Genome-wide Association (GWA) studies have become a widely used method for analyzing genetic data. It is useful in detecting associations that may exist between particular alleles and diseases of interest. This thesis investigates the dataset provided from problem 1 of the Genetic Analysis Workshop 16 (GAW 16). The dataset consists of GWA data from the North American Rheumatoid Arthritis Consortium (NARAC). The thesis attempts to determine a set of single nucleotide polymorphisms (SNP) that are associated significantly with rheumatoid arthritis. Moreover, this thesis also attempts to address the question of whether the one-sided alternative hypothesis that the minor allele is positively associated with the disease or the two-sided alternative hypothesis that the genotypes at a locus are associated with the disease is appropriate, or put another way, the question of whether examining both alternative hypotheses yield more information.

Introduction. Rheumatoid arthritis is a disease that causes the dislocation of joints. Foot deformity and deformity of foot fingers is brought about by inflammatory processes in the joints and due to the changed pressure of body weight on the feet. The computerized method of foot-barography allows one to estimate in what way the pressure of body weight on the feet distributes itself during the process of walking and in the standing posture. This method also allows one to judge about foot deformity as well as the condition of foot joints, ligaments and muscles of the patient. The aim of the research was to study the efficiency of applying the computerized method of foot-barography in the treatment of foot joints damaged by rheumatoid arthritis. Subjects and Methods. The research was carried out at the Polyclinic of the Joint-Stock Company „Ortopedijos technika“ (Orthopedic Technology) in Kaunas. The subjects were 19 females and 3 males suffering from chronic rheumatoid arthritis. The patients were divided into 2 groups: 1) the experimental group, i.e. patients to whom kinesitherapy was applied, and 2) the control group, i.e. patients to whom kinesitherapy was not applied. The feet of the patients have been studied applying the computerized method of foot-barography. The distribution of the pressure of body weight on definite points (5, 7, 10, 13, 17, 18, 19, 20) of the foot as well as on the fingers and hell of the foot has been analysed. Conclusions. As a result of the... [to full text]

Tyrimo objektas: lėtinio reumatoidinio artrito gydymas taikant šaltį (krioterapiją). Tyrimo problema: reumatoidinis artritas sukelia sąnarių skausmą, tuo pačiu mažindamas jų judesio amplitudę, pablogindamas žmogaus fizinę būklę. Skausmas, sąnarių sustingimas ir jų sumažėjusi judesio amplitudė priklauso nuo ligos progresavimo. Didžiausias dėmesys šiame darbe buvo skiriamas skausmo sumažėjimui ir judesio amplitudės padidėjimui po krioterapijos. Tyrimo hipotezė: šalčio (krioterapijos) taikymas du kartus savaitėje penkias savaites turėtų sumažinti reumatoidinio artrito sukeltą sąnarių sustingimą, padidinti judesio amplitudę ir sumažinti sąnarių skausmą. Tyrimo tikslas — nustatyti šalčio (krioterapijos) veiksmingumą sergant lėtiniu reumatoidiniu artritu. Tyrimo uždaviniai buvo: įvertinti tiriamųjų sąnarių skausmą prieš ir po krioterapijos taikymo. Įvertinti tiriamųjų judesio amplitudę prieš ir po krioterapijos taikymo. Įvertinti tiriamųjų sąnarių sustingimą prieš ir po krioterapijos taikymo. Įvertinti tiriamųjų sąnarių skausmą, judesio amplitudę ir sąnarių sustingimą priklausomai nuo krioterapijos procedūrų skaičiaus. Tyrime dalyvavo 40 tiriamųjų (30 moterų ir 10 vyrų). 14 tiriamųjų atliko 5 procedūras; 15 tiriamųjų atliko 10 procedūrų; 11 tiriamųjų atliko 7 krioterapijos procedūras. Tiriamųjų judesio amplitudė ir skausmas buvo įvertinti prieš ir po krioterapijos. Atlikus surinktų duomenų analizę padarytos šios išvados: 1. Tiriamųjų, sergančių reumatoidiniu artritu, sąnarių... [toliau žr. visą tekstą] / Object: range of movement and pain in rheumatoid arthritis applying cryotherapy. Problem: rheumatoid arthritis induces joints’ pain, reduces range of movement, and makes human’s physical condition worse. Pain, joints’ stiffness and reduced range of movement depend on progression of disease. Serious consideration in this work was paid in reducing pain and stiffness and increasing range of movement after applying cryotherapy. Hypothesis: applying of cryotherapy should reduce joints’ stiffness which is caused by rheumatoid arthritis, increase range of movement and reduce pain. The aim of this study was to assess efficiency of cryotherapy in rheumatoid arthritis. The tasks: 1. To evaluate joints’ pain before and after applying cryotherapy; 2. To evaluate range of movement before and after cryotherapy; 3. To evaluate morning stiffness before and after cryotherapy; 4. To evaluate joints’ pain, range of movement and morning stiffness in relation to the number of applied cryotherapy procedures. Subjects: 40 patients (30 females and 10 males) took part in the research: 5 procedures were prescribed for 14 patients, 10 procedures of cryotherapy were prescribed for 15 patients and 7 procedures were prescribed for 11 patients. Range of movement, pain and morning stiffness were measured before and after applying cryotherapy. Statistical methods were used to analyze data. The main findings: 1. Pain of the joints before applying cryotherapy was evaluated as moderate, after applying... [to full text]

