Final publication is available at http://journals.lww.com/otology-neurotology/Pages/default.aspx / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19574号 / 医博第4081号 / 新制||医||1013(附属図書館) / 32610 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 伊佐 正, 教授 一山 智 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

A tribo Hydrops ini constitui um grupo formado pelos gêneros de xenodontíneos Helicops, Hydrops e Pseudoeryx, que se distribuem exclusivamente pelo continente sul-americano. O presente trabalho se propôs a fornecer uma hipótese filogenética, baseada em 47 caracteres morfológicos envolvendo morfologia hemipeniana, osteologia e folidose para 16 das 18 espécies atualmente reconhecidas na tribo. Para essa análise, foram utilizados os princípios da cladística, e os terminais do grupo internos foram analisados simultaneamente com outros nove táxons da subfamília Xenodontinae como grupos externos funcionais. Foram encontradas duas árvores igualmente parcimoniosas com 112 passos, índice de consistência de 0,482 e índice de retenção de 0,768. A análise de ponderação sucessiva dos caracteres indicou uma das duas árvores mais parcimoniosas já na primeira pesagem. Essa árvore foi utilizada para a discussão das relações do grupo interno. A tribo Elapomorphini representa o grupo-irmão de Hydrops ini. O monofiletismo da tribo e dos três gêneros que a compõe foi confirmado e o relacionamento de Farancia abacura e Sordellina punctata com as espécies de Hydropsínios foi rejeitado. A tribo Hydropsini foi organizada em 13 grupos monofiléticos, sendo 11 deles totalmente resolvidos. Diferentemente das propostas anteriores, o gênero Hydrops é indicado como grupo irmão de um clado que reúne Pseudoeryx plicatilis e as espécies do gênero Helicops. A árvore de consenso estrito encontrada, com seus 13 componentes monofiléticos está representada dessa forma: (Hydrops martii; Hydrops triangularis) (Pseudoeryx plicatilis ((Helicops hagmanni; Helicops trivittatus) (((Helicops carinicaudus (Helicops infrataeniatus; Helicops leopardinus; Helicops modestus)) (Helicops danieli ((Helicops angulatus; Helicops gomesi) (Helicops petersi; Helicops scalarisi (Helicops pastazae; Helicops polylepis)))))))). Informações sobre os modos reprodutivos dos Hydropsínios foram otimizadas na topologia encontrada para assim avaliar a origem e evolução da viviparidade neste grupo / The tribe Hydropsini represents a group of three exclusively South American xenodontine genera: Helicops, Hydrops and Pseudoeryx. The aim of the present work is to provide a phylogenetic hypothesis for the tribe Hydropsini, based on Cladistic principles. The data matrix includes 47 morphological characters derived from hemipenial morphology, osteology and scutellation, coded for 16 of the 18 currently recognized species belonging to the tribe. Beside the 16 ingroup terminals, the data matrix also includes nine taxa of the subfamily Xenodontinae that were used as functional outgroups and analyzed simultaneously. Two equally parsimonious trees were found, with a length of 112, consistency index of 0,482, and retention index of 0,768. The successive weighting analysis pointed to one of the two most parsimonious trees found during the first round of analysis. This tree is used to discuss the interrelationships of the ingroup terminals. The tribe Elapomorphini appears as the sister-group of the Hydropsini. The monophyly of the tribe and of the three Hydropsini genera were confirmed, and a closer relationship of the taxa Farancia abacura and Sordellina punctata with the Hydropsini was rejected. The tribe Hydropsini is organized in 13 monophyletic subgroups, from which 11 are unambiguous. Contrary to previously published hypotheses of relationships, the genus Hydrops appears as the sister-group of the clade formed by Pseudoeryx plicatilis and the species of the genus Helicops. The consensus tree for the Hydropsini with the 13 monophyletc components are as follows: ((Hydrops martii; Hydrops triangularis) (Pseudoeryx plicatilis ((Helicops hagmanni; Helicops trivittatus) (((Helicops carinicaudus (Helicops infrataeniatus; Helicops leopardinus; Helicops modestus)) (Helicops danieli ((Helicops angulatus; Helicops gomesi) (Helicops petersi; Helicops scalarisi (Helicops pastazae; Helicops polylepis)))))))). Informations about the reproductive mode of the Hydropsines were optimized in the phylogenetic tree recovered in the present study, in order to evaluate the origin and evolution of viviparity in the tribe.

