Rozprawy doktorskie na temat „Paranasal sinuses”

This study aims to design and develop effervescent proliposomes that could disintegrate in water and liberate liposomes, and to investigate the potential suitability of liposomes generated for aerosolization to target paranasal sinuses. Novel effervescent proliposomes prepared with Soya phosphatidylcholine (SPC) and Dipalmitoylphosphatidylcholine (DPPC) successfully generated stable liposomes with an improved disintegration time of less than 5 min. Differences in lipid composition were found to influence liposome size and drug entrapment of the hydrophobic drug Beclometasone dipropionate (BDP). Mannitol-based formulations developed with DPPC:Chol (1:1) produced liposomes of 7.54±0.15 µm with a drug entrapment efficiency of 82.15±8.29%. Addition of the mucoadhesives alginic acid or chitosan to effervescent proliposomes made with SPC was found to hamper BDP entrapment in liposomes. Effervescent proliposomes produced SPC:Chol liposomes that also proved beneficial for entrapment of the hydrophilic drug Xylometazoline hydrochloride (XH). The Pari Sinus (pulsating aerosol technology) and Pari Sprint (non-pulsating technology) nebulizers were used for liposome delivery to a nasal cast. Choice of carrier did not affect the liposome’s ability to withstand shearing. A novel system of a Sar-Gel® (water indicating paste) coated clear nasal cast fixed to a two-stage impinger system was set up to analyze drug deposition within the nasal cast cavity. Sinus drug deposition with effervescent mannitol, DPPC:Chol formulation was observed to be highest at 48.45±2.75 cm2 with pulsation compared to deposition of 35.52±11.11 cm2 without pulsation. Drug distribution studies indicated that the Pari Sinus deposited 10.47±2.9% drug, while the Pari Sprint deposited only 4.6±1.4%. The degree of drug loss was higher with conventional liposomes in the Pari Sinus nebulizer, indicating that the degree of bilayers disruption depended on formulation.

Sinonasal and dental diseases can be a serious disorder in horses due to the persistence of the former and the common extension of the latter to the supporting bones of the skull. The diagnosis of equine sinonasal and dental disease can be challenging due to the complexity of these and adjacent anatomical structures, and therefore the use of advanced imaging, including computed tomography (CT) has greatly increased recently. A major aim of this study was to improve the morphological characterization of the sinuses and cheek teeth in normal horses of different ages. These studies defined the volumes of the 7 different sinus compartments; showed that the volume of the different compartments increase with age; that in contrast to accepted findings, the Triadan 09 alveoli is located in the caudal maxillary sinus (CMS) in 13% of the youngest group and the Triadan 10 alveoli is fully within the rostral maxillary sinus (RMS) in 53% of cases. The infraorbital canal was found to be susceptible to apical infection-related damage in horses < 2 years of age (< 2 y.o.) due to the intimate relationship of this canal and the medial aspect of the maxillary cheek teeth alveoli. The mean positions of the clinical crowns and apices of the maxillary Triadan 11s were 2.48 cm (adjusted 5.2% of head height) and 2.83 cm (adjusted 6.2% of head height) more rostral, respectively in horses >16 y.o. compared to horses < 6 y.o., consistent with rostral dental drift. Measurements of dental drift could provide further objective radiographic guidelines on ageing horses by dental imaging and also help our understanding of the aetiopathogenesis of cheek teeth diastemata. This study also found that the reserve crown length decreased from a mean of 4.7 cm (adjusted 19.7% of head height) in the youngest (< 6y.o.) group of horses to a mean of 2.9 cm (adjusted 10.5% of head height) in the oldest group (>15y.o.), with the 06s and 09s having the shortest reserve crowns. These data are useful reference information for clinicians and radiologists in the diagnosis and treatment of equine sinonasal and dental disease. Morphological characterization of the ventral and dorsal conchal bullae in horses of different age using CT described the age-related difference in sizes of these structures (smaller in younger horses). In the ventral conchal bulla, this reduction in volume was probably related to protrusion of the large dental alveoli in young horses into the nasal cavity and bulla. Bullae linear measurements and volumes were also associated with head size. The anatomical position of both bullae was associated with specific maxillary cheek teeth, thus increasing the diagnostic value of conventional radiography in the investigation of bulla disease and providing landmarks for the surgical treatment of this disorder. Skull shape analyzed with the use of Procrustes statistical analysis showed landmark variability between different age groups and in particular, high landmark variability between young (< 5y.o.) and old (>16y.o.) horses and less landmark variability between adult (6-15y.o.) and old horses. Future studies could investigate changes in the equine skull in relation to genotype to characterize breed-related diseases affecting teeth and sinonasal compartments. In the second part of the study, 32 infected maxillary cheek teeth extracted from clinical cases were evaluated grossly and histologically and these pathological results were compared to the pre-extraction radiographic and CT imaging findings. This study showed a high sensitivity (97%) of CT in detecting changes in teeth affected by apical infection. In the third part of the study, 30 cheek teeth assessed as being abnormal based on oral, radiographic and CT examinations were extracted along with their alveoli from 27 cadaver heads. Gross and histological examination findings from these teeth and alveoli were compared to the pre-extraction imaging findings, again showed high sensitivity (96.4%) of CT in diagnosing cheek teeth apical infection. Additionally, CT showed a high correlation with histology in detecting dental infection related alveolar bone changes including alveolar bone lysis, sclerosis and bone thickening. This aspect of the study was also the second largest pathological study of equine apical infection published to date and thus has also improved our understanding of the pathogenesis of this disorder. In conclusion, CT was shown to be an excellent imaging modality for improving the morphological characterization of the sinuses and teeth in normal horses of different ages, and thus also improving the value of this modality in diagnosis and treatment of disease affecting sinonasal and dental structures. This study also objectively showed the high sensitivity of CT in detecting cheek teeth apical infection in horses as compared to radiography, including by assessment of alveolar bone changes. Overall, the results of this project improve morphological knowledge of the equine skull and teeth and will have direct clinical benefits by improving the diagnosis and thus the treatment of equine sinonasal and dental disease.

Background: The contribution of the nasal and paranasal cavities to the vocal tract resonator properties is unclear. Here we investigate these resonance phenomena of the sinonasal tract in isolation in a cadaver and compare the results with those gained in a simplified brass tube model. Methods: The resonance characteristics were measured as the response to sine sweep excitation from an earphone. In the brass model the earphone was placed at the closed end and in the cadaver in the epipharynx. The response was picked up by a microphone placed at the open end of the model and at the nostrils, respectively. A shunting cavity with varied volumes was connected to the model and the effects on the response curve were determined. In the cadaver, different conditions with blocked and unblocked middle meatus and sphenoidal ostium were tested. Additionally, infundibulotomy was performed allowing direct access to and selective occlusion of the maxillary ostium. Results: In both the brass model and the cadaver, a baseline condition with no cavities included produced response curves with clear resonance peaks separated by valleys. Marked dips occurred when shunting cavities were attached to the model. The frequencies of these dips decreased with increasing shunting volume. In the cadaver, a marked dip was observed after removing the unilateral occlusion of the middle meatus and the sphenoidal ostium. Another marked dip was detected at low frequency after removal of the occlusion of the maxillary ostium following infundibulotomy. Conclusion: Combining measurements on a simplified nasal model with measurements in a cadaveric sinonasal tract seems a promising method for shedding light on the acoustic properties of the nasal resonator.

Orientador: Emílio Carlos Elias Baracat
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Opacificações dos seios paranasais podem ser encontradas incidentalmente em tomografias de pacientes sem rinossinusite. Esses achados freqüentemente são desprovidos de significado clínico, mas podem trazer dilemas diagnósticos quando são intensos. Objetivos: verificar se anormalidades tomográficas incidentais dos SPN em crianças e adolescentes sem rinossinusite implicam em maior risco de desenvolvimento posterior de sintomas do trato respiratório superior. Casuística e Método: foi realizado um estudo de coorte com pacientes entre zero e 18 anos, submetidos à tomografia computadorizada do crânio por indicações não relacionadas à rinossinusite. As opacificações sinusais foram aferidas por um escore, a razão opacificação/desenvolvimento. A evolução clínica dos pacientes foi então avaliada por questionários durante o mês que se seguia ao exame. Resultados: dos 106 pacientes incluídos, as opacidades acometeram 56%, a maioria representada por espessamento mucoso discreto. Opacidades mais intensas, ditas suspeitas (escore = 15) impuseram maior risco de desenvolvimento de sintomas ao longo do seguimento, com odds ratio de 2,74 (IC95%: 1,10 - 6,83) em relação aos exames normais ou a opacidades discretas. Conclusão: opacidades são encontradas incidentalmente com freqüência em tomografias de crânio de crianças e adolescentes e quanto mais intensas elas são, maior é o risco de evolução posterior de quadros respiratórios
Abstract: Paranasal sinuses opacification are incidentally found on computed tomography of patients without rhinosinusitis. These findings are often of no clinical significance, however may cause diagnostic dilemmas when they are severe. Objective: to verify if incidental abnormalities of the paranasal sinuses on tomography of children and adolescents without rhinosinusitis raise the risk for development of superior respiratory tract symptoms. Methods: a cohort study was conducted on patients with ages varying from 0 to 18 years whose tomographic scans of the head were done for problems not related to rhinosinusitis. Sinuses abnormalities were measured by a score system called opacification-development ratio. Then periodical clinical follow-ups were undertaken by inquiry forms applied during the month next to the scan. Results: From a sample of 106 patients, opacities affected 56%, usually represented by mild mucousal thickening. Moderate and severe opacities, what was called suspicious (score = 15) imposed a higher risk of emerging respiratory symptoms during follow-up, at an odds ratio of 2.74 (CI95%: 1.10 - 6.83), compared with mild opacities or normal scans. Conclusion: Incidental opacities are frequently found on computed tomography of children and adolescents and the more severe they are, the higher the risk of progression to respiratory clinical manifestations afterwards
Doutorado
Saude da Criança e do Adolescente
Doutor em Saude da Criança e do Adolescente

Chronic rhinosinusitis is a common disorder of chronic inflammation of the upper respiratory tract. It is associated with significant symptoms and impairment of the quality of life of sufferers. Despite recent advances in the medical and surgical management of chronic rhinosinusitis, there remains a population of patients who fail to obtain relief from their symptoms. Chronic inflammation of the mucosa of the nasal cavity and paranasal sinuses is one of the hallmarks of chronic rhinosinusitis. This inflammation is demonstrated by an increased number of chronic inflammatory cells, elevated levels of pro-inflammatory cytokines, increased expression of adhesion molecules and metaplastic changes in the epithelium. The current medical treatments for chronic sinusitis aim to reduce this inflammation and consequently improve symptoms. In recent years, evidence has emerged that macrolide antibiotics have an anti-inflammatory effect that is separate from their anti-bacterial effect. This effect was first described in the treatment of diffuse panbronchiolitis, a disorder of chronic inflammation of the lower respiratory tract. Following the success of macrolides in treating this condition it was trialed in chronic rhinosinusitis. Several open-label trials have subsequently demonstrated a beneficial effect. Laboratory studies have investigated the mechanism of the anti-inflammatory effect of macrolides. These have shown that macrolides effect cytokine production, inflammatory cell apoptosis, expression of adhesion molecules, neutrophil oxidative burst, bacterial virulence and mucociliary function. In this thesis we report a series of experiments designed to further investigate the mechanism of action and clinical effect of macrolides. In vitro studies using whole sections of chronic rhinosinusitis mucosa cultured for 24 hours in macrolide, prednisolone or control showed that macrolide and prednisolone produced significant reductions in the production of interleukin-5, interleukin-8 and granulocyte-macrophage colony stimulating factor. The same cultured specimens also showed a reduction in expression of transforming growth factor-?. No reduction was seen in the expression of the key pro-inflammatory nuclear transcription factor Nuclear factor-?B. In our in vivo experiments, biopsies were taken from chronic rhinosinusitis patients who had received a 3-month course of macrolide. These biopsies showed a reduction in the number of neutrophils present following treatment. There was no reduction in the number of other inflammatory cells or in the expression of TGF-? and NK-?B. We have performed the first ever double-blinded, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Patients receiving macrolide showed significant improvements in saccharine transit time, nasal endoscopic scoring and symptom scores following a 12 week course. Patients with low levels of serum immunoglobulin E showed significantly improved outcomes compared to those with high levels. Interleukin-8 levels in nasal lavage fluid were significantly reduced in the patients with low levels of IgE following macrolide treatment. No improvements in any of the objective or subjective outcome measures were seen in the placebo-treated patients. We have performed a series of experiments investigating the anti-inflammatory effect of macrolide antibiotics from 'the bench to the bedside'. These experiments have provided insight into the mechanism of action of macrolides in the laboratory setting and evidence of a beneficial effect in the treatment of chronic rhinosinusitis patients.

