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Gastrointestinal Manifestations and Pathophysiological Mechanisms in Systemic SclerosisFranck-Larsson, Karin January 2010 (has links)
Systemic sclerosis (SSc) is a rare systemic, autoimmune disease characterized by vascular changes and fibrosis of the skin and internal organs. Patients with SSc more frequently than healthy controls reported upper gastrointestinal (GI) symptoms, which was more abundant in the diffuse cutaneous form (dcSSc) of the disease than in the limited (lcSSc). One-third of a population-based cohort of 79 SSc patients reported faecal incontinence, compared to 11% in 158 healthy matched controls (p<0.001), and this symptom negatively influenced general well-being and social life. Impaired rectal sensibility, rectal bleeding, irritable bowel syndrome-like symptoms, abdominal pain, the need for manual assistance at defecation, and the use of oral laxatives were more common in patients than in controls. SSc patients reported lower scores in both physical and mental scales of the SF-36 questionnaire than controls, indicating worse health-related quality of life. Gastric emptying was slower in patients than in controls, and a higher prevalence of delayed gastric emptying in patients with dcSSc indicated more severe GI tract involvement than in lcSSc. Electrogastrographic recordings did not correlate to gastric emptying results, indicating factors other than defective myoelectric signals contributed to disturbed gastric function. SSc patients with faecal incontinence had lower anal squeeze pressures than patients without this symptom. Only patients with faecal incontinence had ultrasonographic abnormalities in the internal and external anal sphincters, and absence of the rectoanal inhibitory reflex. Thus, faecal incontinence in SSc patients may depend on both neurogenic and structural mechanisms. A discrete increase in fibre density observed in a majority of SSc patients might have implications from a disease mechanistic perspective. Sera from 47% of 70 SSc patients had the capacity to induce interferon (IFN)-α, production which correlated to the presence of anti-RNP and anti-SSA autoantibodies. Increased serum levels of IFN-inducible protein were associated with vascular manifestations, and increased serum levels of IFN-α with digital ulcers. Increased serum levels of monocyte chemoattractant protein-1 or IFN-α were associated with lung fibrosis. An activated type I IFN system previously observed in several other systemic autoimmune diseases is also present in SSc and may contribute to vascular pathology and the pro-fibrotic process.
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Time window of TNF-a in innate immunity against staphylococcal infectionAli, Abukar January 2010 (has links)
Staphylococcus aureus (S. aureus) is responsible for many human diseases including septic arthritis and sepsis shock. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in inflammation and produced mainly by macrophages and monocytes. It is believed to be involved in pathogenesis of septic arthritis. Time window of TNF-a in innate immunity against staphylococcal infection was studied in this project. Two experiments were carried out: In the first experiment mice were infected with a low dose (8x106cfu/mouse) of S. aureus to induce septic arthritis whereas in the second experiment the mice were infected with a higher dose (8x107cfu/mouse) of S. aureus to induce sepsis shock. All mice were divided into three groups. The first group was treated with anti-TNF-α 20 minutes after infection. The second group was treated with the anti-TNF-α three days after infection. The third group served as control and was injected with PBS instead of anti-TNF-α. The mice were regularly weighed and signs of arthritis and mortality were recorded. Two weeks after inoculation bacteria viable counts in different organs was done, as well as histopathological assessment of joints and measurement of cytokines in blood. We have observed that mice treated with anti-TNF-α had less severe arthritis and also less mortality. However, they had more bacteria accumulated in the kidneys and lost more weight compared to the control group. The results were mostly seen in the group early treated with TNF-α, compared to the late treated group. We conclude that anti-TNF-α might be potentially used as a therapy against septic arthritis and sepsis shock. This should be combined with antibiotics to eliminate the bacteria while the anti-TNF-α reduces the severity of the inflammation and thus reduce the risk of permanent joint destruction and mortality. We can conclude that blocking TNF-α early on is essential in order to get the best results.
