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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1341

Die Auswirkung der rheumatoiden Arthritis auf den Plantardruck

Kynast, Eike 22 August 2005 (has links)
Fragestellung: Die Studie soll die Frage klären, ob sich mit der elektronischen plantaren Fußdruckmessung (elektronische plantare Pedobarographie) bei Probanden mit Rheumatoider Arthritis Veränderungen der Druckverteilung an der Fußsohle nachweisen lassen. Obwohl sich Geräte zur elektronischen Fußdruckmessung seit einigen Jahren auf dem Markt befinden, gehört ihr Einsatz bei weitem noch nicht zum Standard bei der Optimierung und Kontrolle der Therapie von Fußerkrankungen. Methode: In dieser Studie werden die statischen und dynamischen Druckverteilungsmuster einer Gruppe von dreiunddreißig Rheumatikern erfasst. Diesen wird eine Vergleichgsgruppe Fußgesunder mit einunddreißig Probanden gegenübergestellt. Die Messung des Plantardruckes erfolgte mit dem elektronischen Parotec(R) – System. Ergebnisse: Die Ergebnisse der statischen Messungen zeigen eine deutliche Tendenz der Rheumatiker zur Ausbildung eines Pes planovalgus. Über eine Quotientenbildung aus zu Sensorgruppen zusammengefasstem Druckarealen können als Spreiz-, Senkfuß- und Valgusindex die entsprechenden pathologischen Veränderungen quantifiziert werden. In der dynamischen Belastung zeigt sich im Längsgewölbebereich eine Annäherung der Plantardrücke beider Gruppen. In der Referenzgruppe treten sogar vereinzelt höhere Mittelwerte auf, als bei den Rheumatikern. Dies wird hauptsächlich durch eine räumliche und zeitliche Modifikation der Gangkinematik durch den Rheumatiker erzielt: ein langsameres Gehen; eine kleinere Schrittlänge; die relative Vergrößerung der plantaren Druckverteilungsfläche durch relativ verkürzte monopedale bzw. verlängerte bipedale Belastung ; eine Modifikation der Abrollbewegung des Rheumatikers mit Reduktion der Belastung in drucksensiblen peripheren, insbesondere distalen Bereichen, vor allem im Bereich des Metatarsalköpfchen I. Folgerung: Die Ergebnisse zeigen, dass es deutliche Plantardruckunterschiede in beiden Gruppen gibt, mit Tendenz zur aequibaren Plantardruckverteilung des Rheumatikers im Sinne eines Pes planovalgus. Die funktionelle Auswirkung struktureller Veränderungen des rheumatischen Fußes lassen sich mit dem von uns verwendeten Meßsystem quantifizieren. Durch die Quantifizierbarkeit der pathologischen Veränderungen eignet sich dieses Messverfahren zur Optimierung und Kontrolle der operativen und konservativen Therapie nicht nur von rheumatischen Veränderungen des Fußes. / Question: The study shall clarify the question, whether changes of the pressure distribution at the sole of the foot can be verified by means of electronic plantar foot measurement (electronic plantar pedobarography) in probands suffering from rheumatoid arthritis. Although there are devices of electronic foot measurement on the market, the use is not standard yet in view of the optimisation and check of pedopathy therapies. Method: This study includes the static and dynamic pressure distribution patterns of a group of thirty-three rheumatics. A comparing group of thirty-one probands with healthy feet is compared with it. The measuring of the plantar pressure took place by means of the electronic Parotec(R) system. Results: The results of the static measuring turn out a clear tendency of the rheumatics to the formation of pes planovalgus. The appropriate pathologic changes can be quantified as splayfoot, flatfoot, and valgus index by means of a quotient formation of pressure areas combined in sensor groups. In the event of dynamic load, a convergence of the plantar pressures of both groups is noticed in the area of the longitudinal arch of the foot. The reference group even shows isolated higher mean average values compared with the rheumatics. This is mainly obtained by means of a spatial and temporal modification of the rheumatic’s gait kinematics: slower walking; shorter length of stride; relative increase of the plantar pressure distribution area by means of relatively shortened monopedal, resp. lengthened bipedale load; a modification of the rheumatic’s heel-toe walking motion with reduction of the load in peripheral and distal areas in particular that are sensible to pressure, especially within the area of the metatarsal head I. Conclusion: The results turn out that there are clear differences regarding the plantar pressure of both groups with a tendency to aequibar plantar pressure distribution of the rheumatic within the sense of pes planovalgus. The functional effect of structural changes of the rheumatic foot can be quantified by means of our used measuring system. This measurement method also is suitable for the optimisation and check of operative and conservative therapies other than rheumatic changes of the foot because pathologic changes are quantifiable.
1342