Chronic rhinosinusitis is a common disorder of chronic inflammation of the upper respiratory tract. It is associated with significant symptoms and impairment of the quality of life of sufferers. Despite recent advances in the medical and surgical management of chronic rhinosinusitis, there remains a population of patients who fail to obtain relief from their symptoms. Chronic inflammation of the mucosa of the nasal cavity and paranasal sinuses is one of the hallmarks of chronic rhinosinusitis. This inflammation is demonstrated by an increased number of chronic inflammatory cells, elevated levels of pro-inflammatory cytokines, increased expression of adhesion molecules and metaplastic changes in the epithelium. The current medical treatments for chronic sinusitis aim to reduce this inflammation and consequently improve symptoms. In recent years, evidence has emerged that macrolide antibiotics have an anti-inflammatory effect that is separate from their anti-bacterial effect. This effect was first described in the treatment of diffuse panbronchiolitis, a disorder of chronic inflammation of the lower respiratory tract. Following the success of macrolides in treating this condition it was trialed in chronic rhinosinusitis. Several open-label trials have subsequently demonstrated a beneficial effect. Laboratory studies have investigated the mechanism of the anti-inflammatory effect of macrolides. These have shown that macrolides effect cytokine production, inflammatory cell apoptosis, expression of adhesion molecules, neutrophil oxidative burst, bacterial virulence and mucociliary function. In this thesis we report a series of experiments designed to further investigate the mechanism of action and clinical effect of macrolides. In vitro studies using whole sections of chronic rhinosinusitis mucosa cultured for 24 hours in macrolide, prednisolone or control showed that macrolide and prednisolone produced significant reductions in the production of interleukin-5, interleukin-8 and granulocyte-macrophage colony stimulating factor. The same cultured specimens also showed a reduction in expression of transforming growth factor-?. No reduction was seen in the expression of the key pro-inflammatory nuclear transcription factor Nuclear factor-?B. In our in vivo experiments, biopsies were taken from chronic rhinosinusitis patients who had received a 3-month course of macrolide. These biopsies showed a reduction in the number of neutrophils present following treatment. There was no reduction in the number of other inflammatory cells or in the expression of TGF-? and NK-?B. We have performed the first ever double-blinded, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Patients receiving macrolide showed significant improvements in saccharine transit time, nasal endoscopic scoring and symptom scores following a 12 week course. Patients with low levels of serum immunoglobulin E showed significantly improved outcomes compared to those with high levels. Interleukin-8 levels in nasal lavage fluid were significantly reduced in the patients with low levels of IgE following macrolide treatment. No improvements in any of the objective or subjective outcome measures were seen in the placebo-treated patients. We have performed a series of experiments investigating the anti-inflammatory effect of macrolide antibiotics from 'the bench to the bedside'. These experiments have provided insight into the mechanism of action of macrolides in the laboratory setting and evidence of a beneficial effect in the treatment of chronic rhinosinusitis patients.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text

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CAPES
FACEPE
No presente trabalho, foi realizado um levantamento das doses recebidas por pacientes pediátricos, em exames radiográficos convencionais dos seios da face, realizados no Recife, PE. Para a realização do estudo, foram selecionados dois hospitais que atendem ao Sistema Único de Saúde, com alta demanda de exames pediátricos. Os dados dos pacientes e os parâmetros de irradiação utilizados em 159 exames radiográficos dos seios da face de crianças, com idades entre 0 e 15 anos, foram coletados, sendo 103 radiografias realizadas na projeção lateral (radiografia cavum) e 56 radiografias realizadas nas projeções pósteroanteriores em fronto-naso (FN) e mento-naso (MN) (radiografias Caldwell e Waters, respectivamente). Inicialmente, foram efetuadas as avaliações de desempenho dos dois equipamentos de raios X pertencentes aos hospitais. A partir dos valores dos rendimentos dos tubos de raios X e dos parâmetros de irradiação empregados nos exames, foram estimados os valores de kerma no ar na superfície de entrada (Ka,e) e produto kerma no ar-área (PK,A). Os valores de kerma no ar nas regiões dos olhos e da tireoide foram estimados utilizando dosímetros termoluminescentes (TLD-100). As doses absorvidas médias nos órgãos e a dose efetiva foram estimadas com o software PCXMC® a partir dos dados antropométricos, parâmetros de irradiação e do kerma no ar incidente (Ka,i), obtido com o rendimento. Os resultados mostraram que os valores de Ka,e variaram entre 0,065 mGy e 1,113 mGy, para radiografias cavum, entre 0,13 mGy e 7,99 mGy, para radiografias na incidência Caldwell e entre 0,13 mGy e 10,12 mGy, para radiografias na incidência Waters. Os valores do kerma no ar na região dos olhos variaram entre 0,001 mGy e 0,968 mGy, nas radiografias cavum, e 0,011 mGy e 0,427 mGy, nas incidências Caldwelll e Waters (conjuntamente). Na região da tireoide, os valores de kerma no ar variaram entre 5 μGy e 932 μGy, para as radiografias cavum, e 2 μGy e 972 μGy, para as incidências Caldwell e Waters. 90% dos valores de Ka,e estimados para os exames realizados no Hospital B encontram-se dentro do recomendado pela comunidade britânica, enquanto todos no Hospital A encontram-se acima. O fato do Hospital B apresentar valores de Ka,e dentro do aconselhado não significa que seu serviço esteja otimizado, devido a grande quantidade de filmes rejeitados, cuja imagem apresentava-se clara e inapropriada para o diagnóstico, elevando a dose final recebida pelo paciente pela repetição do exame. Os altos valores de Ka,e devem-se, principalmente, à utilização indiscriminada da grade antiespalhamento, não recomendada para pacientes desta idade. Os valores de PK,A variaram entre 5,7 mGy.cm2 e 92,3 mGy.cm2 para as radiografias cavum, entre 24,4 mGy.cm2 e 340,3 mGy.cm2 para as radiografias Caldwell e, entre 34,0 mGy.cm2 e 378,3 mGy.cm2 para as radiografias Waters. A partir dos dados pode-se concluir que há necessidade de otimização dos procedimentos radiográficos.
In this study, a survey was conducted in order to assess doses received by pediatric patients ongoing conventional radiographs of the sinuses, performed in Recife, PE. For the study, two hospitals of SUS (Sistema Único de Saúde), with high demand for pediatric examinations, were selected. Patient data and irradiation parameters were collected for 159 radiographs of the children’s sinuses with ages between 0 and 15. Among those, 103 radiographs were taken on the lateral projection (cavum radiography) and 56 radiographs were taken in posteroanterior projections in fronto-naso (FN) and mento-naso (MN) (Caldwell and Waters radiographs, respectively). Initially, the performance of the two X-ray equipment was evaluated. Air kerma values at the entrance surface (Ka,e), and air kerma area product (PK,A) were estimated using X-ray tubes output and irradiation parameters used in the examinations. Air Kerma values on the eyes and thyroid were estimated using thermoluminescent dosimeters (TLD-100). The average absorbed organ doses and effective dose were estimated at the PCXMC® software using the anthropometric data, irradiation parameters and the incident air kerma (Ka,i) obtained with the x-ray tube output. The results showed that Ka,e values varied between 0.065 and 1.113 mGy for cavum radiographs; between 0.13 and 7.99 mGy for Caldwell’s view; and between 0.13 and 10.12mGy for Waters’ view. The air kerma values in at the eye region varied from 0.001 mGy to 0.968 mGy for cavum radiographs, and from 0.011 mGy to 0.427 mGy for Caldwell and Waters’ views (together). In the thyroid region air kerma values ranged from 5 μGy to 932 μGy for cavum view and from 2 μGy to 972 μGy for Caldwell and Waters’ views. Tests performed at Hospital B have shown that 90% of the Ka,e values estimated during exams are within the recommended values by British Commonwealth, while all the Ka,e values in the Hospital A were above it. However, even though Hospital B presented Ka,e values within recommended values, this service was not optimized, due to the large amount of rejected films, whose image were inappropriate for diagnosis resulting in increased dose by the patient re-examination. The high Ka,e values are due mainly to the indiscriminate use of anti-scatter grid, not recommended for patient ages assessed in this study. PK,A values varied between 5.7 and 92.3 mGy.cm2 for cavum radiographs, between 24.4 and 340.3 mGy.cm2 for Caldwell’s view and between 34.0 and 378.3 mGy.cm2 for Waters’ view. Thus, it was concluded that there is need for optimization of radiographic procedures.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A identificação biométrica de pessoas na área forense está em constante estudo para facilitar e melhorar as maneiras de identificação mediante a avaliação de diversas estruturas que podem ser utilizadas como características biométricas. Os seios paranasais, cavidades ósseas presentes no crânio, apresentam alta individualidade e permanência, podendo ser utilizados em sistemas biométricos forenses. As maneiras de representação digital dos seios paranasais são modalidades de exames médicos, conhecidos como raios-X e tomografia computadorizada. As imagens de raios-X como ferramentas para obtenção de características dos seios paranasais apresentam alta aplicação nos trabalhos correlatos, entretanto, nesta modalidade de imagem, algumas desvantagens, como a baixa qualidade de resolução dificultam a identificação dos seios paranasais. Com a tomografia computadorizada, uma nova avaliação pode ser realizada para a obtenção das características dos seios paranasais, visto que esta modalidade de exame gera uma sequência de imagens com qualidade superior, tornando a segmentação e extração de características dos seios paranasais mais simples, intuitiva e precisa, facilitando seu uso em sistemas de reconhecimento biométrico. O objetivo desta dissertação foi desenvolver um novo método de identificação humana utilizando estruturas dos seios paranasais, obtidas de imagens de tomografia computadorizada, como características biométricas. Este método propõe avanços significativos principalmente nas etapas de segmentação e extração de características, uma vez que a segmentação das estruturas dos seios paranasais é realizada de forma automática. As características propostas como descritores são baseadas nas regiões e nas formas das estruturas dos seios paranasais. Resultados experimentais obtidos sobre uma base de dados contendo 310 imagens de tomografia computadorizada mostraram que o método automático proposto nesta dissertação obteve taxa de segmentação medida pelo Coeficiente KAPPA igual a 88,52% na segmentação dos seios frontais e 79,30% na segmentação dos seios maxilares. Com relação à identificação de pessoas, o método proposto obteve, no melhor caso, 8,99% de taxa de erro igual (EER). Assim, nesta dissertação de mestrado concluiu-se que: os seios da face podem ser utilizados com êxito para a identificação forense de pessoas, em particular os seios frontais; que os descritores de forma para os seios frontais são mais efetivos do que os descritores de região para a identificação de pessoas, enquanto que para os seios maxilares, os descritores de forma não apresentam alto valor de discriminação entre os indivíduos e; que é possível automatizar o processo de segmentação dos seios frontais e maxilares utilizando-se imagens de tomografia computadorizada.
Biometric identification of people in the forensic field is constantly being studied to facilitate and improve the identification methods through the evaluation of several structures that can be used as biometric features. The paranasal sinuses, bone cavities present in the skull, have high individuality and permanence and can be used in forensic biometric systems. The X-rays and Computed Tomography are modalities of medical examinations used for the digital representation of the paranasal sinuses. X-rays images as a tool to obtain characteristics of the paranasal sinuses are highly applicable in the related works, however, in this imaging modality, some disadvantages, such as low quality resolution, make these structures harder to acquire. With computed tomography representation, a new evaluation can be performed to obtain the paranasal sinuses features, knowing that this exam modality generates an image sequence with higher quality, making the paranasal sinuses segmentation and feature extraction simpler, intuitive and precise, facilitating its use in biometric recognition systems. The objective of this master’s dissertation was the development of a new human identification method that uses paranasal sinuses structures as biometric features, obtained from computed tomography images. This method proposes significant advances, specially on the segmentation and features extraction stages, once the segmentation of the paranasal sinuses structures is performed automatically. The characteristics proposed for the feature descriptors are based on the region and shape of the paranasal structures. The experimental results obtained from a database composed by 310 computed tomography images presented that the automatic method proposed in this dissertation showed 88.52% of frontal sinuses segmentation and 79.30% of correct maxillary sinuses segmentation using the KAPPA coefficient. Relative to the persons identification, the proposed method presented in the best case 8.99% of EER. Therefore, in this master’s dissertation, it was concluded that: the face sinuses, and in particular the frontal sinuses, can be used with success for the forensic human identification; for the human identification based on the frontal sinuses the shape descriptors are more efficient than the region descriptors, while that for the human identification based on maxillary sinuses, the shape descriptors do not presented high discrimination performance and; it is possible to automate the frontal and maxillary sinuses segmentation process using computed tomography images.