A tribo Hydrops ini constitui um grupo formado pelos gêneros de xenodontíneos Helicops, Hydrops e Pseudoeryx, que se distribuem exclusivamente pelo continente sul-americano. O presente trabalho se propôs a fornecer uma hipótese filogenética, baseada em 47 caracteres morfológicos envolvendo morfologia hemipeniana, osteologia e folidose para 16 das 18 espécies atualmente reconhecidas na tribo. Para essa análise, foram utilizados os princípios da cladística, e os terminais do grupo internos foram analisados simultaneamente com outros nove táxons da subfamília Xenodontinae como grupos externos funcionais. Foram encontradas duas árvores igualmente parcimoniosas com 112 passos, índice de consistência de 0,482 e índice de retenção de 0,768. A análise de ponderação sucessiva dos caracteres indicou uma das duas árvores mais parcimoniosas já na primeira pesagem. Essa árvore foi utilizada para a discussão das relações do grupo interno. A tribo Elapomorphini representa o grupo-irmão de Hydrops ini. O monofiletismo da tribo e dos três gêneros que a compõe foi confirmado e o relacionamento de Farancia abacura e Sordellina punctata com as espécies de Hydropsínios foi rejeitado. A tribo Hydropsini foi organizada em 13 grupos monofiléticos, sendo 11 deles totalmente resolvidos. Diferentemente das propostas anteriores, o gênero Hydrops é indicado como grupo irmão de um clado que reúne Pseudoeryx plicatilis e as espécies do gênero Helicops. A árvore de consenso estrito encontrada, com seus 13 componentes monofiléticos está representada dessa forma: (Hydrops martii; Hydrops triangularis) (Pseudoeryx plicatilis ((Helicops hagmanni; Helicops trivittatus) (((Helicops carinicaudus (Helicops infrataeniatus; Helicops leopardinus; Helicops modestus)) (Helicops danieli ((Helicops angulatus; Helicops gomesi) (Helicops petersi; Helicops scalarisi (Helicops pastazae; Helicops polylepis)))))))). Informações sobre os modos reprodutivos dos Hydropsínios foram otimizadas na topologia encontrada para assim avaliar a origem e evolução da viviparidade neste grupo / The tribe Hydropsini represents a group of three exclusively South American xenodontine genera: Helicops, Hydrops and Pseudoeryx. The aim of the present work is to provide a phylogenetic hypothesis for the tribe Hydropsini, based on Cladistic principles. The data matrix includes 47 morphological characters derived from hemipenial morphology, osteology and scutellation, coded for 16 of the 18 currently recognized species belonging to the tribe. Beside the 16 ingroup terminals, the data matrix also includes nine taxa of the subfamily Xenodontinae that were used as functional outgroups and analyzed simultaneously. Two equally parsimonious trees were found, with a length of 112, consistency index of 0,482, and retention index of 0,768. The successive weighting analysis pointed to one of the two most parsimonious trees found during the first round of analysis. This tree is used to discuss the interrelationships of the ingroup terminals. The tribe Elapomorphini appears as the sister-group of the Hydropsini. The monophyly of the tribe and of the three Hydropsini genera were confirmed, and a closer relationship of the taxa Farancia abacura and Sordellina punctata with the Hydropsini was rejected. The tribe Hydropsini is organized in 13 monophyletic subgroups, from which 11 are unambiguous. Contrary to previously published hypotheses of relationships, the genus Hydrops appears as the sister-group of the clade formed by Pseudoeryx plicatilis and the species of the genus Helicops. The consensus tree for the Hydropsini with the 13 monophyletc components are as follows: ((Hydrops martii; Hydrops triangularis) (Pseudoeryx plicatilis ((Helicops hagmanni; Helicops trivittatus) (((Helicops carinicaudus (Helicops infrataeniatus; Helicops leopardinus; Helicops modestus)) (Helicops danieli ((Helicops angulatus; Helicops gomesi) (Helicops petersi; Helicops scalarisi (Helicops pastazae; Helicops polylepis)))))))). Informations about the reproductive mode of the Hydropsines were optimized in the phylogenetic tree recovered in the present study, in order to evaluate the origin and evolution of viviparity in the tribe.

