Parasitische Würmer gehören mit über 3,5 Milliarden Betroffenen zu den weltweit verbreitetesten Infektionskrankheiten. Der Erfolg dieser Parasiten beruht auf ihren ausgefeilten Mechanismen mit denen sie das Immunsystem ihrer Wirte manipulieren. Interessanter Weise gehen Wurminfektionen mit einer geringeren Wahrscheinlichkeit an Allergien zu erkranken einher. Wie genau die Parasiten das Immunsystem manipulieren ist weitgehend unbekannt. Um diese Mechanismen besser studieren zu können, wurde im Rahmen dieser Arbeit versucht RNA interference (RNAi), anhand des Modellmoleküls Tropomyosin zu etablieren. Wie sich am Beispiel des Strongyliden Heligmosomoides polygyrus bakeri zeigte, ist RNAi als Manipulationsmethode für Nematoden nicht oder nur in geringem Maße geeignet. Dies lässt sich auf das Fehlen von Aufnahme- und Verbreitungsmechanismen für Doppelstrang-RNA zurückführen. Desweiteren wurden die Auswirkungen von rekombinantem Tropomyosin der Filarie Acanthocheilonema viteae (rAv-TMY) auf die Entstehung allergischer Atemwegserkrankungen im Mausmodell untersucht. Eine viermalige Behandlung mit rAv-TMY in einem Zeitraum von vier Wochen führte zu verringerten entzündlichen Reaktionen in den Atemwegen. Die Analyse immunologischer Parameter ergab, dass rAv-TMY signifikant den Einstrom von Entzündungszellen in die Atemwege reduziert, allem voran den Einstrom von Eosinophilen. Dies lässt sich durch die verringerte Ausschüttung an IL-5, Eotaxin und MCP-5 zurückführen. Zudem wurde die Bildung von antigenspezifischen IgE verringert während sich die Produktion blockierender IgG1 Antikörper erhöhte. Diese Arbeit belegt somit die anti-allergischen Eigenschaften von rAv-TMY. Damit stellt rAv-TMY ein interessantes Kandidatenmolekül zur Behandlung allergischer Reaktionen dar. Desweiteren kann der Vergleich von allergenem, nicht allergenem und modulatorischem Tropomyosin wichtige Informationen über die allgemeinen Eigenschaften von Allergenen und ihrer molekularen Struktur geben. / Parasitic worms are among the world''s most prevalent infectious diseases with more than 3.5 billion. The success of these parasites is based on their sophisticated ways to manipulate the immune system of their hosts. Interestingly, worm infections abate the risk to develop allergic disorders. How exactly parasitic worms modulate the immune system is so far largely unknown. In order to be able to investigate parasite induced modulation, this work aimed to establish RNA interference (RNAi), a method of genetic manipulation, using tropomyosin as target gene. As shown for the example of Heligmosomoides polygyrus RNAi is not or only to a small extent useful as method to genetically manipulate nematodes. This can be explained with the lack of uptake and spreading mechanisms for double stranded RNA. Furthermore, this work examined the impact of the recombinant muscle protein tropomyosin of Acanthocheilonema viteae (rAv-TMY) on the course of a rodent model of allergic airway inflammation. A four-time treatment with rAv-TMY over a period of four weeks resulted in decreased inflammatory responses in the airways. The analysis of immunological parameters showed that rAv-TMY significantly reduces the influx of inflammatory cells into the airways, especially eosinophils. The reduced eosinophil influx can be attributed to the decreased expression of IL-5, eotaxin and MCP-5 in the airways. In addition, the formation of antigen-specific IgE was impaired whereas the production of the blocking antibody IgG1 was increased. These results demonstrate the anti-allergic properties of rAv-TMY. For this reason rAv-TMY becomes an interesting model molecule for the treatment of allergic diseases. Furthermore, the comparison of allergenic, non-allergenic and modulatory tropomyosin might put some light on the nature of allergens and their molecular patterns.