Introduction: Forensic pathologists may be asked to identify the race group or sex of a cranium of unknown origin. Race group refers to geographic ancestry and sex is biological sex. An analysis of the volumes and measurements of human paranasal sinuses, namely maxillary, ethmoid, sphenoid and frontal sinuses, in dried crania of different race and sex groups (European and Zulu male and female) was undertaken to search for a new improved approach of classifying crania according to race and sex. This anatomical assessment of the human paranasal sinuses identifies race and sex variations in the paranasal sinuses. Variations in paranasal sinus volumes and measurements may mean a variation in anatomical landmarks. The best combination of sinus measurements was selected to classify a cranium according to race group and sex making this research relevant to the field of forensic medicine. Objectives: To compare the paranasal sinus volumes and measurements of dried crania of European and Zulu descent with respect to race group and sex and to develop a method of classifying a cranium according to race group or sex by using dimensions of the paranasal sinuses. Methodology: Documented, cadaver derived, dried crania were obtained from the Raymond A. Dart Collection of Human Skeletons, housed at the School of Anatomical Sciences at the University of the Witwatersrand, Johannesburg, South Africa. Age, race and sex were recorded for each cranium within the collection and hence within the study sample. 26 Adult European crania; 13 male, 13 female. Age range 19-75yrs (mean 49.42yrs) and 27 Adult Zulu crania: 13 male, 14 female. Age range 16-90yrs (mean 40.16yrs) was selected for this study. An additional cranium of unknown origin was also analysed in the research. European crania were from descendants of Europe living in South Africa and Zulu crania were obtained from Zulu patients who were part of the Zulu tribe of South Africa. 53 crania with intact paranasal sinuses (106 individual sinuses for each of the maxillary, ethmoid, sphenoid and frontal sinuses) were studied. In addition, 2 sinuses from the unknown cranium were analysed. The dried crania of European and Zulu origin were assessed by helical, multislice computed tomography using 1mm coronal slices. The area for each slice was obtained by tracing the outline of each slice. A volume was calculated by the CT machine that totaled the slices for each sinus. Measurements of width, length and height were also assessed, as were other craniometrical measurements. Statistical analysis was performed for all European and Zulu male and female sinuses in respect of volumes and measurements. Further statistical analysis searched for classification patterns. In addition, forty patients' scans from the European and Zulu male and female groups in Southern Africa were also assessed. CT scans of 10 adult European males, 10 adult European females, 10 adult Zulu males and 10 adult Zulu females provided 40 pairs of maxillary, ethmoid, sphenoid and frontal sinuses for analysis. Europeans were South African persons of European descent and Zulus were from the Zulu tribe of Kwa Zulu Natal in South Africa. Results: The aim of identifying race and sex differences in this anatomical region is achieved. Significant race and sex variations were found in the European and Zulu, male and female groups when analysing the volumes and measurements of the paranasal sinuses. The very best combinations of classifiable measurements were described and are being put forward as a new tool in human forensic identification studies. The significant sex classification figure of 91.8% by combining ethmoid, sphenoid and frontal paranasal sinus measurements, is a new discovery for using a combination of the sinuses. The significant race classification figure of 95.9 % is an excellent classification figure for classification according to race. This was done using the measurements of maxillary, ethmoid and total distance across the sinuses. All this was achieved by using the measurements of the paranasal sinuses in a European and Zulu, male and female population. Conclusion: Forensic race and sex identification of crania is now possible using a combination of measurements from the paranasal sinuses. A new approach to classifying a cranium into an race or sex group is revealed by way of using a new combination of paranasal sinus measurements. This discovery is of importance to forensic medicine in the realm of identification as it provides a measurable way of assigning race or sex to a cranium within a particular region. Other studies based on other race groups may add further value. What is clear is that the paranasal sinuses are now of established value when assessing race or sex group of a unknown cranium. A new tool for forensic race and sex identification is provided to the armamentarium of the forensic pathologist and associated disciplines.

The paranasal sinuses are a group of four paired air-filled spaces that exist superior and laterally to the nasal cavity. The sinuses are considered to provide an immunological role along with mucus production and air humidification. These sinus tissues are susceptible to obstructive malformation, inflammatory, infectious, and neoplastic processes, sometimes requiring surgical management. Surgical management has moved from open approaches to minimally invasive endoscopic sinus surgery (ESS). This surgical approach, although effective, has a reported complication rate of up to 5%, with cerebrospinal fluid leak due to perforation of the skull base reported to occur in up to 1% of cases. The regions of the skull base at risk of perforation include the cribriform plate medially and the fovea ethmoidalis laterally, with the lateral lamella of the cribriform plate (LLCP) the thinnest structure and hence most susceptible to iatrogenic injury. Thus, examination of pre-operative radiographic imaging, which has transitioned from plain X-rays to the currently preferred computed tomography (CT) modality, is critical for patient safety when performing ESS as at-risk anatomy can be readily identified and protected. However, in radiologist reports of CT scans, landmarks of surgical importance are often not commented upon, requiring thorough and careful re-review by the operating surgeon. These deficiencies not only place the patient at greater risk as concerning structures may be missed but also means clinically relevant information is not reported for detailed attention during surgical review. Recent studies using computer vision based artificial intelligence (AI) tools show significant promise in their ability, after appropriate training, to identify and classify anatomy of interest and to streamline workflows for both radiologists and surgeons in screening for significant anatomic irregularities to highlight for clinician review. Through experimental research, a computer vision based convolutional neural network (CNN) AI model was developed to measure the height of the LLCP and then to categorise it as per the clinically relevant Keros classification system. The research included a systematic review of the published literature to analyse the use of CNNs in analysing radiographic imaging in rhinology, identify algorithms showing promise and their current applicability to clinical practice (Chapter 3). The review indicated a scarcity of published papers and of the 7 papers that used CT scans, all of them used varying CNN models and transfer learning techniques to classify different rhinologic anatomy. Notably, studies show that the CNN algorithms exhibit weaker performance when tested on external image datasets suggesting limitations in generalising trained algorithms for use in different institutions and populations. Therefore, future studies that test the performance and applicability of these AI tools should include validation steps, with external datasets. While these CNN algorithms were able to identify pathologic structures or variations of normal anatomy, they did not measure the size of these pathologies, requiring the need to develop and train a measuring algorithm in this study. The multi-layered CNN AI algorithm developed in this study and trained using randomly selected coronal CT hemi-slices from the prepared image-set was then used to measure the LLCP height in the remaining hemi-slices within the image-set (test images). This CNN AI measured a total of 114 out of 140 LLCPs correctly to within 1mm of the ground truth, an accuracy of 81.4% with an overall mean absolute error of 0.61mm (95% CI = 0.52-0.70mm). The mean absolute percentage error (MAPE) was 15.8% and the Pearson correlation coefficient was 0.58 (95% CI: 0.46 – 0.68). This demonstrates moderately strong agreement between the ground truth, measurements completed by two surgical residents, and the CNN AI measurements. When the measured LLCPs heights were assigned a Keros stage, the algorithm obtained an accuracy of 73.6%, area under the curve of 0.79 (95% CI: 0.71 – 0.86) and a staging agreement kappa statistic of 0.44 (95% CI: 0.29 – 0.59) between the ground truth and the trained CNN, representing moderate correlation (Chapter 4). While various studies have shown that CNN AI algorithms with appropriate training can identify and classify anatomy of interest, the findings of this research have made an original contribution towards using CNN AI algorithms to measure clinically important structures, such as the LLCP, on preoperative CT scans, which can then be to classified according to established staging systems to aid in operative planning. The use of machine learning (ML) tools in the assessment of pre-operative paranasal sinus CT scans and their potential clinical integration warrants further investigation.

Descrição: A rinossinusite fúngica (RSF) é uma infecção oportunística, caracterizada pela inflamação da mucosa nasal e dos seios paranasais. É considerada um problema emergente na clínica médica diária, com prevalência aumentada nas últimas décadas, com etiologia nos mais diversos fungos ubíquos. Objetivos: Este trabalho objetivou analisar todos os casos de RSF pertencentes ao banco de dados do Laboratório de Micologia da Irmandade da Santa Casa de Misericórdia de Porto Alegre, no período de 28 anos (1986-2014), relacionando-os com as características clínicas e epidemiológicas. Materiais e métodos: O estudo foi retrospectivo observacional, resultando em uma série de 82 casos, confirmados histopatologicamente e pelos exames micológicos para identificação de fungos, comparados-os com os achados nas imagens radiológicas. Resultados: Foram identificados 54 casos de RSF por aspergilose, com predominância do agente etiológico Aspergillus fumigatus (14/54), e 27 casos de RSF por fungos diferentes do gênero Aspergillus, com superioridade de isolamento de agentes responsáveis por hialohifomicoses (12/27). Configurado, nestes achados, o ineditismo de três casos em nosso meio, com destaque para o primeiro caso de RSF e infecção humana por Trichoderma asperellum. Conclusões: Estes achados representam a maior casuística brasileira identificada, podendo contribuir para uma melhor compreensão epidemiológica, melhorando os critérios de suspeição médica, refletindo na efetividade dos tratamentos, principalmente, no diagnóstico dos casos de RSF invasiva, com altas taxas de mortalidade.
Description: The fungal rhinosinusitis (FRS) is an opportunistic infection characterized by inflammation of the nasal mucosa and sinuses. It is considered an emerging problem in daily medical practice, with prevalence increased in recent decades, with etiology in diverse ubiquitous fungi. Objectives: This study aimed to analyze all cases of RSF belonging to the Mycology Laboratory of the database of the Brotherhood of the Santa Casa of Misericordia Porto Alegre during the period of 28 years (1986-2014), relating them with the clinical and epidemiological characteristics. Methods: The study was observational retrospective, resulting in a series of 82 cases confirmed by histopathological and mycological examinations for identification of fungi, compared them with the findings on radiographs. Results: We identified 54 cases of aspergillosis by RSF, especially the etiologic agent Aspergillus fumigatus (14/54), and 27 cases of RSF different fungi Aspergillus, with insulation superiority of agents responsible for hyalohyphomycosis (12/27). Configured, these findings, the three cases unprecedented in our country, especially the first case of human infection with RSF and Trichoderma asperellum. Conclusions: These findings represent the largest identified Brazilian series and can contribute to a better epidemiological understanding, improving clinical suspicion criteria, reflecting the effectiveness of treatments, mainly in diagnosing cases of invasive RSF, with high mortality rates.