Ein tieffrequenter lauter Suppressorton verlagert das Corti-Organ periodisch in Richtung Scala vestibuli und Scala tympani. Simultan registrierte DPOAE (Distorsionsprodukte otoakustischer Emissionen) werden in beiden Richtungen unterschiedlich supprimiert. Bei Vorliegen eines endolymphatischen Hydrops (EH) ist die Beweglichkeit der Basilarmembran eingeschränkt, so daß keine oder eine nur geringe Modulation des DPOAE-Pegels entstehen kann. In dieser Arbeit wird die diagnostische Aussagekraft von Messungen tieftonmodulierter DPOAE bei zwei Patientenkollektiven mit Verdacht auf EH im Vergleich mit einem Normalkollektiv (n = 22) geprüft: bei Patienten mit M. Menière (n = 23) und Patienten mit Ohrdruckgefühl ohne Schwindelsymptomatik (n = 8). Bei den M. Menière-Patienten sind die ipsilateralen Modulationstiefen (MD) im Median hochsignifikant geringer als die des Normalkollektivs. Dies wird als Hinweis auf einen EH gewertet. Bei Primärtonpegeln mit L2 = 20 dB SL ergibt sich für den Grenzwert der MD mit 6 dB die Sensitivität von 64% und die Spezifität von 90%. Die kontralateralen MD der M. Menière-Patienten sind im Median signifikant geringer als die des Normalkollektivs. Für Primärtonpegel mit L2 = 20 dB SL liegen 33% der Werte unter dem Grenzwert, von diesen Ohren ist die Hälfte symptomfrei. Auch im kontralateralen Ohr kann ein – eventuell asymptomatischer – Hydrops vorliegen. Die Ergebnisse der Patienten mit Ohrdruckgefühl ohne Schwindel zeigen im Median hochsignifikant geringere MD als die der Normalhörenden und unterscheiden sich nicht signifikant von den Werten der ipsilateralen Ohren der M. Menière-Patienten. Das Ohrdruckgefühl kann auf einen cochleären Hydrops hinweisen und die weitere Entwicklung eines EH ankündigen. Bei den Verlaufsuntersuchungen zeigen die MD beider Patientenkollektive, deren Symptomatik sich während dieses Zeitraums änderte, Variabilitäten: mit Zunahme der Heftigkeit der spezifischen Symptome nimmt die MD ab und umgekehrt. Die Tieftonmodulation scheint den Zustand der Cochlea widerspiegeln zu können. Im Vergleich mit den in der Klinik gängigen Verfahren zur Hydropsdiagnostik wie der ECochG oder dem Glyceroltest erweist sich das in dieser Arbeit angewandte objektive Verfahren als vorteilhaft: es ist schnell durchführbar, nicht belastend und nicht invasiv. Es eignet sich als Screeningverfahren und kann zur Verlaufskontrolle eingesetzt werden. / The cochlear partition is moved periodically towards scala vestibuli and scala tympani by a low-frequency high-level suppressor tone. Simultaneously recorded DPOAEs (distortion product otoacoustic emissions) are suppressed differently in both directions. This modulation of the DPOAE level may be reduced or even missing if the displacement of the basilar membrane is inhibited by endolymphatic hydrops (EH). In this thesis the diagnostic significance of the low-frequency modulation of DPOAEs is tested in two patient groups with suspected EH: patients with Menière’s disease (n = 23) and patients with aural fullness without vertigo (n = 8), compared to a control group of normal hearing adults (n = 22). In the patients with Menière’s disease the ipsilateral modulation depths (median) are high significantly lower than in the control group. This can be interpreted as a sign of EH. At primary tone levels with L2 = 20 dB SL and a limiting value of 6 dB modulation depth (MD), a sensitivity of 64% and a specificity of 90% are found. The contralateral MDs of