Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population in the western world. It is characterised by a tissue specific attack of cartilage in peripheral joints. Collagen induced arthritis (CIA) is one of the most commonly used animal models for (RA), with similar symptoms and histopathology. CIA is induced by immunisation of mice with type II collagen (CII), and the immunodominant part was previously found to be located between residues 256-270. This thesis describes the interaction between the MHC molecule, glycopeptide antigens from CII and the T cells that is essential in development of CIA. The glycopeptide properties for binding to the mouse MHC molecule Aq have been studied, as well as interaction points in the glycopeptide that are critical for stimulation of a T-cell response. The thesis is based on five studies. In the first paper the minimal glycopeptide core, that is required for binding to the Aq molecule while still giving a full T cell response was determined. The second paper studied the roles of amino acid side-chains and a backbone amide bond as T-cell contact points. In the third paper the hydrogen bond donor-acceptor characteristics of the 4-OH galactose hydroxyl group of the glycopeptide was studied in detail. In the fourth paper we established a structure activity relationship (QSAR model) for (glyco)peptide binding to the Aq molecule. Finally, the stereochemical requirements for glycopeptide binding to the Aq molecule and for T-cell recognition was studied in the fifth paper. The study was performed using collagen glycopeptide analogues, which were synthesised on solid phase. Amide bond and hydroxyl group isosteres were introduced for study of hydrogen bond donor-acceptor characteristics. Statistical methods were used to design a representative peptide test set and in establishing a QSAR model. The results give a deeper understanding of the interactions involved in the ternary MHC-glycopeptide-T cell complex. This information contributes to research directed towards finding new treatments for RA.

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Darbo metu buvo išnagrinėta įvairių faktorių (kovariančių) įtaka reumatoidiniu artritu sergančio 531 ligonio mirtingumui. Buvo taikomas vienas iš regresinių išgyvenamumo modelių – Cox’o modelis. Iš minėtos 531 ligonio imties mirę buvo 32 ligoniai. Iš pradžių buvo tiriama ligonių imtis laiko nuo ligos pradžios aspektu. Šiuo atveju prognozuojantys veiksniai buvo amžius, kada liga buvo diagnozuota (AMZDGN), lytis (LYTKOD), gydymas Metotreksatu (GYD_MTX) ir gydymas Azatriopinu/Imuranu (AZA_IMUR). Vėliau, tiriant ligonių mirtingumą kaip amžiaus funkciją, nustatyti svarbiausi lemiantys veiksniai buvo šie: ligonių lytis (LYTKOD) ir gydymas Azatriopinu/Imuranu (AZA_IMUR). Gauti rezultatai, t.y. ligonių išgyvenamumą lemiančios kovariantės (veiksniai), beveik visiškai sutampa su gydytojų nurodytais. Tai dar kartą patvirtina matematinių statistinių modelių, šiuo atveju nagrinėjamo Cox‘o modelio, taikymo realiame gyvenime, svarbą. Kitai duomenų imčiai, t.y. vėžiu sergančių ligonių duomenų aibei, buvo taikomas Persikertančių mirimų intensyvumų (SCE) modelis, t.y. tikrinama Cox‘o modelio adekvatumo duomenims hipotezė. Hipotezė buvo atmesta, nes minėtiems duomenims Cox‘o modelis negalioja. Pagrindinis darbo rezultatas yra šis: gautas kriterijus Cox‘o modelio adekvatumui tikrinti, naudojant nupjautus iš kairės ir cenzūruotus iš dešinės duomenis, sudarytos programos kriterijui realizuoti. Reumatoidinio artrito ligonių duomenų aibei, t.y. nupjautiems iš kairės ir cenzūruotiems iš dešinės... [toliau žr. visą tekstą] / In this work the Cox proportional hazards model was applied to investigate the influence of various factors (covariates) to mortality of rheumatoid arthritis patients of Vilnius. In the first case, the sample of 531 patients was analysed. Analysing survival of patients of the sample as function of time from the beginnig of the disease, the prognostic factors were LYTKOD (the sex of patients), AMZDGN (patients‘ age, when the rheumatoid arthritis was diagnosed), GYD_MTX (treatment with metotrexat) and AZA_IMUR (treatment with Azatriopin/Imuran). When survival was analysed as function of age then the prognostic factor were LYTKOD (the sex of patients) and AZA_IMUR (treatment with Azatriopin/Imuran). The results are almost identical to those, which doctors suggested. This fact confirms the importance of using mathematical statistical models to solve the problems of the real life. In this case, the importance of using the Cox model. On the other hand, Simple cross-effects (SCE) model was aplied for the sample of canser patients. In the case of this model the hypothesis of Cox model fiting for canser patients‘ data was rejected. The most important result of this work is that the criterion of Cox model fitting to left truncated and right censored data was constructed. Also a program of SAS for the criterion was created. The the hypothesis of Cox model fiting for the rheumatoid arthritis patients wasn‘t rejected, because Cox model fit for these data.

