Dissertations / Theses on the topic 'Chronic rhinosinusitus'
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Al-Mot, Sawsan. "Molecular signatures as a new classification scheme for chronic rhinosinusitus." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114268.
Full textLa rhinosinusite chronique (RSC), une inflammation des sinus paranasaux, est un trouble commun avec une étiologie incertaine, qui affecte les voies respiratoires supérieures et les sinus paranasaux. Les biopsies des échantillons prélevés sur des patients atteints de RSC documentent la perturbation de l'architecture normale épithéliale, en plus d'une infiltration de cellules inflammatoires intense constituée principalement par des éosinophiles. La classification clinique actuelle de la RSC est basée sur la présence (CRSwNP) ou l'absence (CRSsNP) de polypose nasale, mais aucune différence consistente de l'aspect histologique caractérise ces deux groupes. Récemment, nous avons identifié des profils d'expression génique distincts dans des cultures de cellules épithéliales provenant de sujets atteints de la RSC ayant subis une chirurgie des sinus. Ces signatures moléculaires, qui diffèrent du phénotype clinique, peuvent aider à mieux différencier ce trouble que le phénotype clinique. Dans notre étude, nous avons étudié l'aspect histologique associé à ces deux différentes signatures moléculaires à partir de biopsies chirurgicales obtenus chez des patients atteints de la RSC et les sujets témoins. Les infiltrats cellulaires ont été identifiés par immunohistochimie (IHC), une coloration à l'aide de trois marqueurs: l'élastase de neutrophile (NE), le CD68 et la protéine basique majeure (MBP). L'état d'activation des macrophages dans les formes classiques et alternativement activés a été vérifié par une double-coloration pour les marqueurs CD68 et CD206. Les résultats ont été rapportés à la fois selon les critères cliniques habituels (CRSwNP et CRSsNP) et aussi en fonction de leur signature d'expression en deux groupes (CRS1, CRS2) et les sujets témoins. Les signatures d'expression ont été validées à l'aide de coloration immunohistochimique pour le marqueur le plus différentiellement exprimé, le CCL2.Les résultats ont montré des différences dans le nombre d'éosinophiles, macrophages et les cellules de neutrophiles chez les patients atteints de la RSC par rapport aux sujets témoins. Selon le critère classique, l'éosinophilie était plus élevée dans le groupe CRSwNP, mais pas très différent entre les deux groupes pour les neutrophiles ou les macrophages. En utilisant les signatures moléculaires pour assigner des groupes, l'éosinophilie était similaire entre les deux groupes, cependant, il y avait une augmentation significative du nombre de neutrophiles et de macrophages dans CRS1 comparativement à CRS2. Le groupe CRS2 avait une incidence plus élevée des macrophages alternativement activés, supportant le concept d'une inflammatoire basse, phénotype CRS2 immunotolérant. La validité de la signature moléculaire a été supportée par la démonstration du niveau accru de la protéine produite par l'expression de CCL2 dans CRS1 par rapport à CRS2.En somme, ces résultats mettent en évidence un phénotype moléculaire de la RSC qui se caractérise par une infiltration neutrophilique marquée, et une seconde qui est nettement moins inflammatoire, accompagnée par l'activation alternative des macrophages. Ceci suggère que ces signatures d'expression peuvent identifier de nouveaux mécanismes basés sur des phénotypes, qui diffèrent du phénotype clinique, et peuvent aider à fournir une meilleure compréhension du mécanisme physiopathologique et les phénotypes de la RSC.
Vaidyanathan, Sriram. "Optimising therapeutic strategies for chronic rhinosinusitis." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/337b63fd-4590-4ef9-a55f-8bf447986906.
Full textErskine, Sally. "The epidemiology and experience of chronic rhinosinusitis." Thesis, University of East Anglia, 2017. https://ueaeprints.uea.ac.uk/66950/.
Full textWallwork, Benjamin, and n/a. "The Anti-Inflammatory Effect of Macrolide Antibiotics in Chronic Rhinosinusitis." Griffith University. School of Biomolecular and Biomedical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070201.160023.
Full textViswanathan, Harishnath. "Mucin Gene Expression and GastricReflux in Chronic Rhinosinusitis and Otitis Media with Effusion." Thesis, University of Newcastle Upon Tyne, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499336.
Full textBall, Stephen Leslie. "The role of epithelial cells and fibroblasts in the pathogenesis of chronic rhinosinusitis." Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3726.
Full textMigliavacca, Raphaella de Oliveira. "Modelo experimental de rinossinusite crônica em coelhos sem utilização de bactérias : comparação de técnicas de indução." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/61886.
Full textExperimental models have an important role in understanding the mechanisms involved in the pathogenesis of chronic rhinosinusitis (CRS). Objectives: To demonstrate that, without the inoculation of pathogenic bacteria, it is possible to induce chronic histological changes in the maxillary sinuses of rabbits secondary to sinus ostium obstruction, producing a consistent and reproducible experimental model for CRS. Secondly, to compare inflammatory findings between two techniques of experimental occlusion of the maxillary sinus ostium with N-butyl cyanoacrylate: transmaxillary and through the roof of the nasal cavity. Methods: In a randomized, blinded, experimental study, 16 New Zealand rabbits were assigned for occlusion of the right maxillary sinus through a transmaxillary approach or through the roof of the nasal cavity. The contralateral sinus was left undisturbed to serve as a control. After 12 weeks of follow-up, the animals were anesthetized and sacrificed for blinded histopathological analysis of the maxillary sinus mucosa. Results: Histopathological changes consistent with CRS were found in eight (100%) of the maxillary sinuses approached transmaxillary and three of thoseapproached through the roof of the nasal cavity (37.5%), p 0.008 and 0.250, respectively, comparing the right to the left control sinus. Comparing the occlusion techniques, the transmaxillary approach was more consistent in causing chronic mucosal changes (p 0.026). Conclusions: The proposed model was successful in causing histological changes compatible with CRS in animals subjected to sinus occlusion with a transmaxillary approach followed-up for 12 weeks. This experimental model can be easily replicated for future cellular studies of the sinus mucosa.
Kuchai, Romana. "The effect of macrolides on allergic rhinitis versus chronic rhinosinusitis- an in-vitro study." Thesis, Queen Mary, University of London, 2009. http://qmro.qmul.ac.uk/xmlui/handle/123456789/568.
Full textPilavakis, Yiannis [Verfasser]. "Occurence and characteristics of allergic rhinitis in 195 patients with chronic rhinosinusitis / Yiannis Pilavakis." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1223171612/34.
Full textCordeiro, Daniel Loiola. "Doença respiratória exacerbada por aspirina: papel da periostina em pacientes com rinossinusite crônica e polipose nasossinusal." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17138/tde-18072018-154146/.
Full textAspirin exacerbated respiratory disease (also known as AERD), is characterized by eosinophilic chronic hypertrophic rhinosinusitis, nasosinusal polyps, asthma and hypersensitivity to Aspirin or other non-steroidal anti-inflammatory drugs. A higher expression of the biomarker periostin has been described in patients with AERD, in nasosinusal tissue, including basal membrane, extracellular matrix and nasal polyps. We evaluated the levels of serum periostin in patients with AERD, and compare those levels with patients with perennial allergic rhinitis (PAR), and with healthy subjects. Twenty-nine patients (20F/9M) with AERD were selected from the Allergy and Otolaryngology Clinics, from the Clinical Hospital of the Ribeirão Preto Medicine School, University of São Paulo (HCFMRP-USP). Those patients underwent confirmatory exams, such as Oral Provocation test with aspirin, and were submitted to polyp biopsy through nasofibroscopy. As a control group, 12 patients (9F/3M) with PAR and 23 healthy subjects (14F/9M) were selected. Eosinophils were quantified in peripheral blood and in polyp tissue or nasal mucosa. Total IgE was determined by ImmunoCAP, and serum periostin was measured by ELISA. The number of tissue eosinophils by high magnification field (HMF), number of eosinophils by cubic milliliter in peripheral blood, total IgE levels and serum periostin levels in patients with AERD were compared with those from patients with PAR and healthy subjects. Patients with AERD were older (median 54 years, and range 22-60) than patients with PAR (median 30 years, range 19-57, p=0,0001) and healthy subjects (median 29 years, range 19-53, p=0,0001), with no difference between genders. The numbers of eosinophils in peripheral blood and in tissue were higher in patients with AERD than patients with PAR or healthy subjects. The median of eosinophil number in peripheral blood was 640eos/µL (range 100-5.100); 200eos/µL (range 100-500); e 100eos/µL (range 100-400) in patients with AERD, PAR and healthy subjects respectively (AERD vs PAR, p=0,0003; AERD vs healthy subjects, p=0,01). The average number of tissue eosinophils was 113,3cels/HMF; 2,5cels/HMF; e 0,7cels/HMF, respectively (AERD vs PAR, p=0,017; AERD vs healthy subjects, p=0,003). The geometric mean for total IgE was 290,18kU/mL (range 59,5-8.140); 69,96kU/mL (range 5,5-898); and 43,14kU/mL (range 4-1.328) in patients with AERD, PAR and healthy subjects respectively, with no difference between the groups. Serum periostin was higher in patients with AERD when compared with healthy subjects. The median for serum periostin was 602ng/ml (range 290,7-1.055); 535,6ng/mL (range 209-733,2); e 496,7ng/mL (range 327,4-713,4), in patients with AERD, PAR and healthy subjects respectively (AERD vs healthy subjects, p=0,01). In a Brazilian subgroup of patients with AERD, we observed an elevated number of eosinophils in peripheral blood and tissue, when compared with patients with PAR and healthy subjects. Higher levels of serum periostin were observed in patients with AERD, when compared with healthy subjects, indicating a strong type 2 response in patients with AERD in our environment.
