This thesis explores the issue of men's access to chronic illness self management programs from a social constructionist perspective. A combination of research methodologies was used; a quantitative analysis to confirm gender differences in levels and patterns of service use; a qualitative analysis to gain an increased understanding of the factors affecting men's access; and a trial to test the application of the research findings. The clients and services of Arthritis Victoria were chosen as the setting for this research. The quantitative analyses were conducted on contingency tables and odds ratios and confirmed that men were under-represented as service users. The analyses also identified gender differences in patterns of service use. The qualitative analysis was based on a series of in-depth, semi-structured interviews. It was undertaken from a grounded theory approach to allow for the development of theoretical explanations grounded in the data. It was found that men's decisions to access chronic illness self management programs were strongly influenced by dominant social constructions of masculinity which constrained help-seeking and health management behaviour. However, the restrictive influence of hegemonic masculinity was progressively undermined by the increasing severity of the chronic condition until a crisis point was reached in terms of the severity of the condition or its impact on lifestyle. This resulted in a reformulation or rejection of hegemonic masculinity. The described conceptual framework was consistent for men from diverse social groupings, although it appeared less prominent in both younger and older men, suggesting that dominant social constructions of masculinity have the greatest influence on health decisions during the middle stage of adulthood when work and family obligations are greatest. The thesis findings informed the development of some guiding principles for reviewing the structure and delivery of chronic illness self management services for men. The guiding principles will have direct application in the planning of Arthritis Victoria programs, and implications for other chronic illness self management programs in Australia, and also in Western countries with a similar health and sociocultural setting to Australia.

Akademisk avhandling--Lund. / Extra t.p., with thesis statement, inserted. Errata slip inserted. Bibliography: p. [117]-125.

B cells are normally regulated to prevent activation against self-proteins through tolerance mechanisms.  However, occasionally there is a break in tolerance and B cells can become self-reactive, which might lead to the development of autoimmune disease. The activation of self-reactive B cells is regulated by receptors on the B cell surface, such as Fc gamma receptor IIb (FcγRIIb), complement receptor type 1 (CR1), and CR type 2 (CR2). In this thesis I have studied the role of FcγRIIb, CR1 and CR2 on B cells in autoimmune arthritis. By using a model for rheumatoid arthritis, I discovered that the initial self-reactive B cell response in arthritis was associated with the splenic marginal zone B cell population. Marginal zone B cells express high levels of CR1/CR2 and FcγRIIb, suggesting that they normally require high regulation. Further, female mice deficient in CR1/CR2 displayed increased susceptibility to arthritis compared to CR1/CR2-sufficient female mice. When investigating whether sex hormones affected arthritis susceptibility, we found that ovariectomy, of the otherwise fairly resistant CR1/CR2-sufficient mice, reduced the expression of CR1 on B cells and rendered the mice more susceptible to arthritis. In humans, a significantly reduced CR1 and FcγRIIb expression was found on B cells in aging women, but not in men. This may contribute to the increased risk for women to develop autoimmune disease as reduced receptor expression may lead to the activation of self-reactive B cells. In agreement, lower CR1, CR2 and FcγRIIb expression was seen in patients with rheumatoid arthritis.   Finally, a soluble form of FcγRIIb was used to investigate FcγRIIb’s ability to bind self-reactive IgG in an attempt to treat autoimmune arthritis. Treatment of mice with established arthritis was associated with less self-reactive IgG antibodies and consequently less disease, suggesting that soluble FcγRIIb may be used as a novel treatment in arthritis.

