Failure to comply with prescribed regimens is a major reason for the failure of treatment programs. This study investigated factors which are related to compliance with prescribed diet revision therapy for food allergies in school-aged children. Forty-five children, aged 6 to 12 years, who were under a physician's care for food allergies, formed the sample. The Health Belief Model was used as the basis for a questionnaire devised to measure these factors. The development of the Diet Revision Therapy Parent Questionnaire involved a pilot test and revisions; the resulting instrument consists of 38 items organized into 4 subtests, of which one 7-item subtest is to be considered optional. The 38-item DRTPQ has a full scale internal consistency reliability of .87, and a composite reliability of .61 for the four subscales. The canonical correlation between 3 types of subjective ratings of compliance and the 4 subtests is .80, with 64% shared variance between these sets of variables. A discriminant function of 3 subtests of the DRTPQ proved capable of discriminating diet therapy dropouts from continuing subjects with 88.9% accuracy. These three subtests measured: 1. Parent and family life factors, such as the amount of perceived interference in normal routines, 2. Child's attitudes to the treatment and his/her normal behavior with respect to cooperation with parental demands, and 3. Belief in the benefits to be derived from the treatment. A fourth category of items measured perceived severity of the condition and perceived susceptibility to illness but proved not to predict compliance in this sample, although it may be useful in clinical practice. Suggestions for interventions to aid compliance are outlined. / Education, Faculty of / Educational and Counselling Psychology, and Special Education (ECPS), Department of / Graduate

M.Tech. / Allergic rhinitis, otherwise referred to as hay fever, is a common allergic reaction affecting the nose, throat, eyes, and respiratory system, of persons of all ages and both sexes. This study attempted to demonstrate the effect of the homoeopathically prepared remedy Sabadilla officinarum 30CH and Sabadilla officinarum 200CH in the treatment of allergic rhinitis. Thirty participants were selected for this one hour, double-blind, placebo-controlled study. The participants were randomly placed into one of three groups of ten, consisting of the control group, and the two experimental groups. The control group received the placebo medication. The first experimental group received Sabadilla officinarum 30CH, and the second experimental group received Sabadilla officinarum 200CH. The patients were all supplied with: a stat dose of medication to use at the time of an allergic rhinitis attack, a diary card on which to score the severity of their symptoms at the time of such an attack, and a response to treatment questionnaire to fill in after the completion of their treatment. The results were statistically analysed using the Wilcoxon Signed Ranks Test, the Kruskal Wallis Test, and descriptive statistics. The results show that treatment with Sabadilla officinarum 30CH and 200CH had a significant effect in improving the symptoms of allergic rhinitis.

Les chimiokines sont un élément essentiel du trafic cellulaire aussi bien homéostatique que dans des situations pathologiques. Outre cette fonction chimiotactique spécifique à ce type de molécules, on leur a récemment attribué une implication dans le profil de polarisation de la réponse adaptative spécifique, en agissant directement sur les lymphocytes T (Lc T) ou indirectement par le biais des cellules dendritiques (DC). CCL18 est une chimiokine exprimé préférentiellement au niveau pulmonaire et de façon moindre au niveau ganglionnaire, capable d’attirer les DC et les Lc T, elle est induite par les cytokines de type Th2 telle que l'IL-4, l'IL-13, mais aussi par la cytokine immunomodulatrice l'IL-10, son récepteur est inconnu à ce jour. Au laboratoire il a été montré une implication du CCL18 dans l’asthme allergique (de Nadai, JI, 2006), et cette chimiokine a été associée à différentes pathologies à tropisme pulmonaire ou non avec un rôle pas toujours très clair. L'objectif de ce travail a été d’étudier l’effet immunitaire de cette chimiokine, en base et en situation atopique. L'effet direct du CCL18 a été évalué