Habib, Al-Rahim. "Association between chronic rhinosinusitis and health-related quality of life in adults with cystic fibrosis." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50407.
Full textMedicine, Faculty of
Population and Public Health (SPPH), School of
Graduate
Tewfik, Marc. "A population-based association study of toll-like receptor signaling pathway gene polymorphisms in chronic rhinosinusitis." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66766.
Full textLa rhinosinusite chronique (RSC) est une maladie fréquente qui cause l'inflammation des sinus. Les récepteurs Toll-like (TLR) sont importants dans l'immunité innée, répondant aux microorganismes. Nous avons évalué les polymorphismes ponctuels de séquence (SNPs) dans les gènes codant les voies de signalisation TLR chez 206 patients atteints de RSC sévère et 200 témoins. Nous avons aussi investigué l'association entre ces SNPs et le niveau d'IgE sanguin. En tout, 96 sur 104 SNPs ont été génotypés avec succès. Bien que nous ne pouvions pas confirmer l'association avec la RSC, 3 SNPs dans le gène IRAK4 – rs1461567, rs4251513, and rs4251559 – étaient associés a un niveau d'IgE sanguin élevé (p < 0.004). Le résultat a été répliqué dans une seconde population indépendante d'individus souffrant d'asthme provenant du Saguenay-Lac-Saint-Jean (p < 0.031). Ces résultats suggèrent qu'une modification génétique dans le gène IRAK4 prédispose à un niveau élevé d'IgE dans les maladies respiratoires.
Cope, Emily K., Andrew N. Goldberg, Steven D. Pletcher, and Susan V. Lynch. "Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences." BIOMED CENTRAL LTD, 2017. http://hdl.handle.net/10150/624075.
Full textRagab, Sameh Mostafa. "Evaluation of the medical and surgical treatment of chronic rhinosinusitis and its effects upon the lower airways." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271395.
Full textDinarte, Vanessa Ramos Pires. "Associação genética do polimorfismo do receptor alfa 1 da interleucina 22 à rinossinusite crônica com e sem polipose nasossinusal." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17151/tde-26042018-171434/.
Full textIntroduction: Chronic rhinosinusitis (CRS), a multifactorial disease, with genetic and environmental factors that may be involved, still have many aspects of its pathogenesis unknown. Genetics has shown itself promising in the elucidation of this complex disease. Some studies have indicated that the expression of IL-22 is reduced in patients with CRS, which may result in reduction of the epithelial barrier and decrease in the production of Th1 proinflammatory cytokines. Objectives: To investigate the frequency of polymorphisms in the IL22RA1 gene in patients with chronic rhinosinusitis with and without nasal polyps and in individuals without these pathologies, using the Sanger sequencing technique for mutation analysis; to compare the frequencies of the polymorphisms found in the IL22RA1 gene between the groups and the medical literature and also to compare the Sanger technique with other conventional techniques in the medical literature. Casuistic and Methods: From May 2011 to February 2016, 247 patients were evaluated, subdivided into three groups: 122 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), 21 cases of chronic rhinosinusitis without nasal polyps (CRSsNP) and 104 volunteers without nasal symptoms. Samples of peripheral venous blood were collected from all cases and controls, and DNA extraction was performed, with subsequent analysis at the Molecular Genetics Laboratory - Ribeirão Preto Medical School Blood Center - USP. After the loss exclusion, there were 70 cases of CRSwNP, 14 CRSsNP and 68 controls. Results: Sequencing indicated 10 polymorphisms in the IL22RA1 gene, exon 2 (rs10903022, c.113_114insA / Q26Pfs * 11, c.74T> A and c.141C> A), exon 4 (rs17852649), exon 5 (rs16829204), exon 6 (rs142356961) and exon 7 (rs17852648, rs34967816 and rs3795299). Polymorphisms in exons 2 (in homozygosis), 5 and 6 were exclusive from the analyzed pathologies group (RSC with and without NP), the latter two being considered non-synonymous variables, that is, with capacity to alter the protein structure, being able to produce impact on the pathogenesis of CRS. The exon 6 alteration was the only variant found, with the minor allele frequency (MAF) under 0.01, exclusive of the RSCcPN group. Conclusions: Three polymorphisms were detected in the IL22RA1 gene, which until now are not described in the literature, and the possibly pathogenic insert c.113_114insA / Q26Pfs * 11, with a higher frequency in the groups with CRS. The polymorphism rs17852649 in heterozygosis in exon 4 was the only one with a statistical difference, with predominance of the mutated allele in the control group, which could confer protection against the phenotype. Also notable is the polymorphism rs142356961, in exon 6, of the non-synonymous type, that is, capable of altering the final structure of the protein, with MAF index <0.01, being exclusive in black patients with chronic rhinosinusitis with nasal polyps. Replication studies and larger cohorts are necessary to rule out the findings at random.
Macdonald, Kristian I. "Development and Validation of an Administrative Data Algorithm to Identify Adults who have Endoscopic Sinus Surgery for Chronic Rhinosinusitis." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35148.
Full textKönig, Katrin Elisabeth [Verfasser], and Moritz [Akademischer Betreuer] Gröger. "Cytokine profiles in nasal secretions of patients with allergic rhinitis and chronic rhinosinusitis / Katrin Elisabeth König ; Betreuer: Moritz Gröger." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1151447277/34.
Full textGutsche, Manuela. "Polyposis nasi: Quantitative Analyse der eosinophilen Granulozyten mit der Laser Scanning Zytometrie." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-64179.
Full textJúnior, Emanuel Capistrano Costa. "Avaliação da associação entre biofilmes bacterianos, bactérias intracelulares e superantígenos estafilocócicos em pacientes com rinossinusite crônica." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17151/tde-10042018-141217/.
Full textIntroduction: Although the pathophysiology of chronic rhinosinusitis (CRS) has not yet been fully elucidated, due to its heterogeneity and multifactorial etiology, there is a growing body of evidence that bacteria play a significant role in the genesis or perpetuation of chronic inflammation. One of the possible forms of acting are bacterial biofilms, which are commonly found in patients with CRS, and are associated with poor clinical outcomes in these patients. In addition to biofilms, there are some evidence pointing out that some bacterial species, especially Staphylococcus aureus (S. aureus), are able to invade into epithelial cells and remain viable intracellulary. Finally, it has been demonstrated that patients with CRS with nasal polyps (CRSwNP) have a high association with the presence of staphylococcal superantigens in the respiratory mucosa, responsible for the stimulation of marked local inflammatory responses. Although these different bacterial forms are well described in CRS, it is still unclear how they are associated in these individuals. Objectives: To evaluate the correlation between the presence of biofilms, intracellular bacteria expression and S. aureus superantigens in CRS patients (with and without nasal polyposis) compared to a control group. Casuistic and Methods: We evaluated the prevalence of bacterial biofilms, intracellular bacteria and the presence of bacterial superantigens in individuals with CRSwNP, without nasal polyp (CRSsNP) and controls, evaluating the association of prevalence distribution of these different groups (Fisher exact test, level of significance set at p<0.05). The biofilms were defined by morphological characteristics by scanning electron microscopy, intracellular bacteria were analyzed by transmission electron microscopy and fluorescence in situ hybridization (FISH) for S. aureus, and S. aureus A-E superantigens were quantified by ELISA. Ninety individuals were included, divided into 38 patients with CRSwNP, 26 patients with CRSsNP and 26 control patients. Results: 42% of patients with CRSwNP (16/38) as well as those with CRSsNP (11/26) presented positive samples for bacterial biofilms, while none of the control patients (0/26) had positive samples. The analysis for intracellular bacteria showed the presence in 31.5% of patients with CRSwNP (12/38), 19.2% in CRSsNP (5/26) and 0% in control patients (0/26). In the FISH study, 58% of patients with CRSwNP (18/31) presented intracellular S. aureus positivity, followed by 54% in patients with CRSsNP (13/24) and in none of the 24 analyzed in the control group. In the ELISA evaluation, only one patient with CRSwNP was positive for the presence of staphylococcal superantigens. The evaluation of the association of bacterial biofilm on the mucosal surface (SEM) with intracellular bacteria (MET) and with intracellular S. aureus by FISH in the two different groups of CRS (with and without nasal polyps) did not show a statistically significant difference. Conclusion: We found a higher prevalence of biofilms and intracellular bacteria in individuals with CRS, either with and without nasal polyps. There was no significant difference between the groups of CRS, with and without nasal polyp, for the presence of biofilms or intracellular bacteria. There was no significant diference on the association of biofilms and intracellular bacteria on pacientes with CRS. Our data indicate that both biofilms on the mucosal surface and intracellular microorganisms may be involved in the pathophysiology of CRS.
Kang, Suzie Hyeona. "Características do acometimento nasossinusal em pacientes adultos com fibrose cística." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/132127.
Full textCystic 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.
Thienhaus, Maike Luisa [Verfasser]. "Die Rolle der antimikrobiellen Peptide humanes beta-Defensin 3 (hBD-3) und LL-37 bei chronisch polypöser Rhinosinusitis und nasaler Besiedelung mit Staphylococcus aureus / Maike Luisa Thienhaus." Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/1046563300/34.