Neste trabalho foi proposto um estudo de análise exploratória de exames de tomografia computadorizada helicoidal, o qual abrange os seios paranasais, a cavidade nasal e as possíveis variações anatômicas que podem estar presentes nestas regiões. A pneumatização dessas estruturas tem grande importância cirúrgica, uma vez que pode levar à exposição e ao comprometimento de estruturas vasculonervosas. O complexo ostiomeatal foi observado e a relação entre seus componentes foi descrita. O estudo foi realizado na forma de análise exploratória de uma amostra de conveniência de 109 tomografias computadorizadas helicoidais. Foi feita a descrição estatística dos dados obtidos. Foram encontradas as seguintes variações: desvio de septo à direita (39,4%), desvio de septo à esquerda (16,5%), septo sinuoso (5,5%) e presença de esporão (9,2%), concha média bolhosa, sendo a pneumatização da lamela basal bilateralmente (2,8%), da lamela vertical à esquerda (6,4%), da lamela vertical à direita (3,7%), da lamela vertical bilateralmente (5,5%), pneumatização da concha média na sua totalidade, do lado direito (4,6%), do lado esquerdo (7,3%) e bilateralmente (11%), pneumatização da concha superior, à direita (1,8%) e bilateralmente (5,5%), curvatura paradoxal da concha nasal média à esquerda (6,4%), à direita (1,8%) e bilateralmente (4,6%), curvatura paradoxal da concha superior esquerda (0,9%) e bilateralmente (2,8%), hipoplasia do seio frontal (15,6%) e do seio maxilar (1,8%), pneumatização do processo pterigóide do lado esquerdo (10,1%), do lado direito (0,9%) e bilateralmente (27,5%), a pneumatização do processo clinóide anterior, do lado esquerdo (3,7%) e bilateralmente (9,2%), processo clinóide posterior do lado esquerdo (0,9%) e 1,8% bilateralmente. Também foi observada a pneumatização do septo nasal (14,7%), do palato ósseo (0,9%) e do processo uncinado (6,4%). Foram observadas as células da crista do nariz (12,8%), infra-orbital (11%), supraorbital (0,9%) e esfeno-etmoidal (11,9%). Das variações anatômicas estudadas, o desvio de septo mostrou-se a mais constante, seguido pela pneumatização da concha média, com a qual mostrou correlação. A tomografia computadorizada permite um estudo com acurácia, da cavidade nasal, dos seios paranasais e das variações morfológicas que possam estar presentes.
This study intends to present the exploratory analysis of tomography scans concerning the paranasal sinus, nasal cavity, and the possible anatomic variations that may be observed in these areas. The enlargement of anatomic structures during surgery may expose important elements to loss or injury. The ostiomeatal complex was observed, and the relation between its elements was described. This study of exploratory analysis was carried out in a convenience group, in which a total of 109 tomography scans were evaluated. A statistics description of the findings was made and the following anatomic variations were noted: septal deviation to the right (39,4%), septal deviation to the left (16,5%), S-shaped septal deviation (5,5%), presence of spur or ridge (9,2%), concha bullosa of the middle turbinate, with pneumatization of the basal lamella, bilaterally (2,8%), of the vertical lamella to the left (6,4%), of the vertical lamella to the right (3,7%), of the vertical lamella bilaterally (5,5%), pneumatization of the entire middle turbinate to the right (4,6%), to the left (7,3%), and bilaterally (11%), pneumatization of the superior turbinate to the right (1,8%) and bilaterally (5,5%), paradoxal curve of the middle turbinate to the left (6,4%), to the right (1,8%) and bilaterally (4,6%), paradoxal curve of the superior turbinate to the left (0,9%) and bilaterally (2,8%), hipoplasia of the frontal sinus (15,6%) and hipoplasia of the maxillary sinus (1,8%), pneumatization of the pterygoid process to the left side (10,1%), to the right side (0,9%) and bilaterally (27,5%), pneumatization of the anterior clinoid process to the left (3,7%) and bilaterally (9,2%), pneumatization of the posterior clinoid process to the left (0,9%) and bilaterally (1,8%). The nasal septum pneumatization was also observed (14,7%), to the hard palate (0,9%) and the uncinate process (6,4%). Nasal crest cell was observed (12,8%), infra orbital ethmoid cell (11%), supra-orbital ethmoid cells(0,9%), spheno-ethmoid cells (11,9%). Among the anatomic variations studied, septal deviation was the most constant, followed by pneumatization of the middle turbinate to which it showed correlation. The computerized tomography was considered the most accurate imaging method to study the nasal cavity and the paranasal sinus.

A fibrose cística (FC) é uma doença genética irreversível, mas os avanços no tratamento têm aumentado a expectativa de vida dos pacientes. O acometimento das vias aéreas superiores, principalmente por alteraçõesdos seios paranasais aos exames de imagem, é prevalente nestes pacientes, embora muitos apresentem poucos sintomas. Poucos trabalhos abordam as características e o manejo das doenças nasossinusais em pacientes adultos com FC. O acometimento nasossinusal, além de ter provável influência nas exacerbações pulmonares, pode afetar negativamente a qualidade de vida.Objetivos:(1) Identificar as características e o grau de acometimento das vias aéreas superiores;(2) Estabelecer associações com as manifestações clínicas e determinar preditores na pontuação do questionário SNOT-22.Métodos: A metodologia adotada para a presenteteseconsistiu na elaboração de três artigos: (1) Artigo original de revisão sistemática sobre achados tomográficos de seios paranasais em pacientes com FC; (2) Artigo de revisão narrativa sobre diagnóstico e tratamento da rinossinusite crônica (RSC) em pacientes com FC; e (3) Artigo original de estudo transversal e prospectivo sobre manifestações nasossinusais e avaliação da qualidade de vida pelo questionário SNOT-22 em pacientes adultos com FC. A revisão da literatura fundamentou-se na busca por artigos com as evidências mais recentes sobre o assunto nos bancos de dados Medline, Embase, Web of Science, Lilacs, Scielo e Cochrane. O estudo transversal consistiu na avaliação de pacientes adultos com FC clinicamente estáveis, sendo submetidos a avaliação clínica, exames de função pulmonar, endoscopia nasal e tomografia computadorizada de seios da face. Todos os pacientes responderam o questionário SNOT-22.Resultados: A literatura relata que os achados tomográficos mais comuns nos pacientes com FC são a opacificação dos seios paranasais, a presença de hipoplasia ou aplasia dos seios frontal e esfenoidal, o subdesenvolvimento pansinusal e a medialização da parede nasal lateral. Quando sintomática, a RSC com pólipos nasais pode afetar a qualidade de vida e desencadear as exacerbações pulmonares, já que os seios paranasais podem ser colonizados por bactérias patogênicas, principalmente a Pseudomonas aeruginosa. Esta bactéria tem papel crucial na morbidade e mortalidade após o transplante pulmonar em pacientes com FC. Embora o tratamento clínico das vias aéreas superiores seja indicado no manejo inicial, a indicação é muitas vezes extrapolada de estudos sobre RSC na população geral. No estudo original da tese, uma idade média maior, idade de diagnóstico mais tardio, sintomas de rinite crônica e critérios clínicos para rinossinusite foram mais observados em pacientes com pontuação maior no SNOT-22. Na análise de regressão múltipla, houve associação positiva da idade e presença de P. aeruginosa no escarro com a pontuação no SNOT-22.Em concordância com a literatura, o estudo também revelou uma alta prevalência de alterações tomográficas, sendo a aplasia/hipoplasia do seio esfenoidal o achado mais frequente.Conclusão:Apesar dasinúmeras alterações tomográficas, os pacientes relatam pouca intensidade dos sintomas nasossinusais. A idade e a presença da P. aeruginosa foram fatores associados a maior pontuação no SNOT-22. Mais estudos são necessários para compreender melhor o acometimento das vias aéreas superiores e melhorar o manejo da RSC na FC, a fim de preservar a função pulmonar, mas evitandoa indicação de procedimentos invasivos e a exposição radiológica desnecessária.
Cystic fibrosis (CF) is an irreversible genetic disease, but advances in treatment have increased the life expectancy of patients. Involvement of upper airways, especially by pathological changes in sinus imaging, is prevalent in these patients, although few exhibit symptoms. There are few studies about characteristics and management of sinonasal diseases in adult CF patients. Sinonasal involvement may initiate pulmonary exacerbations and negatively affect quality of life. Objectives: To identify characteristics and degree of involvement of upper airways, establishing associations with clinical manifestations and determine predictors in SNOT-22 questionnaire score. Methods: The methodology adopted for this thesis included the elaboration of three articles: (1) original systematic review article aboutparanasal sinuses CT findings in CF patients; (2) narrative review article about diagnosis and treatment of chronic rhinosinusitis (CRS) in CF patients; and (3) original article about crosssectional prospective study of sinonasal manifestations and assessment of quality of life by SNOT-22 questionnaire in adult CF patients. The literature review was based on search of articles with the latest evidence on the subject in databases Medline, Embase, Web of Science, Lilacs, Scielo and Cochrane. The cross-sectional study consisted in evaluation of adult CF patients clinically stable. They underwent clinical evaluation, pulmonary function tests, nasal endoscopy and paranasal sinuses CT scan. All patients answered SNOT-22 questionnaire. Results:Literature reports that the most common CT findings in CF patients areparanasal sinuses opacification, presence of sphenoid and frontal sinuses hypoplasia or aplasia, pansinusal underdevelopment and medial bulging oflateral nasal wall. When symptomatic, CRS with nasal polyps can affect quality of life and trigger pulmonary exacerbations. It is explained since paranasal sinuses may be colonized by pathogenic bacteria, especially Pseudomonas aeruginosa. This bacterium plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Clinical treatment of upper airways is indicated as first management, but this indication is often extrapolated from studies on CRS in general population. In the original study, a high average age, age of later diagnosis, symptoms of chronic rhinitis and clinical criteria for rhinosinusitis were more frequently observed in patients with high SNOT-22 scores. In multiple regression analysis, there was a positive association between age and the presence of P. aeruginosa in sputum with the SNOT-22 score. According to literature, this study also revealed a high prevalence of tomographic alterations.Sphenoid sinus aplasia or hypoplasia was the most common finding. Conclusion: Despite CT findings, patients report little intensity of sinonasal symptoms. Age and presence of P. aeruginosa were associated with higher SNOT-22 scores. The most important is to preserve lung function, but avoinding unnecessary invasive procedures and radiation exposure. More studies are needed to better understand the involvement of upper airways and improve management of CRS in CF.

Os seios maxilares constituem cavidades multifuncionais que apresentam íntima relação como elementos dentários súpero-posteriores e/ou o osso alveolar desta região, tornando-os susceptíveis a infecções de origem odontológica; ou, mediante a presença de sinusopatias de diversas naturezas, resultando em insucesso de procedimentos de abordagem direta destes ou em áreas adjacentes. O estudo imaginológico das cavidades dos seios maxilares previamente a procedimentos odontológicos na região dos seios maxilares é indispensável para garantir-se a evolução pós-operatória favorável. A anatomia complexa destas cavidades requer o uso de ferramentas tridimensionais, como a tomografia computadorizada e a ressonância magnética. Recentemente, novas modalidades técnicas, objetivando otimizar o diagnóstico por ressonância magnética, tem sido investigadas em processos patológicos diversos, incluindo aqueles que podem acometer os seios maxilares. Uma dessas modalidades, é o estudo qualitativo e quantitativo da difusibilidade das moléculas de água, que propõe-se a descrever características celulares e funcionais de tecidos, sob o ponto de vista imaginológico. Essencialmente, a ideia do estudo da celularidade e fisiologia dos tecidos é distinguir processos patológicos diferentes, provendo hipóteses diagnósticas acuradas. Não obstante, existem poucos estudos que analisam as doenças inflamatórias e infecciosas dos seios maxilares, que são as afecções mais usuais nestas cavidades. Assim sendo, o objetivo primordial deste estudo foi analisar os valores quantitativos dos coeficientes de difusibilidade das moléculas de água (ADC) em grupos de alterações imaginológicas nos seios maxilares que correspondem à sinais imaginológicos de sinusopatias inflamatórias e/ou infecciosas, afim de verificar se existem diferenças significativas entre estes valores que poderiam auxiliar no diagnóstico por meio da ressonância magnética. Para desenvolver este objetivo, foram analisados 98 seios maxilares de pacientes que realizaram exames de ressonância magnética, classificando as alterações observáveis nesta cavidade em 4 grupos: presença de espessamento da mucosa sinusal, pólipos ou cistos, nível hidroaéreo, presença de conteúdo de sinal heterogêneo em imagens ponderadas em T2 associado a erosões ósseas e presença de calcificações distróficas. Os valores de ADC foram aferidos nos seus respectivos mapas de ADC. Diferenças estatisticamente significativas foram verificadas comparando-se os 4 grupos; ademais, os seios maxilares foram classificados de acordo com o grau de acometimento destas alterações em: ausência de opacificação, totalmente opacificado, parcialmente opacificado e presença de espessamento da mucosa sinusal. Verificou-se que o grau de opacificação mais prevalente na amostra estudada foi o parcialmente opacificado. Os valores de ADC do espessamento da mucosa sinusal são estatisticamente menores do que os dos demais grupos, indicando menor difusibilidade das moléculas de água do espessamento em relação às demais alterações. Concluiu-se que é possível utilizar os valores de ADC na diferenciação do espessamento da mucosa sinusal das demais alterações dos seios maxilares.
The maxillary sinuses are multifunctional cavities closed related with upper- posterior teeth and / or this region alveolar bone, which can lead to susceptibility to sinusal dental origin infections; or, due to the sinus disease, leading to failure in sunuses direct approach or in adjacent areas procedures. The imaging study of maxillary sinus cavities prior to procedures in the region of the maxillary sinuses is indispensable to ensure favorable postoperative evolution. The complex anatomy of these cavities requires the use of three-dimensional tools, such as computed tomography and magnetic resonance imaging. Recently, new technical modalities aiming to optimize the diagnosis by magnetic resonance have been investigated in diverse pathological processes, including those that can affect the maxillary sinuses. One of these modalities is the qualitative and quantitative study of the diffusibility of water molecules, which proposes to describe celularity and functional characteristics of tissues from an imaginary point of view. Essentially, the idea cellularity and tissue physiology study is to distinguish different pathological processes, providing accurate diagnostic hypotheses. Nevertheless, there are few studies that analyze the inflammatory and infectious diseases of the maxillary sinuses, which are the most common affections in these cavities. Thus, the main objective of this study was to analyze the quantitative values of the water molecule diffusibility coefficients (ADC) in groups of imaging alterations in the maxillary sinuses that correspond to signs of inflammatory and / or infectious sinusopathies, in order to verify if there are any significant differences between these values that could aid in the diagnosis through magnetic resonance imaging. To develop this objective, 98 maxillary sinuses of patients that underwent magnetic resonance imaging were evaluated. The maxillary sinuses were classified according to the inflammatory / infectious changes detected in 4 groups: presence of sinus mucosal thickening, polyps or cysts, air-fluid levels, T2 weighted heterogeneous signal associated with erosions and the presence of dystrophic calcifications. The ADC values were measured on their respective ADC maps. Statistically significant differences were observed comparing the 4 groups; In addition, the maxillary sinuses were classified according to the degree of involvement of these alterations in: absence of opacification, totally opacified, partially opacified and presence of mucous thickening. It was verified that the most prevalent degree of opacification in the studied sample was partially opacified. ADC values of the sinus mucosa thickening are statistically lower than those of the other groups, indicating less diffusibility of the thickening water molecules in relation to the other alterations. It was concluded that it is possible to use the ADC values in the differentiation of the mucous thickening of the other alterations of the maxillary sinuses.

