Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10357116 Secondary amyloidosis has decreased in patients with inflammatory joint disease in Finland 1999 We studied whether the high incidence of secondary amyloidosis (SA) is a consistent finding in patients with inflammatory joint disease. A total of 4508 biopsies of patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis were studied at the Rheumatism Foundation Hospital during 1987-1997. The results show that the annual number of findings of SA was reduced from 68 to less than 10. We suggest that a change in medication towards more frequent use of cytostatic agents is the reason for the reduction in incidence of SA.
10371281 A comparative quantitative morphometric study of cell apoptosis in synovial membranes in p 1999 May OBJECTIVES: Inflammatory arthritides/synovitides such as psoriatic (PsA), reactive (ReA) and rheumatoid (RA) arthritis share numerous immunopathological features, but develop different patterns of joint involvement. To investigate whether distinctive cell apoptosis may play a role in this context, we have assessed synovial cell apoptosis in situ in PsA and ReA, and compared it with RA and 'non-inflammatory' controls. METHODS: TdT-mediated dUTP nick end-labelling (TUNEL) of DNA breaks complemented immunoperoxidase staining for CD68 or LCA as the specific cell markers. RESULTS: The proportion of apoptotic synovial lining cells was high in PsA, ReA and RA compared to values in controls (P < 0.05). No differences existed between these inflammatory arthritides in numbers or type of apoptotic lining cells. In RA, however, in contrast to PsA and ReA, apoptotic lining cells were clustered or, in a small subset of samples, were very low in number. Prominent apoptosis of inflammatory cells in the sublining in ReA has accounted for higher overall apoptotic cell numbers in synovial stroma (sublining + perivascular inflammatory cell infiltrates) in this condition than in RA or PsA (P < 0.05). CONCLUSIONS: No disease-specific pattern in the phenotype of apoptotic synovial lining cells could be suggested in any of the inflammatory arthritides studied. However, topological differences in the lining and quantitative differences in the inflammatory cell apoptosis in synovial stroma may in part explain the occurrence of the prominent synovial lining cell hyperplasia distinguishing RA from ReA and PsA. On the other hand, relatively frequent inflammatory cell apoptosis may contribute both to the downregulation of synovial inflammation and to the control of synovial lining hyperplasia in ReA.
9365082 Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis: support fo 1997 Nov OBJECTIVE: A range of functional, biochemical, and psychological indicators was used to test the concept of "responders"/"nonresponders" and to seek predictors of response to 2 nonsteroidal antiinflammatory drugs in 9 patients with rheumatoid arthritis (RA) and 11 with osteoarthritis (OA). METHODS: In a balanced, randomized, double-blind, latin-square study design that involved four 4-week treatment periods, patients received ketoprofen or piroxicam (each for 2 of the 4 periods). Clinical and laboratory responses (pain, tenderness, swelling, patient and physician global assessments, acute-phase protein levels, and disability) were assessed in the last 2 weeks of each period. Responders were those who showed >30% improvement in at least 5 of 7 measures of disease activity. Mood was also assessed. RESULTS: At baseline, variables were higher in RA than in OA patients. The drugs produced clear improvements in patients' visual analog scale scores, physicians' overall assessments, and patients' responses to the McGill Pain Questionnaire, as well as plasma prostaglandin concentrations. In patients with either RA or OA, responders could be distinguished from nonresponders; about one-third of patients were unambiguous responders. In RA, there were responder/nonresponder differences in lymphocyte counts, erythrocyte sedimentation rate (ESR), and levels of tumor necrosis factor alpha, but no differences were seen in OA patients. However, caution in interpretation of the data is necessary because of the small number of patients. Responders had improved mood scores compared with nonresponders in both disease groups. Baseline ESR and white blood cell counts were correlated with responder status in RA patients. CONCLUSION: This study provides support for the responder/nonresponder concept. It also indicates that in RA, pretreatment ESR and lymphocyte counts are possibly useful indicators of therapeutic response.