Full textKeim, Oliver [Verfasser], Stefan [Akademischer Betreuer] Plontke, Andreas [Akademischer Betreuer] Stang, and David [Akademischer Betreuer] Wohlrab. "Ätiologie, Ausprägung und assoziierte Erkrankungen der chronisch-polypösen Rhinosinusitis : eine retrospektive Untersuchung von Patienten der HNO-Klinik des Universitätsklinikums Halle (Saale) in der Zeit von 1/2001 - 12/2007 / Oliver Keim. Betreuer: Stefan Plontke ; Andreas Stang ; David Wohlrab." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2011. http://d-nb.info/1025203003/34.
Full textAlmeida, João Toste Pestana de. "Chronic Invasive Rhinosinusites by Conidiobolus Coronatus." Master's thesis, 2017. http://hdl.handle.net/10316/81897.
Full textRinosinusite crónica fúngica invasiva é uma infeção rara e potencialmente agressiva, caracterizada por obstrução nasal, dor facial e hipósmia, secundárias à infiltração da mucosa, submucosa, ossos ou vasos sanguíneos dos seios paranasais. Conidiobolus é uma etiologia muito rara de Rinosinusite Crónica Fúngica Invasiva, predominando em zonas de florestas tropicas, não sendo encontrado normalmente na Europa.Pretendemos apresentar o primeiro caso de Rinosinusite Crónica Fúngica Invasiva por Conidiobolus diagnosticada num doente português.Apresentamos um doente do sexo masculino, 65 anos de idade, com obstrução nasal progressiva, cefaleia frontal bilateral e hiposmia com 8 meses de evolução. Foi diagnosticada uma rinosinusite crónica fúngica invasiva com hipertrofia dos cornetos inferiores e mucosite nasal ulcerativa. A identificação fúngica foi possível através de biopsias realizadas cirurgicamente, observação macroscópica de colónias, observação microscópica de micelas e técnicas de biologia molecular. O doente foi tratado com Anfotericina B lipossómica, tendo sido seguido durante 3 anos sem intercorrências.A Rinosinusite Crónica Fúngica Invasiva por Conidiobolus já não se encontra restrita às florestas tropicais, devendo os clínicos europeus estar atentos a esta etiologia. O diagnóstico é apenas possível através de fortes suspeições conjugadas com o trabalho conjunto de cirurgiões e patologistas.Rinosinusite crónica fúngica invasiva é uma infeção rara e potencialmente agressiva, caracterizada por obstrução nasal, dor facial e hipósmia, secundárias à infiltração da mucosa, submucosa, ossos ou vasos sanguíneos dos seios paranasais. Conidiobolus é uma etiologia muito rara de Rinosinusite Crónica Fúngica Invasiva, predominando em zonas de florestas tropicas, não sendo encontrado normalmente na Europa.Pretendemos apresentar o primeiro caso de Rinosinusite Crónica Fúngica Invasiva por Conidiobolus diagnosticada num doente português.Apresentamos um doente do sexo masculino, 65 anos de idade, com obstrução nasal progressiva, cefaleia frontal bilateral e hiposmia com 8 meses de evolução. Foi diagnosticada uma rinosinusite crónica fúngica invasiva com hipertrofia dos cornetos inferiores e mucosite nasal ulcerativa. A identificação fúngica foi possível através de biopsias realizadas cirurgicamente, observação macroscópica de colónias, observação microscópica de micelas e técnicas de biologia molecular. O doente foi tratado com Anfotericina B lipossómica, tendo sido seguido durante 3 anos sem intercorrências.A Rinosinusite Crónica Fúngica Invasiva por Conidiobolus já não se encontra restrita às florestas tropicais, devendo os clínicos europeus estar atentos a esta etiologia. O diagnóstico é apenas possível através de fortes suspeições conjugadas com o trabalho conjunto de cirurgiões e patologistas.
Chronic invasive fungal rhinosinusitis is a rare and potentially aggressive infection, characterized by nasal obstruction due to the presence of fungal hyphae infiltrating the mucosa, submucosa, bone, or blood vessels of the paranasal sinuses, facial pain and hyposmia. Conidiobolus is a very rare cause of chronic invasive fungal rhinosinusitis. This fungus predominates in tropical forests and usually is not present in Europe. We aim to present the first case of chronic invasive fungal rhinosinusitis due to Conidiobolus diagnosed in a Portuguese patient. We present a Caucasian 65 years old male patient with progressive nasal obstruction, bilateral frontal headache and a hyposmia with 8 months of evolution. He was diagnosed a chronic invasive rhinosinusitis associated with hypertrophied inferior turbines and ulcerative nasal mucositis. The identification of Conidiobolus was performed in samples from surgical excision biopsies, by macroscopic observation of the colony, microscopic observation of the mycelium and molecular biology techniques. The patient was treated using liposomal B amphotericin and followed up for 3 years without intercurrences.Chronic invasive fungal rhinosinusitis by conidiobolus is not restricted to tropical forests anymore. European physicians must be aware of this possibility. Diagnosis is only possible by strong suspicious and conjugated efforts between surgeons and pathologists.Chronic invasive fungal rhinosinusitis is a rare and potentially aggressive infection, characterized by nasal obstruction due to the presence of fungal hyphae infiltrating the mucosa, submucosa, bone, or blood vessels of the paranasal sinuses, facial pain and hyposmia. Conidiobolus is a very rare cause of chronic invasive fungal rhinosinusitis. This fungus predominates in tropical forests and usually is not present in Europe. We aim to present the first case of chronic invasive fungal rhinosinusitis due to Conidiobolus diagnosed in a Portuguese patient. We present a Caucasian 65 years old male patient with progressive nasal obstruction, bilateral frontal headache and a hyposmia with 8 months of evolution. He was diagnosed a chronic invasive rhinosinusitis associated with hypertrophied inferior turbines and ulcerative nasal mucositis. The identification of Conidiobolus was performed in samples from surgical excision biopsies, by macroscopic observation of the colony, microscopic observation of the mycelium and molecular biology techniques. The patient was treated using liposomal B amphotericin and followed up for 3 years without intercurrences.Chronic invasive fungal rhinosinusitis by conidiobolus is not restricted to tropical forests anymore. European physicians must be aware of this possibility. Diagnosis is only possible by strong suspicious and conjugated efforts between surgeons and pathologists.
Murphy, Jae Viktor. "The Mucosal Barrier in Chronic Rhinosinusitis." Thesis, 2018. http://hdl.handle.net/2440/117794.
Full textThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2018
Singhal, Deepti. "Bacterial & fungal biofilms in chronic rhinosinusitis." Thesis, 2011. http://hdl.handle.net/2440/72282.
Full textThesis (Ph.D.) -- University of Adelaide, School of Medicine, 2011
Chen, Yu-Ting, and 陳玉婷. "Asthma Associated Chronic Rhinosinusitis : A Population-Based Study." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/64f4th.
Full text高雄醫學大學
公共衛生學系公共衛生學碩士班
103
Background: Several studies have reported the association between asthma and chronic rhinosinusitis with/without nasal polyps. However, this relationship has not been investigated demographically . The aim of this study was to utilize the Taiwan National Health Insurance database to analyze the association between asthma and the risk of chronic rhinosinusitis patterns in order to provide information for clinical applications. Methods: Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan from 1997 to 2009. The study was divided into cohort and matched case-control analysis of two parts, which were described as follows: Cohort study included cases with a new primary diagnosis of asthma (ICD-9: 493) between 2000 and 2008. These cases were compared in sex-, age-, residence-, and insurance premium-matched controls, and both groups were followed up until the end of 2009 for instances of chronic rhinosinusitis with/without nasal polyps (CRS w/s NP), defined as ICD-9 codes CRS (473, 473.0, 473.1, 473.2, 473.3, 473.8, and 473.9), with/without NP (471, 471.0, 471.1, 471.8, and 471.9). Both of CRSwNP and CRSsNP analysis were performed. Competing risk-adjusted Cox regression analyses were applied after adjusting for sex, age, residence, insurance premium, steroid use (topical or systemic), hyperlipidemia, diabetes, hypertension, coronary artery disease, Charlson comorbidity index and mortality. In matched case-control study, case group were diagnosed with chronic rhinosinusitis with/without nasal polyps (CRS w/s NP), defined as ICD-9 codes CRS (473, 473.0, 473.1, 473.2, 473.3, 473.8, and 473.9), with/without NP (471, 471.0, 471.1, 471.8, and 471.9) between 2000 and 2009. In the matched case-control study the control groups were matched according to sex, age, residence, insurance premium with the population rate of 1:4 from non-CRS population. Conditional logistic regression models analyses were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) between the asthma and CRS w/s NP risk, adjusted for other types of steroid drugs and comorbidities. Results: In cohort study, among 81,462 subjects, 58 developed CRSwNP and 799 developed CRSsNP with a mean (SD) follow-up period of 5.8 (2.4) years. Asthma was an independent predictor of CRSwNP in the fully adjusted model (HR =1.80; 95% CI = 1.02-3.17; P=0.041). Among the CRSsNP analysis, asthma was also an independent predictor of CRSsNP in the fully adjusted model (HR =2.62; 95% CI = 2.23-3.08; P<0.001). In matched case-control analysis, a total of 1204 subjects were identified as CRSwNP, including 107 with asthma before diagnosed as CRSwNP;a total of 4816 subjects were identified as Non-CRSwNP, including 155 with asthma before diagnosed as Non-CRSwNP between 2000-2009. A total of 11308 people were identified as CRSsNP, including 1617 with asthma before diagnosed as CRSsNP;a total of 45232 subjects were identified as Non-CRSsNP, including 1960 subjects with asthma before diagnosed as Non-CRSsNP between 2000-2009. Conditions logistic regression analysis for which steroid use, hyperlipidemia, diabetes, hypertension, coronary artery disease, and Charlson comorbidity index were adjusted, asthma was positively associated with CRSwNP (Odds-ratio= 2.49; 95% CI = 1.89–3.30; P < 0.001). Asthma was also positively associated with CRSsNP (Odds-ratio= 3.10; 95% CI = 2.87–3.34; P < 0.001). Conclusion: Results of this study show that asthma was associated with an increased risk of CRS w/s NP. The result is consistency with previous reports and confirms that there is an relationship between asthma and CRS w/s NP. It is evident that, in Taiwan, asthma has increased effect on the risk of developing CRSsNP than CRSwNP.
