Cisplatin is an extensively used chemotherapeutic agent in the treatment of a broad spectrum of tumors. Ototoxicity is currently the most frequent dose limiting side-effect of cisplatinum chemotherapy. Ototoxicity has been shown to be the result of two mechanisms: oxidation, and more recently: inflammation. Various agents have been studied to prevent cisplatin ototoxicity. None has been proven effective in clinical trials to this date. Curcumin, a spice derived from a plant called Curcuma longa, possesses antioxidant activity and inhibits mediators of inflammation. However, curcumin low solubility in water and its low bioavailability limit its use. These issues can be solved using a novel technique called nano-encapsulation. In this research project, we wanted to find out whether curcumin could be nano-encapsulated, and, if so, whether the nano-encapsulated curcumin applied transtympanically is ototoxic, and whether it could be detected in the cochlear fluid and the blood. To answer these questions, a polymer of N-isopropylacrylamide (NIPAM), N-vinyl-2-pyrrolidone (VP), Poly(ethyleneglycol) monoacrylate (PEG-A) was formed. Curcumin was then mounted in this polymer. Different measurements were performed to characterize the created molecule such as the fourier transform infrared (FTIR) spectroscopy, the ultraviolet visible (UV-Vis) spectroscopy, and the atomic force microscopy (AFM). Results showed that curcumin was indeed nano-encapsulated. To test the safety of the nano-encapsulated curcumin, it was applied transtympanically to the ears of 5 chinchillas. The hearing was recorded using the auditory brainstem response (ABR) and the distortion product otoacoustic emission (DPOAE). Results of this pilot study showed that the nano-encapsulated curcumin is not ototoxic. To detect the presence of the nano-encapsulated curcumin in the cochlear fluid and the blood, it was applied transtympanically to chinchillas. The cochlear fluids and the blood samples were withdrawn / La cisplatine est un agent chimiothérapeutique largement utilisé dans le traitement d'un vaste éventail de tumeurs. L'ototoxicité est actuellement l'effet secondaire le plus important limitant l'utilisation de la cisplatine. L'ototoxicité résulte de deux mécanismes connus soit : l'oxidation, et plus récemment: l'inflammation. Plusieurs agents ont été étudiés pour éviter l'ototoxicité de la cisplatine. Jusqu'à ce jour, aucun n'a été prouvé efficace en clinique. La curcumine, une épice tirée d'une plante appelée Curcuma longa, possède une activité anti-oxidante et inhibe les médiateurs de l'inflammation. Toutefois, la faible solubilité de la curcumine dans l'eau et sa faible biodisponibilité limite son utilisation. Ces deux problèmes peuvent être résolus en utilisant une nouvelle technique appelée la nano-encapsulation. Dans ce projet de recherche, nous voulions déterminer si la curcumine pourrait être nano-encapsulée, et, si oui, si la curcumine nano-encapsulée appliquée à travers le tympan serait ototoxique, et si elle pourrait être décelée dans le liquide cochléaire et le sang. Pour répondre à ces questions, un polymère de N-isopropylacrylamide (NIPAM), N-vinyl-2-pyrrolidone (VP), et de poly (éthylène glycol) monoacrylate (PEG-A) a été formé. La curcumine a été ensuite incorporée dans ce polymère. Différentes mesures ont été réalisées pour caractériser la molécule créée comme la spectroscopie infrarouge à transformée de fourier (IRTF), la spectroscopie ultraviolet visible (UV-Vis) et la microscopie à force atomique (AFM). Les résultats ont montré que la curcumine a été effectivement nano-encapsulée. Pour tester la sécurité de la curcumine nano-encapsulée, une application transtympanique a été délivrée aux oreilles moyennes de 5 chinchillas. L'audition a été mesurée en utilisant la réponse auditive du tronc cérébral (RAT) et les émissions oto-acoustiques évoquées par produit$

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 68-02, Section: B, page: 0868. Adviser: Ron Chambers. Includes bibliographical references (leaves 77-91) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--The University of Iowa, 2006. / (UMI)AAI3225660. Adviser: Richard S. Tyler. Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3673.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-05, Section: B, page: 2885. Adviser: David M. Gooler. Includes bibliographical references (leaves 103-108) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--Indiana University, Dept. of Speech and Hearing, 2009. / Title from PDF t.p. (viewed on Jul 9, 2010). Source: Dissertation Abstracts International, Volume: 70-10, Section: B, page: 6084. Adviser: Jennifer J. Lentz.