10593566 The B lymphocyte in rheumatoid arthritis: recirculation of B lymphocytes between different 1999 In order to search for further evidence for a pathogenetic role of recirculating, antigen-driven B cell clones in rheumatoid arthritis (RA) rearranged VH genes were analysed for clonal relationship and somatic mutations from synovial tissue and peripheral blood of a patient with RA undergoing synovectomy of several finger joints. DNA was prepared from the synovial tissue of two finger joints and blood. PCR for the different VH families was performed with one specific oligonucleotide for each VH family and a mixture of JH-specific oligonucleotides. The PCR products were separated on a high resolution acrylamide gel differentiating one base pair difference of length. Transfer of the products onto a nylon membrane and hybridization with an oligonucleotide specific for the FR3 region revealed a polyclonal representation of rearranged VH1, VH3, VH4 and VH5 genes. The VH6 family, which is encoded by a single germline gene, was represented by few distinct bands, with some bands of identical height for both joints and blood. DNA from these bands of interest was eluted, reamplified by PCR, cloned and sequenced. Sequence analysis of 27 independent bacterial colonies allowed distribution of the different VH genes to seven B cell clones (A-G). Members of clone A were found in both joints and blood, clones B and C in one joint and blood, clone D in both joints, and clones E, F and G only in one joint. The VH regions were somatically mutated with characteristic patterns for the different clones. In conclusion, our findings confirm the systemic character of RA, because they show that not only expansion and affinity maturation of B cells occur in synovial membranes but antigen-specific B cells recirculate between different joints and blood.
9924209 Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthri 1998 Nov OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.
11178860 Temporomandibular joint replacement in rheumatoid-induced disease. 2001 Feb We report a series of seven patients with rheumatoid arthritis whose temporomandibular joints were replaced using the Christensen joint system. Patients were assessed before and after operation both subjectively (pain and dietary interference) and objectively (interincisal distance). Patient's satisfaction with the outcome of operation was also recorded. All patients showed improved visual analogue scores for pain and dietary interference after their operations and an improvement in interincisal distance was recorded in five of the patients (the remaining two having had the operation for anterior open bite). Overall satisfaction was high and no patient has rejected the prosthesis or had any substantial complications. The mean follow up period is 30 months (range 8-50). We suggest that patients with severe, rheumatoid-induced temporomandibular disease should be considered for arthroplasty as it is possible to restore some normal function and appearance.
11222898 Septic sacroiliitis with hematogenous spread to a total knee arthroplasty. 2001 Feb Septic sacroiliitis is an uncommon infection that comprises <2% of all nontuberculous septic arthritis and osteomyelitis. This case report describes a patient with rheumatoid arthritis who developed septic sacroiliitis that metastasized to her total knee arthroplasty.
9830881 A survey of United States rheumatologists concerning effectiveness of disease-modifying an 1998 Oct OBJECTIVE: To collect the ratings of American rheumatologists regarding relative short-term and long-term effectiveness of disease-modifying antirheumatic drug (DMARD) therapy in the treatment of rheumatoid arthritis and to compare these data with results of a meta-analysis of randomized, controlled clinical trials (RCTs) of these drugs. METHODS: A survey was mailed to 3,200 United States rheumatologists who were members of the American College of Rheumatology during the summer of 1996. The survey was completed by 645 rheumatologists. RESULTS: Methotrexate (MTX) was rated as substantially more effective than any other DMARD after both 1 year and 4 years of therapy. At 1 year, more than 90% of rheumatologists rated MTX as "good or excellent," compared with 35% giving a similar rating to intramuscular (IM) gold, the second-ranked DMARD. At 4 years, MTX was rated as "good or excellent" by 65%, compared with 53% for combinations, 30% for prednisone, and 11% for hydroxychloroquine, the second-ranked single DMARD. These ratings reflect results of long-term observational studies, but differ considerably from a meta-analysis of results of short-term RCTs, in which the efficacy of MTX, sulfasalazine, penicillamine, and IM gold were indistinguishable. CONCLUSION: The ratings of US rheumatologists regarding effectiveness of DMARD therapies are in agreement with observational data, but differ substantially from results of RCTs. These findings suggest that observational studies may yield useful and important information about treatment results, which are complementary to, but not available from, the RCT model. Regulatory agencies should consider long-term observational studies as a part of the evaluation of drugs.
9814658 Hematopoietic stem cell therapy of autoimmune diseases. 1998 Nov Hematopoietic stem cell transplantation is a new therapy for severe autoimmune diseases. Patients who have failed standard therapies and are at high risk of subsequent morbidity and mortality are being considered as candidates. Early results are encouraging. However, the number of patients treated is limited, only short-term follow-up is available, the mechanism of improvement or stabilization is unknown, and the procedure has the potential for life-threatening toxicity.