Psaltis, Alkis James. "The role of bacterial biofilms in chronic rhinosinusitis." 2008. http://hdl.handle.net/2440/50962.
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Thesis (Ph.D.) -- University of Adelaide, School of Medicine 2008
Psaltis, Alkis James. "The role of bacterial biofilms in chronic rhinosinusitis." Thesis, 2008. http://hdl.handle.net/2440/50962.
Full textThesis (Ph.D.) -- University of Adelaide, School of Medicine 2008
Miljkovic, Dijana. "The role of immune cells in chronic rhinosinusitis." Thesis, 2017. http://hdl.handle.net/2440/109806.
Full textThesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2017.
Pant, Harshita. "Eosinophilic mucus chronic rhinosinusitis: an immunological perspective / Harshita Pant." 2005. http://hdl.handle.net/2440/22353.
Full textBibliography: leaves 187-224.
[7], xvii, 229 leaves, [6] : ill. (some col.), maps (col.), plates (chiefly col.) ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Thesis (Ph.D.)--University of Adelaide, School of Medicine, Discipline of Surgery, 2006
Naidoo, Yuresh Sirkari. "Frontal sinus surgery: indications and outcomes in chronic rhinosinusitis." Thesis, 2014. http://hdl.handle.net/2440/85928.
Full textThesis (Ph.D.) -- University of Adelaide, School of Medicine, 2014
Teles, Rafaela da Cruz Vieira Veloso. "Study of the etiopathogenesis of Chronic Rhinosinusitis with Nasal Polyps." Doctoral thesis, 2020. http://hdl.handle.net/10400.6/10315.
Full textIntrodução A rinossinusite crónica (RSC) é uma doença inflamatória crónica do nariz e seios perinasais, que engloba dois fenótipos clínicos: a Rinossinusite Crónica sem Pólipos Nasais (RSCsPN) e a Rinossinusite Crónica com Pólipos Nasais (RSCcPN). Esta última destaca-se pela presença de formações polipoides, hiperplásicas, pedunculadas e edematosas nas cavidades nasais e seios perinasais, geralmente de forma bilateral. A RSCcPN é uma entidade clínica comum, com elevada morbilidade e cronicidade, já descrita no tempo do Antigo Egipto (2000 a.C.) e sobre a qual a investigação científica tem incidido de forma intensa nas últimas duas décadas. No entanto, apesar de toda a pesquisa realizada, a RSCcPN continua a ser um enigma na história da Medicina, permanecendo como uma doença idiopática de prevalência desconhecida, cuja fisiopatologia é em grande parte oculta. Estas incertezas refletem-se na eficácia limitada dos tratamentos disponíveis e explicarão, em parte, a elevada refratariedade da doença ao tratamento médico e cirúrgico. As principais limitações no estudo desta patologia têm sido: a sua sintomatologia inespecífica que dificulta o diagnóstico diferencial com outras patologias nasossinusais; os estudos epidemiológicos pouco fiáveis que estimam a prevalência da doença e avaliam os seus fatores de risco baseando-se em questionários sobre sintomas; a frequente ausência de diferenciação entre os tipos de RSC (RSCsPN e RSCcPN) em diferentes estudos e a inclusão de subtipos de doença (ex. RSCcPN no contexto de Fibrose Quística, Discinésias Ciliares primárias, Vasculites), que sendo casos raros e com mecanismos fisiopatológicos particulares, deverão ser alvo de estudos individualizados. Tendo em conta o consenso atual de que a RSC resultará de uma interação disfuncional entre hospedeiro-ambiente, pretende-se estudar fatores de risco exógenos e endógenos que possam estar na origem e perpetuação da inflamação da mucosa nasal que caracteriza a RSCcPN. Este trabalho tem como objetivos: 1) Avaliar a eficácia da cirurgia endoscópica nasossinusal (CENS) no tratamento da RSCcPN e estabelecer fatores prognósticos de recidiva da doença; 2) Comparar a prevalência da polipose nasal (PN) num grupo de trabalhadores com e sem exposição ocupacional a poeiras; 3) Caracterizar e comparar alterações imunológicas sistémicas dos doentes com RSCcPN versus grupo controlo; 4) Clarificar o papel da alergia alimentar na RSCcPN, comparando os níveis séricos de anticorpos IgE e IgG específicos contra antigénios alimentares em casos e controlos. Material e Métodos 1) Estudo observacional retrospetivo de 85 doentes submetidos a CENS e com um follow-up mínimo de 9 meses. Os dados demográficos, a exposição ocupacional, as comorbilidades, a história cirúrgica prévia, os sintomas pré e pós-operatórios, os dados do exame ORL, resultados da TC e a informação sobre o tratamento médico e cirúrgico foram obtidos através da revisão dos processos clínicos. A análise estatística foi efetuada com recurso ao SPSS v.23. A estatística descritiva foi utilizada na caracterização da amostra. Utilizou-se o teste de McNemar na comparação dos sintomas pré e pós-operatórios. Os doentes com e sem recidiva de RSCcPN foram divididos em dois grupos independentes e foram comparados para múltiplos fatores: na avaliação da associação entre a recidiva e variáveis categóricas utilizou-se o teste de Qui-Quadrado (ou o teste exato de Fisher quando não se verificavam as assunções necessárias à execução do teste anterior); no estudo de associação entre a recidiva e variáveis quantitativas utilizou-se o teste de Mann-Whitney. Realizou-se uma regressão logística multivariada para avaliar a existência de fatores preditivos independentes na recidiva da polipose nasal. O teste de razão de verossimilhança, o teste de Hosmer e Lemeshow, a área sob a curva ROC foram realizados/calculados para avaliação do modelo criado, e procedeu-se à determinação do coeficiente de Nagelkerke’s. O teste de Wald’s e o teste de score foram obtidos para cada variável independente, assim como o Odds Ratio e seu intervalo de confiança a 95%. 2) Estudo epidemiológico transversal numa amostra randomizada de trabalhadores têxteis (n=215) e de trabalhadores de venda a retalho (n=101). Realizou-se uma entrevista clínica sistematizada, que incluiu os questionários RhinoQOL-pv e CATTM, e uma avaliação endoscópica com ótica rígida 0º, com determinação do score endoscópico de Lund-Kennedy em cada participante. A análise estatística foi efetuada com recurso ao SPSS v.23. Utilizou-se a estatística descritiva na caracterização dos dois grupos de trabalhadores e procedeu-se à sua comparação. Na comparação de variáveis categóricas entre os grupos, utilizou-se o teste de Qui-Quadrado (ou teste exato de Fisher, quando adequado) e na comparação de variáveis quantitativas utilizou-se o teste de Mann-Whitney. O teste Binomial foi utilizado na comparação da prevalência de PN no grupo de trabalhadores têxteis com a prevalência de outros estudos publicados na literatura. 3) Estudo caso-controlo de 37 doentes com RSCcPN e 34 controlos sem RSC. Os dados clínicos foram obtidos por entrevista clínica e exame ORL. Realizaram-se TC do nariz e seios perinasais, teste cutâneo de Prick, espirometria; determinação dos parâmetros imunológicos no plasma (contagem diferencial de leucócitos, classes e subclasses de imunoglobulinas) e também dos níveis de 25-hidroxivitamina D (25-HOD), alfa-1-antitripsina (A1AT) e proteína C reativa (PCR). A análise estatística foi efetuada com recurso ao SPSS v.23. Utilizou-se a estatística descritiva na caracterização do grupo de casos e controlos. O teste de Mann-Whitney foi utilizado na comparação de variáveis contínuas entre os dois grupos e o teste de Qui-Quadrado ou o teste exato de Fisher na comparação de variáveis categóricas. Realizou-se uma subanálise com o teste de Kruskal-Wallis na comparação dos parâmetros analíticos entre 3 grupos (grupo controlo sem doenças respiratórias crónicas inferiores (DRCI), grupo RSCcPN sem DRCI e grupo RSCcPN com DRCI), seguido de comparações múltiplas interpares com o teste post-hoc de Dunn. 4) Estudo caso-controlo de 33 doentes com RSCcPN e 31 controlos sem RSC. Os dados clínicos foram obtidos por entrevista clínica, incluindo a aplicação do Questionário de Frequência Alimentar (QFA). Realizou-se o teste de ELISA com o kit OmegaDiagnostics® com 40 antigénios alimentares para determinação de anticorpos IgG específicos e procedeu-se ao teste de imunoensaio usando o ImmunoCAP™ na avaliação de anticorpos IgE específicos contra 11 antigénios alimentares. Procedeu-se à análise estatística dos dados obtidos, com recurso ao SPSS v.23. Utilizou-se a estatística descritiva na caracterização dos dois grupos. O teste de Mann-Whitney foi utilizado na comparação de variáveis quantitativas entre os dois grupos, enquanto o teste de Qui-Quadrado ou o teste exato de Fisher foi utilizado na comparação de variáveis categóricas. O teste não-paramétrico de Spearman foi utilizado na avaliação de correlação entre variáveis quantitativas. Resultados 1) Houve uma melhoria significativa de todos os sintomas rinológicos após a CENS. As prevalências de complicações major e minor foram de 1,2 e 15,3%, respetivamente. A proporção de doentes com RSCcPN com recidiva da patologia após CENS foi de 31%, com 7% a necessitar de reintervenção cirúrgica. 