and so forth); assessing the type, degree and configuration of the hearing loss; exploring the type of hearing symptom onset; documenting case history data such as signs and symptoms of each participant and identifying any associations between obtained signs and symptoms and hearing loss; documenting the names of all medications used and their possible impact on hearing function (specifically ototoxicity monitoring of ART); and comparing the results of the experimental group to those of a control group.

Introdução – As crianças e adolescentes com câncer recebem tratamentos que têm os mais diversos efeitos colaterais, entre eles, a ototoxicidade, que é a capacidade de provocar lesão em estruturas da orelha interna e que pode levar à perda auditiva. Objetivos – Estimar a prevalência de perda auditiva e os fatores associados à ocorrência desta nas crianças e adolescentes tratados no Instituto de Tratamento do Câncer Infantil – ITACI, utilizando três classificações propostas na literatura. Métodos – Foram analisados 94 pacientes atendidos no ITACI, no período de 2003 e 2004. Como a avaliação audiológica não é feita de rotina neste Instituto, os pacientes transferidos e os que foram a óbito não puderam ser incluídos no estudo. Os indivíduos foram submetidos a uma anamnese para verificar qualquer comprometimento auditivo. Em seguida, foi feita a inspeção visual do meato acústico externo, para verificar a presença de qualquer ocorrência que pudesse impedir a realização dos exames audiológicos. Foi realizada a avaliação dos limiares auditivos utilizando-se procedimentos de resposta condicionada (por meio da audiometria tonal liminar, audiometria lúdica condicionada ou audiometria com reforço visual), com a finalidade de determinar os limiares auditivos. Por fim, foram realizadas a timpanometria e a pesquisa dos reflexos acústicos, para avaliar as condições da orelha média. A caracterização da amostra foi realizada por meio da estatística descritiva e a análise da concordância no diagnóstico da perda auditiva para as três classificações, por meio da estatística Kappa. A análise dos fatores associados à presença de perda auditiva foi realizada por meio do teste associação pelo qui-quadrado e modelos de regressão logística univariados e múltiplos. Resultados – Os resultados mostraram prevalência de perda auditiva de 42,5% utilizando a classificação proposta pela American Speech-Language-Hearing Association (ASHA), 40,4% de acordo com a classificação proposta pelo Pediatric Oncology Group Toxicity (POGT) e 12,8% pela classificação de Perda Auditiva Bilateral (PAB). A concordância no diagnóstico de perda auditiva pelas classificações POGT e PAB, e para PAB e ASHA foi fraca (respectivamente, k=0,36 e k=0,33). Já a concordância entre as classificações ASHA e POGT foi quase perfeita (k=0,96). O único fator de risco para perda auditiva, pelas três classificações adotadas, foi o uso da cisplatina e este efeito foi potencializado com o uso concomitante da ifosfamida. Conclusões – A perda de audição é um efeito colateral importante nas crianças e adolescentes com câncer. A monitorização auditiva é fundamental, visto que possibilita a detecção precoce das perdas auditivas e a revisão do tratamento, além de identificar a progressão da seqüela. Recomenda-se que sejam feitas avaliações audiológicas periódicas, mesmo após o término do tratamento e que seja adotada uma classificação que contemple as perdas auditivas discretas, como a proposta pela ASHA. / Introduction – The treatment of childhood cancer has several side effects and the ototoxicity is one of them. It can affect the inner ear structures and may lead to a hearing loss. Aim – To estimate the prevalence of hearing loss and risk factors in children and adolescents attended at the Childhood Cancer Treatment Institute (ITACI), using three classifications proposed in the literature. Methods – 94 patients admitted at ITACI between 2003 and 2004 were analyzed. The evaluation of hearing loss is not usually done in this institution and, because of this, the patients who were transferred and those who died could not be evaluated. The parents answered a questionnaire about demographic and clinical conditions. Then, the visual inspection of the external auditory meatus was done in order to verify if there were clinical conditions to perform the audiologic evaluation. The audiologic evaluation was done using pure tone audiometry (conditioned audiometry, play audiometry or visual reinforcement audiometry), tympanometry and tests of acoustic reflexes. The statistical analysis was done using descriptive statistics, the Kappa statistics, chi-squared test and univariate and multiple logistic regression models. Results – The prevalence of hearing loss was 42,5% using the American Speech-Language-Hearing Association (ASHA) classification, 40,4% using the Pediatric Oncology Group Toxicity (POGT) classification and 12,8%, using the bilateral hearing loss (PAB) classification. The agreement on the diagnosis of hearing loss was weak for POGT and PAB (k= 0.36) and for PAB and ASHA (k=0.33). The agreement between ASHA and POGT was almost perfect (k=0.96). The only risk factor for hearing loss for all classifications was the use of cisplatin and its effect was higher if the patients use also the ifosfamide. Conclusions – Hearing loss is an important side effect in children and adolescents with cancer treated with cisplatin. It is recommended a periodic audiological monitoring, even after the patient has finished the treatment. It can early detect a hearing loss, the schedule of treatment can be reviewed and the speech-language pathologist may be indicated to address the consequences of the hearing loss. It is recommended to adopt a classification that can detect slight hearing loss (ASHA).

