Objective: This retrospective longitudinal study attempts to determine the ontogenetic patterning of nasal septal deviation and if there is a relationship between a deviated septum and facial form growth and development. Methods: Nineteen females and twenty males were selected from the Iowa Facial Growth Study. Eighteen lateral cepalometric variables were analyzed and septal deviation was quantified using a percentage of deviation. A generalized Procrustes analysis was used to scale landmarks and generate principal components. Pearson correlation coefficients were used to analyze differences in shape. A Mann Whitney U-Test was used to analyze changes in septal deviation. Results: The first three principal components explained 56.23% of the variance. Only PC1 was significantly correlated with centroid size (r=0.82, P<0.0001). Mean percentage of septal deviation (0.620% ± 0.463%) was present at the youngest age group (3-4.9 years) and increased in each age group until adulthood, defined as over the age of 20 (0.991% ± 0.519). None of the first three principal components were found to be correlated to percentage of septal deviation. Conclusions: Nasal septal deviation has been found to increase in a longitudinal sample of subjects of northern European descent. Nasal septal deviation represents a disjunction in the growth of the nasal septum with the rest of the face. The amount and timing of nasal septal deviation that can cause nasal obstructions leading to vertical growth changes was not analyzed in this study and will require future study.

Throughout history a diversity of animal species have been used and studied extensively in the development of vaccines for the benefit of humans and animals alike. As mice are a relatively easy species to maintain, handle and manipulate, and have the advantage of being cost effective, they are commonly employed as animal models in the investigation of immunisation strategies against mucosal associated pathogens. Vaccine research against the human gastric pathogen Helicobacter pylori is extensively conducted in a mouse model and typically uses intra-gastric administration for the testing of potential vaccine candidates. An inherent complication with this route, however, is that the vaccine constituents may be inadequately delivered to sites of specific immunity and consequently may not be the optimal method for vaccine delivery. In the present study a mouse model of H. pylori infection was used to determine the efficacy of alternate mucosal routes of immunisation from examination of protective immunity, immune responses and the practical aspects of vaccine administration. Commencing with the optimisation of intra-intestinal immunisation, the direct injection of a H. pylori vaccine to initiator sites of the mucosal immune system established baseline data of dose rates for the comparative analysis of intra-gastric, intra-nasal and intra-rectal immunisation. Following the development of simple administration techniques whilst maintaining the welfare of the animals, intra-nasal immunisation was shown to elicit the highest level of prophylaxis against H. pylori challenge. Effective prophylaxis was also shown to be dependent upon a specific ratio of the vaccine constituents. When using whole cell lysate of H. pylori and the mucosal adjuvant cholera toxin, the ratio of antigen:adjuvant for optimal protective immunity was 10:1. The outcomes of this study have proved conclusively the necessity for optimisation of all aspects of immunisation in an animal model of infection. / Master of Science (Hons)

Transplants of olfactory ensheathing cells (OECs) from olfactory bulbs have recently been shown to support regrowth and reinnervation of damaged spinal cord, which has led to improved functional recovery. Using complete transection in adult rat, the studies presented in this thesis examine the role of peripherally derived olfactory tissue in promoting axonal regeneration and functional recovery. Chapter One and Two provide the background to the area of spinal cord regeneration and the methods used in this thesis. Chapter Three shows that transplants of OECs from rat olfactory lamina propria (OLP) are able to support axon regrowth in the lesioned spinal cord. The BBB score was significantly higher in experimental rats (5.4???0.84) compared with control animals (1.9???0.33) (P&lt0.001). These dissociated OECs from OLP can promote axonal regrowth through the lesion. Histological assessment showed that: 1) axons labelled with Fluororuby grew into the injury site in OECs-transplanted rats, with occasional fibres extending into the rostral cord; 2) brainstem neurons in the raphe nucleus were retrogradely labeled with Fluororuby; and 3) serotonergic axons were detectable distal to the lesion in OECs-transplanted rats. No fibres grew into the injured region and no retrograde labeling