60% dos doentes com RSCcPN reportaram exposição ocupacional a poeiras, das quais 90,4% correspondiam a poeiras de baixo peso molecular (BPM) (<5KDa). Os doentes com exposição ocupacional a poeiras apresentaram uma recorrência da doença significativamente superior ao grupo não exposto (48% vs 3%, p=5,5x10-6). A análise de regressão logística multivariada identificou a exposição ocupacional a poeiras (p=0,001, OR=38,02, IC95%: [4,18; 345,69]) e a asma não-atópica (p=0,012, OR=8,65, IC95%: [1,62; 46,16]) como fatores preditivos independentes de recidiva da RSCcPN ao contrário das outras variáveis analisadas: idade, sexo, asma atópica, rinite alérgica, hábitos tabágicos, classificação endoscópica da polipose nasal, score de Lund-Mackay e uso pós-operatório de corticoide tópico. O modelo logístico apresentou área sob a curva ROC de 0,82 (p<0,001; IC95%: [0,73; 0,91]). O teste de razão de verossimilhança do modelo criado obteve um p=1,2x10-7, o teste de Hosmer e Lemeshow demonstrou um p=0,503 e o coeficiente de Nagelkerke’s foi de 0,44. 2) A PN foi diagnosticada em 19 participantes do grupo dos trabalhadores têxteis (8,8%) e em nenhum do grupo controlo (p=0,001). A prevalência da PN aumentou conforme o estrato etário (p=0,03) e dependendo do número de anos de exposição às poeiras (p=0,017). A degenerescência polipoide do corneto médio foi mais prevalente no grupo exposto (p=0,001), que também obteve um score de Lund-Kennedy mais elevado (p<0,001). No RhinoQOL-pv e no CATTM obtiveram-se scores significativamente mais elevados entre os trabalhadores têxteis. A prevalência de PN nos trabalhadores têxteis (8.8%) foi significativamente superior às prevalências reportadas em estudos endoscópicos prévios (2,7% e 5,5%; p<0,001 e p=0,029, respetivamente). 3) No grupo dos doentes com RSCcPN a prevalência de doenças respiratórias crónicas inferiores (DRCI) foi significativamente superior ao grupo controlo (p<0,001), ao contrário da patologia atópica que não diferiu. Nos doentes com RSCcPN obteve-se uma contagem relativa de eosinófilos (p<0,001) e de basófilos (p=0,022) no plasma significativamente mais elevada do que no grupo controlo, ao contrário dos neutrófilos cuja contagem foi significativamente menor (p=0,013). Os doentes com RSCcPN apresentaram níveis mais elevados de IgG1 (p=0,022), mas mais reduzidos de IgG2 (p=0,014) e IgG3 (p=0,018) comparativamente aos controlos. Essas diferenças observadas foram mais evidentes nos doentes com RSCcPN e DRCI concomitante. Os níveis de IgG4, IgG total, IgA, IgM e IgE não diferiram entre os grupos, assim como a prevalência das deficiências de classes e subclasses de imunoglobulinas; os níveis de 25-HOD, A1AT e PCR também não diferiram de forma significativa. 4) No grupo com RSCcPN verificou-se uma concentração total de anticorpos alimentares do tipo IgG significativamente menor do que a do grupo controlo (p=0,012); esta diferença foi também observada para diferentes anticorpos IgG específicos (milho, soja, leguminosas, maçã e pera, frutos vermelhos, citrinos). No grupo controlo verificou-se uma correlação positiva entre os níveis de IgG1 séricos e a soma da concentração dos anticorpos IgG alimentares (p=0,049). Pelo contrário, no grupo com RSCcPN observou-se uma correlação negativa entra essas variáveis (p=0,048). Os níveis de IgG1 encontravam-se significativamente elevados no grupo com RSCcPN (p=0,041). Os níveis séricos de IgE específicas contra os diferentes alergénios alimentares avaliados, bem como a concentração total de IgE específicas alimentares, não diferiram de forma estatisticamente significativa entre os grupos. Conclusões Apesar da cirurgia endoscópica ser um tratamento eficaz na RSCcPN, com benefícios óbvios na resolução de sintomas no pós-operatório, a recorrência da doença é considerável. O primeiro estudo deste trabalho demonstrou que a exposição ocupacional a poeiras e a asma não-atópica são fatores preditivos independentes de recidiva da doença. A identificação da exposição a partículas de BPM como principal exposição ocupacional reportada é também relevante. Estas partículas de BPM têm sido associadas ao risco de desenvolver asma ocupacional (não-atópica) e ao contrário das partículas de alto peso molecular (APM) que atuam por mecanismos IgE-mediados, não têm os seus mecanismos de ação bem estabelecidos. A distinção realizada entre asma atópica e não-atópica permitiu clarificar o impacto da asma nos resultados pós-operatórios, que era até então controverso. O estudo epidemiológico realizado, baseado em endoscopia, foi pioneiro na avaliação do impacto da exposição ocupacional a poeiras na prevalência da PN e aponta para uma importante associação entre ambas, ao demonstrar uma prevalência da doença significativamente elevada nos trabalhadores têxteis. Os resultados deste trabalho alertam para um relevante problema de Saúde Pública, reforçando a necessidade de medidas de proteção dos trabalhadores expostos a poeiras (ex. uso de máscara com filtros apropriados) e a necessidade de controlo no funcionamento dos sistemas de exaustão de partículas e filtros de ar que garantam a qualidade do ar. Depreende-se assim que os doentes com RSCcPN devem sempre que possível trabalhar em ambientes livres de poeiras, de forma a reduzir o risco de recidiva e melhorar o seu prognóstico. Outros estudos epidemiológicos serão necessários na avaliação de outro tipo de exposições ocupacionais, tentando se possível comparar o impacto de exposição a poeiras de BPM e APM na prevalência de RSCcPN. O estudo prospetivo, clínico-laboratorial, demonstrou ainda que os doentes com RSCcPN apresentam um perfil imune sistémico distinto dos controlos, com variações na contagem diferencial de leucócitos e um desvio IgG1 a nível das subclasses de IgG. Estas diferenças estão de acordo com o que tem sido reportado a nível local, nos pólipos nasais. De notar, que essas diferenças eram mais marcadas nos doentes com DRCI, o que reforça o conceito de “one airway, one disease”. Relativamente ao estudo sobre o impacto da alergia alimentar na RSCcPN, esta não parece ter um papel relevante na sua etiopatogenia, seja esta resposta imune IgG ou IgE mediada. Além do mais, observou-se uma supressão de anticorpos IgG específicos contra antigénios alimentares nos doentes com RSCcPN, uma correlação negativa da sua soma com os níveis séricos de IgG1 e valores de IgG1 significativamente elevados nestes doentes. Esta supressão poderá estar relacionada com um desvio da resposta imune IgG-mediada contra outros agentes (p.ex. partículas inalantes) na RSCcPN e deverá ser investigada no futuro.
Panchatcharam, Beula Subashini. "Staphylococcus aureus Exoproteins on Nasal Epithelial Barrier in Chronic Rhinosinusitis." Thesis, 2020. http://hdl.handle.net/2440/127758.
Full textThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
Bassiouni, Ahmed Mokhtar Abdelkhalek. "The role of surgery and disease load in refractory chronic rhinosinusitis." Thesis, 2015. http://hdl.handle.net/2440/100745.
Full textThesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2015.
Ooi, Lian Li. "Novel Topical Anti-biofilm Agents in the Treatment of Recalcitrant Chronic Rhinosinusitis." Thesis, 2019. http://hdl.handle.net/2440/125940.
Full textThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
Pilavakis, Yiannis. "Occurence and characteristics of allergic rhinitis in 195 patients with chronic rhinosinusitis." Doctoral thesis, 2020. http://hdl.handle.net/21.11130/00-1735-0000-0005-1502-1.
Full textOoi, Eng Hooi. "Cathelicidins and surfactant proteins in chronic rhinosinusitis: a clinical and experimental study." 2007. http://hdl.handle.net/2440/40343.
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Thesis(PhD)-- School of Medicine, 2007
Ooi, Eng Hooi. "Cathelicidins and surfactant proteins in chronic rhinosinusitis: a clinical and experimental study." Thesis, 2007. http://hdl.handle.net/2440/40343.
Full textThesis(PhD)-- School of Medicine, 2007
Nogueira, Simão da Cruz. "SNOT-22: a life quality score questionnaire in Portuguese patients with Chronic Rhinosinusitis." Master's thesis, 2018. http://hdl.handle.net/10316/82275.