9727799 Diffuse panbronchiolitis in rheumatoid arthritis. 1998 Aug The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.
9510098 Influence of light delivery on photodynamic synovectomy in an antigen-induced arthritis mo 1998 BACKGROUND AND OBJECTIVE: Minimally invasive synovectomy techniques have been unsuccessful due to lack of selectivity. The purpose of this study was to evaluate the potential of photodynamic therapy to destroy diseased synovium in an antigen-induced arthritis model. STUDY DESIGN/MATERIALS AND METHODS: Three sets of experiments evaluated the biodistribution and treatment effects of Photofrin (PF) in rabbits with bilateral knee antigen-induced arthritis. The first set of experiments evaluated the biodistribution of PF in articular tissues of 30 rabbits from 6-72 hours after systemic injection of 2 mg/kg. In the second series of experiments, light was delivered to the knee joint via cleaved optical fibers, whereas for the third, light was delivered via a 600 microm diffusion tip fiber. Tissues were harvested at 2 and 4 weeks posttreatment. RESULTS: The biodistribution experiments demonstrated maximal uptake in inflamed synovium at 48 hours and a lack of uptake in normal tissues. With bare cleaved fibers, necrosis was observed in one specimen at 2 weeks and was absent in all specimens at 4 weeks. In the third experiment, synovial necrosis was observed in 3 of 7 specimens at 2 weeks and 3 of 8 at 4 weeks. No damage to articular cartilage or periarticular tissues was seen with either mode of light delivery. CONCLUSION: These studies indicate that selective destruction of synovium can be achieved with PF and suggest that optimization of light delivery techniques will play an important role in development of this new technique.
10857782 Human cartilage gp-39+,CD16+ monocytes in peripheral blood and synovium: correlation with 2000 Jun OBJECTIVE: To investigate the expression of human cartilage (HC) gp-39, a possible autoantigen in rheumatoid arthritis (RA), in peripheral blood and synovium, to characterize its cellular source, and to analyze correlations with clinical features. METHODS: The expression of HC gp-39 in synovium and peripheral blood mononuclear cells (PBMC) was assessed by immunohistochemistry and flow cytometry. Synthesis and secretion were investigated by both reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: PBMC expressing HC gp-39 were increased in RA patients compared with spondylarthropathy patients (P = 0.0029) and with healthy control subjects (P = 0.0013). HC gp-39+ cells were also slightly overrepresented in RA synovium (P = 0.01). In both blood and synovium, HC gp-39+ cells were identified as CD14dim,CD16+ monocytes, a phenotype which can differentiate from classic CD14++ monocytes by maturation in vitro. HC gp-39 messenger RNA was detected in RA synovium and PBMC, and PBMC secreted HC gp-39 in vitro. The number of HC gp-39+ PBMC correlated with serum levels of C-reactive protein (r = 0.39, P = 0.003) and HC gp-39 (r = 0.52, P = 0.014). HC gp-39 expression in RA synovial lining correlated with joint destruction (r = 0.77, P < 0.001). CONCLUSION: CD16+ monocytes, a cellular source of HC gp-39 in vivo, are overrepresented in both RA peripheral blood and synovial tissue. The presence of HC gp-39+ cells in RA synovium is correlated with the degree of joint destruction. These data support a role of these cells in the local autoimmune response that leads to chronic inflammation and joint destruction.
10685797 Anti-MAM antibodies in rheumatic disease: evidence for a MAM-like superantigen in rheumato 2000 Feb OBJECTIVE: Superantigens (SAg) are potent immunomodulatory microbial proteins that can activate T cells, B cells, natural killer cells, and monocytes and are known to trigger experimental autoimmune disease. We investigated whether sera from patients with rheumatic diseases contained elevated antibodies to Mycoplasma arthritidis mitogen (MAM) or staphylococcal enterotoxins A and B (SEA and SEB). METHODS: Standard ELISA were used to measure IgG responses to SAg and IgM and IgG rheumatoid factors and total IgM and IgG levels. Modifications of standard lymphocyte proliferation assays were used to determine functional consequences of the observed antibodies. RESULTS: Antibodies to MAM were elevated in sera from patients with rheumatoid arthritis (RA) compared to sera from patients with systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, or healthy controls. Responses to other SAg were also elevated in rheumatic disease sera, but the levels were not specific for a given rheumatic disease. Anti-superantigen antibody levels did not correlate with the presence of rheumatoid factor. CONCLUSION: The selected elevation of antibodies to MAM in RA sera suggests that MAM or a MAM-like molecule might be associated with RA, whereas elevation of antibodies to SEA and SEB in sera from patients with rheumatic diseases was less specific.