sur la polarisation de la réponse T. Le prétraitement des Lc T mémoire CD4+ CD25-, de sujets non allergiques, avec le CCL18 conduit à leur transformation en Lc T régulateurs CD4+ CD25+ Foxp3+ produisant de l’IL-10 et du TGF-b capables d'inhiber la prolifération des Lc T effecteurs, à la fois par un mécanisme cytokine et contact dépendant. Cependant, cet effet de régulation de CCL18 est perdu lorsque les cellules T proviennent de sujets allergiques (Chang Y et al., FASEB J, 2010). L’effet indirect du CCL18 a été évalué sur la réponse immune via les DC. La différenciation de monocytes de sujets sains en présence de GM-SCF et CCL18 conduit au développement de DC de phénotype semi-mature, expriment le CCR7, produisant de l’IL10 et l’enzyme 2,3-indoleamine dioxigenase et induisant le développent de Lc T régulateurs de type Tr1 produisant de l’IL-10 capables d’inhiber la prolifération de Lc T effecteurs, par un mécanisme cytokine dépendant. Étonnamment, lorsque les monocytes proviennent de patients allergiques, l'effet tolérogène de CCL18 est perdu en liaison avec la diminution de la fixation de CCL18 à son récepteur putatif (Azzaoui I et al., en révision Blood). Par ailleurs, CCL18 pourrait également jouer un rôle dans la résolution de la réaction allergique par un effet chimiotactique vis-à-vis d’une sous population de LcT régulateurs CD4+CD25highCD127lowLAP+ (Chenivesse C et al., en révision JI). L'effet de corticoïdes sur l'expression de CCL18 a ensuite été analysé. Il a été montré que la sécrétion de CCL18 induite par les cytokines IL-4 et IL-10 est potentialisée par la dexaméthasone, ce qui confirme que CCL18 est plutôt une chimiokine à activité anti inflammatoire (Chabrol J et al., en préparation). La dernière étude concerne une approche dans un modèle murin d'asthme allergique, induit par l'ovalbumine chez la souris Balb/cBYJ. D'un point de vue fonctionnel, l'administration de CCL18 recombinant par voie intratrachéale à des animaux sensibilises permet d'inhiber le développement de la réaction asthmatique, en diminuant l'inflammation pulmonaire (réduction de l'infiltration éosinophilique, inhibition de la production locale de cytokines Th2) et protège ces derniers contre l'altération de leur fonction respiratoire (protection contre l'hyperréactivité bronchique, avec inhibition de l'hypersécrétion de mucus). Toutefois, les mécanismes cellulaires à l'origine de cette protection semblent indépendants de grandes voies de régulation de la réaction (Gilet J et al., en préparation). L'ensemble de ces études montre, et pour la première, qu’une chimiokine est capable d’induire le développement d’une réponse tolérogénique. / Chemokines are a key component of homeostatic cell traffic and involved in pathological situations. In addition to this chemotactic function, specific to these molecules, they have been recently assigned an involvement in specific adaptive response polarization, by acting directly on T cells (T Lc) or indirectly through dendritic cells (DC). CCL18 is a chemokine preferentially expressed in lung and lymph nodes, able to attract DCs and T Lc, induced by Th2 cytokines such as IL-4, IL-13 but also by the immunomodulatory cytokine IL-10, and its receptor is still unknown. In our laboratory it was shown an involvement of CCL18 in allergic asthma (de Nadai, JI, 2006), and this chemokine has also been associated with various pathologies without areal clear described role. The purpose of this work was to evaluate the immune effect of CCL18 at baseline and in atopic situation. The direct effect of CCL18 was evaluated on T cell polarization. Pretreatment of memory T cells CD4+CD25-, from non allergic subjects, with CCL18 led to their switch to regulatory CD4+CD25+ Foxp3+ cells, able to produce IL-10 and TGF-b and inhibit effectors T cell proliferation, by a contact and cytokine dependent mechanism. However, this regulatory effect of CCL18 was lost when T cells were derived from allergic subjects (Chang Y et al., FASEB J, 2010). The indirect effect of CCL18 has been assessed on the immune response through DC. Monocyte, from healthy subjects, differentiated in DC with GM-CFS and CCL18 led to development of semi-mature DC, that expressed CCR7 and produced IL10 and the enzyme indoleamine 2,3-inducing dioxigenase. These cells primed regulatory Tr1 cells able to produce IL-10 