or serotonergic fibres were seen in control animals. The role of regenerated serotonergic fibres in OECs-transplanted rats is discussed. Chapter Four demonstrates that solid pieces of OLP dissected from the nose can re-establish the continuity of the transected cord and supply the OECs that can migrate to the cord stumps to support the axon regeneration. Experimental rats which received OLP from olfactory mucosa showed significantly greater locomotive recovery (BBB scores: OLP, 5.0???1.9; control, 1.5???0.5, p&lt0.0001). In animals with OLP transplants, histological analysis indicated that nerve fibres, expressing neurofilament and serotonin were present at the transection site. Locomotive recovery of the hindlimbs occurred, similar to that seen after OECs transplantation. Retrograde labeling of medullary raphe neurons and gigantocellular reticular nucleus occurred following Fluororuby injection in the cord distal to the lesion, further supporting the supraspinal origin of the 5-HT innervation in the present studies. These results indicate that OLP is effective in promoting partial spinal cord repair. Chapter Five examines functional recovery of spinal reflex circuitry, ie., H-reflex excitability using paired stimuli, in OLP-transplanted rats compared with normal and respiratory lamina propria (RLP) transplanted animals. H-reflex amplitude of the conditioned response was significantly reduced in OLP transplanted rats compared to RLP transplanted animals (p&lt 0.05). Therefore, hindlimb reflex excitability can be modulated by OLP transplants after transection of the spinal cord in adult rats. Chapter Six examines whether functional recovery can occur if transplantation of OLP tissue is delayed by 1 month after the spinal cord transection. The BBB score was significantly higher in experimental rats (4.3???0.8 for OLP) compared with control animals (1.0???0.3, P&lt 0.001), but recovery was less than after acute transplantation. Asx before, histological assessment of OLP animals showed: a) serotonergic axons were present in the cord below the transection site; b) brainstem raphe nuclei was retrogradely labeled; c) bisbenzimide pre-labeled cells from OLP transplants migrated in host spinal cord. These changes were not seen in control animals. These results indicate that OLP has the ability to promote axonal regeneration in chronically injured cord of adult rats. Chapter Seven compares the results from these three types of intervention. In conclusion, these studies show that peripherally derived OECs or solid pieces of OLP can promote partial spinal cord repair in acute or chronic transection injuries. Such tissue might provide a potential source for autologous grafting in human paraplegia.

<i>Mycoplasma bovis</i> is generally considered the causative pathogen associated with Chronic Pneumonia and Polyarthritis Syndrome (CPPS) in feedlot cattle. However, <i>M. bovis</i> virulence may vary between strains as it is also isolated from asympytomatic cattle. The following study aims to determine the prevalence of <i>M. bovis</i> in the respiratory tract of western Canadian cattle using two sampling methods and at two time points following feedlot entry. Three study groups were sampled. In the first group nasal swabs (NS) and bronchoalveolar lavages (BAL) were taken from 36 clincally healthy cattle at the University of Saskatchewan feedlot at both 14 and 90 days on feed (DOF). In a second experiment, NS were taken from 56 animals upon arrival at a commercial feedlot and one week to three months later upon treatment for respiratory disease. Lung and joint tissue swabs were collected at necropsy from a third group of 19 animals with CPPS clinical pathology originating in 10 different western Canadian feedlots. All samples were selectively cultured for <i>Mycoplasma</i> spp. DNA was extracted from isolated putative <i>Mycoplasma</i> colonies and amplified with universal 16S rRNA gene primers for identification. Amplified Fragment Length Polymorphism (AFLP) was used to genetically differentiate <i>M. bovis</i> positive isolates. More <i>M. bovis</i> was isolated from NS than BAL and <i>M. bovis</i> prevalence increased with DOF in the feedlot in both the University of Saskatchewan and commercial feedlot trials. Three genetically distinct clusters (A, B, and C) were isolated from the necropsy group. Two of these clusters were primarily associated with isolates collected from feedlot cattle and one strain was exclusively found in CPPS-associated mortalities. No significance difference in the prevalence of <i>M. bovis</i> strains was observed between different days on feed or sampling methods. It was concluded that either the difference in disease state is a host dependent outcome, due to a multi-factorial disease complex, or the AFLP assay was not sensitive enough to differentiate strains based on virulence.

