Inaug.-diss.- Bonn. / At head of title: Aus der Hals-, Nasen- und Ohrenklinik der Universität Bonn ... Lebenslauf. "Literaturverzeichnis": p. 14-16.

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

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Κύριος σκοπός της έρευνας είναι ο έλεγχος και η εξακρίβωση του ρόλου της συγκέντρωσης των ελευθέρων ιόντων Ca που εμπεριέχονται εντός της οσφρητικής βλέννας σε συνάρτηση με το επίπεδο ευαισθητοποίησης του οσφρητικού κυττάρου υποδοχέα. Πραγματοποιήθηκε έλεγχος των μεταβολών της ευαισθησίας του νευροεπιθηλίου προκαλώντας μικρού μεγέθους μεταβολές της ενδοβλεννικής συγκέντρωσης των ελευθέρων ιόντων Ca με την βοήθεια ενός ρυθμιστικού διαλύματος κιτρικού νατρίου και κιτρικού οξέως σε 62 περιστατικά αιτιώμενα υποσμία ή ανοσμία. Απλά και μόνο μειώνοντας την ενδοβλεννική συγκέντρωση των ελευθέρων ιόντων Ca με την βοήθεια του ρυθμιστικού διαλύματος κιτρικών μπορέσαμε σε τελική ανάλυση να βελτιώσουμε την υποκειμενική αίσθηση της οσφρητικής λειτουργίας των 75,81 % των περιστατικών ενώ το 96,77 % του συνόλου βελτίωσε την οσφρητική του λειτουργία όπως αυτή μετρήθηκε από την δοκιμασία οσφρητικής εκτίμησης που χρησιμοποιήθηκε, έστω και προσωρινά. / It is well documented that cytoplasmic Ca++ regulates sensitivity to cyclic adenosine monophosphate (cAMP). There is also evidence that Ca++ in the mucus may also modulate sensitivity to cAMP in vivo. Assuming that mucosal Ca++ could significantly change the excitability of the receptor neurons, we examined the alterations in the olfactory sensitivity by creating small changes in mucosal Ca++. 62 patients complaining of olfactory loss were examined and their olfactory acuity was measured before and after the administration of a sodium citrate buffer solution in the nasal cleft. 60 patients (96,77%) improved their scores during a less than an hour period of time. Furthermore, 47 of them (75,81%) realized an improvement in their own sense of smell.

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 140-160).

Thesis (M.S.)--Ohio University, August, 2003. / Title from PDF t.p. Includes bibliographical references (leaves 116-122)