Arthritisinduktion durch Immunität gegen ein systemisch exprimiertes Autoantigen

Schubert, David 01 June 2005 (has links)
Ungefähr 1% der Bevölkerung der westlichen Welt leidet an rheumatoider Arthritis (RA). In einem T-Zellrezeptor transgenen Mausmodell, dem K/BxN Modell, wird die ubiquitär exprimierte Glukose-6-phosphat Isomerase (G6PI) von autoreaktiven T- und B-Zellen erkannt. Diese Mäuse entwickeln spontan eine antikörpervermittelte Arthritis, die viele Gemeinsamkeiten mit der humanen RA aufweist. In dieser Arbeit wurde untersucht, ob die Immunisierung mit G6PI eine Arthritis auch in nicht-transgenen Mäuse induzieren kann. Die Immunisierung mit heterologer humaner G6PI führte zur Entwicklung einer peripheren symmetrischen Polyarthritis in über 95% der DBA/1 Mäuse. Damit konnte zum ersten Mal gezeigt werden, dass eine Immunreaktion gegen ein systemisches exprimiertes Antigen zur einer organspezifischen Erkrankung in normalen nicht-transgenen Mäusen führt. Die Tiere entwickeln nach 9 Tagen eine Arthritis, die bis Tag 15 ihr Maximum erreicht hat und dann langsam abnimmt. Histologisch ist die Arthritis durch eine frühe Synovitis charakterisiert, gefolgt von massiven Erosionen des Knorpel und Knochens und anschließenden Reparaturprozessen, inklusive Fibrose. Obwohl die Tiere hohe Antikörpertiter entwickeln, kann die Arthritis nicht durch aufgereinigte Antikörper kranker Mäuse transferiert werden. Trotzdem spielen Antikörper eine große Rolle, da FcR-gamma-Kette defiziente Mäuse eine Arthritis mit geringer Inzidenz und mildem Verlauf entwickeln. Die Depletion der CD4 positiven Zellen verhindert die Entwicklung der Arthritis völlig, und eine Depletion während der Erkrankung führt zur schnellen Heilung. Daneben ist für die Entwicklung der Arthritis auch das Komplementsystem und TNF-alpha entscheidend, was durch Depletion von C5 bzw. durch Blockade von TNF-alpha gezeigt wurde. Zusätzlich wurde die Rolle der G6PI bei der Pathogenese der RA im Menschen untersucht. RA-Patienten zeigten keine erhöhte Frequenz von CD4 positiven T-Zellen, die nach Restimulation mit G6PI TNF-alpha oder IFN-gamma produzierten. Außerdem konnten keine erhöhten anti-G6PI Titer in Patienten mit RA oder anderen rheumatischen Erkrankungen detektiert werden. / About 1% of the of the population of the western world suffers from rheumatoid arthritis (RA). In a T-cell receptor transgenic mouse model, the K/BxN model, the ubiquitously expressed glucose-6-phosphate isomerase (G6PI) is recognized by autoreactive T- and B-cells. These mice do develop an antibody dependent arthritis which show a lot of features of human RA. In this study it was examined whether arthritis could be induced in normal non-transgenic mice by immunization with G6PI. Immunization with heterologous human G6PI induces a symmetric polyarthritis in over 95% of DBA/1 mice. Therewith showing for the first time that an immune reaction against an systemic expressed antigen will lead to the development of an organ specific disease in normal non-transgenic mice. The mice develop arthritis 9d after immunization, reach their maximum at d15 and then arthritis slowly resolve. Histologically, the disease is characterized by early synovitis followed by massive cartilage destruction and erosions of the bones and later repair processes including fibrosis. Although antibody titers in the mice are high, transfer of purified anti-G6PI antibodies of sick mice alone do not transfer disease. Anyway, antibodies seem to play a major role since FcR-gamma-chain deficient mice develop disease with a much lower frequency and reduced severity. Depletion of CD4 positive T cells completely prevents disease and depletion during disease leads to an rapid resolution of arthritis. Aside this, complement and TNF-alpha is critical for the development of arthritis, which could shown by depletion of C5 and blockade of TNF-alpha. In addition, the role of G6PI in the pathogenesis of RA in humans was examined. RA patients do not show a higher frequency of CD4 positive T-cells which produce TNF-alpha and IFN-gamma after restimulation with G6PI. Furthermore, no elevated anti-G6PI titers could be detected in RA patients and in patients with other rheumatic diseases.
1343