Plasmin, the central molecule of the plasminogen activator system, is a broad-spectrum serine protease. Plasmin is important for the degradation of fibrin and other components of the extracellular matrix (ECM) during a number of physiological and pathological processes. The aim of this thesis was to elucidate the functional roles of plasmin during pathological inflammation and infection in autoimmune and non-autoimmune diseases. For this purpose, mouse models of rheumatoid arthritis (RA), bacterial arthritis, infection, and sepsis have been used. Previous studies from our laboratory have shown that plasminogen-deficient mice are resistant to the development of collagen type II-induced arthritis (CIA). In contrast, others have shown that plasmin plays a protective role in antigen-induced arthritis (AIA). To investigate the contrasting roles of plasminogen deficiency in models of CIA and AIA, a new animal model of arthritis called local injection-induced arthritis (LIA) was developed. In this model, we replaced methylated bovine serum albumin, which is normally used as an immunogen in the AIA model, with collagen type II (CII) to induce arthritis. When wild-type and plasminogen-deficient mice were injected intra-articularly with CII or 0.9% NaCl following CIA induction, plasminogen-deficient mice developed typical CIA, but the disease was less severe than in wild-type mice and was restricted to the injected joints. When the AIA model was used, plasminogen-deficient mice developed a much more severe arthritis than the wild-type mice. These results indicate that both the antigen and joint trauma caused by the local injection are critical to explaining the contrasting roles of plasminogen deficiency in CIA and AIA. This indicates that CIA and AIA have distinct pathogenic mechanisms and plasmin plays contrasting roles in different types of arthritis models. To study the functional roles of plasmin in the host inflammatory response during infectious arthritis, a Staphylococcus aureus-induced bacterial arthritis model was established. When wild-type mice were injected intra-articularly with 1 × 106 colony-forming units (CFU) of S. aureus per joint, all the bacteria were completely eliminated from the injected joints in 28 days. However, in the plasminogen-deficient mice, the S. aureus counts were 27-fold higher at day 28 than at day 0. When human plasminogen was given to the plasminogen-deficient mice daily for 7 days, the bacterial clearance was greatly improved and the necrotic tissue in the joint cavity was also completely eliminated. Supplementation of plasminogen-deficient mice with plasminogen also restored the expression level of interleukin-6 (IL-6) in the arthritic joints. In summary, plasmin has protective roles during S. aureus-induced arthritis by enhancing cytokine expression, removing necrotic tissue, and mediating bacterial killing and inflammatory cell activation. The functional roles of plasmin during infection and sepsis were also studied in mice. Infection was induced by injecting 1 × 107 CFU of S. aureus intravenously and the sepsis model was induced by injecting 1.6 × 108 CFU of S. aureus. In the infection model, the wild-type mice had a 25-day survival rate of 86.7%, as compared to 50% in the plasminogen-deficient group. However, when sepsis was induced, the average survival for plasminogen-deficient mice was 3 days longer than for wild-type mice. Twenty-four hours after the induction of sepsis, the serum levels of IL-6 and IL-10 as well as the bacterial counts in all organs investigated were significantly higher in wild-type mice than in plasminogen-deficient mice. In wild-type mice, blockade of IL-6 by intravenous injection of anti-IL-6 antibodies significantly prolonged the onset of mortality and improved the survival rate during sepsis. These data indicate that plasmin plays different roles during infection and sepsis. Furthermore, plasmin appears to be involved in the regulation of inflammatory cytokine expression during sepsis. Taken together, our data indicate that plasmin plays multifunctional pro-inflammatory roles in different autoimmune and non-autoimmune diseases. The pro-inflammatory roles of plasmin include activation of inflammatory cells, regulation of cytokine expression, and enhancement of the bacterial killing ability of the host.

Arthritis includes many conditions of the joints characterized by inflammation, pain, and loss of joint function that affect 66 million people in the U.S. alone. During arthritic degeneration, chondrocytes exhibit downregulated synthesis of extracellular matrix molecules and upregulation of proteolytic enzymes. Fibrochondrocytes, found in meniscal fibrocartilage, appear to behave in a similar way. Metalloproteinases, including matrix metalloproteinases (MMP) and a disintegrin and metollproteinase with thrombospondin motif (ADAMTS) class enzymes have demonstrated efficient, distinct aggrecan degradation in models of arthritis. ADAMTS-4 and ADAMTS-5 are thought to be primary mediators of pathologic aggrecan catabolism, while MMP-17 may be involved in ADAMTS activation. There is also growing evidence of metalloproteinase-independent mechanisms in aggrecan catabolism. The cysteine endopeptidase m-calpain has been detected in cartilage from arthritic joints, and chondrocytes can secrete this protease. The overall objective of this work was to investigate metalloproteinases and m-calpain as comediators of aggrecan turnover in articular cartilage and meniscal fibrocartilage. The central hypothesis was that metalloproteinases cooperate with m-calpain to mediate cytokine-induced aggrecan turnover and associated changes in tissue mechanics. Experiments involved using inhibitors to perturb protease systems, antibodies targeting aggrecan neoepitopes to characterize enzyme activity, and established methods of evaluating tissue compressive and shear properties. Models of degradation and de novo tissue assembly were used to investigate tissue-specific differences in aggrecan turnover. The results of this work demonstrate tissue-specific differences in the abundance and structure of aggrecan, and indicate that the mechanisms and extent of aggrecan processing in the meniscus is dependent on location within the tissue. The relationships between aggrecan structure and tissue material properties are discussed, along with implications for development, disease, and repair.