INTRODUÇÃO: A rinite alérgica é uma condição clínica comum que apresenta sintomas diversos num significante número de pacientes, deteriorando a qualidade de vida daqueles refratários aos tratamentos usuais (anti-histamínicos e corticosteróides nasais tópicos). Apresentando princípios curativos similares, a imunoterapia sublingual e a homeopatia podem reduzir os sintomas e a necessidade de medicamentos na rinite alérgica, embora a eficácia e a efetividade de ambas terapêuticas não sejam ainda suficientemente conhecidas. OBJETIVOS: O objetivo deste estudo foi avaliar a efetividade clínica do tratamento homeopático individualizado prolongado, comparativamente ao placebo, em adultos portadores de rinite alérgica perene. MÉTODOS: Um total de 41 pacientes com rinite alérgica perene foi alocado numa primeira fase duplo-cego e placebo-controlada durante seis meses, sendo tratada com doses sublinguais semanais de medicamentos homeopáticos individualizados ou placebo. Após esta fase inicial fechada, todos os pacientes foram convidados a participar de uma segunda fase controlada aberta, em que receberiam tratamento homeopático pelo período máximo de 36 meses, e os resultados foram comparados com a melhora da fase inicial. O escore dos sinais e sintomas, a necessidade de medicamentos de resgate e a qualidade de vida foram mensurados por questionários e avaliações clínicas pessoais, aplicadas por um mesmo avaliador independente, antes e após cada fase. As doses dos medicamentos homeopáticos e de resgate utilizados, assim como os efeitos colaterais, foram documentados num diário pessoal. Os desfechos clínicos primário e secundários foram, respectivamente, os escores dos sinais e sintomas alérgicos específicos e gerais. Títulos da IgE total foram mensurados antes e após cada fase. RESULTADOS: Após os seis meses da fase placebo-controlada inicial, na análise por protocolo de todos os pacientes incluídos no estudo, não foram observadas diferenças significativas entre os grupos ativo e placebo nos escores clínicos, na utilização de drogas de resgate, na qualidade de vida e nos títulos da IgE total. Entretanto, as análises dos subgrupos da segunda fase mostraram uma crescente e significativa melhora nos desfechos clínicos primário e secundários após 12 meses de tratamento homeopático individualizado, comparativamente à variação de melhora dos mesmos pacientes na fase inicial fechada. Diferença significativa na qualidade de vida foi observada apenas após o segundo ano de tratamento homeopático. CONCLUSÃO: Neste estudo, o tratamento homeopático foi acompanhado de um significante efeito placebo. A efetividade da homeopatia pôde ser observada após 12 meses da terapêutica, apresentando efeito preventivo de longa duração após 36 meses de tratamento homeopático individualizado. / INTRODUCTION: Allergic rhinitis is a common clinical condition which presented several symptoms in a significant number of patients, deteriorating the quality of life in those resistant to the usual treatments (antihistamines and topical nasal corticosteroids). Presenting similar curative principles, sublingual immunotherapy and homeopathy can reduce symptoms and medication requirements in allergic rhinitis, although the efficacy and effectiveness of both therapeutics are not still sufficiently known. OBJECTIVES: The objective of this study was to evaluate clinical effectiveness of prolonged individualized homeopathic treatment, compared with placebo, in adults with perennial allergic rhinitis. METHODS: A total of 41 adults with perennial allergic rhinitis were enrolled in a first double-blind placebo-controlled phase for six months, and treated on a weekly basis with sublingual doses of single individualized homeopathic medicines or placebo. After this closed initial phase, all patients were invited to participate in an open label controlled phase, in that they would receive homeopathic treatment for the maximum period of 36 months, and the results were compared with the improvement of the initial phase. Signs and symptoms scores, rescue medication requirements and quality of life were assessed by questionnaires and personal clinical evaluation by a same independent researcher, before and after each phase. Applied homeopathic and rescue drugs dosage, and side effects were documented by diary cards. Primary and secondary clinical outcome were, respectively, specific and general allergic signs and symptoms scores. Total IgE titles were performed before and after each phase. RESULTS: After six months of placebo-controlled phase, analyzing all patients included in the study per protocol, we observed no significant difference between treatment and placebo groups in primary and secondary clinical outcomes, use of rescue drugs, quality of life and total IgE. However, second phase subgroups analysis showed a significant and growing improvement of clinical symptoms after 12 months of individualized homeopathic treatment, comparatively to the same patients\' variation in closed initial phase. Significant difference in quality of life score were observed only after second homeopathic treatment year. CONCLUSION: In this study, homeopathic treatment was accompanied by a significant placebo effect. Effectiveness of homeopathy could be seen after 12 months of therapy, presenting preventive effect of long duration after 36 months of individualized homeopathic treatment.