Rheumatoid arthritis is the inflammatory disease of web, which causes progressive inflammation of joints. Rheumatoid arthritis is on the top according to the number of patients who become invalids. The growing number of invalids in Lithuania becomes not only medical problem, but social problem as well. Everything is done to quell the activity of pathological process, its progression and to return and maintain the functions of moving device of the body with the help of prophylaxis, therapy and rehabilitation. The perfect program of treatment is often created for a year or longer period of time to reach good results. Different methods of treatment and their consistency let to reach better results. Physiotherapy is one of the treatments of rheumatoid arthritis, blocking the progress of the disease. The aim of the research – to estimate the effect of physiotherapy on arm functions of patients with rheumatoid arthritis. The goals of the research: to estimate the state of health of investigative and control groups of people with rheumatoid arthritis according to Keitel indicators before and after physiotherapy; to estimate the force of hand muscles of people with rheumatoid arthritis before and after physiotherapy; to estimate the effect of physiotherapy on the pain of hand joints of people with rheumatoid arthritis; to estimate the mobility of hand joints of people with rheumatoid arthritis before and after physiotherapy. 40 patients (5 men and 35 women) with the average age 57.6... [to full text]

Tyrimo tikslas: įvertinti kineziterapijos taikymo efektyvumą rankų funkcijoms sergant reumatoidiniu artritu. Tyrimo objektas: pacientai sergantys reumatoidiniu artritu tiriant jų rankų funkcinę būklė, sąnarių skausmą, plaštakų raumenų jėga ir judesių amplitudes. Tyrimo uždaviniai: 1. Nustatyti tiriamųjų sergančių reumatoidiniu artritu rankų funkcinę būklę, naudojant Keitel indekso rodiklius, prieš ir po kineziterapijos. 2. Nustatyti tiriamųjų sergančių reumatoidiniu artritu plaštakų raumenų jėgą prieš ir po kineziterapijos. 3. Nustatyti kineziterapijos efektyvumą tiriamųjų sergančių reumatoidiniu artritu rankų sanarių skausmui. 4. Nustatyti tiriamųjų sergančių reumatoidiniu artritu rankų sąnarių judesių amplitudes prieš ir po kineziterapijos. Rezultatai: tyrimo rezultatai parodė, kad po kineziterapijos (KT) taikymo rankų funkcijos pagal Keitel indeksą pagerėjo 2,8 balo. Plaštakos raumenų jėgą tiriamiesiams KT pagerino dešinėje rankoje 3,9 kg, o kairėje rankoje 3,3 kg. Skausmo stiprumas sąnariuose po KT tiriamiesiams sumažėjo 2,9 balo. Judesių amplitudės peties, alkūnės ir riešo sąnariuose po KT padidėjo statistiškai patikimai (p<0,001), lyginant rodiklius prieš KT ir po KT. Tyrimo išvados: kineziterapija pagerino rankų funkcinę būklę (Keitel indeksas), sergantiems reumatoidiniu artritu. Kineziterapija pagerino tiriamųjų plaštakų raumenų jėgą, sergančių reumatoidiniu artritu. Kineziterapija sumažino rankų raumenų skausmus, tiriamiesiams, sergantiems reumatoidiniu artritu... [toliau žr. visą tekstą] / The aim of the research: evaluate the effectiveness of physiotherapy for hand functions in patients with rheumatoid arthritis. Object of the research : patients with rheumatoid arthritis analyzing their hand functional condition, pain in the joints, palm muscle strength and range of motion. The goals of the research: 1. Set of subjects with rheumatoid arthritis hand functional condition using Keitel index indicators before and after physiotherapy. 