Purpose: To determine whether reduced serum levels of AHSG and elevated levels of BMP-2, 4, 7 are associated with post-arthroplasty HO. Patients: Thirty arthroplasty patients were included, 15 with evidence of peri-articular HO and 15 without (NHO). Methods: Blood samples were collected from all patients ≥ 8 weeks after arthroplasty. Analytes were measured using ELISAs. Mann-Whitney U tests were performed to compare serum analyte concentrations between HO and NHO groups, and between arthroplasty patients and healthy humans. Results: There is no difference in serum concentrations of AHSG, BMP-2, 4, 7 between HO and NHO patients. Arthroplasty patients showed significantly higher BMP-2 and BMP-4 and lower AHSG serum levels compared to healthy humans (p < 0.01). Conclusion: Baseline BMP-2, 4, 7 and AHSG serum levels are not markers of acquired HO. However, elevated baseline levels of BMP- 2, 4 and reduced levels of AHSG appear to be markers of severe inflammatory arthritis.

Purpose: To determine whether reduced serum levels of AHSG and elevated levels of BMP-2, 4, 7 are associated with post-arthroplasty HO. Patients: Thirty arthroplasty patients were included, 15 with evidence of peri-articular HO and 15 without (NHO). Methods: Blood samples were collected from all patients ≥ 8 weeks after arthroplasty. Analytes were measured using ELISAs. Mann-Whitney U tests were performed to compare serum analyte concentrations between HO and NHO groups, and between arthroplasty patients and healthy humans. Results: There is no difference in serum concentrations of AHSG, BMP-2, 4, 7 between HO and NHO patients. Arthroplasty patients showed significantly higher BMP-2 and BMP-4 and lower AHSG serum levels compared to healthy humans (p < 0.01). Conclusion: Baseline BMP-2, 4, 7 and AHSG serum levels are not markers of acquired HO. However, elevated baseline levels of BMP- 2, 4 and reduced levels of AHSG appear to be markers of severe inflammatory arthritis.

Le criblage virtuel est largement employé pour la recherche de nouveaux médicaments.La sélection de structures pour les méthodes de criblage virtuel basées sur la structure reste problématique. Nous avons montré que les propriétés physico-chimiques du site de liaison, critères simples et peu coûteux en temps de calcul, pouvaient être utilisées pour guider celle-ci.L’évaluation des méthodes de criblage virtuel, critique pour vérifier leur fiabilité, repose sur la qualité de banques d’évaluation. Nous avons construit la NRLiSt BDB, n’incluant que des données vérifiées manuellement et prenant en compte le profil pharmacologique des ligands. Une étude à l’aide du logiciel Surflex-Dock montre qu’elle devrait devenir la base de données de référence, pour l’évaluation des méthodes de criblage virtuel et pour rechercher de nouveaux ligands des récepteurs nucléaires. L’application d’un protocole hiérarchique de criblage in silico/in vitro, a permis d’identifier de nouveaux composés inhibiteurs de l’IL-6, potentiellement utilisables dans le traitement de la polyarthrite rhumatoïde. Les résultats in vitro devront être confirmés par des tests in vivo. / Virtual screening is widely used in drug discovery processes.Structure selection in structure-based virtual screening methods is still problematic. We showed that simple and “low cost” binding site physico-chemical properties could be used to guide structure selection.The evaluation of virtual screening methods, necessary to ensure their reliability, relies on benchmarking databases quality. We created the NRLiSt BDB, gathering only manually curated data and taking into account ligands pharmacological profiles. A study using Surflex-Dock showed that the NRLiSt BDB should become the reference, both for the evaluation of virtual screening methods and for the identification of new ligands of the nuclear receptors.The use of a in silico/invitro hierarchical approach screening allowed to identify new IL-6 inhibitors, that could be used in rheumatoid arthritis treatment. In vitro results should be confirmed in vivo.

