Inaug.-Diss.--Basel. / At head of title: Aus der Medizinischen Universitäts-Poliklinik Basel. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1942. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 74).

Thesis (M.D.)--Faculté De Médecine De Paris, 1853. / Includes bibliographical references.

The present research was carried out to investigate the chemoattraction activity of rheumatoid and non rheumatoid synovial fluids for human lymphocytes separated from peripheral blood, synovial tissue and synovial fluid. The phenotyping of locomotor cells in response to these fluids was also studied. Established procedures were used to separate lymphocytes from blood, synovial tissue and synovial fluid. The level of the chemotactic factors in the synovial fluid was measured by commercial and in-house developed methods. The inhibitory effect of anti-inflammatory drags on the lymphocyte locomotion was also studied. The chemoattractant activity of synovial fluid for human lymphocytes was investigated using the following methods: i. A Polarization assay which measures the shape change from spherical or round to a polarized shape (i.e from immotile to a motile shape) following stimulation with chemoattractants. ii. Collagen gel invasion, which measures the migration of lymphocytes into collagen gels- containing chemoattractants. Two methods were used for phenotyping the cells responding to the synovial fluids (I) APAAP which allowed the detection of lymphocyte surface markers in stained cytospin preparations, (ii) FACS which allowed the detection of cell surface markers of lymphocytes recovered from collagen gels after collagenase digestion. In addition methods used to measure the levels of chemotactic factors in the synovial fluid, were (I) Commercial single antibody sandwich ELISA kits (R&D) which measured IL-2, IL-8, MIP-1α and MCP-I, (ii) In-house developed multiple antibody sandwich ELISA which measured IL-15 in the fluids. The ability of synovial fluids from patients with rheumatoid (n=35) and other arthritides (n=18) to attract lymphocytes from peripheral blood of normal subjects, from rheumatoid synovia, and from joint fluids, was studied. The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for blood lymphocytes which had been cultured overnight. Three out of five fluids from OA also attracted lymphocytes but to a lesser extent than RA fluids. In addition four of seven fluids from other inflammatory arthritides also gave high responses Rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. In contrast lymphocytes derived from rheumatoid and other synovial fluids were completely unresponsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes and the CD45RO isotype was attracted preferentially. Rheumatoid synovial fluids contained IL-8 , IL-15, MIP-1α and MCP-1 at levels in the nanogram range, sufficient to attract lymphocytes, but levels of IL-2 were too low to exert a chemoattractant effect. In contrast the levels of chemotactic factors in OA fluids were low and these fluids also showed less activity in attracting lymphocytes. The activity of the fluids could not be abolished by treatment with antibodies to IL-8, IL-2, MTP-1α, MCP-1 or IL-15 tested individually, but combinations of these antibodies inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. The accumulation of lymphocytes within the synovial fluids was not correlated with any single chemotactic factor mentioned above, suggesting that such accumulation is due to combined chemoattractants. In the present study it was also observed that neutrophils separated from normal blood gave a strong chemotactic response to the synovial fluids. In contrast neutrophils separated from the synovial fluid were immotile, suggesting that these cells had an intrinsic defect or that their locomotion was selectively blocked by synovial fluid chemotactic inhibitors. Moreover there was no correlation between IL-8 or levels of any other single cytokine and the accumulation of these cells in the fluids, indicating the possibility of multiple chemotactic factor involvement. The manipulation of the locomotion activity of lymphocytes in vitro in response to synovial fluid was studied using anti-inflammatory drugs. It was demonstrated that NSAIDs (including Aspirin, Ibuprofen and indomethacin), DMARDs (including gold, D-penicillamine and primaquine) and cytotoxic drugs including rapamycin and cyclophosphamide had no inhibitory effect on lymphocyte locomotion. On the other hand cyclosporin A and Glucocorticosteroids (including dexamethasone, prednisone and prenisolone) showed a significant inhibitory effect.

Physical disability resulting from arthritis is a widespread problem: when the sufferer is the breadwinner of a family, it is particularly serious, creating the need for special services not only for the disabled person, but also for his family. But the treatment potential of the patient also depends on how far his family is in turn a source of strength or weakness to him. This is a casework "dimension" that is far from fully explored. This thesis considers the family as a treatment resource in the rehabilitation of a group of male arthritic breadwinners who have been in-patients at the Canadian Arthritis and Rheumatism Society (B.C. Division) Medical centre in Vancouver, B. C, for at least three months. While focusing on the patient in his family group, the study undertakes an intensive examination of the material found in case records and related correspondence from the Medical Centre's Social Service Department, a clinical social work setting. The outcome of the exploration was to emphasize two approaches: (a) the recognition of factors in family behaviour toward the patient which connote family strength, and (b) their application in casework to help meet the patient's needs. Four comparative cases (two each of "strong" and "weak" examples) were selected to identify the variables affecting employment, treatment, and family interaction. The results of this analysis were then applied to the process of diagnosis and treatment to the total cases (seven) for which clinical and social information was available. The specific findings are (1) that the patient's family could influence positively the patient's rehabilitation potential; (2) that family strength could be recognized in a clinical setting treating the patient; (3) that certain additional kinds of diagnostic information are required prior to the patient's admission to the Medical Centre for treatment. A rating scale of family strength can be envisaged as an experimental counterpart of this complex adjustment process. Some practical implications for future service are discussed. / Arts, Faculty of / Social Work, School of / Graduate

The therapy of osteo-arthritis is a problem which we have inherited from our forebears. It is a considerable problem; one which affects the community very vitally. The disease produces marked disability which burdens our civic economy. Various methods of therapy have been advocated from time to time such as hydro-therapy, physiotherapy and analgesics of different kinds. This thesis will deal only with the intra-articular injection therapy of osteo-arthritis.

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This thesis tracks how osteoarthritis appeared among prehistoric human populations, and how it changed through time. By examining these changes, information was provided about food acquisition and preparation activities in northwestern Alabama and northeastern Mississippi, from the Archaic period (B.P. 12650-5600) through the Protohistoric (A.D. 1550-1750) Osteoarthritis was also examined to determine whether a sexual division of labor existed among prehistoric populations from these same areas. Individuals from three specific occupations were analyzed: Dust Cave (1LU496), Lyon’s Bluff (22OK520), and Rolling Hills sites (22OK509, 22OK593, 22OK595). Using the Wilcoxon signed-rank test and logistic regression to find and assess patterns, this study showed that arthritis increased in severity, at a given age, among the Archaic males and the Mississippian/ Protohistoric females. Namely, male individuals from Dust Cave and female individuals from Lyon’s Bluff / Rolling Hills developed osteoarthritis earlier and to a greater degree of severity.