Die B-Zell-Antwort im Synovialgewebe von Patienten mit Rheumatoider Arthritis

Scheel, Tobias 09 December 2009 (has links)
Obwohl B-Zellen in der Pathogenese der Rheumatoide Arthritis (RA) eine wichtige Rolle spielen, ist über ihre Aktivierung und Differenzierung im Synovialgewebe (SG) nicht viel bekannt. Ein Merkmal von RA ist das Auftreten von Autoantikörpern (auto-AK). Trotz dessen sind bisher kaum Daten über den Einfluss des SG auf die auto-AK-Produktion und die Frequenz autoreaktiver synovialer B-Zellen bekannt. Diese Arbeit beschäftigt sich mit der Charakterisierung der synovialen B-Zell-Antwort und der Spezifität synovialer B-Lymphozyten. Dazu wurden B- und Plasmazellen (PC) aus dem Synovialgewebe von RA-Patienten mittels Mikrodissektion und Durchflusszytometrie isoliert und ihr Immunglobulin(Ig)-Repertoire bestimmt. Die Analyse der VH-Gene zeigte, dass sowohl naive als auch Gedächtnis-B-Zellen in das SG einwandern können. Ein Vergleich der VDJ-Rearrangements aus B-Zellen und PC belegte, dass hauptsächlich Gedächtnis-B-Zellen Antigen-abhängig aktiviert werden, klonal expandieren und zu PC differenzieren. Dabei können aktivierte B-Zellen ihre Ig-Klasse wechseln. Im Gegensatz dazu wurden nur rudimentäre Anzeichen somatischer Hypermutation nachgewiesen. Um die Spezifität synovialer B-Lymphozyten zu ermitteln, wurden rekombinante AK aus synovialen B-Zellen und PC generiert. Der Polyreaktivitätstest zeigte, dass naive B-Zellen aus dem SG einen hohen Anteil polyreaktiver Zellen besitzen. Im Gegensatz dazu ist die Frequenz von autoreaktiven Gedächtnis-B-Zellen und PC gegenüber naiven B-Zellen erhöht. Daneben konnten auch spezifische AK gegen bakterielle Antigene (insbesondere gegen Parodontitis-auslösende Bakterien) und gegen das Auto-Ag MCV identifiziert werden. Eine Affinitätsmessung des MCV-spezifischen Auto-AK zeigte, dass im SG sezernierte Auto-AK eine sehr hohe Affinität erreichen können. Die hier gewonnenen Daten verdeutlichen, dass B-Lymphozyten entscheidend an der Aufrechterhaltung oder gar Entstehung von RA beteiligt sind / Although B cells have an important impact on the pathogenesis of Rheumatoid arthritis (RA) still surprisingly little is known about their activation and differentiation within the inflamed synovial tissue (ST). A hallmark of RA is the presence of auto-antibodies (auto-Ab). However, still little is known about the frequency of self reactive synovial lymphocytes and it is unclear to which extent the inflamed ST contributes to auto-Ab production. These thesis deals with the characterization of the synovial B cell response and the specificity of synovial B lymphocytes. B and plasma cells (PC) from RA patients were isolated either by Laser Capture Microdissection or by FACS and their immunoglobulin(Ig)-repertoire was determined. The analysis of the VH-genes revealed that both naïve and memory B cells can immigrate the ST. A comparison of VDJ-rearrangements of B cells and PC showed that in ST without ectopic germinal centres mainly memory B cells become activated, expand clonally and differentiate into PC. During this process B cells can switch their Ig-class but do only hypermutate slightly. To determine the specificity of synovial B lymphocytes, recombinant Ab from synovial B cells and PC were generated. The polyreactivity assay showed that particularly naïve B cells were polyreactive. In contrast, the frequency of autoreactive memory B cells and PC was much higher than that of naïve B cells. In addition, Ab specific for bacterial antigens (especially for periodontal bacterias) and for the autoantigen MCV were identified. The affinity measurement of the MCV-specific autoantibody revealed that auto-Ab secreted in the ST can exhibit very high affinities. The data presented here show that B cells seem to play an important role in the maintenance and possibly the development of RA.
1344

Imunogenetické a hormonální predispoziční markery systémových revmatických onemocnění,zejména systémového lupus erythematodu / Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases particularly systemic lupus erythematosus

Fojtíková, Markéta January 2011 (has links)
Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....
1345

Manifestações musculoesqueléticas associadas à hepatite C crônica / Musculoskeletal manifestations associated with chronic hepatitis C