La polyarthrite rhumatoïde (PR) est une maladie auto-immune chronique. Elle est caractérisée par une inflammation persistante touchant de multiples petites articulations, causant douleurs, rougeurs, gonflements et déformations. Des études menées auprès de patients et d’animaux ont démontré que certains auto-anticorps, cytokines et enzymes tissue-déstructives sont des médiateurs importants dans le développement de la PR. Au cours des deux dernières décennies, les traitements de fond (DMARDs en anglais) ont été démontrés très efficaces pour traiter la PR. D'autre part, des effets secondaires ont été rapportés pour ces traitements, par exemple l'augmentation du risque d'infections opportunistes. L’objectif de ce travail est d’acquérir des connaissances sur le rôle du TL1A (TNF-like molécule 1 A; TNFSF15) et son partenaire Nob1 (Pno1 ; YOR145c) dans la pathogenèse de la PR afin de découvrir de nouveaux médicaments contre ces molécules dans l'avenir. TL1A est un membre de la famille du TNF. Il déclenche des signaux co-stimulateurs via le récepteur de mort 3 (DR3) et induit la prolifération ainsi que la production des cytokines pro inflammatoires par les lymphocytes. Des données multiples suggèrent l'implication de la cascade TL1A-DR3 dans plusieurs maladies auto-immunes. Donc, nous avons proposé les hypothèses suivantes:1) la production locale de TL1A dans les articulations est un composant d’un cercle vicieux qui aggrave la PR; 2) dans la PR, la production de TL1A dans les organes lymphoïde augmente la production d’auto-anticorps pathogénique. Au cours de ce travail, nous avons démontré que la TL1A aggrave la maladie chez les souris où l’arthrite a été induite par le collagène (AIC). Par ailleurs, nous avons constaté que l’expression de TL1A est élevée dans les tissus atteints de PR ainsi que dans les ganglions lymphatiques drainant de la souris AIC. Mécaniquement, nous avons découvert que la TL1A est induite par le TNF-α et IL-17 produits par les cellules T in vitro. Ces résultats montrent directement que les TL1A-DR3 jouent un rôle essentiel dans la pathogenèse de la PR. De plus, afin de poursuivre notre étude, la TL1A a été génétiquement supprimée dans les souris (TL1A KO). Nous avons montré que les souris TL1A KO n’ont aucune anomalie apparente et aucun dysfonctionnement du système immunitaire dans des conditions normales. Cependant, ces souris manifestent des AIC améliorées et une réduction significative des niveaux d'anticorps, anti-collagène du type II i dans le sérum. Nous avons trouvé que les ganglions lymphatiques de drainage (dLNs) de souris KO étaient plus petites avec une cellularité inférieure comparativement aux souris WT de 14 jours après l’immunisation. De plus, nous avons découvert que le DR3 a été exprimé par les cellules plasmatiques dans l’étape de la différenciation terminale et ces cellules surviennent mieux en présence de TL1A. La conclusion de cette étude apporte des nouvelles connaissances sur le rôle de TL1A qui amplifie les réponses humorales d’AIC. Nous avons suggéré que TL1A pourrait augmenter la réponse d’initiation d'anticorps contre collagène II (CII) ainsi que prolonger la survie des cellules plasmatiques. Une autre molécule qui nous intéresse est Pno1. Des études antérieures menées chez la levure ont suggéré que Pno1 est essentielle pour la néogénèse du protéasome et du ribosome Le protéasome étant crucial pour la différenciation terminale des cellules plasmatiques pendant les réponses humorales chez les mammifères, nous avons donc supposé que Pno1 joue un rôle dans la production d'anticorps pathogenique dans la PR via la voie du protéasome. Nous avons donc généré des souris génétiquement modifiées pour Pno1 afin d’étudier la fonction de Pno1 in vivo. Cependant, une mutation non-sens dans le Pno1 provoque une létalité embryonnaire à un stade très précoce chez les souris. D'autre part, une réduction de 50% de Pno1 ou une surexpression de Pno1 n’ont aucun effet ni sur le fonctionnent des cellules T et B, ni sur les activités du protéasome ainsi que sur la réponse humorale dans l’AIC. Ces résultats suggèrent que Pno1 est une molécule essentielle sans redondance. Par conséquent, il n’est pas une cible appropriée pour le développement de médicaments thérapeutiques. En conclusion, nos études ont révélé que la TL1A n’est pas essentielle pour maintenir les fonctions du système immunitaire dans des conditions normales. En revanche, il joue un rôle critique dans la pathogenèse de la PR en favorisant l'inflammation locale et la réponse