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Aerobic capacity in rheumatoid arthritis : aspects of associations with cardiovascular risk factors and disease activityÅngström, Lars January 2018 (has links)
Rheumatoid arthritis (RA) is a systemic and inflammatory disease that has been associated with an increased morbidity and mortality in cardiovascular disease (CVD). Low aerobic capacity is one of the strongest independent risk factors for CVD and all-cause mortality in the general population. In patients with longstanding RA, low aerobic capacity has been related with a worse cardiovascular profile and an increased risk of CVD mortality. As a consequence of this, low aerobic capacity might provide an additional risk factor for CVD in patients with RA. The aim of this thesis was to describe the associations between aerobic capacity and risk factors for CVD as well as disease activity in patients with early RA, and also the effects of intensive exercise therapy on traditional risk factors for CVD and disease activity in patients with longstanding RA. Paper I, a cross-sectional study including 67 patients with early RA, mean (SD) age 53.1 (14.4), assessments of aerobic capacity, CVD risk factors, disease activity and functional ability were taken. Data were analysed for the associations between aerobic capacity and CVD risk factors and disease activity. In paper II, an intervention study, including 13 patients with RA, median age (Q1-Q3) 57 (44-64) years, aerobic capacity, pulse wave analysis (PWA), CVD risk factors, and disease activity were analysed for changes after 10 weeks of intensive exercise therapy. Additional follow-up was made after 25 weeks. In paper I, the mean (SD) aerobic capacity was 31.6 (8.7) ml O2/kg/min. CVD risk factors and disease activity were all in favour of patients with higher aerobic capacity. In a multiple regression model, adjusted for age and sex, aerobic capacity was significantly associated with percent body fat (β=-0.502, 95%CI=-0.671;-0.333) and triglycerides (β=-2.365, 95%CI=-4.252;-0.479). In paper II, intensive exercise over ten weeks was shown to be a feasible method to significantly improve aerobic capacity (p=≤0.05), systolic blood pressure (p=≤0.01) and the number of tender joints (p=≤0.05). No detrimental effect on disease activity was recorded. This thesis adds further knowledge of aerobic capacity and its associations with CVD risk factors and disease activity in patients with RA. Also, intensive exercise therapy was a feasible intervention to improve CVD risk factors. To include assessment of aerobic capacity in regular clinical practice may improve patient management as well as patient outcome in patients with RA. / Bakgrund: Reumatoid artrit (RA, ledgångsreumatism) är en kronisk inflammatorisk sjukdom som i första hand angriper leder, men kan även påverka inre organ. Typiska symptom är ledsvullnad, smärta, morgonstelhet och nedsatt funktion i lederna. Patienter med RA har visat sig ha en ökad risk att insjukna i och avlida i hjärt- och kärlsjukdom. I den allmänna befolkningen har låg syreupptagningsförmåga (kondition) visat sig vara en av de starkaste riskfaktorerna för att insjukna i eller att avlida i hjärt- och kärlsjukdom. Tidigare studier har visat att patienter med RA kan ha låg kondition vilket kan utgöra en riskfaktor för hjärt- och kärlsjukdom även vid RA. Syfte: Syftet med denna avhandling var att beskriva sambanden mellan kondition och riskfaktorer för hjärt- och kärlsjukdom och sjukdomsaktivitet. Ett annat syfte var att studera hur intensiv cykelträning påverkar kondition, traditionella riskfaktorer och sjukdomsaktivitet hos patienter med RA. Metod: Studie I är en tvärsnittsstudie, bestånde av 67 patienter med tidig RA, som hade en medelålder på 53 år. De undersöktes avseende; kondition, riskfaktorer för hjärt- och kärlsjukdom och sjukdomsaktivitet för att analysera samband mellan dessa. Studie II är en träningsstudie, bestående av 13 patienter med RA, med en medianålder på 57 år. Kondition, riskfaktorer för hjärt- och kärlsjukdom och sjukdomsaktivitet analyserades för att se förändringar efter tio veckors intensiv cykelträning samt vid en uppföljning efter 25 veckor. Resultat: I studie I visade den studerade gruppen ett konditionsmedelvärde på 31.6 mL. Sambandsanalyser visade att högre kondition var relaterad till lägre grad av riskfaktorer för hjärt- och kärlsjukdom, samt lägre 10 års risk för hjärt- och kärlsjukdom och sjukdomsaktivitet. I studie II fann vi att tio veckors intensiv cykelträning kan vara en användbar metod för att förbättra kondition, blodtryck och antalet ömma leder. Ingen ökad sjukdomsaktivitet noterades. Slutsatser: Dessa studier bidrar med kunskap om samband mellan kondition och riskfaktorer för hjärt- och kärlsjukdom samt sjukdomsaktiviteten hos patienter med RA. De visar också att intensiv cykelträning kan vara en effektiv metod att förbättra kondition och blodtryck hos patienter med RA.
