京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13325号 / 論医博第2193号 / 新制||医||1043(附属図書館) / (主査)教授 黒田 知宏, 教授 藤渕 航, 教授 別所 和久 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduction: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is the commonest benign paediatric neoplasm. There is no curative treatment, but the condition is self-limiting. Current primary treatment is aimed at symptomatic relief, comprising of serial surgical debulking of obstructive papillomas along the respiratory tract, with voice preservation. Adjuvant therapy is indicated in severe cases. Objective: A review of children with JoRRP presenting to the ENT Department at Red Cross War Memorial Children’s Hospital (RCWMCH) over 2 years. Evaluation of the pattern of disease and factors that may contribute to disease severity were reviewed. Method: Retrospective folder review of children with histologically confirmed laryngeal papillomatosis over above the time period. Results: Twenty children were included. Nine were male, 11 were female. The median age at diagnosis was 2.4 years (11 - 109 months). Presentation at < 3 years was noted in 5/7 of the most severe cases. Nine of 20 were HPV serotyped; 5 were type 11, and 4 were type 6. Eighty percent (16/20) were HIV negative; 10% (2/20) HIV positive; and 10% (2/20) were unknown. A total of 90 surgical procedures were performed; the highest number of surgeries per child was 13. Inter-surgical time was 1 to 164 weeks (median 9 weeks). Four received Gardasil vaccination as adjuvant therapy, 3 of who showed a reduction in disease severity. Conclusion: JoRRP commonly presents around the first 3 years of life. Severe cases can be life-threatening, often with multiple hospital admissions for clearance of surgical papillomata. Severe cases presented before 3 years. Gardasil vaccination as adjuvant therapy has promise. No identifiable risk factors in our review were noted. HIV co-infection and HPV type were not risk factors for severity.

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Nasal high flow (NHF) therapy is a recent form of non-invasive respiratory support for patients suffering from respiratory distress that supplies high flows of heated and humidified air, oxygen or a mix via a nasal cannula. A number of in vivo studies have proven its effectiveness at improving blood oxygenation; however, its mechanisms of action remain widely unproven. Two proposed mechanisms of action, the CO2 washout of anatomic dead space and the production of positive airway pressure, are investigated in this thesis for the use of the Fisher & Paykel Healthcare Ltd (FPH) Optiflow™ adult nasal cannula through a range of experiments. Five anatomically correct upper airway models produced from computed tomography (CT) scan data via 3D printing were employed during in vitro experiments and two live subjects participated in in vivo measurements. The human respiratory system was faithfully replicated for CO2 washout experiments with physiological CO2 diffusion into the lung replicated by a constant flow of CO2 into the lung pump. In vivo measurement of a natural breathing flow pattern was scaled to an average population tidal volume and respiratory rate for in vitro use. In vitro measurements of static pressure during natural breathing found similar flow resistances across the nasal passage for inspiratory and expiratory flow directions; however, across the entire upper airway greater resistance was seen for inspiration. Introduction of NHF therapy produced significant increases in all mean and peak airway pressures within the upper airway with a flow rate of 30 LPM fulfilling the inspiratory work requirements presented by the upper airway resistance. In vivo and in vitro hot wire anemometry measurements at the exterior nares indicated low velocity and turbulence intensity flows at peak inspiration and a high velocity jet with high turbulence during peak expiration. At natural breathing an in vitro anterior-posterior velopharynx traverse captured low turbulence intensities during peak inspiration and high turbulence intensities during peak expiration. Introduction of NHF therapy had little influence on the turbulence intensity profile of peak expiration yet did cause significant increases in the turbulence intensities during peak inspiration. Measurements of the CO2 concentration near the lung volume over many breath cycles were used to find time-averaged CO2 concentrations. For the standard airway model an average CO2 concentration of 4.88 ± 0.07 %V/V was determined during natural breathing. Implementation of increasing levels of NHF therapy generated significant washout of CO2 reducing this average concentration to a minimum of 3.81 ± 0.11 %V/V at a flow rate of 80 LPM. It was determined that airway geometry significantly affected the efficacy of the NHF therapy though CO2 washout was observed in all five airway models.