Andréa Aparecida Siqueira Nakamura 09 September 2013 (has links)
INTRODUÇÃO: A infecção pelo vírus C é um grande problema de saúde pública e tem se tornado a principal indicação de transplante de fígado. Com uma distribuição universal, é a segunda doença crônica viral mais frequente no mundo. No entanto, a hepatite C crônica é mais que uma doença hepática. Pacientes com infecção crônica pelo HCV podem desenvolver um grande número de manifestações extra-hepáticas independentemente da gravidade da doença hepática. Há muitas doenças reumatológicas associadas à infecção pelo HCV, incluindo artralgia, mialgia e artrite. MÉTODOS: Um estudo transversal desenvolvido entre os pacientes atendidos no Ambulatório de Hepatites da Divisão de Clínica de Moléstias Infeciosas e Parasitárias do HCFMUSP, na cidade de São Paulo, no período de 2004 a 2008, selecionou 243 pacientes que preencheram os critérios de inclusão e assinaram o termo de consentimento após esclarecimentos sobre a pesquisa. Foi realizada uma entrevista com os pacientes, em que foram coletadas informações demográficas, epidemiológicas e clinico-laboratoriais. Foram realizados exames laboratoriais, bioquímicos, hematológicos, imunológicos, PCR, HCV, RNA quantitativo e genotipagem do HCV. A avaliação das características da infecção pelo HCV (epidemiológica, histológica, virológica), associada às manifestações extra-hepáticas clínicas reumatológicas (aquelas com prevalência > 10%) e laboratoriais (com prevalência > 5%), foi realizada utilizando-se as análises univariada e multivariada (regressão logística). Odds ratios (OR) ajustados e intervalos de confiança de 95% (IC 95%) foram derivados do coeficiente do modelo logístico multivariado final. Todas as análises foram realizadas com o pacote estatístico SPSS. RESULTADOS: Dos 243 pacientes estudados, pudemos determinar a provável forma de infecção em 147 (60,49%). Dos 147 pacientes, 93 (38,27%) sofreram transfusão sanguínea prévia, 10 (4,11%) tinham histórico de uso droga injetável há mais de 1 ano, 15 (6,17%) tinham antecedente de uso do droga inalatória há mais de 1 ano, 11 (4,52%) eram profissionais da saúde com histórico de acidente com material perfuro-cortante, 10 (4,11%) realizaram tatuagem e 8 (3,29%) tinham parceiro portador de hepatite C crônica. Nessa análise, 148 (60,9%) dos pacientes com hepatite C crônica apresentaram queixa de artralgia, 145 (59,7%) apresentaram queixa de mialgia, 144 (59,3%), de cansaço. A artrite esteve presente em 50 (20,57%) dos pacientes avaliados nesse estudo. Dentre estes pacientes, o envolvimento foi predominantemente poliarticular em 36 (72%) deles, acometendo grandes e pequenas articulações, simultaneamente, em 29 (58%). Idade maior que 50 anos, dor nas costas e crepitação em articulações mostraram-se fatores associados à artrite. Observou-se que sexo feminino, tabagismo importante e fibrose hepática avançada (F3 e F4) foram fatores associados à artralgia. Sexo feminino e tabagismo importante foram fatores associados à mialgia. CONCLUSÃO: Foi encontrada elevada prevalência de manifestações musculoesqueléticas entre os pacientes portadores de hepatite C crônica deste serviço. Os fatores de risco mais frequentes para a presença das manifestações extra-hepáticas foram sexo feminino e idade maior que 50 anos. Os autoanticorpos, embora freqüentes, não mostraram significância estatística com relação às principais manifestações musculoesqueléticas analisadas. Infiltrado inflamatório hepático e nível de transaminases também não apresentaram significância estatística / INTRODUCTION: C virus infection is a major public health problem and has become the leading indication for liver transplantation. With a worldwide distribution, is the second most common chronic viral worldwide. However, chronic hepatitis C is more than a liver disease. Patients with chronic HCV infection may develop a large number of extra hepatic manifestations regardless of the severity of liver disease. There are many rheumatic diseases associated with HCV infection including arthralgia, myalgia and arthritis. METHODS: A cross-sectional study carried out among patients treated in outpatient Hepatitis Clinical Division of Infectious and Parasitic Diseases of the HC-USP, in São Paulo, in the period from 2004 to 2008, selected 243 patients who met the inclusion criteria and signed the consent form after clarification of the research. An interview was conducted with patients which were collected demographic, epidemiological and clinical-laboratory. Laboratory tests were carried, biochemical, hematological, immunological, quantitative PCR HCV RNA and HCV genotyping. The evaluation of the characteristics of HCV infection (epidemiological, histological, virological) associated with extrahepatic manifestations rheumatology clinics (those with prevalence > 10%) and laboratory (with prevalence > 5%) were performed using univariate and multivariate analysis (regression logistics). Odds ratios (OR) and adjusted confidence intervals of 95% (95% CI) were derived from the ratio of the final multivariate logistic model. All analyzes were performed with the SPSS statistical package. RESULTS: Of the 243 patients studied were able to determine the likely form of infection in 147 (60.49%). Of the 147 patients, 93 (38.27%) had previous blood transfusion, 10 (4.11%) had a history of injection drug use for more than 1 years, 15 (6.17%) had prior use of the drug is inhaled over 1 year, 11 (4.52%) were health professionals with a history of accidents with sharp objects, 10 (4.11%) underwent tattooing and 8 (3.29%) had a partner with hepatitis C chronic. In this analysis, 148 (60.9%) of patients with chronic hepatitis C complained of arthralgia, 145 (59.7%) complained of myalgia, 144 (59.3%) of fatigue. Arthritis was present in 50 (20.57%) of the patients evaluated in this study. Among patients with arthritis of this study, involvement was predominantly polyarticular in 36 (72%) of them, affecting large and small joints simultaneously in 29 (58%). Age greater than 50 years, back pain and crepitus in the joints proved to be factors associated with arthritis. We observed that female smoking important and advanced liver fibrosis (F3 and F4) were associated with arthralgia. Female gender and smoking were important factors associated with myalgia. CONCLUSION: We found a high prevalence of musculoskeletal manifestations among patients with chronic hepatitis C of this service. The most common risk factors for the presence of extra hepatic manifestations were female and older than 50 years. The autoantibodies, although frequently not statistically significant compared with the major musculoskeletal manifestations analyzed. Inflammatory infiltrate and liver transaminase levels did not show statistical significance
1346