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Att vara ung vuxen med reumatisk sjukdom och leva med kronisk smärta och trötthet : En kvalitativ intervjustudie / To be a young adult with rheumatic disease and live with chronic pain and fatigue : - a qualitative interview studyAdeteg, Sandra, Bergman, Eva-Lena January 2009 (has links)
<p><strong>Syftet</strong> med studien var att fånga in hur trötthet och smärta påverkar vardagen för unga vuxna med reumatisk sjukdom.</p><p><strong>Metoden</strong> är kvalitativ och för datainsamlingen gjordes semistrukturerade intervjuer. Materialet transkriberades transkriberades i sin helt och när det var klart påbörjades analysering av det som framkommit. I analysen sökte vi efter meningsbärande enheter och försökte ordna dem i kategorier och underkategorier.<strong> </strong></p><p><strong>Resultatet </strong>visar att sjukdomen har en stor påverkan på våra informanters liv, men att de också har bra strategier för att kunna leva med sjukdomen. Det visar också på att även om strategierna är bra och de vet hur de ska hantera sjukdomen så stöter de på hinder, till exempel har skolgången blivit negativt påverkad för de flesta av informanterna. Något som visat sig vara extra viktigt har varit vännerna och det sociala nätverket. Alla informanter har på ett eller annat sätt verkligen understrykt betydelsen av vänner som är förstående och som på det sättet hjälper till att hitta det positiva med livet.</p><p><strong>Slutsatsen </strong>som kan dras utifrån detta arbete är att vara ung och ha en reumatisk sjukdom är något som påverkar hela livet. Vi har sett på informanterna i studien att trots detta flyter livet på och de lyckas i de flesta fall att få balans mellan aktivitet och vila. Just denna balans är mycket viktig.<strong></strong></p><p><strong> </strong></p>
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Patienters beroende vid intravenös anti TNF-alfa behandling administrerad av en sjuksköterska - En kvalitativ studieLarsson, Ingrid January 2007 (has links)
<p>Det har skett en utveckling av flera nya biologiska läkemedel sedan slutet av 1990-talet för patienter med en reumatisk sjukdom. Några av dessa läkemedel administreras som intravenösa infusioner, vilket innebär att patienterna är tvungna att komma till en poliklinik för att erhålla sitt läkemedel. Detta kan påverka det dagliga livet samt patienternas oberoende och att undersöka hur patienterna uppfattar denna situation är av betydelse. Inom reumatologin är det ingen studie gjord som undersökt detta. </p><p>Syftet med studien var att beskriva hur patienter med reumatiska sjukdomar uppfattar beroendet vid intravenös anti TNF-alfa behandling administrerad av en sjuksköterska.</p><p>Studien genomfördes med en deskriptiv kvalitativ design och fenomenografisk ansats. Tjugo patienter som får intravenös anti TNF-alfa behandling har intervjuats.</p><p>I resultatet framkom tre beskrivningskategorier: det trygga beroendet (möta kontinuitet, möta kompetens, erhålla tillgänglighet och få information), det delaktiga beroendet (kunna påverka och få frihet), det energigivande beroendet (få avkoppling, bli bemött, bli omhändertagen och möta miljön). Patienterna uppfattade en trygghet och delaktighet i sin behandling och uppgav att det var energigivande att regelbundet träffa en sjuksköterska. Vid utformning av sjuksköterskans roll i polikliniskt omvårdnadsarbetet vid intravenös anti TNF-alfa behandling bör patienternas uppfattning utgöra grunden. Vidare skulle det vara intressant att undersöka hur patienter som sköter sin anti TNF-alfa behandling själva genom subkutana injektioner och som aldrig haft en regelbunden kontakt med en sjuksköterska beskriver sin situation.</p>
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Patienters beroende vid intravenös anti TNF-alfa behandling administrerad av en sjuksköterska - En kvalitativ studieLarsson, Ingrid January 2007 (has links)