Abstract Acute rhinosinusitis (ARS) is a common condition often treated with antibiotics, even though the cause is usually viral. Despite the commonness of ARS, there is limited evidence on the development and diagnosis of bacterial cases. So far, we lack prospective studies where the bacterial cause would have been confirmed with a bacterial culture of the paranasal sinus aspirate. The purpose of the study was to investigate the course of ARS with a prospective inception cohort study among young adults with ARS, using sequential and standardized methods. To differentiate viral and bacterial ARS, maxillary sinus aspiration and a bacterial culture were used as a reference standard for bacterial ARS. Fifty conscripts with ARS were recruited between February and April 2012. Eight patients (16%) had a positive culture from the maxillary sinus aspirate at 9–10 days and thus, had bacterial ARS. Viral and bacterial coinfection resulted in extensive paranasal mucosal abnormalities and increased symptoms during the episode. The paranasal mucosal abnormalities developed rapidly and remained relatively constant during the episode in both bacterial and non-bacterial ARS. A change in inflammatory biomarker levels indicated both local and systemic inflammatory responses, which were strongest at the onset of symptoms. Symptoms or their changes were of little use in diagnosing bacterial ARS, but secretion seen in the nasal cavity, posterior pharynx or middle meatus predicted bacterial ARS quite well. These results suggest that bacterial infection may modify symptoms and paranasal abnormalities already at the beginning of an ARS episode, although the spread of paranasal abnormalities may not be an etiological factor in the development of bacterial ARS. ARS involves local and systemic inflammatory responses, which are strongest at the beginning of the episode. Examination of the nose and throat is recommended for diagnosing bacterial ARS
Tiivistelmä Nenän äkillinen sivuontelotulehdus on tavallinen tauti, jonka hoitoon käytetään paljon antibiootteja, vaikka sen aiheuttaja on useimmiten virus. Bakteerin aiheuttaman tautimuodon kehittymisestä ja diagnostiikasta ei ole julkaistu tutkimuksia, joissa potilaita olisi seurattu taudin alusta lähtien ja bakteerin olemassaolo olisi varmistettu nenän sivuontelosta otetulla bakteerinäytteellä. Tämän väitöskirjatyön tarkoituksena oli selvittää nenän äkillisen sivuontelotulehduksen kulkua käyttämällä toistuvia, standardisoituja menetelmiä. Bakteerin aiheuttama tauti todettiin poskiontelopistolla ja bakteeriviljelyllä. Tutkimukseen osallistui viisikymmentä (50) äkilliseen ylähengitystieinfektioon sairastunutta varusmiestä keväällä 2012. Kahdeksalla (16 %) potilaalla todettiin bakteerin aiheuttama tauti poskiontelopiston avulla 9–10 päivää oireiden alkamisen jälkeen. Viruksen ja bakteerin sekainfektio aiheutti laajemmat sivuonteloiden tulehduslöydökset ja voimakkaammat oireet kuin pelkän viruksen aiheuttama tauti. Sivuonteloiden tulehduslöydökset kehittyivät nopeasti ja pysyivät sekä bakteerin että viruksen aiheuttamassa taudissa varsin muuttumattomina. Tulehdusmerkkiaineiden muutokset osoittivat sekä paikallisen, että yleisen tulehdusreaktion, jotka olivat voimakkaimmillaan taudin alussa. Oireet tai niissä taudin aikana tapahtuneet muutokset eivät osoittautuneet hyviksi merkeiksi bakteerin aiheuttaman taudin toteamiseksi, mutta eritteen näkyminen nenässä, nielussa tai keskikäytävässä ennakoi hyvin bakteerin aiheuttaman sivuontelotulehduksen toteamista. Bakteeri saattaa vaikuttaa oireisiin ja sivuonteloiden tulehduslöydöksiin jo nenän äkillisen sivuontelotulehduksen alussa, mutta tulehduslöydösten laajuus ei välttämättä liity bakteerin aiheuttaman taudin kehittymiseen. Nenän äkilliseen sivuontelotulehdukseen liittyy paikallinen ja yleinen tulehdusreaktio, jotka ovat voimakkaimmillaan taudin alussa. Potilaan nenän ja nielun tutkiminen on tärkeää bakteerin aiheuttaman nenän sivuontelotulehduksen toteamiseksi

Abstract Surgery for ear, nose and throat (ENT) diseases most often aims to improve quality of life (QoL). The extent of having QoL as an outcome in papers included in evidence-based medicine databases is not known. In primary sinonasal surgery, the QoL outcomes and predictors and usability of various QoL instruments need more clarification. The aim was to: 1. Find out with a systematic literature review how the Cochrane database currently includes the QoL dimension. 2. Investigate the effect of primary sinonasal surgery on QoL, to identify predictors of QoL outcomes and to compare QoL instruments. In total 160 adults undergoing primary septoplasty (SP) or endoscopic sinus surgery (ESS) were recruited in 2010–2014 with 206 controls for a prospective matched cohort study. QoL was measured with a disease-specific Sino-Nasal Outcome Test–22 (SNOT–22) and generic RAND–36 before surgery and 12 months after surgery. Retrospective Glasgow Benefit Inventory (GBI) was also used. QoL was an outcome measure in 10% (3 out of 30) of trials included in Cochrane databases on most common ENT surgeries. The use of QoL since the year 2000 has increased. The total SNOT–22 score improved in both patient groups after surgery, almost to the level of the controls, In the SP group (N=64) from 34.9 to 19.1 and in ESS (N=70), from 35.1 to 19.3. The control cohort’s SNOT–22 was 17.7 at entry and after follow-up, 15.3 (N=165). RAND–36 and GBI also improved after surgery. The best predictor for a good QoL outcome in multivariate analysis after surgery was a high preoperative (≥20) SNOT–22 score in the SP and ESS groups (adjusted odds ratio 10; 95% confidence interval 1.6–64 and 12; 2.5–55, respectively). In receiver operating characteristic curve analysis, the highest preoperative SNOT–22 total score of 30 was the most sensitive (74%) and specific (70%). GBI seemed to be the most sensitive instrument to detect a change, but the three instruments in this study agreed in only about 10% of the patients who had the worst impact before surgery or best outcome. The results suggest that papers on the Cochrane databases on ENT surgeries have rarely addressed the QoL outcome. Septal deviation and recurrent acute or chronic rhinosinusitis lowered QoL. Primary surgery on these conditions improved QoL almost to the level of the control population, which was not symptom-free either. A high preoperative SNOT–22 total score was the best predictor of a beneficial outcome. The QoL instruments identified different patients experiencing the best improvement after surgery
Tiivistelmä Korva-, nenä- ja kurkkutautien (KNK) kirurgia tähtää useimmiten elämänlaadun (EL) parantamiseen. EL:n huomioinnin yleisyys näyttöön perustuvien tietokantojen sisältämissä tutkimuksissa ei ole tiedossa. Primaareissa nenäleikkauksissa EL:n tulokset, ennustekijät ja eri mittareiden käytettävyys kaipaavat lisätietoja. Tarkoituksena oli 1: Tutkia systemaattisella kirjallisuuskatsauksella miten nykyiset Cochrane-suositukset huomioivat EL:n. 2: Tutkia primaarin nenäkirurgian vaikutus EL:uun, tunnistaa EL:n ennustekijöitä ja vertailla eri mittareita. Yhteensä 160 primaariin nenän väliseinäleikkaukseen (VL) tai sivuonteloiden tähystysleikkaukseen (ESS) tulevaa aikuista ja 206 ikä- ja sukupuolivakioitua verrokkia osallistui etenevään kaltaistettuun kohorttitutkimukseen vv. 2010-2014. EL mitattiin tautispesifillä Sino-Nasal Outcome Test -22:lla (SNOT–22) ja yleisellä RAND–36:lla ennen leikkausta ja 12 kk leikkauksen jälkeen. Kolmantena mittarina käytettiin taannehtivaa Glasgow Benefit Inventoryä (GBI). Cochrane-tietokannan yleisimpien KNK-leikkausten tutkimuksista 10 %:ssa (3 30:stä) sisälsi EL-tuloksia. Vuoden 2000 jälkeen EL:n käyttö on lisääntynyt. SNOT–22 kokonaispistemäärä parani VL- ja ESS-ryhmissä lähes kontrollien tasolle, VL-ryhmässä (N=64) 34.9:stä 19.1:een ja ESS-ryhmässä (N=70) 35.1:stä 19.3:een. Kontrollien SNOT–22 oli alussa 17.7 ja seurannan jälkeen 15.3. Myös RAND–36 ja GBI paranivat leikkauksen jälkeen. Monimuuttuja-analyysissä hyvän EL-tuloksen paras ennustetekijä oli korkea leikkausta edeltävä SNOT–22 sekä VL- että ESS-ryhmissä (vakioitu vetokertoimien suhde 10; 95 % luottamusväli 1.6–64 ja 12; 2.5–55, ryhmittäin). ROC (receiver operating characteristic) -käyräanalyysissä leikkausta edeltävä arvo 30 antoi parhaan herkkyyden (74 %) ja tarkkuuden (70 %). GBI vaikutti herkimmältä aistimaan muutoksen, mutta mittarit olivat samaa mieltä vain noin 10%:ssa niistä potilaista, joilla oli huonoin EL ennen leikkausta tai paras tulos leikkauksen jälkeen. Tulosten mukaan Cochrane-tietokannassa olevat KNK-tautien kirurgian tutkimukset ovat ottaneet harvoin elämänlaadun huomioon. Nenän väliseinän vinous ja toistuva äkillinen tai krooninen sivuontelotulehdus laskivat EL:ua. Näiden tautien primaarikirurgia paransi EL:n lähes samalle tasolle kuin kontrolliryhmällä. Korkea leikkausta edeltävä SNOT–22 –kokonaispistemäärä ennusti parhaiten hyvää tulosta. Eri EL-mittarit tunnistivat eri potilaat, jotka hyötyivät parhaiten leikkauksista