11145033 A reappraisal of HAQ disability in rheumatoid arthritis. 2000 Dec OBJECTIVE: To investigate the course of self-reported disability in rheumatoid arthritis (RA) using the major self-report measure of functional impairment, the Health Assessment Questionnaire (HAQ). METHODS: The course of HAQ disability was assessed in 32,525 observations (1,843 patients) in which the HAQ was administered. In addition, a subset of 2,189 visits from 50 patients, followed on average for 17 years, was studied to model the effect of disease duration on the course of HAQ disability in individual patients. Linear and fractional polynomial regression as well as smoothing algorithms were applied to the group of RA patients and then to the individual course of patients. RESULTS: Group linear and nonlinear models of the effect of disease duration on HAQ disability were found to have 3 characteristics: 1) HAQ disability scores are high at disease onset rather than gradually increasing; 2) HAQ disability increases very slowly over time (0.03 units per year); and 3) all such models fit very poorly, explaining only 5% of the variance in HAQ disability scores. However, application of nonlinear models to individual patient courses (as opposed to groups of patients) explains 37% of the HAQ disability score variation. In some patients, the course of HAQ disability was either 1) chaotic (scores change without any pattern) or 2) determinable, but unrelated to time. When covariates were added to the group model, however, the course of HAQ disability became clearer, and 51% of the variance in the disability score could be explained, statistically, by pain, depression, erythrocyte sedimentation rate, and disease duration. CONCLUSION: Individual RA patients have differing, characterizable courses: 1) nonlinear, 2) chaotic, or 3) non-time determined. The model that self-reported physical disability, as measured by the HAQ, occurs as a function of disease acting over time does not fit the data well and is an inadequate model. This discrepancy may also be the result of the patient's upward reappraisal of functional ability with increasing time. The predominant determinants of HAQ disability in RA are disease activity, pain, and psychosocial factors rather than structural abnormality. Although the HAQ is a useful clinical tool and a central measure of disease outcome, it measures both process and outcome, and usually more process than outcome. Individual patient models that include all that is known about the patient--the paradigm of clinical care-may be a more effective way to examine the course of RA than are conventional group-based models.
11762951 Differential expression pattern of the antiapoptotic proteins, Bcl-2 and FLIP, in experime 2001 Dec OBJECTIVE: To examine the relationship between apoptosis and the expression of antiapoptotic proteins in the pathogenesis of experimental inflammatory arthritis. METHODS: Clinical and histologic assessment of adjuvant-induced arthritis (AIA) was performed over a 42-day period. The induction of apoptosis was measured by TUNEL analysis, and the antiapoptotic proteins, Bcl-2 and FLIP, were examined by immunohistochemistry with the use of monospecific antibodies. The percentage of Bcl-2- and FLIP-positive cells was correlated with histologic markers of AIA. RESULTS: Arthritis developed by day 14 following adjuvant injection. Few TUNEL-positive cells were observed between days 0 and 21, indicating that apoptosis did not occur at these time points. An increase in the number of TUNEL-positive cells was observed at day 28, particularly outside sites of cartilage or bone erosion, which dramatically declined by day 35. Immunohistochemical analyses of Bcl-2 and FLIP revealed that the synovium was positive for Bcl-2 and FLIP on day 0. On day 14, Bcl-2 was present at the sites of early erosions and correlated with the erosion and inflammation scores. FLIP was also highly expressed at sites of erosion and was localized to the pannus starting on day 21. Although TUNEL positivity peaked at day 28, a time point in which Bcl-2 and FLIP were present, the areas that displayed intense positivity for expression of Bcl-2 and FLIP were TUNEL negative. In addition, the number of neutrophils in the synovial lining and pannus significantly decreased from day 28 to day 35, suggesting that the cells undergoing apoptosis were neutrophils. Furthermore, at day 42 when TUNEL-positive cells were absent, Bcl-2 expression was diminished, while FLIP remained highly expressed in the pannus. CONCLUSION: The overall percentage of TUNEL-positive cells in the ankle was <1% except on days 28 and 35 post-adjuvant injection, suggesting that in AIA, similar to rheumatoid arthritis, a lack of apoptosis may contribute to disease progression. Furthermore, Bcl-2 and FLIP are temporally and differentially expressed during the pathogenesis of AIA. Inhibition of these molecules may augment synovial apoptosis and ameliorate the disease.