Det har skett en utveckling av flera nya biologiska läkemedel sedan slutet av 1990-talet för patienter med en reumatisk sjukdom. Några av dessa läkemedel administreras som intravenösa infusioner, vilket innebär att patienterna är tvungna att komma till en poliklinik för att erhålla sitt läkemedel. Detta kan påverka det dagliga livet samt patienternas oberoende och att undersöka hur patienterna uppfattar denna situation är av betydelse. Inom reumatologin är det ingen studie gjord som undersökt detta. Syftet med studien var att beskriva hur patienter med reumatiska sjukdomar uppfattar beroendet vid intravenös anti TNF-alfa behandling administrerad av en sjuksköterska. Studien genomfördes med en deskriptiv kvalitativ design och fenomenografisk ansats. Tjugo patienter som får intravenös anti TNF-alfa behandling har intervjuats. I resultatet framkom tre beskrivningskategorier: det trygga beroendet (möta kontinuitet, möta kompetens, erhålla tillgänglighet och få information), det delaktiga beroendet (kunna påverka och få frihet), det energigivande beroendet (få avkoppling, bli bemött, bli omhändertagen och möta miljön). Patienterna uppfattade en trygghet och delaktighet i sin behandling och uppgav att det var energigivande att regelbundet träffa en sjuksköterska. Vid utformning av sjuksköterskans roll i polikliniskt omvårdnadsarbetet vid intravenös anti TNF-alfa behandling bör patienternas uppfattning utgöra grunden. Vidare skulle det vara intressant att undersöka hur patienter som sköter sin anti TNF-alfa behandling själva genom subkutana injektioner och som aldrig haft en regelbunden kontakt med en sjuksköterska beskriver sin situation.
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Autoantibodies and genetic variation in rheumatoid arthritis : aspects on susceptibility and disease courseKastbom, Alf January 2007 (has links)
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and subsequent destruction of synovial joints. Although its causes remain largely unknown, a substantial genetic contribution is known to exist. During the last decades the benefits of early aggressive treatment have become evident, and more potent therapeutic options have become available. These advances have increased the demands for rapid accurate diagnosis and prognostic markers of disease course and therapy response. The ‘rheumatoid factor’ (RF) has long been used as a diagnostic and prognostic marker of RA. In this thesis, the utility of measuring antibodies to cyclic citrullinated peptides (CCP) was investigated. In a population-based arthritis incidence study, 69 very early arthritis patients (symptom duration < 3 months) were identified. The anti-CCP test, performed at baseline and related to diagnosis at the 2-year follow-up, had a diagnostic specificity for RA of 96% and a sensitivity of 44%, both of which were superior to RF. In a prospective cohort of 242 incident cases of RA (symptom duration < 1 year), 64% of the patients tested positive for anti-CCP at baseline (equal to RF). Despite receiving more active anti-rheumatic therapy, the anti-CCP-positive patients had a more aggressive disease course during 3 years as compared to those testing negative. The 158VV genotype of Fcγ Receptor type IIIA (FcγRIIIA), which binds IgG with higher affinity than 158FF, was associated with an increased susceptibility to RA in men, but not in women. Previous studies report conflicting results, and none stratified according to gender. The 158V/F polymorphism of FcγRIIIA was not found to influence outcome of anti-tumour necrosis factor therapy in 282 RA patients, contradicting hints from previous studies. Genetic variation in proteins of the inflammasome, an interleukin-1 (IL-1) regulating intracellular protein complex, is associated with rare autoinflammatory conditions and possibly with Crohn’s disease. In this first study on genetic variation of the inflammasome in RA, we describe a compound polymorphism of the genes CIAS1 and TUCAN that associates both with susceptibility to RA and to the severity of the disease. Hypothetically, these genes may identify a subgroup of RA patients that would benefit from anti-IL-1 therapy. This thesis work emphasizes the benefits of testing for anti-CCP in the diagnosis and outcome prediction in early arthritis. FcγRIIIA genotype is likely to affect RA susceptibility and further work should apply a gender perspective. Inflammasome genetics may influence the risk of developing RA. Additional studies are warranted to settle whether it also identifies a subgroup of RA patients benefiting from IL-1 targeted therapy.