Full textIntrodução: O uso de questionários de qualidade de vida relacionados com a saúde tem vindo a aumentar na prática clínica para avaliar o impacto da intervenção médica e medir o resultado da intervenção de cuidados de saúde na qualidade de vida de um paciente. O questionário SNOT-22 foi considerado a ferramenta mais adequada para avaliar a rinossinusite crónica. Este estudo tem como objetivo determinar o impacto funcional do tratamento cirúrgico das doenças naso-sinusais na qualidade de vida dos pacientes, medido através um questionário de qualidade de vida, o SNOT-22.Métodos: Estudo observacional prospectivo com 52 pacientes com rinossinusite crónica submetidos a cirurgia que responderam ao questionário SNOT-22-pt. Os dados foram recolhidos no período pré-operatório e 3 meses após a cirurgia e foram analisados para determinar a consistência interna e a capacidade de resposta do questionário SNOT-22.Resultados: Este estudo constatou que houve uma diminuição estatisticamente significativa (P <0.0001, t = 9.643) nos scores de SNOT-pt 22 referidos pelos pacientes (média 21) em comparação com antes da cirurgia (média 51), mostrando capacidade de resposta clínica. O SNOT-22-pt mostrou um alto nível de consistência interna (alfa de Cronbach de 0.895). O tamanho total do efeito foi de 1.91, que é considerado grande. A diferença minimamente importante foi 28, o que significa que uma mudança de menos de 28 pontos não é percebida pelo paciente como uma melhoria real. O score pós-operatório normal é inferior a 25 pontos.Conclusão: Verificamos que a versão Portuguesa do questionário SNOT-22 é um instrumento válido e de fácil utilização para avaliar pacientes com RSC, pois demonstrou alta consistência interna, capacidade de resposta e facilidade de interpretação clínica. O SNOT-22-pt deve ser usado como uma ferramenta para facilitar a prática clínica de rotina na avaliação do impacto da RSC na qualidade de vida de um paciente e também para medir a eficácia das intervenções cirúrgicas.
Introduction: Health-related quality of life questionnaires use has been increasing in clinical practice to assess the impact of medical intervention and measure the outcome of health care intervention in a patient quality of life. The SNOT-22 questionnaire has been considered the most appropriate tool to evaluate chronic rhinosinusitis. This study aims to determine the functional impact of surgical treatment of nasosinusal diseases on patients' quality of life, measured by a quality of life questionnaire, the SNOT-22.Methods: Prospective observational study with 52 patients with chronic rhinosinusitis submitted to surgery who answered the SNOT-22-pt questionnaire. Data were collected preoperatively and 3 months after surgery and analysed to determine the internal consistency and responsiveness of the SNOT-22 questionnaire.Results: This study found that there was a statistically significant (P < 0,0001, t = 9,643) decrease in patient reported SNOT-22-pt scores (mean 21) compared to before surgery (mean 51), showing clinical responsiveness. SNOT-22-pt showed a high level of internal consistency (Cronbach’s alpha of 0.895). The overall effect size was 1.91, which is considered large. The minimally important difference was 28, which means that a change of less than 28 points is not perceived by the patient as a real improvement. Normal post operative scores cut-off are below 25 points.Conclusion: We found that the Portuguese version of the SNOT-22 questionnaire is a valid and easy to use instrument to evaluate patients with CRS, as it demonstrated a high internal consistency, responsiveness and easy clinical interpretability. The SNOT-22-pt should be used as a tool to facilitate routine clinical practice to assess the impact of CRS on a patient’s quality of life and also to measure the effectiveness of surgical interventions.
Drilling, Amanda Jane. "Bacteriophage therapy for application against Staphylococcus aureus infection and biofilm in chronic rhinosinusitis." Thesis, 2015. http://hdl.handle.net/2440/103502.
Full textThesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2015.
Vediappan, Rajan Sundaresan. "Modifying Post-Surgical Wound Healing." Thesis, 2021. http://hdl.handle.net/2440/130740.
Full textThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2021
Lin, Tzu-Kai, and 林子凱. "The analysis of treatment effects in chronic rhinosinusitis patients with amphotericin B nasal irrigation." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/60554978659555794023.
Full text中國醫藥大學
醫務管理學研究所碩士班
94
Background: Chronic rhinosinusitis (CRS) is a prevalent disease among the general population and is recognized to have a great impact on a patient’s quality of life. No medical care procedure has been proved as treatment standard yet. Antibiotics, intranasal steroid, and endoscopic sinus surgery (ESS) are used to treat CRS, but none of these treatments have satisfactory long-term outcome. Recently fungal infection has been suggested to play an important role in the causation of CRS. In addition, traditional outcome measures of CRS often focus on the physiologic parameters and not enough attention on patient’s quality of life. Recently, health-related quality of life was advocated as one of the primary and important outcome variables. However there is still not any disease-specific questionnaire available for CRS in Taiwan. Objectives: We tested the hypothesis that intranasal antifungal treatment improves the quality of life and the objective nasal endoscopic scores and fungal burden of CRS in a prospective, double-blind, randomized, and placebo-controlled clinical trial. Another focus of this study is to evaluate the Chinese-version of RSOM-31 and the quality-of-life data from CRS patients in Taiwan. Methods: From September 2005 to March 2006, 40 CRS patients at Taichung Veterans General Hospital were recruited with 37 patients completed the trial. Patients applied 500 mL amphotericin B saline solution (0.04mg/mL) or placebo to each nostril twice a day by using pulsatile nasal irrigation. The nasal endoscopy, fungus culture rate and RSOM-31 were evaluated pre- and post-treatment. Results: The overall Cronbach’s alpha coefficient of Chinese-version RSOM-31 was 0.92, suggesting a high degree of internal consistency. The average Symptom-Impact score was 6.4, which was a little higher compared to Dr. Piccirillo’s score 5.8. The domains most affected were sleep and emotional. The amphotericin B group had a better quality-of-life improvement compared to the placebo group after treatment, especially in general symptoms and practical problems subscales. However the endoscopic disease-severity score and fungus culture rate were not significantly different between groups after treatment. Conclusions: The Chinese-version of RSOM-31 was proved to be a convenient and valid tool for evaluating the CRS health status and quality of life. Patients with amphotericin B nasal irrigation in the described dosing and time schedule appear to be both safe and effective and have better life quality compared to placebo. Keywords: Chronic rhinosinusitis, Quality of life, RSOM-31, Nasal irrigation, Amphotericin B
Lin, Ching-Chia, and 林敬家. "Health Services Utilization of Chronic Rhinosinusitis– Using Panel Claims Data of National Health Insurance Beneficiaries." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/bgft22.
Full text國立中興大學
高階經理人碩士在職專班
99
Chronic rhinosinusitis is one of the common infectious diseases. The prevalence rate and consumption of the related medical resource are increasing nearly everyday. The purpose of this study is to examine the health care utilization and related factors of chronic sinusitis patients. This source of the data came from claims data of beneficiaries of National Health Insurance from 2004 to 2008. ICD-9-CM with initial four codes as 471 or 473 were selected from the panel database. All statistical analyses were performed by using SAS 9.1 software. Multiple liner regression analysis was used to explore health services utilization and its related factors. The results indicated that within 5 years, a total of 98,412 visits in ambulatory care and emergency, belonging to 28,080 persons, and 2,338 persons in hospitalization were identified in this study. Male, age over 60 years, medical center, other division of visits, and Northern region branch had higher medical expenses in single visit outpatient and ambulatory care and emergency analysis of statistics. All kinds of ambulatory and emergency care expenses per person were significantly higher medical costs if male, age over 60 years, sinusitis without polyposis, sinusitis with co-morbidities (asthma, allergic rhinitis, otitis media, nasal septum deviation). The statistic analysis of hospitalization showed that: male, age over 60 years, and received functional endoscopic sinus surgery have higher medical expenses in hospitalization. According to the results of this study, we suggest that the health organizations could consider other supporting methods when chronic rhinosinusitis patients would be implemented with the case payment systems. In future studies, if questionnaire survery, patient clinical data, and other factors can be used simultaneously, it will make the research more perfect.
Rong-San and 江榮山. "Effect of Functional Endoscopic Sinus Surgery on the Olfactory Function of Patients with Chronic Rhinosinusitis." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/16268797292612734205.
Full text中山醫學大學
醫學研究所
96
Objectives: This study aims to investigate the change of olfactory function in patients with chronic rhinosinusitis after functional endoscopic sinus surgery and explore the potential prognostic factors. Methods: Patients with chronic rhinosinusitis who had previously undergone functional endoscopic sinus surgery were enrolled in the study. On the day before FESS, olfactory function was evaluated by a symptom score, a phenyl ethyl alcohol odor detection threshold test (STT), the University of Pennsylvannia Smell Identification Test (UPSIT) and a short-term odor memory/discrimination test, and re-evaluated by the same methods 6 months after FESS. The potential prognostic factors (nasal obstruction, cross-sectional area of nasal cavity, rhinosinusitis severity, preoperative olfactory loss, nasal polyps, allergic rhinitis, concurrent septoplasty and turbinal surgery, postoperative steroid treatment) for improvement in olfaction after FESS were also evaluated in these patients. Results: A total of 70 patients with chronic rhinosinusitis were enrolled in the study. Fifty-two patients noticed their olfactory function was impaired before surgery, but the olfactory threshold was above –6 in 66 patients, and 62 patients’ UPSIT scores were below 30. After surgery, the olfactory function was improved in 27 patients using patients’ reports, in 30 patients by STT and in 36 patients by UPSIT. A good agreement existed between STT and UPSIT results and patients’ reports. Among potential prognostic factors, nasal obstruction, cross-sectional area of nasal cavity, rhinosinusitis severity, preoperative olfactory loss, nasal polyps and allergic rhinitis were not significantly reliable to predict improvement in olfaction after surgery, but patients with severe rhinosinusitis and severe preoperative olfactory loss and those with allergic rhinitis or without nasal polyps tended to show olfactory improvement. Concurrent septoplasty and turbinal surgery did not increase the rate of olfactory improvement after FESS, but postoperative use of nasal steroids did increase the rate of olfactory improvement, although the difference was not significant. Conclusion: Although many methods have been used to evaluate olfactory function, and the domains of olfactory function evaluated were not the same among these methods, our study showed that UPSIT should be the test of choice for evaluating olfactory function in patients with chronic rhinosinusitis. For these patients, disease severity, coexistence of nasal polyps and allergic rhinitis, and postoperative use of nasal steroids were found to be more reliable prognostic factors for improvement in olfaction after FESS, but these factors were not significantly reliable.