El tratamiento de la poliposis nasal en la actualidad no está resuelto. El tratamiento quirúrgico o el tratamiento médico (corticoterapia) están condenados a elevados índices de recurrencias, especialmente entre los enfermos con poliposis que asocian además intolerancia al Ácido Acetilsalicílico y asma. El desconocimiento de la etiología de la poliposis y de los mecanismos fisiopatológicos más íntimos, no permite un tratamiento eficaz.La observación casual del posible efecto del Omeprazol en la mejoría de la insuficiencia nasal respiratoria en una paciente afecta de poliposis e intolerancia al Ácido Acetilsalicílico, dio paso a un estudio empírico, meramente observacional e incontrolado, de varios pacientes con poliposis nasal tratados con Omeprazol. Los datos arrojados por este estudio preliminar, confirmaron nuestra observación inicial del posible efecto beneficioso del Omeprazol en la mejoría de la insuficiencia nasal respiratoria en los pacientes con poliposis nasal y muy especialmente en el subgrupo de pacientes que además asociaban intolerancia al Ácido Acetilsalicílico.Desarrollamos una hipótesis fisiopatológica y farmacodinámica que nos permitiera justificar la supuesta acción del Omeprazol en la poliposis nasal, puesto que hasta entonces no estaba descrita. Para ello partimos del hecho no demostrado del efecto cierto del Omeprazol.Existían dos posibilidades:- Que la acción farmacológica del Omeprazol fuera exclusivamente la inhibición de la bomba de protones, en cuyo caso su efecto beneficioso debía relacionarse íntimamente con las consecuencias derivadas de esta inhibición.- Que el Omeprazol, o en su defecto un metabolito de su catabolismo, tuviera una actividad colateral al margen de inhibir la bomba de protones, con efecto directo sobre los pólipos nasales.El estudio previo y su conclusión, está basado en observaciones empíricas, sin control, por lo que está sujeto a todas las críticas científicas inherentes a este tipo de estudios. Por ello decidimos realizar un ensayo clínico randomizado, de grupos paralelos, enmascarado a doble ciego y controlado con placebo, que nos permitiera validar nuestra observación empírica como hecho científico, o en su defecto, certificar que se trataba de una falsa interpretación.Diseñamos un ensayo clínico fase IV-II, estudio piloto, en el que incluímos 30 pacientes afectos de poliposis grado III-IV. La dosificación fue de dos cápsulas (placebo o 20mg Omeprazol) al día por la mañana y por vía oral diariamente durantes 28(+/-2)días. Utilizamos como variables de evaluación, la escala visual analógica para los síntomas y la rinomanometría anterior activa informatizada e introdujimos algunas variables que nos permitieran estudiar el efecto placebo.Al finalizar el estudio el 48.15% de los pacientes refirieron haber mejorado, considerando el tratamiento recibido eficaz. / The treatment of nasal polyposis has yet to be resolved. Surgical treatment or medical treatment (corticotherapy) are plagued by high indices of recurrences, especially among patients with polyposis who additionally suffer from intolerance to acetylsalicylic acid and asthma. Ignorance of the etiology of polyposis and its most intimate physiopathological mechanisms do not allow for efficient treatment.Casual observation of the possible effect of Omeprazol in improvement of nasal respiratory insufficiency in patients affected by polyposis and intolerance to acetylsalicylic acid gave way to an empirical study, merely observational and uncontrolled, of various patients with nasal polyposis treated with Omeprazol. The data collected from this preliminary study confirms our initial observation of possible benificial effects of Omeprazol in the improvement of nasal respiratory insufficiency in patients with nasal polyposis, especially in the subgroup of patients who additionally showed intolerance to acetylsalicylic acid.We developed a physiopathological and pharmacodynamic hypothesis which would permit us to justify the supposed action of Omeprazol in nasal polyposis, given that until then it hadn't been described. As starting point we took the observed, though unproven, effect of Omeprazol.There existed two possibilities:- That the pharmacological action of Omeprazol was exclusively the inhibition of the proton pump, in which case its beneneficial effect owed to being intimately related to the consequences derived from this inhibition.- That Omeprazol, or at least a metabolite of its catabolism, had some colateral activity marginally inhibiting the proton pump, with a direct effect on the nasal polyps.The previous study and its conclusion are based on empirical observations, without control, for which it is subject to all scientific criticism inherent to these types of studies. Therefore we decided to realize a randomized clinical study, in parallel groups, double blind, and controlled by placebo, which would permit us to validate our empirical observation as scientific fact, or at least certify that we were dealing with a false interpretation.We designed a phase IV-II clinical pilot study, in which we included 30 patients affected with grade III-IV polyposis. The dosage was two capsules (placebo or 20mg Omeprazol) a day in the morning and taken orally daily for 28(+/-2) days. As variables of evaluation we used the visual analog scale for the symptoms and computerized active anterior rhinomanometry and introduced other variables which would permit us to study the placebo effect.At the end of the study 48.15% of the patients claimed improvement, considering the treatment received effective.