Introdução As crianças e adolescentes com HIV/Aids podem apresentar diferentes alterações auditivas as quais são mais frequentes e, muitas vezes, mais graves quando comparadas às outras crianças. Objetivos Estimar a prevalência de perda auditiva nas crianças e adolescentes tratados no Instituto da Criança ICr e verificar os fatores associados à ocorrência da mesma, utilizando duas classificações propostas na literatura. Métodos Foram analisados 106 pacientes com HIV/Aids (idade 5 19 anos) que estão em acompanhamento no ambulatório do ICr. Os indivíduos e/ou seus responsáveis responderam a diversos questionários e foram submetidos a uma anamnese para verificar qualquer sintoma ou queixa auditiva e foi feita a inspeção visual do meato acústico externo para verificar a presença de qualquer ocorrência que pudesse impedir a realização dos exames audiológicos. A avaliação audiológica foi composta pela pesquisa dos limiares auditivos testes de fala, timpanometria e pesquisa dos reflexos acústicos. A caracterização da amostra foi realizada por meio da estatística descritiva e a análise da concordância no diagnóstico da perda auditiva para as duas classificações, por meio da estatística Kappa. Para a comparação de médias de idade e tempo de uso de medicamentos antirretrovirais foi utilizado o teste t-Student. A análise dos fatores associados à presença de perda auditiva foi realizada por meio do teste associação pelo qui-quadrado e modelos de regressão logística univariados e múltiplos. Resultados Os resultados mostraram prevalência de perda auditiva de 35,8por cento utilizando a classificação proposta pelo Bureau Internacional d´Audio Phonologie (BIAP) e 59,4por cento de acordo com a classificação proposta pela American Speech-Language-Hearing Association (ASHA). A concordância no diagnóstico de perda auditiva pelas duas classificações foi boa (k=0,55). O único fator de risco para perda auditiva pelas duas classificações foi a ocorrência de otite média supurada. Pela classificação BIAP, também foi fator de risco o uso do antirretroviral lamivudina (3TC). Pela classificação ASHA, a ocorrência de doenças graves, em especial, a encefalopatia pelo HIV apresentou-se de risco para a perda de audição. Conclusões Este estudo evidenciou que a ocorrência de otite média supurada, o histórico de doenças de caráter grave, em especial a encefalopatia pelo HIV, e o uso de lamivudina contribuem efetivamente para a perda de audição nas crianças e adolescentes com HIV/Aids. O monitoramento auditivo é fundamental, visto que possibilita a detecção precoce das perdas auditivas, além de identificar a progressão da sequela. Recomenda-se que sejam feitas avaliações audiológicas periódicas / Introduction Children and adolescents living with HIV/Aids may suffer from a variety of hearing problems which are more frequent and sometimes more severe when compared to other children. Aim To estimate the prevalence of hearing loss and risk factors in children and adolescents attending at the Childrens Institute (ICr). Methods 106 patients (5 19 years) were analyzed. Patients and caregivers answered several questionnaires about demographic and clinical conditions. Subsequently, the visual inspection of the external auditory meatus was performed in order to verify if there were clinical conditions to perform the audiologic evaluation. The audiologic evaluation was conducted using pure tone audiometry, speech audiometry, tympanometry and tests of acoustic reflexes. The statistical analysis was done using descriptive statistics, Kappa statistics, Students t-test, chi-square test and univariate and multiple logistic regression models. Results The prevalence of hearing loss according to the Bureau Internacional d´Audio Phonologie (BIAP) classification and to the American Speech-Language-Hearing Association (ASHA) classification was 35.8per cent and 59.4per cent, respectively. The agreement in the diagnosis of hearing loss was good between BIAP and ASHA (k= 0.55). The only risk factor for hearing loss for both classifications was the occurrence of suppurative otitis media. For the BIAP classification, the use of lamivudine (3TC) was a risk factor for hearing loss. For the ASHA classification, the occurrence of severe illness, specially encephalopathy, was a risk factor for hearing loss. Conclusions The occurrence of suppurative otitis media, the history of a severe disease, specially encephalopathy, and the use of lamivudine effectively contribute to hearing loss in children and adolescents with HIV/Aids. Auditory monitoring is critical because it allows early detection of hearing loss and identification of its progression. It is highly recommended periodic hearing assessments