Introdução: No Brasil, a leishmaniose tegumentar americana (LTA) é uma importante antropozoonose endêmica na maioria das regiões do país. Apesar da expansão da doença nos últimos anos, a LTA continua a ser uma doença negligenciada. A leishmaniose mucosa (LM) tem como principal agente causador a Leishmania (V.) brasilienses, e habitualmente ocorre meses ou anos após a infecção cutânea sintomática ou assintomática. Aproximadamente 5% dos pacientes com leishmaniose cutânea não tratada adequadamente irão desenvolver a LM, forma que causa importante morbidade aos pacientes. A LM é uma doença progressiva, que acomete cartilagens e estruturas ósseas da face, faringe e laringe. Complicações associadas à leishmaniose mucosa já foram descritas, embora não existam estudos que avaliem as alterações estruturais da face e seios paranasais utilizando métodos radiológicos e que estimem a prevalência de sinusopatia nesta população ou que a compare com a população geral. Objetivo: Avaliar o grau de opacificação dos seios paranasais em pacientes com leishmaniose mucosa tratada, assim como eventuais alterações anatômicas na face associadas à LM, através de tomografia computadorizada multislice (TCM) dos seios paranasais e comparar os achados encontrados nesta população com um grupo controle formado por pacientes que realizaram TCM de órbita. Este estudo também tem o escopo de determinar a prevalência de sinusopatia crônica nos pacientes com LM pós-tratamento, bem como encontrar prováveis variáveis preditoras que possam estar relacionadas com a gravidade da sinusopatia e das alterações tomográficas encontradas. Métodos: Foram avaliados 54 pacientes com LM tratada, que foram submetidos à TCM dos seios da face, e comparados com grupo controle de 40 pacientes que realizaram TCM de órbita. A análise das tomografias foi realizada a partir de reconstruções multiplanares nos planos axial, coronal e sagital. Foram avaliados o grau de opacificação (sinusopatia) dos seios paranasais, bem como a existência de eventuais alterações na face que pudessem estar relacionadas à LM. O grau de sinusopatia foi estabelecido seguindo-se os critérios de Lund-Mackay, segundo os quais foram atribuídos um valor para o grau de opacificação de cada sistema sinusal e dos complexos ostiomeatais, comparando o score dos casos com o dos controles. Posteriormente foi realizada uma análise comparativa entre os pacientes do grupo leishmaniose mucosa, que foram divididos em dois subgrupos, de acordo com a presença (Lund-Mackay >= 4) ou ausência (Lund-Mackay < 4) de doença sinusal, sendo 40 e 14 pacientes respectivamente. Após esta divisão foram feitas análises univariadas exploratórias em busca de variáveis preditoras que pudessem estar associadas com uma maior gravidade de sinusopatia apresentada. O nível de significância foi estabelecido com p<0,05. Resultados: Quarenta dos 54 pacientes com antecedente de LM (74,1%) apresentaram score tomográfico compatível com sinusopatia crônica (Lund-Mackay >= 4). Os pacientes do grupo leishmaniose mucosa apresentaram maior score de Lund-Mackay que os pacientes do grupo controle, bem como maior número de alterações na TCM dos seios paranasais, provavelmente associadas à leishmaniose. Estes pacientes também apresentaram graus mais severos de opacificação parcial e espessamento mucoso pansinusal 23/54 (42.6%). Além disso, opacificação total de pelo menos um dos seios paranasais só foi observada nos pacientes do grupo leishmaniose mucosa. Os pacientes com leishmaniose com score de Lund-Mackay >= 4 apresentaram maior tempo de sintomas até o primeiro tratamento e doença mais grave no momento do diagnóstico, sendo portanto prováveis variáveis preditoras de gravidade da sinusopatia. Conclusão: As tomografias computadorizadas dos seios paranasais dos pacientes com LM apresentaram diversas alterações estruturais, demonstrando o poder destrutivo desta doença. A alta prevalência de sinusite crônica observada nas tomografias computadorizadas desses pacientes quando comparados ao grupo controle, sugere que a LM pode ser um fator de risco para o desenvolvimento de sinusite crônica nesta população. Sexo masculino, tempo de sintomas até o primeiro tratamento e gravidade da LM no momento do diagnóstico podem ser consideradas prováveis variáveis preditoras de sinusite crônica nesses pacientes
Introduction: American tegumentary leishmaniasis (ATL) is an important anthropozoonosis that is endemic in most regions in Brazil. Despite the spread of the disease in recent years, ATL remains a neglected disease. Mucosal leishmaniasis (ML) is mainly caused by Leishmania (V.) brasiliensis agent, and usually occurs months or years after symptomatic or asymptomatic skin infection. Approximately 5% of patients with untreated cutaneous leishmaniasis will develop ML, a presentation that causes significant morbidity to patients. The mucosal leishmaniasis is a progressive disease that affects cartilage and bone structures of the nose and paranasal sinuses as well as other upper respiratory tract structures. Complications associated with ML have been described, but there is a lack of studies which evaluate the structural changes of the nose and paranasal sinuses in ML using radiological methods. Objective: To assess the degree of opacification of the paranasal sinuses in patients with treated mucosal leishmaniasis as well as any anatomic changes in the face associated with ML through multidector computed tomography scans (MDCT) of the sinuses, and compare the findings in this population with a control group. This study also aims at determining the prevalence of chronic sinusitis in patients with treated ML as well as finding probable predictive variables that may be related to the severity of sinus disease and CT findings. Methods: We evaluated 54 patients with treated ML who were submitted to MDCT of the sinuses, and compared with a control group of 40 patients who underwent MDCT of orbit. Analysis of the scans was performed from multiplanar reconstructions in the axial, coronal and sagittal views. The degree of sinus disease was assessed according to the Lund-Mackay criteria, in which a value was assigned to the degree of opacification of each sinus system and ostiomeatal complexes, and the scores from the mucosal leishmaniasis group were compared to the control group. A comparative analysis was then performed among patients in the mucosal leishmaniasis group, who were divided into 2 subgroups according to the presence (Lund-Mackay >= 4) or absence (Lund-Mackay < 4) of sinus disease, with 40 and 14 patients respectively. Following this subdivision, exploratory univariate analysis were performed to identify predictive variables that could be associated to the presentation of greater severity of sinus disease. The level of significance was defined as p <0.05. Results: Forty of the 54 patients with a history of ML (74.1%) had a tomographic score compatible with chronic sinusitis (Lund- Mackay >= 4). CT scans in the leishmaniasis and control groups demonstrated significant differences in terms of facial structural alterations. Patients from the mucosal leishmaniasis group showed more severe levels of partial opacification and pan sinus mucosal thickening 23/54 (42.6%), furthermore complete opacification of at least one paranasal sinus was only observed in the leismaniasis group. Patients from the mucosal leishmaniasis group with Lund-Mackay score >= 4 presented greater length of symptoms before treatment and more severe presentation of the disease at the diagnosis. Conclusion: CT scans of the sinus of patients with ML also presented several structural alterations, expressing the prominent destructive feature of the disease. The higher prevalence of chronic rhinosinusitis observed in CT scans of patients with treated ML in this study when compared to the control group suggests that ML can be seen as a risk factor for chronic rhinosinusitis in this population. Male sex, having the disease for more than two years before first treatment and/or a more severe presentation of ML at diagnosis, can be considered as predictive variables of chronic sinusitis in these patients

Orientador: Jose Dirceu Ribeiro
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Muitos estudos têm avaliado os aspectos clínicos e funcionais do comprometimento das vias aéreas inferiores na fibrose cística (FC). Entretanto, poucos estudos têm sido realizados para avaliar as alterações clínicas e funcionais das vias aéreas superiores. O objetivo do presente trabalho foi correlacionar variáveis obtidas por endoscopia nasossinusal, laboratoriais e tomográficas dos seios paranasais e, verificar a associação com a gravidade e o genótipo de pacientes com fibrose cística, de um centro universitário de referência em tratamento de FC no Brasil. Realizou-se um estudo clínico, laboratorial com 50 fibrocísticos. Todos foram submetidos a tomografia computadorizada dos seios paranasais, estudo genético das mutações da FC, endoscopia nasossinusal e bacterioscopia dos seios maxilares, orofaringe e traquéia. A gravidade da FC foi avaliada pelo escore de Shwachman. A prevalência de polipose na população estudada foi de 36% e maior entre homozigotos para ?F508. O escore de Shwachman correlacionou-se com a idade. Não houve correlação do genótipo e do grau de gravidade com as outras variáveis estudadas. Os sujeitos apresentaram alta prevalência de colonização precoce para P. aeruginosa. Concluiu-se que a doença sinusal em pacientes fibrocísticos é muito freqüente, apresenta alterações nasofibroscópicas, tomográficas e clínicas, embora a maioria das variáveis estudadas, não apresenta correlação com a gravidade e o genótipo da doença
Abstract: Many studies have assessed clinical and functional aspects of lower airway affections in cystic fibrosis. Conversely, few studies have been performed to assess the clinical and functional affections of upper airways. The objective of the present study was to correlate the variables obtained by nasal and paranasal sinuses endoscopy, paranasal sinus laboratory and computed tomography (CT) scan findings, and to check the association with severity and genotype of cystic fibrosis patients. Clinical and laboratory study of 50 patients with cystic fibrosis at a university center. All patients were submitted to CT scan, nasal and paranasal endoscopy and bacterioscopy of maxillary sinus, trachea and oropharynx secretion. Severity of cystic fibrosis was assessed by Shwachman score and the most frequent genetic mutations were identified. The prevalence of polyposis in the studied population was 36% and it was greater among homozygote for ?F 508. Shwachman score was correlated with age (p=0,003). The genotype was correlated with nasal polyposis (p=0,006). There was no association between affections in CT scan and severity of cystic fibrosis (CF). Patients presented high prevalence of early colonization of Pseudomonas aeruginosa. Sinus disease in CF patients are very frequent and presents several clinical, endoscopic and tomographic affections and most of them are not correlated with severity and disease genotype
Doutorado
Otorrinolaringologia
Doutor em Ciências Médicas

Objectif - Réaliser une étude en morphométrie géométrique pour définir la variabilité des sinus frontaux et maxillaires au sein d’une population adulte et pour l’établissement du profil biologique des individus à partir de la géométrie des sinus frontaux et maxillaires.- Valider un modèle de simulation numérique des écoulements pour l’étude de la ventilation nasosinusienne chez l’adulte et observer l’influence de la conformation sinusienne sur la ventilation nasosinusienne.Nous avons défini 20 landmarks fiables et reproductibles pour les sinus frontaux et maxillaires. Nous avons décrit la variabilité des sinus frontaux et maxillaires au sein d’un échantillon de population adulte. Enfin, nous avons mis en évidence l’existence d’allométries pour les sinus frontaux et maxillaires mais aussi l’existence d’un dimorphisme sexuel pour la conformation des sinus maxillairesNous proposons un modèle fiable de simulation numérique des écoulements à partir d’examen tomodensitométriques. Sur la base de ce modèle, nous n’avons pas mis en évidence d’influence de la conformation sinusienne sur la ventilation nasale et le conditionnement thermique de l’air inspiré et expiré
Objectives - to conduct a morphometric geometric study in order to define the variability of the frontal and maxillary sinuses in an adult population and to determinate the sex of individuals - to validate a Computational fluid dynamic model of the nasal airflow and to describe the influence of the sinus conformation on the nasal airflow.We defined twenty reliable and reproducible landmarks for frontal and maxillary sinuses. We described the variability of the frontal and maxillary sinuses in an adult population sample. Finally, we highlighted the existence of allometries for frontal and maxillary sinuses but also the existence of a sexual dimorphism in the conformation of the maxillary sinusesComputational fluid dynamics:We offer a reliable model for numerical simulation of flows from CT examination. Based on this model, we have not shown any influence of the conformation on the nasal sinus ventilation and thermal conditioning of the inhaled and exhaled air. We showed no ventilation in the sinuses in the nasal respiratory cycle. Future studies will endeavor to define a humidity conditioning air model and a simulation model of production of NO and gas exchange between sinuses and nasal cavities

La polypose nasosinusienne est une entité clinique bien définie et communément rencontrée dans les pays industrialisés dont l'étiologie demeure obscure. Plusieurs hypothèses ont été avancées, allant de la théorie mécanique à l'implication du système immunitaire local. Il est admis à ce jour que le polype est le siège d'une réaction inflammatoire pérennisée par des facteurs cellulaires et solubles. Parmi ces facteurs, les éosinophiles sont présents de façon constante et prolongée au sein du tissu polypeux. Le micro-environnement local auquel participent les cytokines favoriserait leur accumulation et leur rétention. Le moindre drainage de ce tissu favorise également la formation de la structure polypeuse. Le traitement corticoi͏̈de est efficace sur cette pathologie mais les patients semblent améliorés sans que disparaissent pour autant ces éosinophiles de leurs sécrétions ni de leurs tissus. Nous nous sommes proposés dans ce travail d'analyser le compartiment leucocytaire des sécrétions nasales et son contenu en médiateurs solubles de l'immunité innée dans le cadre de la polypose nasosinusienne et d'autres pathologies rhinologiques. Par ailleurs, nous avons exploré l'histologie des polypes, d'une part par une analyse rétrospective tenant également compte du traitement corticoi͏̈de,̉ d'autre part par une recherche de marqueurs d'activation de la muqueuse nasale sur des échantillons de tissu polypeux, Enfin, une vaste étude clinique a été réalisée afin d'observer la corrélation entre l'effet clinique des corticoi͏̈des locaux et généraux et la cellularité des sécrétions nasales, en particulier la place occupée par le polynucléaire éosinophile au sein de ce compartiment.