Made available in DSpace on 2016-04-26T20:21:46Z (GMT). No. of bitstreams: 1 Maria Cecilia Cury Chaddad.pdf: 2206986 bytes, checksum: 82564a4366fdadb6ebbc1aee18a566f3 (MD5) Previous issue date: 2013-06-11 / This study aim to protect the rights to health and adequate food of the population with food allergy, estimated at about 8% of children and 3% to 5% of adults, arguing there is a need for the provision of information about allergens on product labels, as well as along consumers service assistance (such as electronic websites and phone numbers). It is pointed the interrelationship between the right to health and right to life as well as that between the right to health and the right to adequate food, rights whose effective protection depend on the consumers access to information. The relevance of the topic regarding the right to information about the presence of allergens and feasibility of the proposal of the obligation of allergens labeling are demonstrated through the analysis of existing standards relating to food labeling in Brazil, as well as which treatment given to the issue of labeling of allergens in comparative law. Finally, on the premise that people with food hypersensitivity need to maintain a diet that excludes the presence of allergens, as a way to ensure their well-being and their life with dignity, it is pointed to the State's responsibility to protect the rights to health and to adequate food of this portion of the Brazilian population, with the regulating of the duty of providing information about the presence (or absence) of such substances in food available for consumption for part of the food industry, although this presence give up unintentionally (traces), which depends on compliance with good manufacturing practices for food products and careful risk assessment / Este trabalho objetiva tutelar os direitos à saúde e à alimentação adequada da população com alergia alimentar, estimada em cerca de 8% das crianças e entre 3% e 5% dos adultos, sustentando a necessidade de que haja a disponibilização de informações a respeito de substâncias alérgenas nos rótulos dos produtos, assim como junto aos canais de atendimento ao consumidor (como sítios eletrônicos e telefones). Como fundamentação, aponta para a inter-relação existente entre o direito à saúde e o direito à vida, assim como aquela existente entre o direito à saúde e o direito à alimentação adequada, direitos cuja tutela efetiva dependem do acesso à informação por parte dos consumidores. A relevância do tema, atinente ao direito à informação quanto à presença de alérgenos e a viabilidade da proposta de rotulagem obrigatória, é demonstrada a partir da análise das atuais normas relacionadas à rotulagem de alimentos no Brasil, assim como qual o tratamento conferido ao tema da rotulagem de alérgenos no direito comparado. Por fim, partindo da premissa de que as pessoas com hipersensibilidade alimentar necessitam manter uma dieta que exclua a presença de alérgenos, como forma de se garantir o seu bem-estar e sua existência digna, aponta-se a responsabilidade do Estado em proteger os direitos à saúde e à alimentação adequada desta parcela da população brasileira, através da regulamentação do dever de disponibilização de informações quanto à presença (ou ausência) de tais substâncias nos alimentos disponibilizados ao consumo por parte das indústrias alimentícias, ainda que tal presença se dê de forma involuntária (traços), o que depende da observância de boas práticas de produção de produtos destinados à alimentação e criteriosa avaliação de riscos

Ce travail de thèse a porté sur l’étiologie des leucémies aigües (LA) de l’enfant, et s’est concentré sur les questions (1) du risque de LA chez les enfants conçus par assistance médicale à la procréation (AMP) ; (2) du rôle protecteur d’une supplémentation maternelle en acide folique ; (3) du rôle protecteur de l’exposition précoce à des facteurs induisant une stimulation du système immunitaire ; (4) d’un effet protecteur des antécédents d’allergie sur le risque de LA de l’enfant. Les données analysées proviennent de l’étude cas-témoins française, ESTELLE, réalisée en 2010-2011. Les cas ont été identifiés par le Registre National des Hémopathies malignes de l’Enfant et les témoins ont été recrutés en population générale par téléphone, avec une stratification sur l’âge et le sexe. L’échantillon comportait 636 cas incidents de leucémie aiguë lymphoblastique (LAL), 100 cas incidents de leucémie aiguë myéloblastique (LAM), et 1421 témoins de moins de 15 ans. Les données ont été recueillies auprès des mères à l’aide d’un questionnaire téléphonique standardisé, identique pour les cas et les témoins. Les odds ratios (OR) ont été estimés par régression logistique non conditionnelle ajustée sur l’âge, le sexe, le niveau d’éducation maternel, la catégorie socio-professionnelle du foyer, et les facteurs de confusion potentiels. Nous n’avons pas observé d’augmentation du risque de LA chez les enfants dont la conception avait été difficile (OR=0,9[0,7-1,2]), ou avait nécessité la prise d'un traitement d’infertilité (OR=0,8[0,5-1,1]). La supplémentation préconceptionnelle en acide folique était inversement associée au risque de LA (OR=0,7[0,5-1,0]), sans spécificité de