DOES INCREASING FLOW TO A HIGH FLOW NASAL CANNULA AFFECT MEAN AIRWAY PRESSURE IN AN IN VITRO MODEL? Introduction: High-flow nasal cannulas (HFNC) have become popular with many institutions for administration of oxygen (O2). HFNCs are also being used in pediatric and neonatal populations for administration of continuous positive airway pressure (CPAP) as a treatment for respiratory distress. Adult patients are being treated with HFNCs in a effort to provide a high percentage of O2 and correct hypoxemia and other related conditions. The purpose of this study was to examine the effect of increasing flow via a HFNC to an in vitro model to examine the effect of flow on mean airway pressure (MPAW). Method: An in vitro model to simulate non-labored and labored spontaneous breathing was developed using a Michigan Instrument Laboratory Test and Training Lung (MIL TTL) driven by a Hamilton Galileo ventilator to produce a negatively based, inspired tidal volume. Flow was introduced to the MIL TTL via a 41 French double lumen endotracheal tube. Airway pressure measurements were observed via a pressure monitoring port placed between the MIL TTL and the endotracheal tube and connected to the auxiliary pressure monitoring port located on the front of the Galileo ventilator. A Vapotherm 2000i with adult transfer chamber and adult cannula, a Fisher Paykel Optiflow, and a generic HFNC consisting of a concha column and a Salter labs high-flow cannula were tested at 20, 30, and 40LPM flowrates. Data was recorded using two respiratory rates (12 and 24) and two peak flowrates (35 and 65LPM) to simulate non-labored and labored breathing. All other parameters were unchanged and the I:E ratio was consistent. Data Analysis: SPSS 16.0 for Windows was used to analyze all data for this study. Descriptive statistics, one-way analysis of variance (ANOVA), and post hoc Bonferroni was used for this study. A p value less than 0.05 were considered significant. Results: Average MPAW for all devices were increased at all three flowrates. MPAW was highest at 40LPM flow producing 3.1cmH2O averaged for all HFNCs and both respiratory patterns. The difference in MPAW produced by the three HFNCs were also significant with at p=0.000 at all flow rates. Post hoc Bonferroni adjusted probabilities further showed all device comparisons significant except for Vapotherm-Vapotherm Labored at 30 and 40 LPM flow rates and Vapotherm-Generic Labored at 20 LPM at p<0.05. These three comparisons were at p>0.05 and were statistically equal. The generic HFNC produced the highest MPAW (3.5cmH2O). Conclusion: Increased flow via a HFNC does increase MPAW. The Vapotherm, Optiflow, and generic HFNC did not produce the same level of MPAW in this study.

Background: HFNC system is a novel device used with aerosol therapy and seems to be rapidly accepted. Although there are some studies conducted on HFNC and vibrating mesh nebulizer, the effect of HFNC on aerosol delivery using jet nebulizer or pressurized metered-dose inhaler (pMDI) has not been reported. In an effort to examine the effect of HFNC on aerosol deposition, this study was conducted to quantify aerosol drug delivery with or without a HFNC using either pMDI or jet nebulizer. Methodology: The SAINT model, attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc., Englewood, CO, USA) for aerosol collection, was connected to a pediatric breathing simulator (Harvard Apparatus, Model 613, South Natick, MA, USA). To keep the filter and the SAINT model in upright position to collect aerosolized drug, an elbow adapter was connected between the absolute filter and the breathing simulator. An infant HFNC (Optiflow, Fisher & Paykel Healthcare LTD., Auckland, New Zealand) ran at 3 l/min O2 was attached to the nares of the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Aerosol drug was administered using: 1) Misty-neb jet nebulizer (Allegiance Healthcare, McGaw Park, Illinois, USA) powered by air at 8 l/min using pediatric aerosol facemask (B&F Medical, Allied Healthcare Products, Saint Louis, MO, USA) to deliver albuterol sulfate (2.5 mg/3 mL NS), and 2) Four actuations of Ventolin HFA pMDI (90 μg/puff) (GlaxoSmithKline, Research Triangle Park, NC, USA) combined with VHC (AeroChamber plus with Flow-Vu, Monaghan Medical, Plattsburgh, NY, USA). Aerosol was administered to the model with and without the HFNC and another without (n=3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. Independent t tests were performed for data analysis. Statistical significance was determined with a p value of <0.05. Results: The mean inhaled mass percent was greatest for pMDI with (p = 0.0001) or without HFNC (p = 0.003). Removing HFNC from the nares before aerosol treatment trended to increase drug delivery with the jet nebulizer (p = 0.024), and increased drug delivery by 6 fold with pMDI (p = 0.003). Conclusions: Aerosol drug may be administered in pediatrics receiving HFNC therapy using either jet nebulizer or pMDI. However, using pMDI, either with or without HFNC, is the best option. When delivering medical aerosol by mask, whether by jet nebulizer or pMDI, removing HFNC led to an increase in inhaled mass percent. However, the benefit of increased aerosol delivery must be weighed against the risk of lung derecruitment when nasal prongs are removed.