Introdução: As afecções nasais e sinonasais em cães possuem causas variadas, e algumas vezes cursam com sinusites, sendo raros os casos que não há doença nasal pré-existente. O diagnóstico presuntivo é baseado nas manifestações clínicas como secreção nasal uni ou bilateral anormais, esternutações, esternutações reversas paroxísticas, respiração estertorosa, engasgos, halitose, epistaxes, rinorragia, tosse, distrição respiratória, dor e deformação facial. Para concluir o diagnóstico, são indicados exames de imagem, rinoscopia, culturas, citologia e histopatológico. Objetivo: O presente estudo observacional teve como objetivo avaliar a contribuição ao diagnóstico das afecções da cavidade nasal e seios paranasais de cães, da radiografia, tomografia computadorizada e rinoscopia, realizando-se a comparação dos métodos diagnósticos mediante ao escore comparativo idealizado para este fim. Materiais e métodos: Foram utilizados 20 cães atendidos do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, com manifestações clínicas compatíveis com afecção nasal e submetidos a exame radiográfico, tomográfico e rinoscópico. A biópsia foi realizada, em 18 cães, por meio da rinoscopia, nos casos em que visibilizou-se proliferação tecidual, úlcera ou alteração na mucosa nasal sendo encaminhadas para estudo histológico. Resultados: Foram observados resultados estatisticamente significativos, baseados pelo escore, a radiografia em conjunto com a tomografia computadorizada, a rinoscopia associada à tomografia computadorizada e, também, a rinoscopia isoladamente, como métodos diagnósticos mais específicos na diferenciação de lesão maligna. A rinoscopia demonstrou como vantagem a visibilização direta diferenciando a presença ou não de inflamação ou proliferação tecidual, alteração anatômica, corpo estranho e placa fúngica. Conclusão: Os resultados do presente estudo indicam que embora possuam especifidade diferentes a utilização da radiografia, tomografia computadorizada e rinoscopia se complementaram como métodos diagnósticos nas afecções nasais e sinonasais dos cães avaliados. Nos casos de proliferação tecidual o estudo histológico demonstrou ser mais útil para conclusão diagnóstica em comparação aos exames de imagem e a rinoscopia.
Introduction: The nasal and sinus disorders in dogs have various causes, and sometimes go with sinusitis that there is no pre-existing nasal disease. The presumptive diagnosis is based on clinical manifestations as nasal discharge, sneezing, reverse sneezing, gagging, stertor, halitosis, epistaxis, cough, open-mouth breathing, pain and facial deformation. To complete the diagnosis, image examinations, rhinoscopy, cultures, cytology and histopathological fidings. Objectives: This observational study aimed to evaluate the contribution to the diagnosis of disorders of the nasal cavity and paranasal in dogs, radiography, computed tomography and rhinoscopy, performing comparison of diagnostic methods through the comparative score conceived for this purpose. Materials and methods: This study used 20 dogs of Veterinary Hospital of the Faculty of Veterinary Medicine and Zootechny of the University of São Paulo, with clinical signs compatible with nasal disorder and undergone radiographic examination, computed tomography and rhinoscopy. The biopsy was performed on 18 dogs through rhinoscopy, where is tissue proliferation, ulcer or change in the nasal mucosa histology study being forwarded to. Results: Significant results were observed by the score with radiography, computed tomography, rhinoscopy associated with computed tomography, and also, separately, as rhinoscopy diagnostic methods more specific differentiation of malignant lesion. The rhinoscopy demonstrated how advantage to visualize directly differentiating presence or not of inflammation or tissue proliferation, alteration, foreign body and fungal plaques. Conclusion: The results of this study indicate that although having different specific utilization, radiography, computed tomography and rhinoscopy as diagnostic methods arranged in nasal disorders of dogs and evaluated. In cases of tissue proliferation, histological study proved most useful in final diagnostic compared to the image exams and rhinoscopy.

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Paranasal sinus are important objects of study to rhinosinusitis diagnostic, having some papers related incidence between asthma and allergic rhinitis.Many applications can calculate to various parts of the human body, getting a CT scan or MRI input, and returning information about the region of interest observed as volume and area. The accumulated mucus in the sinuses is one of the areas of interest that have not yet been implemented methods for the calculation of volume and area. In the present scenario, the patient monitoring is done visually, depending largely on perception of the evaluator. Therefore, we seek to implement more accurate metrics to facilitate medical care to the patient and it can help prevent the worsening of rhinitis in a given patient, developing mechanisms of visual and numerical comparison, where it is possible observe the progress of treatment. This work contains a detailed study of how certain existing techniques, combined into one methodology can segment and calculate the accumulated mucus in the maxillary sinus. In addition to techniques such as Thresholding, Gaussian filter, Mathematical Morphology, Metallic Artifacts Reduction during processing and segmentation, MUNC and DTA to calculate the volume and area, and visualization techniques as the Marching Cubes, it was also necessary some adjustments in the algorithm for limit the region of interest where the thresholding combined with the gaussian filter has not been effective of retaining edges. The application will use two open source platforms, one for processing, ITK, and another for visualization, VTK. The results demonstrated that it is possible to perform segmentation and the calculation with the use of platforms as well as the methodology used is adequate to solve this problem.
Os seios paranasais são importantes objetos de estudo para o diagnóstico de rinossinusites, tendo alguns estudos relacionado a incidência de asma na fase adulta a quadros de rinite alérgica na infância. Muitas aplicações atendem a diversas partes do corpo humano, obtendo de entrada uma tomografia computadorizada ou ressonância magnética, e devolvendo, muitas vezes, números que dizem respeito ao objeto de interesse observado, como volume e área. O muco acumulado nos seios paranasais é uma das regiões de interesse que ainda não tiveram métodos implementados para o cálculo do volume e área. No cenário atual, o acompanhamento do paciente é feito de forma visual, dependendo muito da percepção do avaliador. Portanto, busca-se a implementação de métricas mais precisas para facilitar o acompanhamento médico ao paciente e ajudar na prevenção do agravamento de um quadro de rinite em um determinado paciente, criando mecanismos de comparação visual e numérica, onde é possível observar a evolução do tratamento. Este trabalho contém um estudo detalhado de como determinadas técnicas existentes, combinadas em uma metodologia, podem segmentar e calcular o muco acumulado nos seios paranasais maxilares. Além de técnicas como a Binarizacão, Filtro Gaussiano, Morfologia Matemática, Redução de Ruídos Metálico durante o processamento e segmentação, MUNC e DTA para o cálculo do volume e área, e técnicas de visualização como o Marching Cubes, foram necessários também ajustes no algoritmo para limitar a área segmentada onde a binarizacão combinada ao filtro não foi capaz de manter as bordas da região de interesse. A aplicação fará uso de duas plataformas de código livre, sendo uma para o processamento, ITK, e outra para visualização de imagens, VTK. Os resultados demonstraram que é possível realizar a segmentação e o cálculo com o uso das plataformas, bem como a metodologia empregada é adequada a resolução deste problema.

Thesis (M.Sc.)--University of Alberta, 2010.
A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Medical Sciences, Temporomandibular Disorders/Orofacial Pain. Title from pdf file main screen (viewed on April 23, 2010). Includes bibliographical references.

碩士
中國醫藥大學
醫學研究所碩士班
95
Background: Nasopharyngeal carcinoma (NPC) is the second common head and neck cancer in Taiwan. Radiotherapy (RT) is the standard treatment for NPC. RT-induced rhinosinusitis is a common side effect in post-irradiated NPC patients. Nasal irrigation is frequently recommended for treatment of post-RT rhinosinusitis. To our knowledge, there was no study related to this subject till now. The purpose of this study was to find the RT effect on the paranasal sinuses in patients with NPC, including the incidence and the timing course. And we try to evaluate the efficacy of nasal irrigation for RT-induced rhinosinusitis. Materials and Methods: A retrospective study was preformed first for estimate the incidence of IMRT-induced rhinosinusitis in our institute and the timing course of sinus mucosal change in the first post-treatment year. Patients who received full course RT for NPC and had 4 times CT scans at baseline, post RT 3months, 6 months and 12 months in our hospital were retrospectively recruited from January 2002 to June 2004. From October 2004 to May 2006, patients with NPC were consecutively recruited. Patients who did not complete RT, who had residual or recurrent nasopharyngeal tumor during the study period, and who lost to follow-up after RT were excluded. All patients were randomly allocated to irrigation or non-irrigation groups. Patients in irrigation group received daily nasal irrigation till 6 months after RT. The endoscopy and questionnaire scores were recorded at baseline (the week before radiotherapy), at 4th week of RT, at the week RT completed and at post-RT 1, 2, and 3, 6 and 12months. Results: Fifty patients with NPC were enrolled for the retrospective study. The CT scores rose after RT and gradually decreased at post-RT 6 months. The CT scores at post-RT 12 months remained slightly higher than the baseline. It seemed the RT effect on paranasal sinuses had acute and late phases. The prospective study designed under this hypothesis enrolled 107 patients with NPC: When patients were grouped as irrigation or non-irrigation, patients in the irrigation group had lowered endoscopic and questionnaire scores than patients in non-irrigation group. Significant differences between two groups were observed when including all follow-up points till post-RT 6 months both in endoscopic and questionnaire scores (p=0.0001 and 0.0012, respectively). The between-group differences were most obvious at post-RT 2 and 3 months. However, the mean endoscopic and questionnaire scores decreased to near the baseline level at post-RT 12 months, both in irrigation and non-irrigation groups. Conclusions: The results of this study confirmed that rhinosinusitis was a common RT side effect in patients with NPC. With the advances of radiotherapy technique, most IMRT-induced rhinosinusitis improved after 6 months. Nasal irrigation was proved as a safe and effective management for relief the acute post-RT nasal symptoms.

The equine paranasal sinuses are a frequent site of disease. They are anatomically complex structures encased in bone that are difficult to visualize. Because of their complexity and location, accurate diagnosis and treatment of the affected sinus(es) is difficult without a good understanding of their anatomy. Use of 3-D computer models in anatomy education has increased in recent years and shows promise in teaching anatomy of complex structures. The goal of this thesis was to develop a computer program illustrating a 3-D model of the equine paranasal sinuses to aid teaching the anatomy of the paranasal sinuses. A CT scan of a horse’s head was performed and a 3-D reconstruction was generated. The paranasal sinuses were illustrated in the reconstructed images using Adobe Photoshop 6.0. Adobe Flash Professional CS5 was used to create an interactive computer program from the images. The resulting computer program depicts the sinuses and features of the skull at five key points plus or minus nine degrees of rotation.