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Introdução: Dependendo da magnitude da má oclusão de Classe III, esta é uma alteração difícil de ser tratada apenas com a correção ortodôntica. Tanto as cirurgias de recuo mandibular quanto as bimaxilares promovem uma melhora na oclusão, na função mastigatória e na estética facial, ao corrigirem as posições da mandíbula e/ou maxila, mas um importante aspecto da cirurgia ortognática, que não pode ser negligenciado, são os efeitos que os movimentos esqueléticos das bases ósseas podem provocar na região das vias aéreas, ao alterar a posição do osso hióide e da língua. O estreitamento das vias aéreas superiores (VAS) pode comprometer o sono dos pacientes submetidos à correção cirúrgica e predispor ao desenvolvimento da apneia/hipopneia obstrutiva do sono (AOS). Objetivos: O presente trabalho tem como objetivo avaliar as alterações de volume e área axial mínima do espaço aéreo faringeo em pacientes com má oclusão de Classe III esquelética, submetidos à cirurgia ortognática bimaxilar, pela técnica de osteotomia Le Fort I da maxila e osteotomia sagital bilateral da mandíbula. Material e Métodos: As avaliações foram feitas em tomografias computadorizadas Cone-beam, utilizando-se o Programa Dolphin Imaging 11.7. As tomografias de 50 pacientes, de ambos os sexos, com média de idade de 33,40 (± 9,38) anos, foram analisadas nos períodos pré e pósoperatório e as medidas de volume e área axial mínima foram mensuradas. Foi utilizado o teste t pareado e os testes foram realizados utilizando-se o programa Statistica 7.0, adotando-se um nível de significância de 5%. Resultados: ao calcular o erro do método, não foram encontrados erros casuais e nem sistemáticos (p> 0,05 em todas as medidas). As cirurgias bimaxilares para correção da Classe III esquelética promoveram um aumento de 16,68% (±22,61) no volume e 23,58% (± 31,46) na área axial mínima. Conclusões: Mesmo que os efeitos da cirurgia de avanço maxilar e recuo mandibular sobre as vias aéreas não sejam completamente previsíveis, podemos observar que a maioria dos pacientes não apresentaram prejuízos na anatomia faringeana que resulte em diminuição do volume aéreo e área axial mínima, predispondo-o ao desenvolvimento da AOS. / Introduction: Depending on the extend of Class III malocclusion, it becomes difficult to be treated only with orthodontic correction. Both mandibular setback surgery as bimaxillary surgery, promote an improvement in occlusion, masticatory function and facial aesthetics, correcting the position of the mandible and/or maxilla. But an important aspect of orthognathic surgery that cant be overlooked, are the effects that the skeletal movements of the bone bases causes in the airway space, since they change the position of the hyoid bone and tongue. The narrowing of the pharingeal airway space (PAS) may impair the patient\'s sleep and predispose to the development of obstructive sleep apnea (OSA). Purpose: This study aims to evaluate surgical changes in the airway volume and minimal cross-sectional area in the pharyngeal airway space (PAS) in patients with skeletal Class III malocclusion, submitted to bimaxillary surgery, using a Le Fort I maxillary osteotomy and bilateral sagittal split ramus osteotomy technique. Material and Methods: The evaluations were made through Cone-beam computed tomography (CBCT), using Dolphin Imaging program version 11.7. The CT scans of 50 patients of both genders, with a mean age of 33.40 (± 9.38), were analyzed pre and postoperatively and volume and minimum axial area were measured. Paired t test was used and tests were performed using Statistica 7.0 software, adopting a 5% significance level. Results: Method error were done and no random or systematic errors were found (p> 0.05 for all measures). Bimaxillary surgery for skeletal Class III correction promoted an increase of 16.68% (± 22.61) in volume and 23.58% (± 31.46) at the minimum axial area. Conclusion: Even if the effects of the maxillary advancement and mandibular setback surgery on the airway are not completely predictable, we observed that most patients didnt have pharyngeal airway anatomy damage, that could result decreased on airway volume and minimum axial area predisposing to OSA development.