humorale contre des auto-antigènes. Par conséquent, une inhibition de la TL1A pourrait être une stratégie thérapeutique pour le traitement de la PR. Au contraire, Pno1 est essentiel pour la fonction normale des cellules. Une délétion totale pourrait entraîner des conséquences graves. Il n’est pas une cible appropriée pour développer des médicaments de la PR. / Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of multiple small joints, which manifests pain, redness, swelling, and deformation. Studies with patients and animal models have found that autoantibodies, cytokines and tissue-destructive enzymes are important mediators of the pathogenesis of RA. In the past two decades, biologic disease-modifying antirheumatic drugs (DMARDs) have achieved great success in the treatment of RA. On the other hand, they are also associated with adverse effect like increasing the chance of opportunistic infections. The aim of present work was to investigate the roles of TNF-like molecule 1A (TL1A; TNFSF15) and partner of Nob1 (Pno1; YOR145c) in the pathogenesis of RA for developing novel drugs based on these molecules in the future. TL1A is a member of the TNF superfamily. It triggers costimulatory signals though death receptor 3 (DR3) and induces the proliferation and pro-inflammatory cytokine production in lymphocytes. Multiple lines of evidence suggest the implication of TL1A-DR3 signaling in several autoimmune diseases. Therefore, We hypothesized that 1) local TL1A production in the joints is a component of a vicious circle aggravating RA; 2) in RA, TL1A production in lymphoid organs enhances pathogenic autoantibody production. We demonstrated that the TL1A aggravates disease in murine collagen-induced arthritis (CIA). Moreover, we found elevated TL1A expression in RA-affected tissues, as well as in the draining lymph nodes (dLNs) of CIA mice. Mechanistically, we discovered that TL1A induces TNF-α and IL-17 production by T cells in vitro. These findings provided direct evidence that TL1A-DR3 signaling plays a critical role in the pathogenesis of RA. TL1A knockout (TL1A KO) mice were generated to further our study. We showed that TL1A KO mice have no visual anomaly, and no malfunction of immune system under a normal circumstance. However, they display ameliorated CIA and significantly reduced anti-Collagen II antibody levels in sera. We found that the draining lymph nodes (dLNs) from KO mice were smaller in size and lower in cellularity compared with their WT counterparts 14 days after immunization. Furthermore, we discovered that terminally differentiated plasma cells express DR3 and they survive better in the presence of TL1A. Our findings in this study present novel knowledge about the role of iii TL1A promoting the humoral responses in CIA; we suggest that TL1A could elevate the initial Ab response against Collagen II (CII), as well as prolong the survival of plasma cells producing such pathogenic Abs. Another molecule we were interested in present study is Pno1. Previous studies conducted in yeast suggest that Pno1 is essential to the proteasome and ribosome neogenesis. Since proteasome is crucial for the terminal differentiation of plasma cells during the humoral response in mammals, we hypothesized that Pno1 plays a role in the pathogenic Ab production in RA by affecting the proteasome assembly. For this purpose, we generated pno1 gene- modified mice to investigate the function of Pno1 in vivo. However, null-mutation in pno1 causes embryonic lethality in mice at a very early stage. On the other hand, a half amount reduction or overexpression of Pno1 is neither harmful nor useful to the T and B cell function, proteasome activities as well as humoral immune responses in CIA. These findings suggest that Pno1 is a vital molecule with no redundancy and is absolutely required for cell function, but animals can function normally with a small fraction of the normal Pno1 expression level. Thus, it might not be an appropriate target for developing therapeutic drugs. In conclusion, our studies suggest that TL1A seems not essential in maintaining the immune functions under normal circumstances, but plays critical roles in the pathogenesis of RA by promoting local inflammation and humoral immune responses against autoantigens. Therefore, inhibiting TL1A could be a propitious therapeutic strategy for treating RA. In contrast, Pno1 is vital to the normal cell function, and its disruption could cause disastrous consequences. Thus, it might not be a good drug target for treating RA.