Introduction: Sinonasal inverted papilloma (SNIP) is an uncommon benign tumor with a high recurrence rate, significant malignant potential and unknown etiology. The population in Hong Kong is unique in its high population density and having a majority of Chinese people who are ethnically and geographically predisposed to certain cancers. Research on the etiology, pathogenesis, diagnosis and treatment of the neoplasm and comparison with reported findings from other parts of the world may contribute to management of the condition in terms of prevention, staging and treatment.
Aims: The aim of the thesis is to describe the common and unique clinico-pathological characteristics of SNIP in Hong Kong and compare these with reported characteristics in populations from other geographical areas and in other races with the expectation of attaining new insights into the diagnosis and management of SNIP in Hong Kong patients.
Methods: Four studies designed to evaluate the risk factors, viral associations, cell-cycle protein expression, radiological features, clinical features, treatment approaches and treatment outcomes were conducted. The findings of these studies were compared with those reported from different geographical areas of the world. Study 1: Evaluation of the risk factors associated with SNIP by a case-controlled epidemiological study of 50 patients with SNIP and 150 matched control patients. Study 2: Evaluation of the prevalence of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21 and p53 expression in SNIP and comparison with reports from the literature. In a case-control study, 73 SNIP, 48 nasal polyps (NP) and 85 hypertrophied turbinates (HT) specimens were examined by polymerase chain reaction (PCR) for HPV. Seventy-three SNIP, 30 NP and 32 HT specimens were examined by in-situ hybridization (ISH) for EBV and by immunohistochemistry (IHC) for p21 and p53. SNIP results were compared with those of NP and HT (as controls). Study 3: Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP of plain computed tomography by an observational study of plain CT scans and operative findings from 30 patients with SNIP. Study 4: Evaluation of the clinico-pathological features and treatment outcomes of SNIP in 56 patients seen between 1990 and 2008 with follow-up of more than 2 years and comparison with the results of the literature.
Results and conclusions: There are certain unique clinico-pathological features of sinonasal inverted papilloma (SNIP) in Hong Kong which are related to its predominantly Chinese population, high population density, heavy pollution and, accessible and efficient specialist services. Concordant with the results of another case-control study in the literature, the study described herein demonstrated that occupational chemical exposure, but not smoking, is a risk factor for SNIP. This is the first case-control study demonstrating that alcohol intake, allergic rhinitis, nasal polyposis, sinusitis, non-sinonasal papilloma and non-sinonasal malignancy are not risk factors for SNIP. The low prevalence of HPV in non-malignant sinonasal inverted papillomas (NMIPs) in Hong Kong suggests that it does not play a significant pathogenic role. The absence of EBV in SNIPs in Hong Kong concurs with most reports that EBV is not a causative agent. The high p21 and low p53 expression in SNIPs compared with the average values reported from other studies further support the presence of a non-p53-dependent p21 regulatory pathway. The higher prevalence of both HPV and p53 in malignant sinonasal inverted papilloma (MIP) than in NMIP agrees with other reports that both could be markers of malignant transformation. However, their inverse relation suggests they are independent factors. Although most plain CT signs are the same as those previously reported and not pathognomonic for SNIP, the high predictive value of the “pedunculation sign and absence of intra-tumor calcification are unique to Hong Kong patients. Concordant with other reports, “bony strut or focal hyperostosis is highly accurate in predicting the site of SNIP origin. This is the first report on the accuracy of preoperative CT staging, which is slightly lower than that of preoperative MRI staging (80% versus 86%). The estimated incidence of SNIP (2.4/1,000,000/year) is low but may be an underestimation as the number from the private sector is undetermined. The male:female ratio of SNIP patients in both Hong Kong and Asia is low, suggesting a geographic or racial influence on sex predilection. The absence of extrasinonasal extension, low rates of cellular atypia, dysplasia and synchronous malignancy in the Hong Kong SNIPs may reflect less aggressive tumor behavior as well as accessibility to efficient specialist services. The distribution of tumor origins, presenting symptoms and presenting stages of the Hong Kong SNIPs are similar to those reported elsewhere. The higher recurrence rate in the Hong Kong series is related to inadequate treatment of the tumor origin and inadequate conversion to combined external approaches in the early cases. Contrary to previously reported statistics, combined extranasal approaches were used more often in secondary cases than in primary cases. As in previously reported series, the recurrence rate in secondary cases tended to be higher than that in primary cases. Concordant with previous reports from the endoscopic era, most recurrences in Hong Kong occurred at the original tumor site and were discovered within the first 2 years after surgery. The average time of diagnosis of the first recurrence was much shorter than that of the pre-endoscopic era (1.2 years vs. 4.3 years). As reported elsewhere, about one-third of recurrences required combined external approaches for salvage. This is the first report comparing 2-, 5- and 10-year-follow-up results, and suggesting a minimum of 2 years’ follow-up before reporting results to avoid underestimation of recurrences.
Sham, Cheuk-lun.
Thesis (M.D.)--Chinese University of Hong Kong, 2012.
Includes bibliographical references (leaves 215-237).
CHAPTER 1
Introduction
Chapter 1.1 --- Sinonasal inverted papilloma --- p.1
Chapter 1.1.1 --- Nomenclature and classification --- p.1
Chapter 1.1.2 --- Etiology and pathogenesis --- p.4
Chapter 1.1.3 --- Gross and histological pathology --- p.9
Chapter 1.1.4 --- Site of tumor attachment and extension --- p.10
Chapter 1.1.5 --- Association with malignancy --- p.11
Chapter 1.1.6 --- Incidence and demographics --- p.11
Chapter 1.1.7 --- Clinical features --- p.12
Chapter 1.1.8 --- Radiological features --- p.13
Chapter 1.1.9 --- Staging --- p.14
Chapter 1.1.10 --- Treatment modalities --- p.16
Chapter 1.1.11 --- Treatment outcomes, recurrence and residual disease --- p.17
Chapter 1.2 --- Unique characteristics of the Hong Kong population --- p.19
Chapter 1.3 --- Research aims, areas and hypotheses --- p.22
Chapter 1.3.1 --- Research aims --- p.22
Chapter 1.3.2 --- Research areas and hypotheses --- p.23
Chapter 1.4 --- Research plan and methodology --- p.25
Chapter 1.5 --- Summary of Chapter 1 --- p.28
CHAPTER 2
Risk factors associated with SNIP
Chapter 2.1 --- Background --- p.29
Chapter 2.2 --- Hypothesis --- p.29
Chapter 2.3 --- Patients and methods --- p.30
Chapter 2.4 --- Results --- p.35
Chapter 2.5 --- Discussion --- p.39
Chapter 2.6 --- Summary of Chapter 2 --- p.45
CHAPTER 3
Evaluation of the prevalence of HPV, EBV, p21 and p53 expression in SNIP in Hong Kong and comparison with results reported in the literature
Chapter 3.1 --- Background --- p.46
Chapter 3.2 --- Hypothesis --- p.48
Chapter 3.3 --- Patients and methods --- p.48
Chapter 3.4 --- Results --- p.55
Chapter 3.4.1 --- Overall results --- p.55
Chapter 3.4.2 --- Comparison of the results of HPV studies --- p.57
Chapter 3.4.3 --- Comparison of the results of EBV studies --- p.68
Chapter 3.4.4 --- Comparison of the results of p21 studies --- p.71
Chapter 3.4.5 --- Comparison of the results of p53 studies --- p.74
Chapter 3.5 --- Discussion --- p.79
Chapter 3.5.1 --- HPV and SNIP --- p.79
Chapter 3.5.2 --- EBV and SNIP --- p.95
Chapter 3.5.3 --- p21 and SNIP --- p.98
Chapter 3.5.4 --- p53 and SNIP --- p.103
Chapter 3.6 --- Summary of Chapter 3 --- p.115
CHAPTER 4
Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP by plain computed tomography
Chapter 4.1 --- Background --- p.117
Chapter 4.2 --- Hypothesis --- p.118
Chapter 4.3 --- Patients and methods --- p.118
Chapter 4.4 --- Results --- p.120
Chapter 4.5 --- Discussion --- p.135
Chapter 4.6 --- Summary of Chapter 4 --- p.142
CHAPTER 5
Evaluation of the clinico-pathological features and treatment outcomes of SNIP and comparison with results reported in the literature
Chapter 5.1 --- Background --- p.143
Chapter 5.2 --- Hypothesis --- p.144
Chapter 5.3 --- Patients and methods --- p.144
Chapter 5.4 --- Results --- p.148
Chapter 5.4.1 --- Incidence --- p.148
Chapter 5.4.2 --- Demographics --- p.150
Chapter 5.4.3 --- Presenting symptoms --- p.154
Chapter 5.4.4 --- Site of tumor origin --- p.156
Chapter 5.4.5 --- Rate of association with malignancy --- p.158
Chapter 5.4.6 --- Staging of disease (Krouse system) and recurrence rate --- p.163
Chapter 5.4.7 --- Treatment approaches and recurrence rates --- p.165
Chapter 5.4.8 --- Comparison between patients with and without previous surgery --- p.167
Chapter 5.4.9 --- Time and site of recurrence --- p.170
Chapter 5.4.10 --- Surgical approaches used in salvage surgery --- p.175
Chapter 5.4.11 --- Complication rate --- p.176
Chapter 5.5 --- Discussion --- p.178
Chapter 5.5.1 --- Incidence --- p.178
Chapter 5.5.2 --- Demographics --- p.179
Chapter 5.5.3 --- Present symptoms and duration --- p.180
Chapter 5.5.4 --- Sites of tumor origin --- p.181
Chapter 5.5.5 --- Association with malignancy --- p.182
Chapter 5.5.6 --- Disease stages (Krouse system) and recurrence rate --- p.184
Chapter 5.5.7 --- Treatment approaches and recurrence rates --- p.186
Chapter 5.5.8 --- Comparison between patients with and without previous surgery --- p.187
Chapter 5.5.9 --- Time and site of recurrence --- p.189
Chapter 5.5.10 --- Surgical approaches used in salvage surgery --- p.191
Chapter 5.5.11 --- Complication rate --- p.192
Chapter 5.5.12 --- Management principles based on clinico-pathological features --- p.193
Chapter 5.6 --- Summary of Chapter 5 --- p.197
CHAPTER 6
Summary of thesis and future perspective --- p.201
REFERENCES --- p.215
APPENDIX
Questionnaire for study of risk factors of SNIP --- p.238

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
O Fibroma Ossificante Juvenil é uma neoplasia fibro-óssea rara que afeta sobretudo os ossos da órbita e seios perinasais. Apesar de benigno, apresenta um comportamento localmente agressivo e uma elevada taxa de recidiva pelo que um diagnóstico precoce e tratamento multidisciplinar são cruciais para melhorar o prognóstico e prevenir sequelas. O diagnóstico de neoplasias dos seios perinasais e porção medial da órbita é realizado através da correlação entre clínica, imagiologia e histopatologia, sendo que a TC e biópsia pré-operatória desempenham um papel muito importante. O tratamento de primeira linha passa pela resseção cirúrgica sendo recomendada a via endoscópica endonasal devido estar associada a menor taxa de morbilidade. No entanto, em alguns casos, outras opções devem ser consideradas de forma a possibilitar a resseção completa e preservação da função. O presente trabalho relata o caso clínico de uma jovem com Fibroma Ossificante Juvenil do tipo psamomatóide com afeção do aspeto medial do Annulus de Zinn, sujeita a tratamento cirúrgico misto com descompressão do nervo ótico, combinando via aberta transcraniana bicoronal e endoscopia endonasal. O sucesso na abordagem clínica do Fibroma Ossificante Juvenil com compromisso da órbita pode ser alcançado através de um plano pré-operatório rigoroso, avaliação multidisciplinar e utilização das técnicas mais adequadas a cada caso, dependendo essencialmente das caraterísticas do tumor, especialmente tamanho e localização.Palavras-chave: Neoplasias Seios Perinasais; Fibroma Ossificante; Cirurgia Endoscópica de Orifícios Naturais; Rinocirurgia.
Abstract: Juvenile ossifying fibroma is a rare fibro-osseous neoplasm that mainly affects the bones of the orbit and paranasal sinuses. Although benign, it presents a locally aggressive behavior and a high relapse rate. In specific locations, it poses a great treatment challenge so that early diagnosis and multidisciplinary treatment are crucial to improve the prognosis and delay clinical sequelae. Sinuses and medial orbit neoplasms diagnosis is made from clinical, imaging and histopathological exams. CT-scans and preoperative biopsy play an important role. The treatment of choice is a surgical resection. Endoscopic nasal approach is recommended because of its lower morbidity. However, there are some cases in which other options must be considered to perform resection as complete as possible and preserve function. We report a case of a young woman with psammomatoid type juvenile ossifying fibroma of the medial aspect of the Zinn´s annulus, undergoing surgical optic nerve decompression, combining a transcranial bicoronal open and endonasal endoscopic surgery. Functional success in clinical practice dealing with juvenile ossifying fibroma of the orbit is associated to a rigorous preoperative planning, multidisciplinary approach, and the use of the most appropriate techniques for each case, depending mostly on the characteristics of the tumor, especially size and location.Keywords: Paranasal Sinus Neoplasms; Fibroma, Ossifying; Natural Orifice Endoscopic Surgery; Rhinosurgery