A respiração predominantemente oral é constantemente citada como um dos fatores associados ao desenvolvimento da deficiência transversal da maxila. A Expansão Rápida da Maxila (ERM) é um excelente método para a correção desta alteração, por meio da abertura da sutura palatina. A tomografia computadorizada por feixe cônico é tem sido descrita como um método preciso de exame de imagens e diante das limitações dos métodos radiográficos convencionais o objetivo deste estudo é avaliar as alterações morfológicas imediatas, decorrentes da ERM, na cavidade nasal e na região da naso e orofaringe, por meio da TCFC. Foram avaliadas 15 pares de imagens tomográfica, correspondentes a 15 pacientes portadores deficiência transversal da maxila, tratados com ERM, que realizaram a TCFC ao início e após o período de contenção de 4 meses. Os resultados encontrados mostram que a cavidade nasal apresenta aumento transversal significativo em seu terço inferior, nas regiões anterior (p=0,045), média (p=0,009) e posterior (p=0,001). Não há alteração significativa do volume (p=0,11), área sagital mediana (p=0,33) e menor área axial (p=0,29) decorrente da ERM na nasofaringe. Há alteração significativa do volume (p=0,05), área sagital mediana (p=0,01) e menor área axial (p=0,04) nos momentos antes e imediatamente após a ERM, na orofaringe. Após análise dos resultados concluímos que a ERM é capaz de aumentar a largura transversal da cavidade nasal, não tendo o mesmo efeito na região da nasofaringe, e que as alterações encontradas na orofaringe podem ser decorrentes de falta de padronização o posicionamento da cabeça e lingual no momento da aquisição da imagem. / The predominantly oral breathing is constantly cited as an etiological factor for the transverse maxillary deficiency. Rapid Maxillary Expansion is an excellent method for the correction of malocclusion, through the opening of the midpalatal sutures. The literature shows that the benefits of this procedure are beyond the dental benefits, and could have repercussions in the upper airways, due to its close relationship with the maxilla. The cone beam computed tomography has been described as is an accurate method of taking pictures and before the limitations of conventional radiographic methods the aim of this study is to evaluate the immediate morphological changes resulting from the ERM, the nasal cavity and the nasal region and oropharynx, through the CBCT. We evaluated 15 patients with maxillary width deficiency were treated with RME, which hosted the CBCT to the beginning and after the retention period of 3 months. The results show that the nasal cavity presents significant increase in cross their lower third, in the anterior (1.08 mm ± 0.15), medium (1.28 mm ± 0.15) and posterior (0.77 mm ± 0.12). No significant change in volume (p=0.11), median sagittal area (p=0.33) and lower axial area (p=0.29) resulting from the RME in nasopharynx. There is significant change in volume (p = 0.05), median sagittal area (p = 0.01) and lower axial area (p = 0.04) before and immediately after the RME in the oropharynx. After analysis and discussion of results in this study, we concluded that RME is able to increase the transverse width of the nasal cavity, not having the same effect in the nasopharynx, and that the changes found in the oropharynx may be due to the lack of positioning standardization of the head and tongue at the time of image acquisition.

名古屋大学博士学位論文 学位の種類:博士（医療技術学）（課程） 学位授与年月日:平成19年3月23日 / "Daytime polysomnography and portable recording device for diagnosis and CPAP therapy in patients with obstructive sleep apnea syndrome" Sleep and Breathing, v.11, n.2 (2007) pp.109-115 を、博士論文として提出したもの。

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