the patients with Menière’s disease (median) are significantly lower than in the control group. At primary tone levels with L2 = 20 dB SL, 33% of the MDs are below the limiting value, half of these ears are symptom-free. So in the contralateral ear a possibly asymptomatic hydrops may be present as well. The patients with aural fullness without vertigo show high significantly lower MDs (median) than the normal hearing adults and no significant difference to the ipsilateral MDs of the patients with Menière’s disease. Aural fullness can be a sign of cochlear hydrops and may indicate the further development of EH. During the course of disease the MDs of both patient groups vary when symptoms change: with increasing intensity of the specific symptoms the MD is reduced and vice versa. Low-frequency modulation seems to reflect the state of the cochlea. Compared to the generally used clinical tests for the assessment of EH like ECochG or the glycerol test, the objective method presented in this thesis is advantageous: it is fast, not straining and non-invasive. It is suitable for screening and can be used to monitor the course of disease.

Techn. Universiẗat, Diss., 2005--München.

Grâce à la miniaturisation de la technologie ainsi qu'a l'augmentation constante des capacités de calcul numérique, les méthodes objectives et les appareils de mesures de la physiologie auditive évoluent. C'est dans l'optique de créer de nouveaux outils diagnostics que la société Echodia a été créée en 2009. Celle-ci finance aujourd'hui mes recherches sous convention CIFRE.Les présents travaux proposent, dans une première partie, de présenter comment deux méthodes de mesures non invasives ont été mises en oeuvre pour être applicables au diagnostic de l'hydrops cochléaire. Les méthodes sont basées sur le fait que les réponses des cellules ciliées de la cochlée à des stimuli sonores dépendent de la position au repos de leur touffe de stéréocils. Or, l'hydrops cochléaire, l'une des principales caractéristiques de la maladie de Menière, est susceptible de venir perturber cet environnement. Une variation chimique ou mécanique de celui-ci peut ainsi être mise en évidence par différentes méthodes d'exploration objectives. La première est basée sur un enregistrement électrophysiologique. En étudiant le Potentiel de sommation (SP) de l'ÉlectroCochléoGraphie (ECochG), nous allons recueillir une image du tour basal de la cochlée. La deuxième méthode est basée sur un enregistrement acoustique dans le méat acoustique externe. En monitorant le déphasage des Produits de distorsion desoto-émissions acoustiques (DPOAE), nous allons enregistrer les réponses du tour apical de la cochlée.La deuxième partie est consacrée à une étude au cours de laquelle nous avons enregistré de manière concomitante le SP (basal) ainsi que le DPOAE (apical) chez 73 patients souffrant de vertiges de Menière, à proximité d'une attaque (n = 40) ou entre les attaques, sans symptômes cliniques (n = 33). Dans le cas des DPOAE, c'est la phase du produit de distorsion (PDA) à 2*f1-f2 qui a été étudiée en réponse à des sons stimulants de fréquence f1 = 1 kHz et f2 = 1,2 kHz. La puissance des deux fondamentaux a été fixée entre 70 et 75dB SPL en fonction du niveau du DPOAE. Le rapport entre SP et le Potentiel d’action global (AP) a, quant à lui, été mesuré de manière extra-tympanique en réponse à des clics de 95dB nHL. Ces deux mesures ont été effectuées plusieurs fois pendant un test de