and to suppress LcT effectors proliferation by a cytokine dependent mechanism. Surprisingly, when monocytes were derived from allergic patients, the tolerogenic effect of CCL18 was lost, in association with a decreased binding of CCL18 to its putative receptor (Azzaoui I and al., in revision Blood) Moreover, we have shown that CCL18 may also play a role in the resolution of the allergic reaction with a chemotactic effect, by recruitment of a subpopulation of regulatory T cells CD4+CD25highCD127lowLAP+ (Chenivesse C et al., in revision JI). The effect of corticosteroids on CCL18 expression was analyzed. These results showed that the secretion of CCL18 induced by cytokines IL-4 and IL-10 is potentiated by dexamethasone (Chabrol J et al., in preparation) which confirms the anti inflammatory role of CCL18. The last study was an approach in a murine model of allergic asthma induced by ovalbumin in mice Balb/cByJ. Intratracheal administration of recombinant CCL18 to sensitized animals, inhibits asthmatic reaction development, by decreasing pulmonary inflammation (reduced eosinophil infiltration, and inhibition of local production of Th2 cytokine) and protects them against the deterioration of their respiratory function (protection against bronchial hyperresponsiveness, and inhibition of mucus hypersecretion). However, the cellular mechanisms behind this protection appear independent of major regulatory pathways of the reaction (J Gilet et al., in preparation). All these studies show, for the first time, that a chemokine is able to induce a tolerogenic response. However, this feature is absent in allergic donors who exhibit a defect in the binding of CCL18 to its putative receptor. This may participate to the lack of tolerance response observed in allergic diseases. This data suggest that CCL18 and its putative receptor may represent therapeutic targets.

Described for the first time approximately 30 years ago, exercise-induced anaphylaxis is a rare disorder characterized by development of a severe allergic response occurring after mild-to-strenuous physical activity. This disorder is especially important to recognize with the recent increase in physical activity and health fitness fads. A number of predisposing factors (eg, prior ingestion of particular food groups) linked to exercise-induced anaphylaxis has been outlined over the years. Mechanisms govern big the condition are still being unveiled, and it is likely that one mechanism involves mast cell degranulation and inflammatory mediator generation resulting from the biochemical effects of exercise, sometimes in the presence of an ingested allergen such that wheat or shell fish. Clinical manifestations usually occur after around 10 minutes of exercise, and follow a specific sequence, starting with pruritis and widespread urticarial lesions, evolving into a more typical anaphylactic picture with respiratory distress and vascular collapse. Fatality is exceedingly rare, with only one documented casein the literature. There is an overlap of symptoms with other syndromes (such as systemic mastocytosis and cholinergic urticaria), and these should be remembered when establishing a differential. Treatment of exercise-induced anaphylaxis consists of immediate stabilization geared toward the anaphylactic response with epinephrine and antihistamines. The patient needs to be educated on preventive measures and equipped with an epinephrine autoinjector in the event of an emergency. Exercise-induced anaphylaxis remains a potentially serious disorder, and the health care provider should be aware of its clinical features and effective management strategies.

As the chemist increases his knowledge and understanding of the complex and delicate nature of the proteins, many of the methods which are used in the handling and treatment of protein systems need to be reviewed and reexamined in the light of the new information which is now available. This study has endeavored to take the biologically active protein system from the pollen or timothy grass (Phleum pratense) and examine its stability under currently used methods of extraction, purification, and storage. New chemical agents were studied in connection with the above mentioned protein tor their possible use in the place of phenol as more appropriate bactericidal or bacteriostatic preservatives.