Imunogenetické a hormonální predispoziční markery systémových revmatických onemocnění,zejména systémového lupus erythematodu / Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases particularly systemic lupus erythematosus

Fojtíková, Markéta January 2011 (has links)
Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....
1347

Charakterisierung muriner und humaner Fibroblasten mit knorpelerosivem Potential: Characterization of murine and humane fibroblasts with cartilage-erosive potential

Hoffmann, Matthias 14 January 2014 (has links)
Die rheumatoide Arthritis (RA) ist eine chronisch-entzündliche Bindegewebserkrankung mit bevorzugtem Befall der Gelenke. Es bestimmen Knorpel- und Knochendestruktionen das Krankheitsbild. Eine Schlüsselrolle in der Pathogenese nehmen proliferierende, synoviale Fibroblasten (RASF) durch Auflösung der extrazellulären Matrix (EZM), durch Interaktion mit immunkompetenten Zellen und durch Produktion pro-inflammatorischer Zytokine ein. Die vorliegende Arbeit zeigt die Migrationseigenschaften von RASF und zwei verschiedenen murinen (LS48) und humanen (TK188) Fibroblastenzelllinien in einem In-vitro-Migrationsassay. Es wird der Einfluss von Antikörpern sowie verschiedener EZM-Komponenten auf die Migration der Zelllinien untersucht. Die nachfolgende Analyse phänotypischer Charakteristika stellt dabei die besondere Rolle der genannten Fibroblastenzelllinien heraus, welche eine Reihe von Gemeinsamkeiten untereinander und mit RASF besitzen. Sie zeigen ebenso erhöhte Migrationsaktivität unter dem Einfluss eines Chemoattraktants und besitzen ähnliche Destruktionsmuster von Kollagenmatrizen. Beide Zellreihen exprimieren mehr RASF-typische Proteasen, Adhäsionsmoleküle und immunologisch agierende Proteine als nicht pathologisch transformierte Fibroblasten. Ebenso weisen sie eine gesteigerte Stoffwechselaktivität und Proliferationstätigkeit auf. Diese in vitro erbrachten Hinweise auf mögliche Knorpeldestruktionen sollten Anlass für weitere In-vivo-Studien zu den genannten Zelllinien geben.
1348

Wait Times to Rheumatology and Rehabilitation Services for Persons with Arthritis in Quebec