posture afin d'évaluer leur stabilité.Les limites normales de déphasage du DPOAE en réponse à la posture [-18 °, +38 °] ont été dépassées chez 75% des patients étant venus consulter à proximité d'une crise. Sur ces mêmes sujets, l'étude du ratio entre SP et AP a dépassé la valeur normale (<0,40) dans 60% des cas. De plus, chez les patients à proximité d'une crise de vertige, les deux types de mesures révèlent des fluctuations entre deux répétitions. Ces écarts mettent en évidence combien l'hydrops entrave le bon fonctionnement de la mécanique cochléaire. Le fait de constater des variations sur des échelles de temps aussi courtes pourrait expliquer la sensibilité imparfaite des tests diagnostics. En effet, les protocoles de mesure du SP ou des DPOAE nécessitent un moyennage des acquisitions qui, par définition, a tendance à niveler les fluctuations transitoires. / Thanks to technology miniaturization as well as digital computing abilities steadily increasing, objective measurement methods and their related devices evolve. Echodia company was created in 2009 with the goal to create new diagnostic tools. The company currently supports my research work through a CIFRE convention.The first part of this thesis presents two non-invasive measurement methods that have been implemented to the diagnosis of cochlear hydrops. The methods are based on the responses of cochlear hair cells to sound stimuli, depending themselves on the resting position of their stereocilia bundles. Cochlear hydrops, a hallmark of Meniere's disease, is likely to disturb this environment. A chemical or mechanical variation of this environment may be observed by various objective exploration methods. The first method is based on an electrophysiological recording. By studying the Summating Potential (SP) of the Electrocochleography (ECOG) we will register activity in the basal part of the cochlea. The second method is based on a sound recording in the external acoustic meatus. By monitoring the phase shifts of Distortion-Product OtoAcoustic Emissions (DPOAE), we will record the apical responses of the cochlea.The second part of this thesis focuses on a study in which we recorded concomitantly the SP (basal) and the DPOAE (apical) in 73 patients with Menière's disease, close to an attack (n = 40) or between attacks without clinical symptoms (n = 33). In the case of DPOAE, the phase at 2*f1-f2 has been studied in response to pure sinusoidal sounds at frequency f1 = 1 kHz and f2 = 1,2 kHz. The power of the two primary was set between 70 and 75dB SPL based on the level of the DPOAE. The SP to Action Potential (AP) ratio has been measured by extra-tympanic electrode in response to 95dB nHL clicks. These two measurements were performed several times during a postural test to evaluate their stability.The normal limit of the phase shift of the DPOAE during a postural test [-18 °, +38 °] was exceeded in 75% of patients near an attack. On these subjects, the study of the SP/AP ratio exceeded the normal value (<0.40) in 60% of cases. In addition, the two types of measurements made on patients near a vertigo attack reveal fluctuations between reiteration. These differences highlight how hydrops hinders the proper functioning of the cochlear mechanics. This short time scales fluctuations might explain the imperfect diagnostic sensitivity of SP and DPOAE tests, as averaging procedures would tend to level out transient fluctuations characteristic of hydrops.