Asthma is the most common chronic respiratory disease affecting young children and adults all over the world. An estimated 34.1 million Americans have reported asthma in their lifetime and the disease costs ~US $56 billion dollars to treat each year. Current treatment is based on a paradigm of asthma as a non-infectious atopic condition whose root cause is inflammation. Chronically administered anti-inflammatory medications, primarily inhaled corticosteroids (ICS), ameliorate asthma symptoms in many patients. However, up to 50% of asthmatics, characterized by neutrophil infiltration, IL-17 secretion and increased risk of fatality are refractory to ICS treatment. Chlamydia pneumoniae, a ubiquitous, obligate intracellular pathogen with an innate propensity to persist and cause chronic infections, along with Mycoplasma pneumoniae have been implicated in the development of chronic, refractory asthma. C. pneumoniae infections are common in infants and young children, often coinciding with the development of early onset asthma in the population. These facts lead the Webley lab to evaluate the carriage of Chlamydia in pediatric respiratory disease patients and the work confirmed that respiratory infections caused by Chlamydia is a significant risk factor in asthma development and live Chlamydia was isolated from the lungs of children with chronic asthma. However, the exact mechanism underlying chlamydial involvement in the disease remained unknown and we believed that a better understanding could shed important light on expanded treatment options and mechanisms of this infectious asthma phenotype. The work presented here provides new insight into how (1) early life chlamydial infection can lead to asthma initiation and exacerbation (2) respiratory chlamydial infection induces cellular and chemical immune responses that support asthmatic inflammation (3) other respiratory pathogens (eg. Mycoplasma) can drive similar immunological responses resulting in significant lung pathology.

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<p>The work in this thesis encompasses (a) the development of a robust analytical method suitable for the comprehensive analysis of polar and non-polar metabolites in a single analysis and (b) the application of this method to the study of the metabolites involved in peanut allergy. During the course of this work the methods for the analysis of large metabolite data sets evolved significantly and the approaches used in this work evolved in parallel to the literature. This work constitutes the first comprehensive metabolomic investigation of an allergy response.</p> <p>Hypersensitivity or allergy to peanuts is an increasingly problematic health concern around the world involving approximately 1-2% of children in North America. There are no useful clinical biomarkers for this allergy. Comprehensive metabolomics holds vast potential for the discovery of metabolites and metabolite pathways that may be involved during the development of peanut allergy and during peanut-induced anaphylaxis. The comprehensive study of metabolites involved in peanut allergy presented a significant challenge since no single analytical technique is capable of analysis of all metabolites within a single analytical run.</p> <p>The thesis begins with development of a tandem column liquid chromatography-electrospray ionization-mass spectrometry method which allowed the separation and analysis of both polar and non-polar metabolites in a single analysis. This tandem column technique was also shown to significantly reduce the amount of ion suppression observed compared to the ion suppression observed when using either column independently.</p> <p>This methodology was applied to the comprehensive metabolomics analysis of blood serum samples obtained from mice which were (a) being sensitized to peanuts and (b) undergoing anaphylaxis. This analysis discovered a profound impact on metabolites involved with purine metabolism, resulting in an elevation of uric acid levels. This discovery led to further investigations which confirmed that uric acid is essential for peanut sensitization in mice. This discovery was only possible due to the use of a comprehensive metabolomics approach.</p> <p>The analytical methodology was then applied to the study of metabolomic changes in sensitized mice as they experienced peanut-induced anaphylaxis. A number of metabolomic changes including taurine level elevation were correlated with peanut-induced anaphylaxis. Finally, a serendipitous opportunity arose to analyze blood serum samples from peanut allergic children that had undergone an oral peanut challenge. The comprehensive metabolomic study of these samples revealed massive changes in their serum metabolomes as a result of peanut exposure. A number of lipids and lysophospho-lipids were shown to have increased dramatically and may represent novel biomarker candidates for peanut-induced anaphylaxis in humans.</p> <p>In summary, this thesis had demonstrated that comprehensive metabolomic analyses can be successfully applied to complex syndromes such as peanut allergy and yield useful mechanistic and clinical insights to this disorder.</p> / Doctor of Philosophy (PhD)