Delaurier, Ashley 08 1900 (has links)
L’arthrite est l’une des causes principales de douleur et d’incapacité auprès de la population canadienne. Les gens atteints d’arthrite rhumatoïde (AR) devraient être évalués par un rhumatologue moins de trois mois suivant l’apparition des premiers symptômes et ce afin de débuter un traitement médical approprié qui leur sera bénéfique. La physiothérapie et l’ergothérapie s’avèrent bénéfiques pour les patients atteints d’ostéoarthrite (OA) et d’AR, et aident à réduire l’incapacité. Notre étude a pour but d’évaluer les délais d’attente afin d’obtenir un rendez-vous pour une consultation en rhumatologie et en réadaptation dans le système de santé public québécois, et d’explorer les facteurs associés. Notre étude est de type observationnel et transversal et s’intéresse à la province de Québec. Un comité d’experts a élaboré trois scénarios pour les consultations en rhumatologie : AR présumée, AR possible, et OA présumée ; ainsi que deux scénarios pour les consultations en réadaptation : AR diagnostiquée, OA diagnostiquée. Les délais d’attente ont été mesurés entre le moment de la requête initiale et la date de rendez-vous fixée. L’analyse statistique consiste en une analyse descriptive de même qu’une analyse déductive, à l’aide de régression logistique et de comparaison bivariée. Parmi les 71 bureaux de rhumatologie contactés, et pour tous les scénarios combinés, 34% ont donné un rendez-vous en moins de trois mois, 32% avaient une attente de plus de trois mois et 34% ont refusé de fixer un rendez-vous. La probabilité d’obtenir une évaluation en rhumatologie en moins de trois mois est 13 fois plus grande pour les cas d’AR présumée par rapport aux cas d’OA présumée (OR=13; 95% Cl [1.70;99.38]). Cependant, 59% des cas d’AR présumés n’ont pas obtenu rendez-vous en moins de trois mois. Cent centres offrant des services publics en réadaptation ont été contactés. Pour tous les scénarios combinés, 13% des centres ont donné un rendez-vous en moins de 6 mois, 13% entre 6 et 12 mois, 24% avaient une attente de plus de 12 mois et 22% ont refusé de fixer un rendez-vous. Les autres 28% restant requéraient les détails d’une évaluation relative à l’état fonctionnel du patient avant de donner un rendez-vous. Par rapport aux services de réadaptation, il n’y avait aucune différence entre les délais d’attente pour les cas d’AR ou d’OA. L’AR est priorisée par rapport à l’OA lorsque vient le temps d’obtenir un rendez-vous chez un rhumatologue. Cependant, la majorité des gens atteints d’AR ne reçoivent pas les services de rhumatologie ou de réadaptation, soit physiothérapie ou ergothérapie, dans les délais prescrits. De meilleures méthodes de triage et davantage de ressources sont nécessaires. / Arthritis is a leading cause of pain and disability in Canada. Persons with rheumatoid arthritis (RA) should be seen by a rheumatologist within three months of symptom onset to begin appropriate medical treatment and improve health outcomes. Early physical therapy (PT) and occupational therapy (OT) are beneficial for both osteoarthritis (OA) and RA and may prevent disability. The objectives of the study are to describe wait times from referral by primary care provider to rheumatology and rehabilitation consultation in the public system of Quebec and to explore associated factors. We conducted a cross-sectional study in the province of Quebec, Canada whereby we requested appointments from all rheumatology practices and public rehabilitation departments using case scenarios that were created by a group of experts. Three scenarios were developed for the rheumatology referrals: Presumed RA; Possible RA; and Presumed OA and two scenarios for the rehabilitation referrals: diagnosed RA and diagnosed OA. Wait times were evaluated as the time between the initial request and the appointment date provided. The statistical analysis consisted primarily of descriptive statistics as well as inferential statistics (bivariate comparisons and logistic regression). Seventy-one rheumatology practices were contacted. For all scenarios combined, 34% were given an appointment with a rheumatologist within three months of referral, 32% waited longer than three months and 34% were refused services. The odds of getting an appointment with a rheumatologist within three months was 13 times greater for the Presumed RA scenario versus the Presumed OA scenario (OR=13; 95% Cl[1.70;99.38]). However, 59% of the Presumed RA cases did not receive an appointment within three months. One hundred rehabilitation departments were also contacted. For both scenarios combined, 13% were given an appointment within 6 months, 13% within 6 to 12 months, 24% waited longer than 12 months and 22% were refused services. The remaining 28% were told that they would require an evaluation appointment based on functional assessment prior to being given an appointment. There was no difference with regards to diagnosis, RA versus OA, for the rehabilitation consultation. RA is prioritized over OA when obtaining an appointment to a rheumatologist in Quebec. However, the majority of persons with RA are still not receiving rheumatology or publicly accessible PT or OT intervention in a timely manner. Better methods for triage and increased resource allocation are needed.
1349

Évaluation du lavage articulaire avec des salines hypertoniques dans le traitement de l’arthrite septique chez le veau