sous-type. Le risque de LAL était inversement associé aux infections banales avant l’âge de 1 an (OR=0,8[0,6-1,0]), à la fréquentation d’une crèche avant 1 an (OR=0,7[0,5-1,0]), à l'allaitement maternel (OR=0,8[0,7-1,0]) , et à des contacts réguliers avec les animaux domestiques à un âge précoce (OR=0,8[0,7-1,0]). En revanche, nous n’avons pas observé d’influence du mode d’accouchement sur le risque de LA. Enfin, les LA étaient inversement associées aux antécédents de rhinite allergique, d’eczéma, de dermatite atopique, d’allergie alimentaire; et d’asthme ou bronchite asthmatiforme traité par antihistaminique. Ces résultats ne sont pas en faveur d’un risque de LA associé aux techniques d’aide médicale à la procréation. Ils renforcent l’hypothèse d’un effet protecteur de la supplémentation préconceptionnelle en acide folique pour les LA. Enfin, ils apportent des arguments supplémentaires en faveur du rôle d’une stimulation précoce du système immunitaire dans la survenue des LAL. / The aim of this study was to investigate whether the following factors: 1) conception by assisted medical procreation (AMP), 2) maternal folic acid supplementation, 3) factors related to early stimulation of the immune system, and 4) the history of allergy were related to the risk of childhood acute leukemia (CL). The data were obtained from the national registry-based case-control study, Estelle, carried out in France in 2010-2011. Population controls were recruited by random digit dialing, with quotas on age and sex. The sample included 636 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloblastic leukemia (AML), and 1421 controls less the 15 years old and frequency matched on age and sex. The data were collected by telephone interview of the mothers, using the same standardized questionnaire for cases and controls. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, sex, maternal education, parental socioeconomic status , and potential confounders. We did not observe any increase in CL risk in children who were conceived with difficulty (OR=0,9[0,7-1,2]) or with the use of any fertility treatments (OR=0,8[0,5-1,1]). Preconceptional folic acid supplementation was inversely associated with CL (OR=0,7[0,5-1,0]), without subtype-specificity. Early common infections before 1 year (OR=0,8[0,6-1,0]), attendance to day-care before 1 year (OR=0,7[0,5-1,0]), breastfeeding (OR=0,8[0,7-1,0]) and regular contact with pets in the first year (OR=0,8[0,7-1,0]) were inversely associated with ALL. However, the mode of delivery was not associated with ALL. Finally, reported history of eczema, atopic dermatitis, food allergy, allergic rhinitis, asthma or asthmatic bronchitis treated with anti-histaminic was inversely associated with CL. Our findings do not suggest that fertility treatments are risk factors for CL. They suggest that folic acid supplementation during pregnancy may reduce the risk of CL. They also support the hypothesis that some conditions promoting the maturation of the immune system may decrease the risk of ALL.

Contexte: La compréhension de l’histoire naturelle de l’asthme et des allergies au cours de la petite enfance est encore parcellaire. De plus, il persiste encore des incertitudes quant à la contribution des facteurs comportementaux et environnementaux au développement de ces maladies. Objectifs: 1) Etudier l’histoire naturelle des symptômes respiratoires et allergiques chez l’enfant de 0 à 4 ans en identifiant des phénotypes basés sur ces symptômes par des analyses de cluster, 2) Caractériser ces phénotypes au regard de leurs co-morbidités et de leurs facteurs de risque, en particulier ceux liés à l’environnement de vie des enfants incluant leur exposition précoce à la pollution atmosphérique d’origine automobile (PAA). Matériel et méthodes: Ce travail de thèse s’inscrit dans le cadre du suivi de la cohorte de naissances PARIS (Pollution and Asthma Risk: an Infant Study) mise en place en 2003 et incluant 3840 nouveau-nés. Des auto-questionnaires régulièrement renseignés par les parents ont permis de documenter l’état de santé des enfants en termes de symptômes et de pathologies respiratoires/allergiques, ainsi que leur mode et cadre de vie. La sensibilisation allergénique a été déterminée par dosage des IgE spécifiques dans le sang à l’âge de 18 mois. L’exposition à la PAA intégrant les différents lieux de vie (domicile, lieu de garde) a été évaluée pour la première année de vie des enfants par un modèle de dispersion, l’indice ExTra. L’identification de phénotypes respiratoires/allergiques entre 0 et 4 ans a été effectuée par des analyses de cluster transversales et longitudinales. Les co-morbidités et facteurs de risque associés aux phénotypes ont été étudiés. Résultats : Entre 0 et 4 ans, des sifflements ont été rapportés chez 31% des enfants, et une toux sèche nocturne chez 38%. Ils sont respectivement 43% et 38% à avoir éprouvé des symptômes évocateurs de rhinite allergique et de dermatite atopique. La prévalence cumulée des maladies diagnostiquées par un médecin était de 12,2% pour l’asthme, 39,4% pour l’eczéma et 3,8% pour le rhume des foins. L’étude des trajectoires des symptômes de sifflements, toux sèche nocturne, rhinite allergique et dermatite atopique a permis d’identifier