Introdução – As crianças e adolescentes com câncer recebem tratamentos que têm os mais diversos efeitos colaterais, entre eles, a ototoxicidade, que é a capacidade de provocar lesão em estruturas da orelha interna e que pode levar à perda auditiva. Objetivos – Estimar a prevalência de perda auditiva e os fatores associados à ocorrência desta nas crianças e adolescentes tratados no Instituto de Tratamento do Câncer Infantil – ITACI, utilizando três classificações propostas na literatura. Métodos – Foram analisados 94 pacientes atendidos no ITACI, no período de 2003 e 2004. Como a avaliação audiológica não é feita de rotina neste Instituto, os pacientes transferidos e os que foram a óbito não puderam ser incluídos no estudo. Os indivíduos foram submetidos a uma anamnese para verificar qualquer comprometimento auditivo. Em seguida, foi feita a inspeção visual do meato acústico externo, para verificar a presença de qualquer ocorrência que pudesse impedir a realização dos exames audiológicos. Foi realizada a avaliação dos limiares auditivos utilizando-se procedimentos de resposta condicionada (por meio da audiometria tonal liminar, audiometria lúdica condicionada ou audiometria com reforço visual), com a finalidade de determinar os limiares auditivos. Por fim, foram realizadas a timpanometria e a pesquisa dos reflexos acústicos, para avaliar as condições da orelha média. A caracterização da amostra foi realizada por meio da estatística descritiva e a análise da concordância no diagnóstico da perda auditiva para as três classificações, por meio da estatística Kappa. A análise dos fatores associados à presença de perda auditiva foi realizada por meio do teste associação pelo qui-quadrado e modelos de regressão logística univariados e múltiplos. Resultados – Os resultados mostraram prevalência de perda auditiva de 42,5% utilizando a classificação proposta pela American Speech-Language-Hearing Association (ASHA), 40,4% de acordo com a classificação proposta pelo Pediatric Oncology Group Toxicity (POGT) e 12,8% pela classificação de Perda Auditiva Bilateral (PAB). A concordância no diagnóstico de perda auditiva pelas classificações POGT e PAB, e para PAB e ASHA foi fraca (respectivamente, k=0,36 e k=0,33). Já a concordância entre as classificações ASHA e POGT foi quase perfeita (k=0,96). O único fator de risco para perda auditiva, pelas três classificações adotadas, foi o uso da cisplatina e este efeito foi potencializado com o uso concomitante da ifosfamida. Conclusões – A perda de audição é um efeito colateral importante nas crianças e adolescentes com câncer. A monitorização auditiva é fundamental, visto que possibilita a detecção precoce das perdas auditivas e a revisão do tratamento, além de identificar a progressão da seqüela. Recomenda-se que sejam feitas avaliações audiológicas periódicas, mesmo após o término do tratamento e que seja adotada uma classificação que contemple as perdas auditivas discretas, como a proposta pela ASHA. / Introduction – The treatment of childhood cancer has several side effects and the ototoxicity is one of them. It can affect the inner ear structures and may lead to a hearing loss. Aim – To estimate the prevalence of hearing loss and risk factors in children and adolescents attended at the Childhood Cancer Treatment Institute (ITACI), using three classifications proposed in the literature. Methods – 94 patients admitted at ITACI between 2003 and 2004 were analyzed. The evaluation of hearing loss is not usually done in this institution and, because of this, the patients who were transferred and those who died could not be evaluated. The parents answered a questionnaire about demographic and clinical conditions. Then, the visual inspection of the external auditory meatus was done in order to verify if there were clinical conditions to perform the audiologic evaluation. The audiologic evaluation was done using pure tone audiometry (conditioned audiometry, play audiometry or visual reinforcement audiometry), tympanometry and tests of acoustic reflexes. The statistical analysis was done using descriptive statistics, the Kappa statistics, chi-squared test and univariate and multiple logistic regression models. Results – The prevalence of hearing loss was 42,5% using the American Speech-Language-Hearing Association (ASHA) classification, 40,4% using the Pediatric Oncology Group Toxicity (POGT) classification and 12,8%, using the bilateral hearing loss (PAB) classification. The agreement on the diagnosis of hearing loss was weak for POGT and PAB (k= 0.36) and for PAB and ASHA (k=0.33). The agreement between ASHA and POGT was almost perfect (k=0.96). The only risk factor for hearing loss for all classifications was the use of cisplatin and its effect was higher if the patients use also the ifosfamide. Conclusions – Hearing loss is an important side effect in children and adolescents with cancer treated with cisplatin. It is recommended a periodic audiological monitoring, even after the patient has finished the treatment. It can early detect a hearing loss, the schedule of treatment can be reviewed and the speech-language pathologist may be indicated to address the consequences of the hearing loss. It is recommended to adopt a classification that can detect slight hearing loss (ASHA).