Background and aim: As an experienced paediatric nurse I have recognised that adolescents with persistent chronic childhood diseases fall between two chairs. International studies support this recognition. Norwegian adolescents with juvenile idiopathic arthritis are no exception. Chronic arthritis from childhood might have far-reaching consequences for the growth and development of the child, and for the family and community. The fact that a considerable proportion of children with JIA continue to have active disease and disease residua through adolescence into adulthood underlines the importance of illuminating the situation in a public-health perspective. Through this study I aim at exploring physical and psychosocial health among young adults with JIA in a life-span perspective from childhood and adolescence into adult life. Methods: The thesis has a qualitative and a quantitative approach. Study I had an abductive explorative design. The experiences and perceptions of health-care transition were explored by focus-group interviews with young people with JIA and related health professionals respectively. Qualitative content analysis was utilised. Study II had an abductive explorative design with qualitative interviews to explore young adults’ experiences of living with JIA in a life-span perspective. Qualitative content analysis was utilised. Study III had a longitudinal deductive design. The standardised questionnaires of Health Assessment Questionnaire, General Health Questionnaire version 30, and Visual Analogue Scales of pain, fatigue, and illness were utilised to explore physical ability, psychosocial health, pain, fatigue, and illness in a cohort of patients with JIA 18.3 years after symptom-onset. Comparisons with baseline and first follow-up were performed. Data were analysed by descriptive statistics and non parametric tests. Study IV had a cross-sectional deductive design. In addition to the questionnaires utilised in study III, the questionnaire of SF-36 Health Survey and data on education, employment, need of assistive equipment at work, and use of health services the previous year were employed. Comparisons with Norwegian population- based data were performed. Data were analysed by descriptive statistics, and parametric and non parametric tests. Findings: In study I, ability to live a meaningful and responsible adult life seemed to be a common goal. Obstacles for the young people were the nature of the disease, a lack of focus on transition processes, and overprotective parents and health professionals. Obstacles for the health professionals were lack of inter-professional and inter-institutional formal co-operation and agreed practice, and lack of competence on adolescent development and health. Study II demonstrates that living with JIA implies a constant oscillation between struggle and adjustment to an insecure everyday life and an unpredictable life course. This was expressed as bodily experiences of limitation and freedom, interpersonal experiences of being included or set on the sidelines, and intrapersonal perceptions of insecurity and confidence. Of the 55 young adults with JIA in study III, 21 reported physical disability, and 12 reported psychiatric distress within the clinical range. Furthermore, 26 patients reported illness, 27 pain, and 33 fatigue above 10 on the VAS scale (0-100). Significant correlations were found between physical disability, pain, illness and fatigue, and between psychiatric distress, pain, and fatigue. Comparisons from first to second follow-up of the cohort showed no significant changes in physical or psychosocial functioning, pain, or fatigue. In study IV, physical ability and pain were significant predictors of the average variation of physical health while psychiatric distress and female gender were significant predictors of the average variation of mental health. Impaired physical health was associated with low rates of psychiatric distress. As compared to the general Norwegian population, impaired HRQL in the physical domain was found, but not in the mental domain, and a higher level of education, but similar employment