Kao, Stephen Shih-Teng. "Nasal mucus: friend or foe? The effect of mucus on mucosal barrier dysfunction in chronic rhinosinusitis." Thesis, 2020. http://hdl.handle.net/2440/128698.
Full textThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
YIH-JENG, TSAI, and 蔡易錚. "The Regulatory Mechanism of Bradykinin and Thromboxane A2 in Nasal Mucosa Derived Fibroblasts of Patients With Chronic Rhinosinusitis." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/21486692882578872798.
Full text輔仁大學
化學系
105
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis and neutrophilic inflammation. However, the pathophysiology of CRS, especially CRSsNP, remains unclear. In the fist part of the study, CRSsNP specimens were analyzed by immunohistochemistry and noted the submucosa, perivascular areas, and the mucous glands were highly expressed with fibroblasts. Therefore, the effects of bradykinin (BK), an autacoid known to participate in inflammation, were investigated in human CRSsNP nasal mucosa-derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA expression with EC50 ranging from 0.15~0.35 μM. Moreover, BK enhanced cell proliferation and upregulated the proinflammatory molecules expression, including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2 expressions. These effects functionally caused an increase in monocyte adhesion to fibroblast monolayer. The BK-induced CXCL1 and -8, cell proliferation, COX, and CAMs expressions were mainly through the B2 receptor, as demonstrated by the pharmacological intervention and siRNA knockdown assay. Accordingly, the B2R was preferentially expressed in the NMDFs than B1R. In parallel, the B2R was highly expressed in the CRSsNP than control specimens, while the B1R and kininogen (KNG)/BK expression was slightly increased in the CRSsNP mucosa. Collectively, we demonstrate here that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP mucosa and BK upregulates chemokine expression, proliferation, and proinflammatory molecules expression in NMDFs via B2R activation, which lead to a functional increase in monocyte-fibroblast interaction. This reveals a critical role of fibroblast, KNG/BK, and BKRs in CRSsNP development. Thromboxane A2 (TXA2), an arachidonic acid metabolite, participates in platelet aggregation and tissue inflammation. In the second part of the study, the CXCL1/8 chemokine and TXA2-TP receptor expression in the CRSsNP mucosa was investigated. The immunohistochemistry results indicated that CXCL1 and CXCL8 were highly expressed in the submucosal stroma of the CRSsNP mucosa compared with the corresponding expression in the controls; however, the TP receptors were expressed in both mucosa. Therefore, U46619 and IBOP, a TXA2 analog and TP agonist, were used to explore the role of TP activation in CXCL1/8 expression; both of these induced CXCL1/8 mRNA and protein expression in CRSsNP mucosa-derived fibroblasts. U46619 phosphorylated p38 MAPK, PI-3K-JNK, cyclic AMP (cAMP)/PKA, PKC, and cAMP response element (CREB). We observed that activation of cAMP/PKA, PKC, and CREB was the major cxcl1/8 gene transcription pathway and that the p38 MAPK pathway regulated CXCL1/8 secretion. Additional pharmacological and siRNA knockdown analyses revealed that activation of cAMP/PKA and PKCμ/PKD pathways were required for CREB phosphorylation and PKA/C crosstalk with the PI-3K-JNK pathway. The second part of our study provides the first evidence for abundant TP receptor and CXCL1/8 expression in CRSsNP mucosa and for TXA2 stimulation inducing CXCL1/8 expression in nasal fibroblasts primarily through PKA, PKCμ/PKD, and CREB-related pathways.
Chao, Pin-Zhir, and 趙品植. "Levels of RANTES, Eotaxin in the patients with chronic rhinosinusitis and its correlation with severity of the disease." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/nc9gu9.
Full text臺北醫學大學
醫學研究所
93
Chronic rhinosinusitis and nasal polyps mainly develop in the ethmoid sinus, maxillary sinus and middle turbinate area, often in relation to inflammatory and allergic conditions. Their exact etiology and pathogenesis are still under debate. Histologically, inflammatory cell infiltrations of nasal mucosa predominated by eosinophils are typical for such disease, and may be due to the chemotactic activity of chemokines specific for eosinophils. This findings suggest that nasal polyp is an inflammatory growth that is controlled by the local environment and the immunologic defense mechanism of the host. The CC-chemokine Eotaxin and RANTES (regulated on activation normal T cell expressed and secreted) have been postulated to be involved in the recruitment of eosinophils toward inflamed tissues. To explore their possible roles in chronic rhinosinusitis, we examined the concentraion of Eotaxin and RANTES protein in the serum of patients and correlated these results to the severity of disease graded by sinus CT imaging. Serum samples were obtained from 20 of patients undergoing endoscopic sinus surgery, and blood samples of 20 normal control subjects were also drawn. Enzyme-linked immunosorbent assay(ELISA) for Eotaxin and RANTES protein of serum was performed, and the relationship between these results and the Lund-MacKay rhinosinusitis scoring system and the percentage of peripheral eosinophil were investigated. In comparison to normal control group, we found significant elevation of Eotaxin and RANTES protein in the serum of experimental group(p<0.05). The levels of serum Eotaxin and RANTES in patients were correlated with the severity of the disease; with Eotaxin showed a more statistical significance. Besides, RANTES and Eotaxin levels were correlated with the percentage of peripheral eosinophil(p<0.05). These data suggest that, in patients of chronic rhinosinusitis with nasal polyp, disease severity correlates mainly with Eotaxin, and that RANTES may play a less important role in the mobilization of eosinophils from the blood into inflamed tissues. Further larger experiment was anticipated to validate this correlation.
Kuo, Yen-Ling, and 郭妍伶. "Association of climate factors with the incidence of chronic rhinosinusitis and allergic rhinitis: a nationwide population-based study." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/s7bx99.
Full text國立陽明大學
生理學研究所
104
Abstract Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are two of the most common upper airway diseases worldwide. Generally, CRS was regarded as a syndrome with multiple etiologies. Therefore, CRS may be a common endpoint for the interactions of different factors, including microbial factors, environmental factors, and host factors. Allergic rhinitis is defined by Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines as “a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation”. Recently, it has been noted that after exposure to allergens from snares, systemic humoral recirculation of allergic cells would nonspecifically recruit back to the diseased sinuses. In the past studies, climate factors, such as relative humidity, average daily temperature, and northeasterly winds were found to be related to worsening asthma, an allergic lower airway disease. However, the association between climate factors with CRS or AR has not been clarified. We conduct a retrospective analysis by using the National Health Insurance database during 2003 to 2012. The meteorological data will be obtained from the Central Weather Bureau of Taiwan, including relative humidity, average temperature. Five geographic zones and the related outpatient rates (Taipei city, Taichung city, Kaohsiung city, Hualien county, and I-Lan county) were analyzed. From 2003 to 2012, 476,833 patients were included in the study, with a male: female ratio of 1.02: 1. Twenty seven percent of patients were under eighteen years old. The outpatient rate of AR is increasing by time, but in CRS, it shows a decreasing pattern. The outpatient rate of AR presents with seasonal changes but CRS dose not. In AR, significant interactions between any single city/county and time, and generally, when temperature or relative humidity elevates, the rate of outpatient drops. In CRS, the rate of outpatient drops when temperature or relative humidity elevates, and variant interactions between any single city/county with temperature or relative humidity were found. The rates of outpatient of AR and asthma shows strong correlation (r=0.947, p<0.0001), and rates of outpatient of CRS and asthma also shows strong correlation by time (r=0.906, p<0.0001). In summary, the rates of outpatient of CRS and AR were influenced by two of the climate factors, relative humidity and temperature. In Taiwan, though the etiologies of CRS were multiple, it shows strong relation between CRS and atopy. The prevention of these two nasal diseases should be point on the prevention of allergen exposures.
Sousa, Joana Maria Ramalho de Almeida e. "Evaluation of intranasal administration of fluoroquinolones and their potential in the treatment of chronic rhinosinusitis: ciprofloxacin and levofloxacin." Doctoral thesis, 2018. http://hdl.handle.net/10316/42556.