un groupe avec une faible prévalence de symptômes [n=1236, 49,0%] et quatre phénotypes respiratoires/allergiques distincts: deux transitoires («rhinite transitoire» [n=295, 11,7%] et «sifflements transitoires» [n=399, 15,8%]), non associés avec la sensibilisation IgE dépendante, et deux persistants («toux/rhinite» [n=284, 11,3%] et «dermatite» [n=308, 12,2%]), associés à la sensibilisation allergénique. Le phénotype «rhinite transitoire» était associé à l'exposition postnatale au tabagisme, pouvant irriter les voies respiratoires. Le phénotype «sifflements transitoires» était lié au sexe masculin et au contact avec d'autres enfants (frères et sœurs plus âgés, fréquentation d'une crèche). Les facteurs de risque des deux phénotypes associés aux IgE comprenaient la présence d’antécédents parentaux d'allergie, ainsi que l'exposition potentielle à des allergènes et au stress, connues pour jouer un rôle dans le développement des maladies allergiques. Nos résultats montrent également qu’au regard de la symptomatologie allergique, l’exposition précoce à la PAA semble impacter davantage certains sous-groupes d’enfants (ceux de sexe masculin, ceux ayant un terrain familial d’asthme/d’allergie et ceux dont la mère a souffert d’un problème grave de santé). Conclusion: Ce travail contribue à mieux comprendre l’histoire naturelle des manifestations respiratoires et allergiques durant les années préscolaires et suggère l'existence de différents phénotypes avant l'âge scolaire. Le fait qu'ils diffèrent en termes de facteurs de risque et de sensibilisation renforce la plausibilité de profils distincts, potentiellement liés aux irritations et aux infections pour les phénotypes transitoires, et à l'allergie pour les phénotypes persistants. / Background: The natural history of asthma and allergies during childhood is still not fully understood. In addition, there are still some uncertainties about the contribution of behavioral and environmental factors to the development of these pathologies. Objectives: 1) To study the natural history of respiratory and allergic symptoms in children from birth to age 4 years by identifying phenotypes based upon these symptoms using cluster analyses, 2) To characterize these phenotypes with regard to their comorbidity and risk factors, especially those related to the life environment of children, including their early exposure to traffic-related air pollution (TAP). Methods: This work is part of the follow-up of the PARIS (Pollution and Asthma Risk: an Infant Study) birth cohort, implemented in 2003 and including 3840 newborns. Self-administered questionnaires regularly filled in by parents were used to collect information about the health status of children in terms of respiratory/allergic symptoms and diseases, as well as about lifestyle/environment characteristics. IgE-mediated sensitisation was determined at the age of 18 months. Exposure to TAP integrating the different places of residence and day-care was assessed in the first year of life of children using a dispersion model, the ExTra index. Respiratory/allergic phenotypes were identified between 0 and 4 years by cross-sectional and longitudinal cluster analyses. Comorbidity and risk factors associated with phenotypes were studied. Results: Between 0 and 4 years, wheezing has been reported in 31% of children, and dry night cough in 38%, whereas 43% and 38% have experienced symptoms suggestive of allergic rhinitis and atopic dermatitis, respectively. The prevalence of doctor-diagnosed diseases in the first 4 years was 12.2% for asthma, 39.4% for eczema and 3.8% for hay fever. The study of joint trajectories of symptoms such as wheezing, dry night cough, allergic rhinitis and atopic dermatitis identified a group with low prevalence of symptoms [n=1236, 49.0%] and four distinct phenotypes: two transient ("transient rhinitis" [n=295, 11.7%] and "transient wheeze" [n=399, 15.8%]), without any relation with IgE sensitisation, and two persistent ("cough/rhinitis" [n=284, 11.3%] and "dermatitis" [n=308, 12.2%]) associated with allergic sensitisation. Transient rhinitis phenotype was only associated with tobacco smoke exposure, which could irritate the airways. Transient wheeze phenotype was related to male sex and contact with other children (older siblings, day-care attendance). Lastly, risk factors for both IgE-associated phenotypes encompassed parental history of allergy, potential exposure to allergens and stress, known to be associated with the development of allergic diseases. With regard to allergic symptomatology, our results also show that the impact of early exposure to TAP could be more important in some subgroups of children (boys, children with parental history of allergy, and children whose mother experienced a serious health problem). Conclusion: This work contributes to a better understanding of the natural history of respiratory/allergic symptoms during preschool years, and provides evidence for the existence of different phenotypes before school age. The fact they differ in terms of sensitisation and risk factors reinforces the plausibility of distinct profiles, potentially linked to irritation and infections for the transient phenotypes, and to allergy for the persistent phenotypes.