rate. Conclusion: The four studies demonstrate complementary findings. Discrepancies between interviews and inquiries indicate that the interviews illuminate a depth and breadth of life with JIA in a life-span perspective that not is possible to unveil solely by standardised inquiries. Although persistent favourable outcomes are found physically and psychosocially from first to second follow-up, young adults with JIA reveal that life with JIA encompasses struggle and adjustment to an insecure life situation physically, psychologically, and socially. / Bakgrunn og mål: Mange års erfaring som pediatrisk sykepleier har vist meg at unge mennesker med kroniske barnesykdommer faller mellom to stoler i overgangen til voksent liv. Internasjonale studier støtter denne erfaringen, og norske ungdommer med juvenil idiopatisk artritt er ikke noe unntak. Kronisk barneleddgikt kan ha vidtrekkende konsekvenser for barnets vekst og utvikling, for familien og samfunnet for øvrig. Det faktum at mange barn fortsetter å ha aktiv sykdom og senvirkninger av sykdommen gjennom ungdomsårene og inn i voksent liv, understreker betydningen av å belyse de unges helse og livssituasjon i et folkehelseperspektiv. Gjennom denne avhandlingen ønsker jeg å undersøke fysisk, psykisk og sosial helse blant unge voksne med barneleddgikt i et livsløpsperspektiv. Metode: Avhandlingen har en kvantitativ og en kvalitativ tilnærming. Studie I hadde en abduktiv eksplorerende design. Gjennom fokusgruppeintervjuer med respektivt unge mennesker med barneleddgikt og helsepersonell innen revmatologi ble opplevelser og erfaringer med overgangen til voksenhelsetjenesten undersøkt. Kvalitativ innholdsanalyse ble benyttet. Studie II hadde også en abduktiv eksplorerende design med kvalitative intervjuer for å utforske livet med barneleddgikt blant unge voksne i et livsløpsperspektiv. Kvalitativ innholdsanalyse ble benyttet også her. Studie III hadde en longitudinell deduktiv design. Standardiserte spørreskjemaer om fysisk funksjon (Health Assessment Questionnaire), psykososial helse (General Health Questionnaire versjon 30), og sykdomsfølelse, smerte og trøtthet (Visual Analogue Scales) ble anvendt for å undersøke selvvurdert helse blant kohorten 18.3 år etter symptomdebut. Sammenligning med baselinestudien og første oppfølging ble gjort. Deskriptiv statistikk og non parametriske tester ble benyttet i dataanalysen. Studie IV var en deduktiv tverrsnittsstudie. I tillegg til spørreskjemaene som ble benyttet i studie III, ble spørreskjemaet SF-36 Health Survey benyttet for å undersøke selvvurdert helserelatert livskvalitet. Data fra telefonintervjuet om utdanning, yrkesaktivitet, behov for hjelpemidler på jobb, og behov for helsetjenester siste året ble inkludert. Sammenligninger ble gjort med norske normdata. Deskriptiv statistikk, parametriske og non parametriske tester ble benyttet i dataanalysen. Funn: Studie I viste at det å være i stand til å leve et meningsfylt og ansvarsbevisst voksenliv var et felles mål. Hindringer for de unge viste seg å være sykdommens natur, manglende fokus på overgangsprosessen, og overbeskyttende foreldre og helsepersonell. Hindringer blant helsepersonell var mangel på formelt samarbeid og omforent praksis på tvers av profesjoner og institusjoner, og mangel på kompetanse om ungdoms helse og utvikling. Studie II viste at livet med barneleddgikt innebærer en konstant veksling mellom kamp og tilpasning til et usikkert dagligliv og et uforutsigbart livsløp. Dette kom til uttrykk i erfaringer om kroppslige begrensninger eller frihet, interpersonlige opplevelser av å bli inkludert eller satt til side, og intrapersonlige opplevelser av usikkerhet eller trygghet. Blant de 55 unge voksne med barneleddgikt i studie III rapporterte 21 fysiske funksjonshemninger og 12 psykiatrisk distress. Videre rapporterte 26 pasienter sykdomsfølelse, 27 smerter, og 33 trøtthet med en skåring på 10 eller mer på VAS-skalaene (0-100). Signifikante korrelasjoner ble funnet mellom fysisk funksjonshemning, smerter, sykdomsfølelse og trøtthet, og mellom psykiatrisk distress, smerter og trøtthet. Sammenligninger fra første til andre oppfølging