Achard, Damien 08 1900 (has links)
L’arthrite septique chez les bovins est une affection le plus souvent d’origine bactérienne qui est une cause de boiterie fréquente associée à des pertes économiques importantes. Le traitement, qui doit être initié le plus rapidement possible, s’appuie sur l’utilisation combinée d’anti-inflammatoires non stéroïdiens, d’un ou de plusieurs lavages articulaires ainsi que d’antibiotiques administrés de façon systémique pour un minimum de 3 semaines. Cette durée d’administration constitue une difficulté pour les élevages dits biologiques pour lesquels un cahier des charges strict limite un recours prolongé aux antibiotiques. Ainsi le traitement efficace de diverses conditions infectieuses et celui de l’arthrite septique en particulier dans ces élevages peut être compromis. L’objectif de ce travail est de s’appuyer sur les propriétés antimicrobiennes des solutions de saline hypertonique (SSH) pour limiter l’utilisation des antibiotiques dans les cas d’arthrite septique chez les veaux en intégrant ces solutions pour le lavage des articulations infectées. Notre première étude a consisté à déterminer la sécurité d’emploi de deux concentrations de SSH (une commerciale à 7.2% et une maison à 15%) dans des articulations supposées saines chez le veau. Une synovite sévère associée à des signes cliniques caractéristiques d’atteintes articulaires a été observé lors de l’utilisation de SSH 15%. Son utilisation clinique comme solution de lavage articulaire est par conséquent déconseillée. Concernant la SSH 7.2%, malgré une synovite d’intensité variable, nous n’avons pas noté des signes cliniques caractéristiques d’atteintes articulaires. Son utilisation dans un contexte expérimental d’infection articulaire nous a paru réaliste. Notre seconde étude a permis d’évaluer les effets du lavage articulaire avec de la SSH 7.2% dans un modèle expérimental d’infection à Escherichia coli. Trois groupes de traitement ont été constitués. Dans le premier groupe (traitement standard), un lavage était effectué avec du lactate de Ringer (LRS) et les veaux recevaient une administration biquotidienne de ceftiofur par voie intraveineuse pour 21 jours. Dans le deuxième groupe (LRS), un lavage était effectué avec du LRS et aucun antibiotique n’était administré. Enfin dans le troisième groupe (SSH), un lavage était effectué avec de la SSH 7.2% sans qu’aucun antibiotique ne soit administré. Tous les veaux ont reçu du kétoprofen quotidiennement pendant 3 jours. L’inoculation s’est fait au jour 1 et les traitements ont débuté au jour 2. L’efficacité des traitements a été établie sur des critères cliniques, bactériologiques et cytologiques. Dans le modèle que nous avons utilisé, les trois groupes de traitements ont conduits à une guérison clinique et bactériologique satisfaisante (absence de boiterie, de douleur et de croissance bactérienne dans le liquide articulaire en fin d’étude). La guérison cytologique n’a quant à elle pas été jugée satisfaisante avec des moyennes de comptage et de pourcentage en neutrophiles tout groupe confondu bien supérieures aux valeurs normales (11.39x109/l de neutrophiles représentant 74.73% des leucocytes en fin d’étude). Le traitement avec la SSH 7.2% s’est révélé être significativement plus traumatique et pas plus efficace dans l’élimination de l’infection comparativement au traitement LRS. D’autre part, le lavage articulaire au LRS s’est révélé être aussi efficace et sécuritaire que le traitement standard de l’arthrite septique qui incluait 21 jours de ceftiofur administré par voie intraveineuse. Ainsi, bien que le lavage avec de la SSH 7.2% n’est pas démontré de résultats satisfaisants qui permettrait de limiter le recours aux antibiotiques dans les filières biologiques, l’association d’un lavage au LRS avec le ketoprofen s’est révélée être une alternative possible. De nouvelles études sont requises pour confirmer ses résultats et pour déterminer le rôle respectif du lavage articulaire et du ketoprofen dans la guérison lors d’arthrite septique. / Septic arthritis in cattle is mainly an infectious bacteriological disease that is a frequent cause of lameness and is associated with great economic losses. Treatment must be prompt and includes non steroidal anti-inflammatory drugs with one or several joint lavage along with systemic antibiotics for at least 3 weeks. This long course of administration is unachievable for organic production systems where the use of antibiotics is strictly regulated. Thus the treatment of infectious disease with septic arthritis in particular may be jeopardized in these herds. The objectives of this work is to use antimicrobial properties of hypertonic saline solution (HSS) to limit the use of antibiotics in septic arthritis cases in calves, using HSS for joint lavage. In our first study, we assessed the safety of two HSS of different concentrations (commercial 7.2% and home-made 15%) in healthy calves joint. A severe synovitis associated with typical clinical signs of joint lesions was observed when HSS 15% was used. Therefore this solution cannot be recommended for joint lavage in calves. A synovitis of variable degree was observed when HSS 7.2% was used. However no clinical signs or joint lesions were noted. Based on these results, we felt that HSS 7.2% could be tested in an experimental setting of joint infection. In our second study, we evaluate the effects of joint lavage with HSS 7.2% in an experimental infection model with Escherichia coli. Three treatment groups were formed. In the first group, the joint lavage was realized with Lactated Ringer’s Solution (LRS) and calves also received ceftiofur intravenously two times a day for 21 days. In the second group, the joint lavage was realized with LRS and saline was used instead of ceftiofur. In the last group, the joint lavage was realized with HSS 7.2% and saline was used instead of ceftiofur. All calves in this study received ketoprofen once a day for 3 days intravenously. Inoculation of bacteria took place on day 1 and all treatments started on day 2. Treatment’s effectiveness was established upon clinical, bacteriological and cytological criteria. In our model, all treatment groups led to clinical and bacteriological recovery (no lameness, pain or positive culture in the synovial fluid at the end of the experiment). Whatever the treatment group, cytological recovery was no achieved at the end of the study with mean number and percentage of neutrophils far superior when compared to usual values (11.39x109/l of neutrophils representating 74.73% of total leucocytes at the end of the experiment). Joint lavage with HSS 7.2% combined with ketoprofen successfully treat septic arthritis in this model but was significantly more harmful compared to joint lavage with LRS combined with ketoprofen. On the other hand, joint lavage with LRS combined with ketoprofen was found as efficient and safe than the standard treatment of septic arthritis which includes a 21 day administration of intravenous ceftiofur. Therefore, even if HSS 7.2% joint lavage cannot be a good choice to treat septic with the restriction of use of antibiotics in organic herds, the combination of a LRS joint lavage with ketoprofen showed promising results. Further studies are warranted to confirm these latter results and to determine specific effects of the lavage and of ketoprofen.
1350