2. Set of subjects with rheumatoid arthritis hand muscle strength before and after physiotherapy. 3. Determine the effectiveness of physiotherapy for subjects with rheumatoid arthritis to their hand joint pain. 4. Set of subjects with rheumatoid arthritis in hand joints range of motion before and after physiotherapy. Results: the results showed that after physiotherapy, both hand functions by Keitel index improved 2.8 points. Hand muscle strength for subjects after physiotherapy increased 3.9 kg in the right hand and 3.3 kg in left hand. The severity of pain in joints after physiotherapy for subjects decreased by 2.9 points. Range of motion of the shoulder, elbow and wrist joints after physiotherapy increased significantly (p <0.001) compared to rates before physiotherapy and after physiotherapy. Research conclusions: for the purposes of physiotherapy for subjects with rheumatoid arthritis improved hand function condition (Keitel index). For the purposes of physiotherapy for subjects increased hand muscle strength. For the purposes... [to full text]

Multiple myeloma is a painful and uncurable malignant disease with an increasing incidence and mortality in several countries, e.g., Sweden. Some factors are suspected to be of aetiological significance, such as ionising radiation and chronic antigenic stimulation in certain inflammatory diseases. A familial factor has also been indicated. Furthermore, some studies have demonstrated farming as an occupation entailing an increased risk for the disease. The aim of this investigation was to further elucidate the impact of different aetiological factors in relation to multiple myeloma. The knowledge of aetiology is always a prerequisite for prevention. A case-control study on multiple myeloma was performed in a high-inddence area, the northern part of Sweden. One part of this study dealt with occupations and different exposures. The results supported farming as being an occupation with an increased risk. Within farming two kinds of pesticides, phenoxyacetic adds and DDT, and contact with certain domestic animals, i.e., cattle, horses and goats, were assodated with multiple myeloma. Farming as a risk factor was also confirmed by a register-based linkage study using the Swedish Cancer Environment Register. In this study a time trend was indicated, with increasing standardized inddence ratios over the different time periods studied. Another part of the case-control study showed that rheumatoid arthritis entailed an increased risk for multiple myeloma, a finding earlier suggested from register-based linkage studies, but not from any çase-control study. A third part of the case-control study indicated an increased risk for multiple myeloma if any first-degree relative had a history of haematological malignancy, or other malignant tumour, espedally prostatic cancer, brain tumour, and renal cancer. A case study encompassing 942 patients with haematological malignandes in the county of Jämtland, Sweden, during a 22-year period showed that about 5% of the patients had at least one relative who also suffered from such a disease. An espedally strong familial occurrence was found in the group of chronic lymphoprohferative diseases, including multiple myeloma. / <p>S. 1-69: sammanfattning, s. 71-129: 5 uppsatser</p> / digitalisering@umu