av kohorten viste ingen signifikante endringer i fysisk eller psykisk funksjonsevne, smerter eller trøtthet. Studie IV viste at fysisk funksjons-hemning og smerter var signifikante prediktorer for den gjennomsnittlige variasjonen i fysisk helse, mens psykiatrisk distress og kvinnelig kjønn var signifikante prediktorer for den gjennomsnittlige variasjonen i mental helse. Sviktende fysisk helse var ikke assosiert med psykiatrisk distress. Sammenlignet med norske normdata fant vi sviktende helserelatert livskvalitet i det fysiske domene, men ikke i det mentale domene, og høyere utdanningsnivå, men ingen forskjell i yrkesaktivitet. Konklusjon: Funnene fra de fire delstudiene kompletterer hverandre. Diskrepansen mellom funnene fra intervjuene og spørreskjemaene belyser en bredde og dybde i opplevelsene avlivet med barneleddgikt som det ikke er mulig å avdekke bare gjennom bruk av standardiserte spørreskjemaer. Selv om funnene viser vedvarende positive utfall av sykdommen både fysisk og psykososialt fra første til andre oppfølging, viser unge mennesker med barneleddgikt at livet innebærer kamp og tilpasning til en usikker livssituasjon fysisk, psykisk og sosialt.

Darbo tikslas. Įvertinti sergančiųjų reumatoidiniu artritu darbingo amžiaus žmonių gyvenimo kokybės sąsajas su sveikatos paslaugų prieinamumu Prienų rajone. Uždaviniai. Įvertinti sergančiųjų reumatoidiniu artritu darbingo amžiaus žmonių klinikinę charakteristiką ir sąsajas su socialiniais – ekonominiais veiksniais. Ištirti sergančiųjų reumatoidiniu artritu darbingo amžiaus žmonių savarankiško judėjimo ir apsitarnavimo galimybes. Įvertinti sergančiųjų reumatoidiniu artritu darbingo amžiaus žmonių gydymo įstaigos pasiekiamumo ir aptarnavimo galimybes. Įvertinti sergančiųjų reumatoidiniu artritu gyvenimo kokybės ir skausmo intensyvumo sąsajas su aptarnavimu ir sveikatos priežiūros paslaugų prieinamumo galimybėmis. Tyrimo metodika. Kiekybinis momentinis tyrimas. Anketinė apklausa, naudota SF – 36, DAS 28 ir paruoštas bendrojo pobūdžio klausimynas. Analizuojamosios imties dydis – 67 reumatoidiniu artritu sergantys asmenys. Atsako dažnis – 74,4 proc. Gautiems duomenims apdoroti naudota SPSS 22.0. Rezultatai. Tyrime dalyvavo 61,2 proc. moterų ir 38,8 proc. vyrų. Patenkinamai savo sveikatos būklę dažniau vertino dirbantys respondentai, gyvenantys santuokoje, kaime. Nustatyta, kad sąnarių skausmas dažnai vargina 50,7 proc. respondentų, sąnarių sutinimas – 40,3 proc. tiriamųjų, rytinis sąnarių sustingimas – 34,3 proc. apklaustųjų, sąnarių judesių ribotumas – 52,2 proc. Nedirbantys, gaunantys mažas pajamas respondentai dažniau teigė turintys daugiau sutinusių ir skausmingų sąnarių... [toliau žr. visą tekstą] / Aim of the study. To evaluate the quality of life and its links with accessibility to healthcare services for working age patients with rheumatoid arthritis in Prienai region. Objectives. To evaluate the clinical characteristics and their links to the social - economic factors for working age patients with rheumatoid arthritis. To analize the self-movement and the self-service capabilities for working age patients with rheumatoid arthritis. To evaluate the reach of medical institutions and the service capabilities for working age patients with rheumatoid arthritis. To evaluate the quality of life, the intensity of pain and their links with accessibility to healthcare services for working age patients with rheumatoid arthritis. Methods. Quantitative cross sectional research. The size of the sample under analysis – 67 patients with rheumatoid arthritis. The frequency of the response is 74,4 %. The statistical analysis of data was performed using statistical package SPSS Statistics 22.0. Results. 61,2% women and 38,8% man participated in the study. Working in, living in marriage, living in the village respondents their health evaluated satisfactory more often. The pain of joints more often suffer 50,7% of respondents, the swelling of joints – 40,3%, morning stiffness – 34,3%, limitation of joint movement – 52,2%. The unemployed, with low incomes respondents affirmed about the swollen and the painful joints more often. Respondents living in the village and the employed... [to full text]