ABSTRACT BACKGROUND: Arthritis is increasingly becoming a public health concern as it is the leading cause of disability. Glucosamine and chondroitin, which are alternative dietary supplements, are commonly marketed for persons with joint pain. The purpose of this study is to examine if self-reported 12-month and past 30-day use of glucosamine and/or chondroitin among persons with any arthritis, unspecified arthritis, and rheumatoid arthritis is associated with reports of past 12-month improved health and reports of past 30-day joint pain, aching, and stiffness, respectively. METHODS: The 2012 National Health Interview Survey (NHIS), a nationally representative cross-sectional household interview survey, was used for this study. The adult sample consisted of 34,525. Subgroup analyses were conducted on 7,654 respondents with any arthritis, 6,016 with unspecified arthritis, and 898 with rheumatoid arthritis. The independent variables were defined as the use of glucosamine only, chondroitin only, or glucosamine and chondroitin one or more times in the past 12 months and past 30 days. The dependent variables were defined as self-reported past 12 month improved health and past 30 day joint pain, aching, and stiffness. Descriptive, bivariate, and multivariate analyses were conducted using SAS 9.4 accounting for the complex survey design, computing missing values as missing completely at random for variance estimation. All multivariate logistic regression models included sociodemographics, use of other observed alternative therapies, and other chronic conditions. RESULTS: Approximately 21.8% of U.S adults had any arthritis, 17.0% had unspecified arthritis and 2.5% had rheumatoid arthritis. Among persons with any arthritis, approximately 3.7% used glucosamine, 0.4% used chondroitin, and 3.4% used both glucosamine and chondroitin within the past 12 months while approximately 5.1% used glucosamine, 0.6% used chondroitin, and 0.4% used both glucosamine and chondroitin within the past 30 days. Among persons with unspecified arthritis, approximately 3.7% used glucosamine, 0.5% used chondroitin, and 3.8% used both glucosamine and chondroitin within the past 12 months while 5.5% used glucosamine, 0.5% used chondroitin, and 0.4% used both glucosamine and chondroitin within the past 30 days. Among persons with rheumatoid arthritis, approximately 2.4% used glucosamine, 0.3% used chondroitin, and 2.1% used both glucosamine and chondroitin within the past 12 months while approximately 2.9% used glucosamine, 0.7% used chondroitin, and 0.5% used both glucosamine and chondroitin within the past 30 days. Women used more of all supplements (past 12 months and past 30 days) except past 12 month use of chondroitin among persons with any arthritis. Persons 56 to 70 years old had the highest proportion of past 12 month and 30 day supplement use among persons with unspecified arthritis. After adjusting for sex, age, race, BMI, poverty level, other health conditions, and other CAM therapies (acupuncture, energy, mind-body, and chiropractic/osteopathic therapies), the use of chondroitin only (adjusted OR= 0.6; p= <0.01) and the use of both glucosamine and chondroitin (adjusted OR= 5.7; p= <0.01) during the past 30 days was associated with self-reported past 30 day joint pain, aching, and stiffness among persons with any arthritis. After adjusting for age, BMI, poverty level, region, other health conditions, and other CAM therapies (acupuncture, energy, mind-body, and chiropractic/osteopathic therapies), the use of chondroitin only was also associated with past 30 day joint pain, aching, and stiffness among persons with unspecified arthritis (adjusted OR= 0.5; p= 0.02). CONCLUSION: Chondroitin alone was associated reports of past 30 day joint pain, aching, and stiffness among persons with any arthritis and unspecified arthritis highlighting a potential effective role and use for this supplement. In addition, the use of both glucosamine and chondroitin were associated with reports of past 30 day joint pain, aching, and stiffness among persons with any arthritis. Marketing may play a role in these relationships and should be further examined.

