Thesis (doctoral)--Karolinska Institutet, Stockholm, 1982. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Previous epidemiological studies have shown that the diabetic population has a poor oral status compared to healthy subjects. While changes of the local microcirculation observed during diabetes can somehow explain periodontal pathologies this hypothesis does not stand for the carious decay. We propose the hypothesis that the increase of carious incidence might be linked to changes in the salivary composition, such as an increase of salivary glucose concentrations.The amount of glucose in saliva has been widely discussed in various scientific articles. Subsequently, we performed an initial study that allowed us to confirm that the concentration and excretion of glucose in the saliva were higher in diabetic patients compared to normal patients. In diabetic patients, the relative increase in salivary glucose concentration is even comparable to the rise of blood glucose.We conducted experimental studies in animals in order to investigate the presence and the level of expression of glucose transporters (GLUT1, GLUT2, GLUT4, SGLT1) in rat parotid glands. Through immunohistochemical labeling techniques, gene expression studies and protein expression studies, we demonstrated that GLUT1, GLUT4 and SGLT1 were found in rat parotid glands of normal and diabetic rats. Functional studies targeting the activity and the flux through those glucose transporters strengthened our hypothesis on the potential role of glucose transporter in salivary glucose.This original work introduce for the first time the hypothesis of a secretion mechanism of glucose by the salivary glands through GLUT1 & SGLT1 transporters, the first one being located on the apical and baso-lateral membranes of acinar cells, while the second one is located on the baso-lateral membrane. Secretion of glucose by the parotid gland is no longer at any doubt even though further studies must now specify the specific mechanisms. / Doctorat en Sciences dentaires / info:eu-repo/semantics/nonPublished

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Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 7 uppsatser.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [111]-126).

Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Objectifs : Notre travail avait pour objectifs (i) d’évaluer le bénéfice dosimétrique et de prédire le bénéfice clinique d’une radiothérapie adaptative pour des cancers des voies aéro‐digestives supérieures, à la fois en termes de toxicité et de contrôle local, (ii) d’identifier les patients bons candidats à une stratégie de radiothérapie adaptative, et (iii) d’identifier le meilleur schéma de radiothérapie adaptative pour épargner les parotides. Matériels et méthodes : Le bénéfice dosimétrique a été évalué en utilisant les données de patients inclus dans une étude de phase III évaluant le bénéfice clinique d’une radiothérapie adaptative. La dose cumulée sans et avec radiothérapie adaptative a été estimée par des méthodes de recalage élastique. Une évaluation des différents algorithmes de recalage a été faite à la fois en termes de précision spatiale et d’impact sur la dose estimée. Des modèles de prédiction du risque de surdosage ont été développés en utilisant des modèles linéaires généralisées mixtes et une validation croisée par leave‐one‐out. L’évaluation de différents schémas de radiothérapie adaptative (en termes de fréquence et de nombre) a été réalisée en se basant sur l’épargne des parotides. La valeur prédictive de paramètres quantitatifs issus de la TEP a été évaluée à travers une revue systématique de la littérature. La valeur prédictive de paramètres intensité issue de la TEP a été analysée dans 2 cohortes indépendantes. Résultats : Nos travaux ont confirmé qu’en l’absence de radiothérapie adaptative pour des cancers des VADS, il existe un risque de surdosage des parotides de plus de 2 Gy pour les 2/3 des patients. Il s’y associe un risque de sous dosage de la tumeur de plus de 1 Gy pour 50 % des patients. Une radiothérapie adaptative permet de corriger à la fois le surdosage des parotides (bénéfice clinique estimée de 10 % de diminution du risque de xérostomie) et le sous dosage de la tumeur. Basés sur des paramètres issus de la planification et de la première semaine de traitement, des modèles de prédiction du risque de sur dosage des parotides ou de sous dosage de la tumeur ont été développés. Les paramètres TEP prédictifs du risque de récidive ont été identifiés. Un nomogramme a pu être développé et validé dans une 2nd cohorte de patients. Conclusion : Nos travaux confirment le bénéfice d’une radiothérapie adaptative pour épargner les parotides et maintenir la couverture tumorale. Ce bénéfice dosimétrique devrait permettre une diminution de la toxicité et une amélioration du contrôle local. Des paramètres anatomiques et dosimétriques simples permettent l’identification des patients à risque de surdosage des parotides ou de sous dosage de la tumeur. L’utilisation de la TEP permet d’identifier précocement les patients à haut risque de récidive, candidats potentiels à une intensification thérapeutique. Ces résultats justifient la poursuite des travaux sur une cohorte de patients plus importante, idéalement dans le cadre d’études cliniques de phase III. / Objectifs: The aims of this work were (i) to evaluate the dosimetric benefit and to predict the clinical benefit of adaptive radiotherapy for head and neck cancer, regarding both toxicities and local control, (ii) to identify patients whose good candidate for an adaptive strategy, and (iii) to identify the best adaptive strategy to spare the parotid glands. Materials and methods: The dosimetric benefit was assessed using data from a phase III study evaluating the clinical benefit of an adaptive radiotherapy. Cumulated dose with and without adaptive was estimated using deformable image registration. Different methods of deformable image registration were evaluated regarding both spatial and dose estimation accuracy. Predictive model of the risk of parotid gland overdose was computed using generalized linear mixed model and cross validation by leave‐one‐out. The dosimetric benefit of numerous replanning strategies, defined by various numbers and timing of replanning, with regard to parotid gland sparing, was quantified. We performed a systematic review to evaluate the predictive value of quantitative PET parameters. The predictive value of PET intensity parameters was assessed using two independent cohorts of patients. Résultats: Without adaptive radiotherapy, 65% of the patients had a PG overdose of more than 2 Gy and 50% of the patients had a tumor underdose of more than 1 Gy. Adaptive radiotherapy allows to correct both parotid gland overdose and tumor underdose. Based on parameters calculated at the planning and at the first week of treatment, predictive models of PG overdose and tumor underdose were computed. PET parameters correlated with overall survival were identified. Using two independent cohorts of patients, a nomogram to predict survival was build and externally validated. Conclusion: Our studies showed the benefit of adaptive radiotherapy to spare the parotid glands while increasing tumor coverage. These benefits should allow to decrease the toxicities while increasing local control. Early anatomical and dosimetric parameters allow identifying patients at risk of tumor underdose or parotid gland overdose. PET performed before the treatment allows identifying patients with a high‐risk of locoregional failure and death, potentially candidates for treatment. These results justify further studies on a larger cohort of patients, ideally in phase III clinical trials.