Full textChronic rhinosinusitis is a persistent inflammation of the nasal cavity and paranasal sinuses mucosa with high prevalence and significant impact in patients´ quality of life. Although the exact etiology and pathophysiology of this multifactorial and difficult to treat disease are still unclear, there is growing evidence about the involvement of bacterial biofilms and their association with the refractory and chronic nature of the disease. Bacteria in biofilms show an increased resistance to antibiotics that can be as high as 1000-fold that of their corresponding planktonic form, which explains the lack of effectiveness of systemic administration of antibiotics in this clinical condition. High concentrations required to eradicate bacteria are difficult to attain without significant risks of systemic toxicity using the conventional routes of administration. Intranasal administration emerges as an alternative option to deliver drugs directly to the target site (sinonasal mucosa) achieving high local concentrations with minimal systemic exposure and consequent systemic adverse effects. The aim of the present thesis was to evaluate the potential of intranasal administration of fluoroquinolones by comparing their pharmacokinetic behavior after intranasal and intravenous delivery in Wistar rat biological matrices adequate to probe the risks and benefits of this topical strategy. The progression of experimental work led to the selection of ciprofloxacin and levofloxacin which are two of the most commonly used and well-known fluoroquinolones. To support the in vivo pharmacokinetic studies and thus achieve the above objectives, a high performance liquid chromatography method coupled with fluorescence detection was developed and validated to quantify ciprofloxacin and levofloxacin in rat nasal mucosa, plasma and olfactory bulb, probing drug efficacy as well as systemic and central nervous system safety, respectively. For intranasal administration a thermoreversible in situ gel was used to deliver ciprofloxacin and levofloxacin to Wistar rats at a dose of 0.24 mg/kg, a much lower dose than that administered by intravenous route, namely 10 mg/kg. After intranasal administration, markedly higher concentrations were attained in the anterior nasal mucosa compared to those found in the posterior region. This heterogeneous deposition pattern of formulation in nasal cavity contrasts with the intravenous homogeneous distribution and makes the application site more advantageous for this topical approach. Dose-normalized concentrations and exposure pharmacokinetic parameters obtained for nasal mucosa were two or one order of magnitude higher – in anterior and posterior nasal regions, respectively – by intranasal administration than by intravenous route. A similar comparison for plasma and olfactory bulb lead to the conclusion of a lower systemic exposure after topical intranasal administration and of a possible contribution of drug direct nose-to-brain transport that should be carefully taken into account. The results confirm the significant advantage of topical intranasal administration to deliver ciprofloxacin and levofloxacin to the biophase in comparison with the intravenous administration. Given the typically lower doses used for intranasal route, both systemic and central nervous system safe profiles were also demonstrated by the minimal or negligible values attained with the intranasal dose of 0.24mg/kg. Therefore, intranasal administration of topical-acting fluoroquinolones may represent a promising and safe alternative approach to be implemented in the management of chronic rhinosinusitis.
A rinossinusite crónica é uma inflamação persistente da mucosa da cavidade nasal e dos seios perinasais com elevada prevalência e um impacto significativo na qualidade de vida dos doentes. Embora a etiopatologia desta doença mulifatorial e difícil de tratar permaneça ainda por elucidar, existe evidência crescente do envolvimento de biofilmes bacterianos, sendo este o aspeto mais apontado para explicar a natureza crónica e refratária da doença. Com efeito as bactérias em biofilmes revelam uma resistência aos antibióticos que pode ser até 1000 vezes superior à da correspondente forma planctónica, o que explica a ineficácia terapêutica da administração sistémica de antibióticos. Utilizando vias convencionais de administração, as elevadas concentrações necessárias para erradicação das bactérias dificilmente se atingem sem riscos significativos de toxicidade sistémica. A administração tópica intranasal surge assim como uma estratégia alternativa para a entrega direta de fármacos na biofase (mucosa naso-sinusal) por forma a obter elevadas concentrações locais e exposição sistémica mínima, sem os efeitos adversos/tóxicos associados. O objetivo central desta dissertação foi a avaliação do potencial da administração intranasal de fluoroquinolonas, através da análise do risco/benefício envolvidos neste tipo de administração, utilizando matrizes biológicas estreitamente relacionadas com a segurança e a eficácia dos fármacos e comparando o respectivo comportamento farmacocinético após administração intranasal e intravenosa dos mesmos. A progressão do trabalho experimental conduziu à seleção da ciprofloxacina e levofloxacina, duas das fluoroquinolonas mais conhecidas e frequentemente utilizadas na clínica. Sendo a bioanálise um passo essencial de suporte aos estudos in vivo farmacocinéticos, procedeuse ao desenvolvimento e validação de uma técnica de cromatografia líquida de alta eficiência com deteção por fluorescência, para quantificar a ciprofloxacina e levofloxacina na mucosa nasal, plasma e bolbo olfativo de ratos Wistar. Um gel com propriedades termorreversíveis, capaz de gelificar na cavidade nasal, foi utilizado para a entrega tópica intranasal de uma dose de 0,24 mg/kg de ciprofloxacina e de levofloxacina, muito inferior à de 10 mg/kg administrada por via intravenosa. Após administração intranasal as concentrações obtidas na mucosa nasal da região anterior foram acentuadamente mais elevadas do que as encontradas na região posterior, esta distribuição heterogénea da formulação na cavidade nasal contrasta com a distribuição homogénea observada por administração intravenosa e põe em evidência a situação mais vantajosa para o local mais próximo da aplicação tópica. As concentrações e os parâmetros de exposição farmacocinéticos normalizados à dose obtidos na mucosa nasal por administração intranasal foram superiores aos da administração intravenosa - duas ordens de grandeza na região anterior e uma ordem de grandeza na região posterior. Uma comparação idêntica (portanto independente da dose) entre ambas as vias para o plasma e bolbo olfactivo permitiu inferir que a exposição sistémica foi inferior por administração intranasal e que a estreita relação do nariz com o sistema nervoso central não deve ser ignorada face os resultados obtidos no bolbo olfactivo. Confirma-se portanto a vantagem significativa da administração intranasal para entrega da ciprofloxacina e levofloxacina na biofase, face à administração intravenosa. Os valores negligenciáveis ou mínimos atingidos no plasma e bolbo olfactivo após administração de uma dose de 0,24 mg/kg demonstram um perfil seguro tanto a nível sistémico como a nível do sistema nervoso central. Em conclusão, a administração intranasal de fluoroquinolonas demonstrou ser uma abordagem promissora e segura, podendo representar um contributo importante no tratamento tópico da rinossinusite crónica.
Lin, Chih-Feng, and 林志峰. "CpG-ODN Augments Cytokines Release of Cultured Nasal Epithelial Cells: A Model of Chronic Rhinosinusitis with Acute Exacerbation." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/40081484070626671170.
Full text臺灣大學
臨床醫學研究所
98
Background : Chronic rhinosinusitis (CRS) is defined as inflammation and infection involving the nasal mucosa and the adjacent sinus cavities. Clinically, the patients with CRS may suffer from symptoms of mucopurulent discharge, nasal obstruction, facial pain, and hyposmia. Antibiotics, saline irrigations, steroids, and anti-leukotrienes may be given for symptoms relief. However, episodes of recurrence or acute exacerbation occurred to these patients, and caused some irreversible changes in airway structure and function. The pathophysiology of frequent acute exacerbation in these patients is still unclear, making treatments particularly challenging. CpG-ODN refers to sequences that include an unmethylated cytosine and guanosine ,which are relatively common in the genomes of most bacteria and DNA viruses. CpG-ODN had been implicated as a major structural component of bacterial biofilm, and contributed to the persistence of chronic infection. Clinically, recalcitrant CRS is associated with biofilm formation, and biofilm may cause the unfavorable outcomes of surgery for CRS. However, the molecular significance of CpG-ODN in CRS is still unclear. We aim to investigate the immune-modulation effects of CpG-ODN ,and elucidate the role of biofilm in CRS. Hypothesis : 1.The existence of CpG-ODN may maintain a low profile of cytokines production in the sinus mucosa, and play a role in the persistence of inflammation in chronic rhinosinusitis. 2.During CRS with acute exacerbation, CpG–ODN synergistically up-regulate the immuno-reactions of pro-inflammatory mediators, augments intranasal cytokines release, and contribute to the complications and severity of CRS with acute exacerbation. Materials and Methods: Twenty patients who are diagnosed as CRS and underwent surgery were included prospectively. None of them receives any treatment at least one month before operation. The one who has atopy, asthma, or allergic rhinitis was previously excluded. The nasal epithelial cells harvested from nasal polyps were collected for ALI (air-liquid interface) culture. At the end of culture (Day 20 after confluence), CpG-ODN , IL-1β , and TNF-α were added in single regimen or in combination to stimulate the nasal epithelial cells. After 24 hours-treatment, the culture medium of each well was collected and immediately stored at -80℃for later IL-6,IL-8 and MCP-1 measurement using ELISA. Statistical analysis : The paired samples test was used for evaluation of differences between experiments and controls. ANOVA was used when there is a multiple sample comparison. P values less than 0.05 was considered significant. Results : 1.A model mimicking the in vivo microenvironment of stable CRS was created. 2.Intrinsic IL-1β and TNF-α levels were undetectable in this model, and IL-6 , IL-8 ,MCP-1 levels were detectable during 21-days culture period, with a trend toward homogeneity . 3.Extrinsic IL-1β and TNF-α were used to stimulate the cultured nasal epithelial cells, to initiate a condition resembles CRS with acute exacerbation. IL-1βinduced IL-6,IL-8 and MCP-1 expressions in a dose-dependent fashion, while TNF-α only induced these cytokines release insignificantly. 4. CpG–ODN induced MCP-1 expression with a dose-dependent fashion, but not in IL-6 and IL-8. 5. CpG-ODN synergistically potentiate IL-6,IL-8, and MCP-1 release in the presence of IL-1 β and TNF-α. Conclusion : CpG-ODN is associated with the chronicity of CRS. Elimination of such substances in the management of CRS is mandatory. CpG-ODN augments intranasal cytokines release in patients with acute exacerbated sinusitis. Strategies such as local debridement or short-term immuno-suppressants are needed to stop the vicious circle.