In order to identify neurophysiological correlates of the changes in the level of conciousness associated with general anesthesia, the 40 Hz auditory steady-state response (ASSR), the electroencephalogram (EEG) and the N1 and P3 components of the transient auditory evoked potential were recorded before anesthesia (pre-induction), at the onset of anesthesia (induction), during surgical anesthesia, at the time of emergence and during recovery from anesthesia. The amplitude of the ASSR, was reduced significantly during late induction and dropped below noise levels during surgical anesthesia. It increased during emergence and further increased during recovery although the amplitude during recovery was significantly less than pre-induction values. Total EEG power increased significantly after induction. The EEG median frequency and 95% quantile frequency decreased significantly during surgery and increased significantly during emergence. Muscle artifacts could account for many of the EEG changes. The results for the transient auditory evoked potential indicated that, except during emergence, detection was associated with clear N1 and P3 waves whereas undetection was not. The lack of either N1 and P3 for detection during emergence perhaps occurred because the patients were not yet fully conscious. (Abstract shortened by UMI.)

This thesis presents two approaches investigating how the human auditory system processes the brief frequency changes that occur in speech sounds. Section 1 of the thesis consists of a critical review of the literature on human auditory event-related potentials (ERPs) and speech perception. Section 2 consists of three experiments evaluating ERPs to non-speech frequency changes. The experiments evaluated steady state and transient auditory evoked potentials (EPs) to tones that were sinusoidally modulated in frequency and to tones that alternated between two frequencies with a linear ramp. The tones were presented at modulation rates typical of average syllable production. The steady state responses to sinusoidal FM were small and difficult to record at both the first and second harmonics. Ramp FM evoked larger and more consistent second harmonic steady state responses than the sinusoidal FM. Only the ramp FM stimuli elicited transient EPs and these only at low modulation rates. These responses were larger to upward ramps than to downward ramps. The response to two simultaneously presented ramp FM tones differed from the sum of responses to the individual tones indicating some interaction in the processing of the two stimuli. Since the first study found that steady state responses were not as reliable as ERPs to discrete frequency changes, the second study used speech sounds containing discrete frequency changes. In Section 3 of the thesis computer-modified speech sounds from the /ba/ to /da/ continuum were presented to reading subjects as a train of standard speech sounds interspersed with two types of infrequent deviant speech sounds. One deviant stimulus lay within the same category as the standard and the other lay across the categorical boundary from the standard, but both were acoustically equidistant from the standard in terms of the second formant transition. When the standard stimulus was drawn from the /ba/ end of the continuum, the across-category deviants elicited a clear mismatch negativity (MMN) in the auditory event-related potential whereas the within-category deviants did not. This MMN began at about 60-120 ms after stimulus onset and was present for several hundred ms. These results suggest that categorical processing of speech sounds occurs independently of attention at an early echoic memory stage. When the standard stimulus was drawn from the /da/ end of the continuum, the MMN to across-category deviants was not larger than the MMN to within-category deviants. Grand mean waveforms suggested that both deviant stimuli elicited small MMNs. Although this may indicate processing along an acoustic continuum, the results of the psychophysical tests suggest that the standard stimulus in this condition was too close to the category boundary for the deviants to evoke a consistent categorical mismatch.

The research reported in this study centred around the experience of adopting auditory-verbal therapy from the perspective of parents whose children wear cochlear implants. Although it has been asserted that family involvement is pivotal to the communication attainment of children with hearing loss, and despite the significant parental commitment required to implement auditory-verbal therapy, there have been no studies thus far that have examined the auditory-verbal process from the parents' perspective. Therefore, the major research question was: What are parents' experiences in making the transition to auditory-verbal therapy with their children who wear cochlear implants? A qualitative case study methodology, framed in Bronfenbrenner's ecological theory of human development and family systems theory guided this exploratory study. Bronfenbrenner indicates that an ecological transition occurs "whenever during the life course, a person undergoes a change in role either within the same or a different setting" (Bronfenbrenner & Crouter, 1983, p. 381). Parents whose children are diagnosed with a hearing loss and who adopt auditory-verbal therapy experience such a transition. Participants were 9 parents and 2 auditory-verbal therapists. Data collection procedures included individual interviews, observation sessions, a group discussion and a family information questionnaire. The major themes were: personal characteristics and family interactions (microsystem level of Bronfenbrenner's model); choice, compliance and support (mesosystem); support (exosystem); and accessibility and inclusion (macrosystem). This is the first time that Bronfenbrenner's model has been used as a theoretical framework for examining auditory-verbal therapy. The study revealed the importance of parent and child personality traits and their compatibility. It underlined that support from the cochlear implant team, as well as funding from the provincial Ministries assist the parents' transition. It emphasized that ease of access to technology, therapy and speaking role models, as well as inclusion in mainstream education also facilitate this transition.

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