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Att vara ung vuxen med reumatisk sjukdom och leva med kronisk smärta och trötthet : En kvalitativ intervjustudie / To be a young adult with rheumatic disease and live with chronic pain and fatigue : - a qualitative interview studyAdeteg, Sandra, Bergman, Eva-Lena January 2009 (has links)
Syftet med studien var att fånga in hur trötthet och smärta påverkar vardagen för unga vuxna med reumatisk sjukdom. Metoden är kvalitativ och för datainsamlingen gjordes semistrukturerade intervjuer. Materialet transkriberades transkriberades i sin helt och när det var klart påbörjades analysering av det som framkommit. I analysen sökte vi efter meningsbärande enheter och försökte ordna dem i kategorier och underkategorier. Resultatet visar att sjukdomen har en stor påverkan på våra informanters liv, men att de också har bra strategier för att kunna leva med sjukdomen. Det visar också på att även om strategierna är bra och de vet hur de ska hantera sjukdomen så stöter de på hinder, till exempel har skolgången blivit negativt påverkad för de flesta av informanterna. Något som visat sig vara extra viktigt har varit vännerna och det sociala nätverket. Alla informanter har på ett eller annat sätt verkligen understrykt betydelsen av vänner som är förstående och som på det sättet hjälper till att hitta det positiva med livet. Slutsatsen som kan dras utifrån detta arbete är att vara ung och ha en reumatisk sjukdom är något som påverkar hela livet. Vi har sett på informanterna i studien att trots detta flyter livet på och de lyckas i de flesta fall att få balans mellan aktivitet och vila. Just denna balans är mycket viktig.
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Lymphoma studies in patients with Sjögren's syndromeVasaitis, Lilian January 2017 (has links)
Patients with primary Sjögren’s syndrome (pSS) are at increased risk of developing malignant lymphoma. The studies in this thesis aim at broadening our understanding of the association between these two conditions. Germinal centre (GC)-like structures were found in minor salivary gland biopsies taken at the time of pSS diagnosis in 25% of 175 studied patients. Lymphoma development was observed in 86% of the GC-positive pSS patients and 14% of the GC-negative patients. GC-like structures in salivary gland biopsies at pSS diagnosis might identify pSS patients at high risk for later lymphoma development. We used the National Patient Register and the Cancer Register to identify pSS patients with lymphoid malignancy for the following studies. The lymphoma tissues were reviewed and classified according to the WHO classification. In a study of 79 patients with available lymphoma tissues, we identified histopathological and clinical features compatible with IgG4-related disease (IgG4-RD) in one patient (1.3%). Histological features of IgG4-RD in lymphoma tissue in patients with an initial pSS diagnosis seem to be rare but, if present, may indicate underlying IgG4-RD. We identified and compared pSS patients with (n=18/17%) and without (n=87) pre-existing lymphoma at pSS diagnosis and found similar pSS characteristics in both groups. Mucosa-associated lymphoid tissue (MALT) lymphoma in salivary glands was more common in patients with pre-existing lymphoma. The findings support the removal of pre-existing lymphoma as a general exclusion criterion for a pSS diagnosis in classification criteria. Further, the findings suggest an investigation for pSS in patients presenting with MALT lymphoma in salivary glands. We compared the distribution of lymphoma subtypes with a general population reference. Both diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma (MZL) (31%) were common, but only MZL (MALT lymphomas) occurred at an increased relative frequency compared to the general population. Men constituted 15% of 105 pSS patients with lymphoma. Men had a shorter time between the pSS and lymphoma diagnoses and more often had lymphoma in the salivary glands compared with women. Increased awareness of signs of lymphoma in salivary glands already during the first years after pSS diagnosis is justified in men with pSS.