Over the past several decades and increasingly in recent years, blood transfusions in the United States have plummeted as surgery has gotten more precise and less invasive. Alongside this decrease in general transfusions has been an increase in specific blood products for patients whose immune systems require special treatment. Simultaneously, trends in healthcare in the United States have incentivized regional hospitals to join large conglomerates. These coexisting factors have left regional blood banks, traditionally economically viable, in much weakened states. This thesis was born out of an initial curiosity to discover whether or not genetic science, and genotyping in particular, could benefit small regional blood banks by allowing them to bring down their costs of pre-transfusion blood testing or offer new products. I focus on the San Diego Blood Bank (SDBB) as a case study of the larger blood banking industry. In the course of this research, economic factors were taken into consideration as well as social and health. A minor question that was also discussed was whether genotyping not only help regional blood banks survive fiscally but also open the gateway to better patient outcomes and lower costs nationally of blood transfusions and their associated costs. Feasibility analyses and financial modeling suggest support for genotyping blood donors and transfusion recipients in order to more perfectly match blood transfusions through extended antigen matching.

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug response studies in patient-derived xenograft models of triple-negative breast cancer are also discussed. Taken together, data from these studies highlight LCI’s versatility as a tool for clinical, translational, and basic research applications.

Amalgam has been used as a dental restorative material for centuries, but its potential health effects and biopersistance has lead to a decreased use especially in the Nordic countries. New materials have been introduced, partly to replace the mercury containing amalgam and partly because of esthetical reasons. The possible health effects of amalgam have been studied extensively and the material has been replaced with other less well-examined materials during the last few decades. The prevalence of side effects of dental materials is considered to be low in relation to the vast number of dental treatments undertaken. With the introduction of new and more complex materials, side effects related to dental treatment may increase. Epidemiological data suggest that the side effects of dental resins that have almost completely replaced amalgam fillings in Scandinavia, possess a risk for adverse reactions; however, the causal relation has not been fully established. Therefore, the type and extent of side effects caused by resin-based materials are of great interest. The aims of the study were: - to describe the change in health over time for patients with problems related to their dental materials. The hypothesis was that the patients could be divided into subgroups based on their symptoms and that the ability to recover differs between these groups [Paper I]. Furthermore, to determine whether factors such as the replacement of dental restorative materials and follow-up time had any impact on the perceived health. - to assess the long-term development of symptoms and their social consequences among patients referred for diagnosis and treatment of symptoms related to dental materials [Paper II] - to investigate the possible risks with dental restorative materials other than amalgam [Paper III]. - to describe side effects assessed to be caused by resin-based materials that occurred in a group of patients as well as treatment and long-term consequences of the reactions [Paper IV]. A questionnaire was sent to 614 patients [Paper I and II] that had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental materials. The questionnaire contained questions on, among others; civil status, present health, medical and dental treatment and other measures and precautions taken because of psychosocial problems related to current employment situation, feelings, self-image and coping behavior. Moreover, information was collected [Paper III] from the Swedish Dental Materials Register 2003 (DentMr), a compilation of MSDS for 487 materials, and information from the user guide of the materials. The Material Safety Data Sheets (MSDS) included in the DentMR were examined regarding the given composition of the products, the occurrence of CAS-numbers and the risk- and safety phrases of the substances. Information was collected [Paper IV] on 36 patients with reactions to resin-based restorative materials from the Swedish National Register of Side-Effects of Dental Materials. Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with local symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. However, the reason for this improvement was unclear. Replacement of dental restorative materials had no significant impact on the ability to recover completely. Our results also indicate a relationship between patients’ self-related health and social consequences in daily life. Those with remaining complex symptoms had more often stopped working or had decreased their work hours because of their symptoms The information about hazards with dental materials seems insufficiently described in MSDS and there might be materials with side effects unknown to both patients and dental professionals. A literature search indicated that some of the listed substances had possible hazards, e.g. substances with embryotoxic and neurotoxic potential. The patients were very heterogeneous; a few with only local symptom free reactions while other had more complex symptoms. The latter group would gain from a multidisciplinary approach, i.e. dental, medical, as well as social and psychological factors have to be considered when developing care management programs for this group of patients. Furthermore, there is a need for stronger regulations of dental materials, such as those applied to pharmaceutical drugs. Finally, it was found that the majority of symptoms suspected to be caused by resin-based materials were local or a combination of local and extra-oral symptoms that appeared within the first 24 hours after treatment. The most frequent adverse effect reported was skin problems/dermatitis. It appears as though immediate reactions to resin based materials are not uncommon and more prevalent than allergic reactions. Still, we have had, difficulties in verifying associations between the dental restorative materials and adverse reactions and also to identify the offending component.

L'allergie au lait de vache (ALV) représente l'allergie alimentaire la plus fréquemment rencontrée durant l'enfance. Cette allergie a longtemps été reconnue comme transitoire mais des données récentes révèlent que celle-ci est persistante chez environ 15% des enfants qui en sont touchés durant l'enfance, posant ainsi un risque à leur santé. La présente étude examine 26 enfants avec ALV et 12 enfants contrôles recrutés au CHU Sainte-Justine durant l’hiver 2011-2012. L'objectif étant de comparer la densité minérale osseuse (DMO) et les niveaux sériques de 25(OH)D d'enfants prépubères avec ALV non résolue à un groupe contrôle d'enfants avec autres allergies alimentaires, en plus d'évaluer les apports en calcium et en vitamine D ainsi que l'adhérence à la supplémentation chez cette population. La DMO lombaire (L2-L4) ne diffère pas significativement entre les groupes. Cependant, une faible densité osseuse, caractérisée par un score-Z entre -1,0 et -2,0 pour l'âge et le sexe, est détectée chez plus de 30% des enfants avec ALV et plus de 16% du groupe contrôle, sans allergie au lait. Tel qu'attendu, les apports en calcium sont significativement moins élevés chez les enfants avec ALV comparé au groupe contrôle, avec près de 90% de tous nos participants ne rencontrant pas les besoins pour l’âge en vitamine D. Plus de la moitié des enfants avec ALV présentent une concentration de 25(OH)D inférieure à 75 nmol/L. Cependant, notre étude n'a décelé aucune différence entre les niveaux sériques de 25(OH)D des enfants avec ALV comparativement au groupe contrôle. Enfin, l'adhérence à la supplémentation est jugée adéquate chez plus de 75% de notre groupe d'enfants avec ALV, soit ≧ 4 journées par semaine, un facteur aussi associé à une meilleure atteinte de leurs apports nutritionnels en calcium et en vitamine D. Enfin, ces résultats soulignent l'importance de suivre la santé osseuse d'enfants avec ALV ainsi qu'avec allergies multiples, qui présentent un risque de faible densité osseuse. L'intervention nutritionnelle devrait suivre l'adhérence à la supplémentation chez les enfants avec ALV non résolue, afin d'optimiser les apports nutritionnels insuffisants en calcium et en vitamine D / Cow's milk allergy (CMA) is the most frequent food allergy seen during childhood. Though usually recognized as transient, recent data suggest that the evolution of CMA has changed over time, having become more persistent and therefore, more capable of jeopardizing child growth and development. The following study included 26 children with proven CMA and 12 controls, recruited at Sainte-Justine hospital, during the winter of 2011-2012. The aim of this study was to compare bone density and vitamin D status (25(OH)D) in prepubertal children with CMA to a control group of children without milk allergy and to document calcium and vitamin D intake as well as the adherence to supplementation in this population. Bone mineral density did not differ significantly between groups. However, low bone mass, as defined by a z score between -1,0 and -2,0 for gender and age, was detected in over 30% of cow's milk allergic children and in over 16% of allergic controls. Calcium intake was significantly lower in children with CMA. Overall, nearly 90% of our study population failed to meet daily recommended intakes for vitamin D, with over 50% of cow's milk allergic children presenting vitamin D status below 75 nmol/L. No difference was detected regarding vitamin D status between groups. Finally, the majority of children with CMA presented a good adherence to calcium and vitamin D supplementation, ≧ 4 days per week, a factor that was associated with a better overall dietary intake of these nutrients. It is therefore important to follow bone health of children with CMA as well as with multiple food allergies, as they present a risk for low bone mass during a period of skeletal growth. Nutrition interventions should monitor supplement adherence in children with CMA to optimize dietary intake of calcium and vitamin D, which are presently insufficient.