Low-energy trauma and fragility fractures represent a major public health problem. The societal cost of the fragility fractures that occurred in Sweden 2010 has been estimated at €4 billion. In rheumatoid arthritis (RA), patient outcomes have improved greatly in recent years. However, the therapeutic decision making is still hampered by a lack of effective validated biomarkers. The cost of RA in Sweden 2010 has been estimated at €600 million, of which biologic drugs was €180 million. Digital X-ray radiogrammetry (DXR) is a method to measure bone mineral density (BMD) in the metacarpals of the hand. It can be applied opportunistically in several workflows where a person is already at an X-ray machine, including fracture repositioning follow up, mammography screening and hand imaging in RA. This thesis explored DXR-BMD as a marker to identify individuals who would benefit from anti-osteoporotic treatment, change rate of DXR-BMD as a biomarker in RA and under what conditions historical X-ray images can be used to estimate DXR-BMD. An automated method for measurement of joint space width in metacarpophalangeal and interphalangeal joints was also developed and evaluated as a biomarker in RA. Low DXR-BMD was predictive for hip fractures and predicted fragility fractures to a comparable degree as other BMD measurement sites. Rapid decrease of DXR-BMD was a strong and independent predictor for progression of radiographic damage in RA when manual radiographic progression scores were not available. Change of metacarpal joint space width was a statistically significant but weak predictor of joint space narrowing score progression. Guidelines and considerations for use of historical X-ray radiographs for DXR-BMD measurements in clinical trials have been developed and published.

Eine Dysregulation neuro-immunologischer Interaktionen und eine veränderte Stressantwort werden als Teil der Pathogenese der Rheumatoiden Arthrtitis (RA) diskutiert. Dabei könnte eine autonome Dysfunktion eine wichtige Rolle spielen. Um dem nachzugehen, wurde an Patienten mit unterschiedlicher Krankheitsaktivität die Aktivität des autonomen Nervensystems in Ruhe und in Reaktion auf minor Stress sowie erstmals deren Assoziation zu Gen-Polymorphismen β2- adrenerger Rezeptoren (β2ARs), welche sich u.a. auf Immunzellen befinden, untersucht. Zur Bestimmung autonomer Aktivität wurde an 112 RA- und 48 Osteoarthrose-Patienten die sympathische Hautantwort (SSR) sowie die Herzratenvariabilität (HRV) getestet. Standardisierte Stresstests kamen zur Anwendung. Eine Allel-spezifische Polymerase-Ketten-Reaktion diente zur Ermittlung der Varianten des β2ARs an Aminosäureposition 16, 27 und 164. Es konnte gezeigt werden, dass die autonome Aktivität bei RA in Ruhe durch eine signifikant erhöhte Herzfrequenz, ein Überwiegen des Sympathikus im Verhältnis zum Parasympathikus sowie eine signifikant erniedrigte Parasympathikusaktivität gekennzeichnet ist. Die Stressantwort bei RA war signifikant häufiger pathologisch als bei der Kontrollgruppe und durch signifikante Hypoaktivität und Hyporeaktivität des Parasympathikus sowie eine signifikant erniedrigte HRV charakterisiert. Das Zusammenspiel beider Schenkel des ANS erschien gestört. Die SSR-Werte befanden sich im Normbereich. Schlechtere Werte waren jedoch signifikant mit hohem CRP assoziiert. Desweiteren war Heterozygotie an allen Gen-Positionen der β2ARs signifikant mit RA assoziiert. Gln27Gln (signifikant häufiger für Gesunde) ging mit signifikant niedrigerer Krankheitsaktivität einher. Starkes Überwiegen des SNS in Ruhe sowie niedrige parasympathische Aktivität (HRV-Daten) waren signifikant mit hoher Krankheitsaktivität assoziiert. Zusammenfassend weist die vorliegende Arbeit auf eine autonome Dysregulation bei Patienten mit RA hin, was mit klinischen Parametern der RA assoziiert war. Weiterhin unterstreicht die Studie die Assoziation von β2AR Polymorphismen mit einer RA und liefert einen weiteren Beitrag zum Verständnis der Pathogenese dieser Erkrankung.