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The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies : Implications for pathogenesis, classification and diagnosisDanielsson, Olof January 2016 (has links)
Background: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with severe consequences for the life of affected patients. Dermatomyositis, polymyositis and inclusion body myositis (IBM) are the classical representatives of this group. The treatments given today often have limited effects, and are taken at the cost of side effects. Major obstacles in the search for more effective treatments are; (1) an incomplete understanding of the disease mechanisms, (2) difficulties to delineate homogeneous disease groups for clinical studies and (3) the sometimes challenging task to diagnose these diseases. Aims: We addressed a number of “loose ends” in the areas of pathogenesis, classification and diagnosis; mechanisms of muscle fiber degeneration in IIM, with a focus of programmed cell death (apoptosis) and invasion of muscle fibers by inflammatory cells (partial invasion); protecting and mediating factors present in muscle; the association of other diseases with IIM, in particular celiac disease ; the evaluation of two classification systems and laboratory methods for increased diagnostic performance. The studies: We included 106 patients, diagnosed at the Neuromuscular unit in Linköping, Sweden, with pathological muscle findings consistent with IIM. The incidence in the county of Östergötland (during 5 years) was 7.3 per million/year (3 patients each year). Of 88 patients with confirmed IIM 4 (4.5 %) had celiac disease, 33 (38%) had an associated systemic inflammatory disease and 5 (5.7 %) had a malignancy. Ninety-nine patients were included for a comparison of two classification systems using criteria of the European Neuromuscle Centre (Amato/ENMC), and the widely used Bohan and Peter classification, both with the addition of IBM according to Griggs et al. Using the Amato/ENMC criteria the most prevalent diagnostic group after IBM (30%) was nonspecific myositis (23%), followed by polymyositis (20%) and dermatomyositis 17%). A substantial number of patients meeting Bohan and Peter (or Griggs) criteria were excluded by Amato/ENMC criteria, most (21/23) due to lack of detectable muscle weakness. Extended muscle sectioning increased the sensitivity of a muscle biopsy by 15 % and the specificity by 22%, and showed an overlap between disease groups. Muscle biopsies from patients with IIM and controls were used to investigate pathological findings considered specific for disease groups, and for the presence of programmed cell death (apoptosis) and disease protecting and mediating factors in muscle. The presence of apoptotic muscle fiber nuclei was detected in muscle with partial invasion (however not in the invaded fibers) in the presence of granzyme B and CD8+ cytotoxic T cells. The major apoptosis inhibiting protein Bcl-2 was shown to be constitutionally expressed in healthy muscle but weakened in IIM. Conclusion: We present apoptosis as a possible disease mechanism in parallel with partial invasion of fibers. Furthermore, partial invasion may not be a suitable distinguishing feature in the pathogenesis, or for classification and diagnosis of IIM. We also introduce the anti-apoptotic Bcl-2 as a possible relevant muscle fiber protecting factor. A more extensive pathological work-up improves classification and diagnosis of IIM. The proposed Amato/ENMC creates a substantial portion of patients with non-specific or unclassified myositis. Associated diseases are common in IIM, and also include celiac disease.
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