Ménière’s disease (MD) is an idiopathic inner ear disorder, characterised by episodes of vertigo, tinnitus, sensorineural hearing loss, and aural fullness in the affected ear. The relatively high variability of symptomological changes renders it difficult to confirm the MD diagnosis. The purpose of this study is to compare the diagnostic power of an instrumental method, electrocochleography (ECochG), and two subjective methods, including the criteria based on the clinical guidelines provided by the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing Equilibrium (AAO-HNS CHE) and Gibson’s Score. A quota sampling method was used to include subjects. A total of 250 potential MD patients who were referred to the Department of Otolaryngology at the Christchurch Hospital between year 1994 and 2009 have had their signs and symptoms documented and ECochG testing completed. A selection of details obtained from both AAO-HNS CHE and ECochG assessment results were examined as a chart review in regard to its function as a diagnostic tool for MD. The between-method reliability was found to be high, with a few disagreements on individual diagnosis. Based on a receiver operating characteristic (ROC) curve analysis, the ECochG measures were shown to be pertinent to the diagnosis of MD. It was also found that patients tested “positive”, as compared with those tested “negative”, tended to show higher correlations among the four key symptoms of MD and among the ECochG measures derived from the auditory evoked responses to tone bursts at frequencies in close proximity to each other.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

Abstract The symptom complex originating from the inner ear, known as Meniere's disease, was studied especially from the epidemiologic point of view. A total of 442 patients' charts were retrospectively analysed in several hospital districts of Finland. The period of 1992-1996 was covered. The main focus was on the epidemiological assessment of the disease in Finland. To clarify the epidemiological figures, the validity of the diagnostic assessment was examined using the latest guidelines (1995) of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) as a gold standard. The diagnostic tools used in the different hospitals were documented and evaluated, and diagnostic accuracy at the different levels of the health care system was evaluated. The clinical picture of Meniere's disease was characterised, and the therapeutic modalities used were evaluated. The audiometric configurations were classified according to two principles. The prognosis of hearing impairment was specified by creating a multivariable model. Half of the patients (N = 221) fulfilled the AAO-HNS criteria for definite disease. The prevalence and incidence of definite cases of Meniere's disease appeared to be lower in Finland than could be expected based on previous international studies. A prevalence of at least 43 per 100,000 and an average annual incidence of 4.3 per 100,000 were obtained. The prevalence rates in the catchment areas of the university and central hospitals did not differ statistically, but a significant (p &lt; 0.001) difference was found between the average prevalences in the northern and southern Finnish hospital districts. Fluctuation of hearing in repeated audiometric measurements appeared to be a highly sensitive (94%) diagnostic test to detect definite Meniere's disease. According to the multivariable model created in this study, the hearing impairment in Meniere's disease affects equally males and females, and the deterioration is about 1 dB per year due to the duration of the disease and 0.5 dB per year due to aging. The disease was controlled conservatively in 69% of the cases. A gently sloping high-frequency audiometric pattern was most prevalent according to the EU Work Group classification and a flat pattern according to the mid-frequency-based classification. The variability of diagnostic criteria, diagnostic tools and therapeutic modalities shows an evident need for up-to-date therapy recommendations for Meniere's disease in Finland.

Ménière’s disease is the third most common inner ear disorder. The individual course of Ménière’s disease in different patients makes it difficult to diagnose on the basis of symptomatology alone. The impact of Ménière’s disease on quality of life has highlighted the importance of an additional tool to support the diagnosis of Ménière’s disease. Apart from the patient’s history, audiological data provide the most relevant information for confirming the diagnosis. The aim of this study was to analyse and describe the clinical and audiological features of a cohort of subjects diagnosed with Ménière’s disease, in order to develop understanding of the pathophysiology of the disease and to facilitate the diagnostic process. The research is based on a retrospective study of the medical records of 135 subjects with Ménière’s disease which were selected according to a non-probability sample. Descriptive statistics were used to organize, analyse and interpret the data. Sixty one percent of subjects presented with definite Ménière’s disease, 14 % with probable Ménière’s disease and 25 % with possible Ménière’s disease. The results showed a higher incidence of Ménière’s disease in females especially in the vestibular type. Three percent of subjects indicated a family history of Ménière’s disease. Bilateral Ménière’s disease presented in 39 % of subjects. The results confirmed that vertigo was the most debilitating symptom in Ménière’s disease. Correlating the clinical features of subjects with audiometric and vestibular tests highlighted the clinical value of an audiological test battery including the following tests: Pure tone audiometry, Speech discrimination, Oto-acoustic emissions, Electronystagmography and Electrocochleography. This confirms the role of the audiologist in the diagnostic and rehabilitation process in patients with Ménière’s disease. / Dissertation (Communication Pathology)--University of Pretoria, 2007. / Speech-Language Pathology and Audiology / unrestricted