Monocytes are no longer regarded as a homogenous cell population but can be divided, both phenotypically and functionally, into different subsets. In rheumatoid arthritis, the subpopulation of CD14bright/CD16+ monocytes is expanded and prone towards generation of Th17 cells. CD56+ monocytes represent a different subpopulation, which is also expanded in conditions associated with autoimmunity like inflammatory bowel diseases. The aim of the study was the quantification and functional characterization of the CD56+ monocyte subset in rheumatoid arthritis (RA). The work at hand shows that the frequency of CD56+ monocytes is also expanded in RA; moreover, this subpopulation seems to increase with age in healthy controls. This age association is completely lost in patients suffering from RA. Further functional investigations could demonstrate a dysregulated cytokine response to lipopolysaccharide (LPS) with an increased production of pro-inflammatory cytokines like TNFα as well as an increased spontaneous reactive oxygen intermediate (ROI) production. A longitudinal treatment study using Etanercept as an established TNFα-blocking agent revealed a decrease of the frequency of that cell population under therapy. This decrease was more pronounced in patients with a good treatment response as judged by the reduction of the disease activity score (DAS) 28. Summing up those results, the CD56+ monocyte subset might be involved in immunosenescence as well as in the pathogenesis of RA.

Varje år diagnostiseras cirka 200 barn med juvenil idiopatisk artrit (JIA) i Sverige. Det är inte bara inom specialistvården sjuksköterskor möter barn med JIA, utan även inom allmän sjukvård. Syftet med studien var att belysa omvårdnad för barn med juvenil idiopatisk artrit. Studien är en litteraturstudie. Resultatet belyser vad som är viktigt vid omvårdnaden för barn med JIA. Detta presenteras i tre teman: Bemötande, Information och undervisning och Emotionellt stöd. Ett bra bemötande är viktigt för att barnen skall känna tillit till sjukvården. Det är viktigt att göra barnen delaktiga. Barnen är experter på upplevelsen av sin egen sjukdom. Barnen behöver få emotionellt stöd för att kunna hantera sin vardag. Stödet kan komma från sjuksköterskorna eller Internetsidor. För att barnen skall kunna hantera sin sjukdom och sin situation krävs undervisning och information. Information kan ges i form av broschyrer och böcker samt från sjuksköterskorna och Internet. Önskvärt hade varit om grundutbildningen för sjuksköterskor innefattade omvårdnad för barn. De kunskaper grundutbildade sjuksköterskor har med sig efter examen kan tas tillvara genom att de kan uppmärksamma symtomen som ett barn med JIA har, och utefter det forma omvårdnadsåtgärder. Forskning på JIA är begränsad ur ett omvårdnadsperspektiv, och kunskapsluckorna behöver uppmärksammas. / Every year about 200 children are diagnosed with juvenile idiopathic arthritis (JIA) in Sweden. It is not only in specialized care nurses meet children who suffer from JIA, but also in universal health care. The aim of the study was to express the nursing care for children with juvenile idiopathic arthritis. This study is a literature study. The result highlights what is important in the nursing care of nursing children with JIA. This is presented in three themes: Attitudes, Information and teaching and Emotional support. A good attitude towards the children is very important so they feel a trust to the health care. It is important to make the children involved. Children are experts on the experience of their own illness. The children need emotional support to handle their everyday life. The support can come from the nurse or from Internet pages. If children shall be able to manage their condition and their situation, it requires education and information. The information can be provided from brochures, books, the nurse or the Internet. It would be desirable if nursing school would include nursing children. The knowledge a regular nurse has after the graduation can be taken advantage because they can pay attention to the symptoms a child with JIA has and shape nursing interventions. The research within JIA is limited from a nursing perspective, and knowledge gaps need attention.