Biotribology, the study of lubrication, wear and friction within the body, has become a topic of high importance in recent times as we continue to encounter debilitating diseases and trauma that destroy function of the joints. A highly successful surgical procedure to replace the joint with an artificial equivalent alleviates dysfunction and pain. However, the wear of the bearing surfaces in prosthetic joints is a significant clinical problem and more patients are surviving longer than the life expectancy of the joint replacement. Revision surgery is associated with increased morbidity and mortality and has a far less successful outcome than primary joint replacement. As such, it is essential to ensure that everything possible is done to limit the rate of revision surgery. Past experience indicates that the survival rate of the implant will be influenced by many parameters, of primary importance, the material properties of the implant, the composition of the synovial fluid and the method of lubrication. In prosthetic joints, effective boundary lubrication is known to take place. The interaction of the boundary lubricant and the bearing material is of utmost importance. The identity of the vital active ingredient within synovial fluid (SF) to which we owe the near frictionless performance of our articulating joints has been the quest of researchers for many years. Once identified, tribo tests can determine what materials and more importantly what surfaces this fraction of SF can function most optimally with. Surface-Active Phospholipids (SAPL) have been implicated as the body’s natural load bearing lubricant. Studies in this thesis are the first to fully characterise the adsorbed SAPL detected on the surface of retrieved prostheses and the first to verify the presence of SAPL on knee prostheses. Rinsings from the bearing surfaces of both hip and knee prostheses removed from revision operations were analysed using High Performance Liquid Chromatography (HPLC) to determine the presence and profile of SAPL. Several common prosthetic materials along with a novel biomaterial were investigated to determine their tribological interaction with various SAPLs. A pin-on-flat tribometer was used to make comparative friction measurements between the various tribo-pairs. A novel material, Pyrolytic Carbon (PyC) was screened as a potential candidate as a load bearing prosthetic material. Friction measurements were also performed on explanted prostheses. SAPL was detected on all retrieved implant bearing surfaces. As a result of the study eight different species of phosphatidylcholines were identified. The relative concentrations of each species were also determined indicating that the unsaturated species are dominant. Initial tribo tests employed a saturated phosphatidylcholine (SPC) and the subsequent tests adopted the addition of the newly identified major constituents of SAPL, unsaturated phosphatidylcholine (USPC), as the test lubricant. All tribo tests showed a dramatic reduction in friction when synthetic SAPL was used as the lubricant under boundary lubrication conditions. Some tribopairs showed more of an affinity to SAPL than others. PyC performed superior to the other prosthetic materials. Friction measurements with explanted prostheses verified the presence and performance of SAPL. SAPL, in particular phosphatidylcholine, plays an essential role in the lubrication of prosthetic joints. Of particular interest was the ability of SAPLs to reduce friction and ultimately wear of the bearing materials. The identification and knowledge of the lubricating constituents of SF is invaluable for not only the future development of artificial joints but also in developing effective cures for several disease processes where lubrication may play a role. The tribological interaction of the various tribo-pairs and SAPL is extremely favourable in the context of reducing friction at the bearing interface. PyC is highly recommended as a future candidate material for use in load bearing prosthetic joints considering its impressive tribological performance.