<i>Mycoplasma bovis</i> is generally considered the causative pathogen associated with Chronic Pneumonia and Polyarthritis Syndrome (CPPS) in feedlot cattle. However, <i>M. bovis</i> virulence may vary between strains as it is also isolated from asympytomatic cattle. The following study aims to determine the prevalence of <i>M. bovis</i> in the respiratory tract of western Canadian cattle using two sampling methods and at two time points following feedlot entry. Three study groups were sampled. In the first group nasal swabs (NS) and bronchoalveolar lavages (BAL) were taken from 36 clincally healthy cattle at the University of Saskatchewan feedlot at both 14 and 90 days on feed (DOF). In a second experiment, NS were taken from 56 animals upon arrival at a commercial feedlot and one week to three months later upon treatment for respiratory disease. Lung and joint tissue swabs were collected at necropsy from a third group of 19 animals with CPPS clinical pathology originating in 10 different western Canadian feedlots. All samples were selectively cultured for <i>Mycoplasma</i> spp. DNA was extracted from isolated putative <i>Mycoplasma</i> colonies and amplified with universal 16S rRNA gene primers for identification. Amplified Fragment Length Polymorphism (AFLP) was used to genetically differentiate <i>M. bovis</i> positive isolates. More <i>M. bovis</i> was isolated from NS than BAL and <i>M. bovis</i> prevalence increased with DOF in the feedlot in both the University of Saskatchewan and commercial feedlot trials. Three genetically distinct clusters (A, B, and C) were isolated from the necropsy group. Two of these clusters were primarily associated with isolates collected from feedlot cattle and one strain was exclusively found in CPPS-associated mortalities. No significance difference in the prevalence of <i>M. bovis</i> strains was observed between different days on feed or sampling methods. It was concluded that either the difference in disease state is a host dependent outcome, due to a multi-factorial disease complex, or the AFLP assay was not sensitive enough to differentiate strains based on virulence.

The clinicopathological feature of primary cutaneous lymphomas according to WHO/EORTC classification and their relationship to EBV in Taiwan has never been reported. This retrospective study collected the patients with cutaneous lymphomas from 1990 and 2006. The morphology, EBER in situ hybridization and immunohistochemistry of primary cutaneous lymphomas were studied to reclassify based on the WHO/EORTC classification. A total of 54 patients were included. Twenty-nine were primary cutaneous lymphomas and 25 were secondary cutaneous lymphomas. The age ranged from 21 to 86 years old (mean 62 years old). Twenty-one (72.4%) were primary cutaneous T-cell and NK-cell lymphoma, including 5 extranodal NK/T-cell lymphoma, nasal type (17.2%), 5 primary cutaneous peripheral T-cell lymphoma, unspecified (17.2%), 4 mycosis fungoides (13.8%), 1 Sezary syndrome, 3 primary cutaneous anaplastic large cell lymphoma, 2 primary cutaneous small-medium CD4+ T-cell lymphoma and 1 subcutaneous panniculitis-like T-cell lymphoma. Eight cases were primary cutaneous B-cell lymphoma (27.6%) including 3 cutaneous marginal zone B-cell lymphoma (10.3%), 3 cutaneous follicle center B-cell lymphoma (10.3%), and 2 diffuse large B-cell lymphoma, leg type (6.9%). Seventeen cases were secondary cutaneous T-cell and NK -cell lymphoma. Eight cases were secondary cutaneous B-cell lymphoma. All primary and secondary extranodal NK/T-cell lymphoma, nasal type, were positive for EBER, however, one of them (10%) without both angiocentric growth pattern and necrosis in histomorphological examination. This is the first clinicopathological study of cutaneous lymphoma according to recent WHO/EORTC classification in Taiwan. In comparison with the Western countries, mycosis fungoides is less common whereas primary extranodal NK/T-cell lymphoma, nasal type, and peripheral T-cell lymphoma, unspecified, is more common in Taiwan. EBER in situ hybridization study is helpful in the diagnosis of extranodal NK/T-cell lymphoma, nasal type, especially in tumor without both angiocentric growth pattern and necrosis.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Medical Sciences - Orthodontics. Title from pdf file main screen (viewed on November 29, 2009). Includes bibliographical references.