Ao se estudar as causas da perda auditiva relacionada ao trabalho, geralmente a perda auditiva induzida por ruído é a mais referida, embora a literatura especializada aponta outros agentes presentes no ambiente de trabalho que podem ser nocivos à saúde do trabalhador. Os solventes são considerados alguns desses agentes e seus efeitos sobre o sistema auditivo vêm sendo investigado por alguns pesquisadores. O uso industrial destes solventes é vasto e, normalmente as condições de trabalho presentes num grande número de indústria brasileiras expõem o trabalhador a elevadas concentrações de solventes. A convivência com as substâncias químicas nos dias atuais é, portanto, obrigatória e permanente sendo particularmente importante para os trabalhadores envolvidos em processos produtivos que direta ou indiretamente utilizem estas substâncias em razão dos danos à saúde e ao ambiente que podem resultar de sua utilização. O risco e o perigo que estão relacionados com as substâncias químicas devem ser trabalhados nas suas várias dimensões entre as quais destacamos: o potencial de dano do produto, as condições ambientais e do trabalho em que as atividades se desenvolvem e o histórico conhecido daquela realidade e de outras semelhantes a partir dos dados epidemiológicos produzidos e do conhecimento científico existente. Este estudo avaliou o perfil audiológico e caracterizou o ambiente de trabalho de frentistas de postos de combustíveis. Os procedimentos desta pesquisa foram realizados em uma clínica particular de fonoaudiologia na cidade de Bariri, e a análise laboratorial foi realizada no laboratório São José, também na cidade de Bariri. Foram utilizados audiometria convencional e de altas frequências, logoaudiometria, imitanciometria, pesquisa das emissões otoacústicas, do Potencial Evocado Auditivo de Tronco Encefálico, exames clínicos laboratoriais, assim como avaliação do ruído ambiental. Nos resultados foram encontrados limiares dentro da normalidade em todos os casos, porém, todos eles apresentaram o traçado característico da perda auditiva ocupacional em evolução, ou seja com entalhes nas frequências de 3 a 6 KHz. Houve ainda alteração nos resultados do PEATE, com aumento de latência em 20 das 32 orelhas testadas. A pressão sonora variaram entre os postos, sendo que o Posto 1 não ultrapassou 80dB, enquanto o Posto 2 apresentou picos que superaram 100dB. O Hemograma se mostrou alterado, com redução de leucócitos, em 9 dos 16 participantes. Não houveram alterações nos demais exames. Concluiu-se que esta população apresentou desencadeamento de PAIR, dentro da normalidade. Os Níveis de Pressão Sonora se apresentaram acima do previsto em lei, e a maioria dos frentistas apresentaram leucopenia, o que pode estar relacionado à exposição aos solventes em questão. Tais conclusões mostram a importância de novos estudos voltados a este ambiente e a esta população. / By studying the causes of work-related hearing loss, usually noise-induced hearing loss is the most reported, although the literature points to other agents present in the workplace that can be harmful to workers health. The solvents are considered some of these agents and their effects on the auditory system are being investigated by some researchers. The industrial use of these solvents is vast and usually working conditions present in a large number of Brazilian industry expose workers to high concentrations of solvents. Living with chemicals nowadays is therefore mandatory and permanent is particularly important for workers involved in production processes that directly or indirectly use these substances because of damage to health and the environment that may result from its use. The risk and the danger that are related to chemicals must be worked in its various dimensions among which: the product of damage potential, environmental conditions and the work in which the activities are developed and the known history of that reality and other similar produced from epidemiological data and current scientific knowledge. This study assessed the audiological profile and characterized the attendants of desktop gas stations. Were used Conventional audiometry and high frequency, speech audiometry, tympanometry, otoacoustic emissions, the brainstem auditory evoked potential brainstem, clinical laboratory tests, and assessment of environmental noise. The recognition and analysis of the risks related to chemical agents are priority activities to qualify intervention in defense of workers\' health. The results were found thresholds within normal limits in all cases, however, they all showed the typical route of occupational hearing loss in evolution. The sound pressure levels varied between the posts, and the station 1 has not exceeded 80 dB, while the station 2 showed peaks which exceed 100dB. The blood count was abnormal, with leukocyte reduction in 9 of the 16 participants. There were no changes in other tests. It was concluded that this population presented onset of NIHL, normal. The sound pressure levels presented above provided by law, and most attendants showed leukopenia, which may be related to exposure to solvents in question. These findings show the importance of new studies related to this environment and this population.