Osteoarthritis (OA), the most common form of arthritis in older adults, often results in pain, disability and poor psychological well-being. Compared to White adults, Black adults consistently report more pain, more activity limitations, and have different perceptions about OA. Racial disparities also exist in treatments, and prevalence of arthritis. It is imperative to have effective interventions and treatment options for older Blacks. Yet, few arthritis interventions have included Black participants in their samples, and nearly all of those have failed to report separate analyses indicating the effectiveness for Black adults, thus leaving a gap in the literature. The purpose of this study is to begin to identify factors needed to design arthritis interventions that will reduce barriers and increase appeal to Blacks. The present dissertation consists of one study with two related parts. The first part consists of a needs assessment that examined intervention preferences, barriers to healthcare, knowledge about interventions and care, utilization, and health beliefs among Black and White adults with self-reported physician-diagnosed OA. The second part evaluated materials used in an existing arthritis intervention for acceptability. The study was based on the Arthritis Self Management Program (ASMP). Frequencies were examined to determine needs related to arthritis healthcare of Blacks and Whites recruited from the community. Independent samples t-tests and Pearson’s Chi-square analyses were examined to determine group differences between Blacks and Whites. Blacks were more likely to report cost, lack of trust, fear of being the only person of their race, lack of recommendation from their doctor, and lack of recommendation of a family or friends as barriers to participating in arthritis interventions. In addition, Blacks were more likely to prefer the intervention content, structure and delivery, and arthritis resources presented in the needs assessment in comparison to Whites. As for the evaluation of the intervention materials, Blacks and Whites were similar on most sections. Based on our findings we suggest that practical adaptations (e.g., cost) be made to existing arthritis interventions to increase cultural sensitivity. Such adaptations have the potential to minimize barriers and offer a program that would be appealing to Blacks with OA.

The total annual incidence of arthritis in this prospective cross-sectional study on adults was 115/100 000. The annual incidence of rheumatoid arthritis (RA) was 24/100 000, 29/100 000 for women, and 18/100 000 for men. For reactive arthritis (ReA) the annual incidence was slightly higher, 28/100 000, and for undifferentiated arthritis 41/100 000. The annual incidence of Lyme disease and sarcoid arthritis was low. The annual incidence of arthritis in this study compares well with findings in earlier reports from both registers and case review studies. Almost 50% of the patients in the series of 71 patients with arthritis of less than 3 months’ duration had a preceding infection. Campylobacter jejuni ReA dominated the enteric ReA group. We found only a few patients with preceding Chl. trachomatis, Chl. pneumoniae, Borrelia burgdorferi or parvovirus B19 infections. The arthritis patients with a preceding infection went into remission more often than the patients without a preceding infection. The disease specificity of anti-CCP antibodies for RA was high, 96%, confirming earlier results. Anti-CCP antibodies differentiated RA from other arthritides. Several patients in the different diagnosis groups had raised serum COMP levels, indicating cartilage involvement very early in the disease, even in mild and self-limiting disease with good prognosis. The economic burden of early joint inflammation was found to be considerable already during the first few months of the arthritis irrespective of diagnosis. Surprisingly, patients with ReA generated almost as high costs as patients with RA during thefirst few months of the disease, even though most of the ReA patients had a relatively mild disease. Sick leave accounted for about 50% of the costs. The distribution of costs in the different patient groups was skewed. The median cost per patient for the group of patients with RA was US$4385, for ReA US$4085, for other types of specified arthritis US$3361, and for undifferentiated arthritis US$1482. This underlines the necessity of quick referral and therapy, not only to decrease the inflammation and prevent functional impairment, but also to decrease the costs of early arthritis.

No description available.

Katecholamine beeinflussen durch direkte Stimulation über adrenerge Rezeptoren die Funktion von Immunzellen. Ziel der Untersuchungen an Patienten mit Rheumatoider Arthritis war es, das Expressionsprofil unterschiedlicher adrenerger Rezeptorsubtypen in CD4(+)T-Lymphozyten dieser Patienten zu bestimmen. Zur Quantifizierung der Expression wurden semiquantitative RT-PCR-Analysen durchgeführt. Die Untersuchung zeigte, dass alpha1-adrenerge Rezeptoren in CD4(+)-T-Lymphozyten von RA-Patienten exprimiert werden. Es scheint eine Korrelation zwischen bestimmten extraartikulären Organmanifestationen (z.B. Sicca-Sydrom und Tenosynovitis) und der Expression alpha1-adrenerger Rezeptoren zu bestehen. Die gefundene differenzielle Expression der Rezeptoren in CD4(+)-T-Lymphozyten von RA-Patienten legen vertiefende Untersuchungen zur Relevanz des adrenergen Systems bei der Lymphozytenfunktionsmodulation nahe.