Relargage d’ions métalliques après l’arthroplastie de la hanche à grand diamètre avec couple de frottement métal sur métal

Amzica, Traian 08 1900 (has links)
La dégénérescence articulaire sévère de la hanche est une pathologie fréquente et son traitement ultime est le remplacement prothétique. L’arthroplastie la plus répandue au monde est la prothèse totale de hanche (PTH) avec un couple de frottement métal-sur-polyéthylène (MPE). Cependant ce type d’intervention présente une longévité limitée à cause de l’usure de PE et ne convient pas aux patients actifs souffrant de coxarthrose sévère tôt dans leur vie. Afin de palier à ce problème, une nouvelle génération de surfaces de frottement métal-sur-métal (MM) est actuellement employée. Ces surfaces de frottement sont utilisées en PTH avec tête de 28 mm, en resurfaçage (RH) et avec la PTH à tête de grand diamètre. Alors qu’il y a beaucoup d’évidence à l’égard du bon fonctionnement des implants PTH 28 mm et du RH, les données quant aux performances in vivo des PTH MM à grand diamètre manquent. Malgré cela, ces implants sont utilisés à grande échelle. Dans un premier temps, l’objectif de ce travail de recherche était d’évaluer l’effet et de comparer les taux d’ions chrome (Cr) et cobalt (Co) chez des sujets porteurs de PTH MM à grand diamètre à ceux de 64 porteurs de RH, tous deux possédant des surfaces de frottement aux propriétés tribologiques identiques. Dans un deuxième temps, nous avons comparé les taux ioniques (Cr, Co et titane (Ti)) entre quatre PTH MM à grand diamètre provenant de fabricants différents (Zimmer, DePuy, Smith & Nephew et Biomet). Les mesures d’ions étaient effectuées dans le sang entier dans un laboratoire indépendant par la technique de spectrophotométrie de masse à haute résolution HR-ICP-MS, pour l’ensemble de ce travail de recherche. Les deux comparaisons ont démontré le rôle crucial joué par la modularité au niveau de la jonction tête-col des PTH MM à grand diamètre. En effet, des écarts considérables dans les concentrations ioniques de Co ont été retrouvés entre les RH et PTH Durom ayant un couple de frottement identique, ainsi qu’entre les 4 différents designs de PTH MM à grand diamètre comparés entre eux. La PTH MM à grand diamètre Durom était la moins favorable alors que celle de Biomet était la plus performante. Nos observations démontrent que des sources inattendues comme la jonction tête-col de certains implants PTH MM à grand diamètre peuvent contribuer au relargage ionique systémique. Une meilleure compréhension de ce phénomène est indispensable avant l’utilisation clinque de nouveaux implants de ce type. / The treatment for advanced degenerative hip disease consists in replacing the native joint with artificial implants. This is a very common procedure and the type of arthroplasty most practiced worldwide is metal-on-polyethylene (MOPE) total hip replacement (THR). However, this type of bearing has limited lifespan and is not adapted for active patients struggling with hip osteoarthritis early in their lives. In order to increase implant longevity, new generation, metal-on–metal (MOM) bearing surfaces is used nowadays in this particular population. These MOM bearings are used in 28 mm THR, in resurfacing hip arthroplasty (RH) and in large diameter head THR. Although consistent results have been obtained with the 28 mm THR and RH, large diameter head THR are increasingly used despite lack of scientific data about their performances. The main purpose of our first paper was to compare chromium (Cr) and cobalt (Co) concentrations among patients implanted with large diameter head THR and with RH. In this case, both bearing surfaces presented identical tribological properties. In the second paper, we compared performances in terms of ion release (Cr, Co and titanium (Ti)) from four different manufacturers of large diameter head THR systems (Zimmer, DePuy, Smith & Nephew and Biomet). Whole blood was used for all samples and ion measurements were conducted by an independent laboratory in a blinded fashion, using high-resolution inductive coupled plasma mass spectrophotometry (HR-ICP-MS). Both papers have emphasized the crucial role played by modularity at the head-neck junction in metal ion release from large diameter THR MOM bearings. In fact, significant differences were found in Co ion concentration between large head THR and HRA as well as among the different designs of large head THRs. Briefly, the Durom large head THR system was the least favorable implant while the Biomet large head THR system showed the best results. Our results prove that systemic ion release might origin from surprising sources such as modularity at the head-neck junction in patients implanted with certain large head MOM THR systems. A better comprehension of head-neck junction biomechanics is necessary before clinical use of such new devices.

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