La surveillance de la santé humaine et le diagnostic anticipé des cancers (poumon et peau) en analysant le volatolome et en particulier les biomarqueurs présents dans l’haleine ou émis par une zone de peau affectée, est un domaine de recherche émergent. Il s'agit d'une technique non invasive, peu coûteuse, rapide et fiable qui peut être utilisée pour la détection des cancers à ses premiers stades au niveau clinique. Les capteurs de vapeur chémo-résistifs quantiques à base de nanomatériaux (vQRS) peuvent fournir une solution pour développer des nez électroniques (e- nose) à cet effet. La constitution d’une matrice de capteurs performante (e-nose) est nécessaire pour l'analyse de l’haleine ou des COV émis par la peau, car tous deux sont des mélanges complexes de COV incluant différents biomarqueurs. L'objectif de cette thèse était de développer un assortiment de capteurs hautement sensibles et sélectifs pour l'analyse de certains biomarqueurs du cancer du poumon et de la peau. Pour cela, une matrice de senseurs de haute performance a été fabriquée à partir de nanocomposites polymère conducteurs dont l’architecture conductrice construite à base de nanotubes de carbone a été fonctionnalisée par différentes matrices polymères pour en modifier la sélectivité vis-à-vis de différents COV. Dans un premier temps, des mélanges binaires de COV et d'eau ont été analysés avec une matrice de senseurs simple pour évaluer le comportement des capteurs en présence d'humidité. Ensuite, un e-nose plus complexe a été préparé avec neuf capteurs sensibles et sélectifs pour détecter une petite quantité de biomarqueurs du cancer présents dans une grande quantité d'autres COV. Les empreintes gazeuses obtenues à l'aide d'un outil statistique pour les divers mélanges de COV ont permis d'identifier la présence de biomarqueurs. Enfin, différents échantillons d’haleine ont été testés avec le même e-nose. Les échantillons d’haleine ont été recueillis dans différentes conditions et l’e-nose a pu les discriminer efficacement et les situer sur les cartes d’empreintes d’haleines obtenues par analyse statistique. / A Human health monitoring and anticipated diagnosis of cancers (lung and skin) by the analysis of the volatolome and in particular the biomarkers present in exhaled breath or emitted by affected skin area is an emerging area of research. This is a non-invasive, inexpensive, fast and reliable technique which can be used for cancers’ detection in their early stages at the clinical level. Nanomaterials based quantum resistive vapour sensors (vQRS) can provide solutions for developing electronic noses (e-nose) for this purpose. A complex sensors’ array is required for the analysis of exhaled breath or VOC emitted by skin as both of them are complex blend of various VOC biomarkers. The objective of this thesis was to develop highly sensitive and selective sensors for cancer biomarker analysis. Therefore, several high-performance sensors’ arrays have been fabricated based on conducting nanocomposites. The carbon nanotubes used to build the conducting architecture were functionalized with different polymer matrices for tuning their selectivity towards different VOC. Initially, binary blends of VOC and water were analysed with simple sensors’ array to evaluate the sensors behaviour in the presence of moisture. Later, a complex e-nose has been prepared with nine differently sensitive and selective sensors to detect subppm amounts of cancer biomarkers present in a large quantity of other VOC. Fingerprints were obtained using a statistical tool for various biomarkers blends which were able to identify the presence of biomarkers. Finally, exhaled breath samples were tested with the same e-nose. The breath samples were collected in different conditions and the e-nose was able to discriminate the different samples effectively by locating them on the breath maps obtained by a statistical analysis.

The purpose of this study was to examine the effect that the patient's level of consciousness and the degree of nasogastric tube flexibility would have on the ease of insertion of the tube in patients with an endotracheal tube in place. The statistical hypotheses tested were: 1. The Degree of nasogastric tube flexibility will not influence the ease with which the tube is inserted. 2. The level of consciousness of the patient will not influence the ease with which the nasogastric tube is inserted. 3. There will be no interaction between the degree of flexibility of the nasogastric tube to be inserted and the level of consciousness of the patient in whom the tube is placed. The sample from whom data was collected for the study consisted of 121 patients admitted to the respiratory intensive care unit of a large teaching hospital who required endotrachea intubation and subsequent placement of a nasogastric tube. The number of attempts per patient for successful placement of each tube were recorded over a four month period and the data analysed using a 2 X 3 factorial design. The two independent variables were degree of nasogastric tube flexibility with two levels: flexible and rigid, and level of consciousness with three levels: conscious, obtunded and unconscious. The data collected from the study indicate that the degree of nasogastric tube flexibility significantly affects the ease with which a tube can be inserted in an intubated patient (α=.05) the rigid tube requiring a statistically fewer number of attempts than the flexible tube. The difference among levels of patient consciousness were not found to be statistically significant in this investigation but the interaction between the degree of tube flexibility and level of patient consciousness revealed statistical significance. / Applied Science, Faculty of / Nursing, School of / Graduate

This laboratory is involved in physiological and histochemical studies of olfactory tissue grown in cell culture in an attempt to create an in vitro model of the olfactory system. The present study is an in-depth ultrastructural study of the morphology of cultured olfactory cells to determine the extent of similarities and differences between cultured tissues and the intact olfactory system in vivo.