Cette recherche porte sur les conséquences sociales, au Québec, de la maladie cœliaque et des allergies alimentaires. Elle vise à expliquer et comprendre comment la maladie cœliaque et les allergies alimentaires influencent les relations sociales, les activités sociales et les perceptions des personnes qui vivent avec ces conditions, ainsi que celles de leurs proches. Pour ce faire, des entrevues semi-dirigées ont été effectuées auprès de 11 participants qui étaient soit cœliaque, allergique ou membre de l’entourage. Durant ces entrevues, il a été question de diagnostic, d’accidents alimentaires, d’accessibilité, d’activités amicales, de la réaction et de l’adaptation de la famille, de perceptions et de relations amoureuses. Une comparaison, entre les expériences des cœliaques et des allergiques, est réalisée suite à la description celles-ci. Les données d’entrevues ont été analysées avec le concept d’habitus de Bourdieu (1980), les concepts d’agency et de règles de Giddens (1979), les concepts d’exclusion et d’identité ainsi qu’avec les différentes définitions de la maladie et une échelle de gravité des perceptions. De cette recherche, on notera que les perceptions de la maladie sont différentes chez les cœliaques et les allergiques. La maladie cœliaque tend à être moins prise en charge par les professionnels de la santé et être considérée avec moins de sérieux, par les cœliaques et la population générale, que les allergies alimentaires. Les deux conditions amènent une modification de l’habitus et une période d’adaptation. Par contre, cet exercice semble être plus difficile et complexe pour les cœliaques que les allergiques, dû à l’âge où la condition est découverte. Dépendant de la souplesse de l’habitus individuel et de groupe, la confrontation à cette reformulation de l’habitus se produira plus ou moins bien. Dans le cas où la confrontation prend une tangente négative, il en découlera une désapprobation sociale ou un déni personnel qui mènera à l’exclusion. La littérature indique généralement que la qualité de vie des cœliaques et des allergiques diminue progressivement avec le temps, entraînant des conséquences négatives au niveau social, émotif et physique. Mes participants semblent, toutefois, bien vivre avec leur condition respective puisqu’ils profitent d’un bon support de la part de leur entourage. / This research is about the social consequences, in Québec, of the celiac disease and food allergies. Its aim is to bring an explanation and a better understanding of how celiac disease and food allergies influence the social relations, the social activities and the perceptions of the people that are living with those conditions and their close relations. With this aim in mind, semi-directed interviews were carried out with 11 participants that were either celiac, allergic or near relations. During these interviews, diagnostic, food accidents, accessibility, activities with friends, the family’s reaction and adaptation, perceptions and relationships were the main topics that were discussed. The experiences of the people living with celiac disease (CD) or food allergies (FA) were compared following their description. The data stemming from the interviews was analysed by using Bourdieu’s habitus concept (1980), Giddens’s concepts of agency and rules (1979), concepts of exclusion and identity as well as the definitions of sickness, illness and disease and a gravity scale of perceptions. From this research will be noticed that perception of illness is different for the people living with CD than those living with FA. CD tends to be taken less in charge by health professionals and to be taken with less seriousness, by people living with CD and the general population, than FA are. Both conditions lead to a modification of habitus and an adaptation phase. Nevertheless, these changes seem to be harder to deal with and more complex for people living with CD than for people living with FA because of the age period where the condition was revealed. Depending on the flexibility of the individual and group habitus, the confrontation to the recasting of habitus will go more or less well. If the confrontation is more on the negative side of the spectrum, social disapproval or personal denial will take place, leading to exclusion. The literature generally shows that the quality of life for people living with CD and FA gradually diminishes over time, bringing negative social, emotional and physical consequences. My participants, however, are apparently living well with their respective conditions because they benefit from a good support of their peers.