10460192 Tumour necrosis factor alpha stimulated rheumatoid synovial microvascular endothelial cell 1999 Sep OBJECTIVE: To investigate endothelial cell adhesion molecule expression and leucocyte adhesion to endothelial cells isolated from the microvasculature of rheumatoid arthritic synovial tissue (SMEC) in comparison with similar cells isolated from healthy subcutaneous adipose tissue (ADMEC) or from umbilical veins (HUVEC). METHODS: Cultured endothelial cells were treated with tumour necrosis factor alpha (TNFalpha) for 2-24 hours before the assessment of cell surface E-selectin, vascular (VCAM-1) or intercellular cell adhesion molecule-I (ICAM-1) expression. Neutrophil and T lymphocyte adhesion to TNFalpha treated endothelial cells was assessed using static and shear dependent assay systems. RESULTS: VCAM-1 expression by SMEC was significantly less sensitive to TNFalpha stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared to be more sensitive to TNFalpha stimulation and maximal expression was about 30% greater in comparison with HUVEC or ADMEC. Sensitivity to TNFalpha induction and maximal ICAM-1 expression was similar in all three endothelial cell types. Static neutrophil adhesion to TNFalpha stimulated SMEC was significantly increased in comparison with HUVEC, however this phenomenon was dependent on the presence of neutralising antibodies to ICAM-1. At shear rates in excess of 2.4 dynes/cm(2) significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNFalpha stimulated SMEC than HUVEC. CONCLUSION: Rheumatoid synovial endothelial cells differentially regulate E-selectin and VCAM-1. The increased ability of TNFalpha stimulated synovial endothelial cells to support leucocyte adhesion may help to explain the leucocyte, in particular CD45RO+ T-lymphocyte, recruitment observed in the rheumatoid synovium.
11282569 A double blind randomized controlled trial of Maharishi Vedic vibration technology in subj 2001 Apr 1 To explore ancient Vedic medical techniques, one hundred and seventy-six subjects with arthritis participated in a controlled study through the non-pharmacologic approach known as the Maharishi Vedic Vibration Technology (MVVT). Using a double-blinded and randomized experimental design, the findings showed significant reductions of pain and stiffness, and improvement in range of motion in the study sample. One hundred percent relief of symptoms was the most commonly reported category of improvement due to treatment. For the group as a whole, differences in mean response of treatment and control conditions with respect to relief of pain, limitation of motion, and reduction in stiffness were highly significant: t values ranged from a low of 5.609 in stiffness to a high of 20.950 in pain, p = 0.000009 to <10-49 respectively. Analysis by sub-categories of peripheral arthritis, painful conditions of the spine, and rheumatoid arthritis likewise produced significant results. Mechanisms of action were proposed, drawing on Maharishi Vedic Science, developments in quantum field theory, and specifically the theories of chaos and self-organizing systems as they relate to physiological functioning. The instantaneous relief of pain and improvement in function in such a high proportion of subjects with chronic arthritis is unparalleled in modern medical science
10323455 Association of rheumatoid arthritis with a functional chemokine receptor, CCR5. 1999 May OBJECTIVE: To investigate whether the pathogenesis of rheumatoid arthritis (RA) is associated with the functional chemokine receptor CCR5, which is the primary CC chemokine receptor expressed by T cells in rheumatoid synovium, and its nonfunctional receptor, delta32CCR5, which is generated by the homozygous 32-basepair deletion (delta32) in the CCR5 gene. METHODS: The frequency of the CCR5 genotype was compared among 673 patients with RA, 113 patients with systemic lupus erythematosus (SLE), and 815 control subjects. The CCR5 genotype was studied by polymerase chain reaction amplification of the region flanking the delta32 deletion (delta32CCR5). RESULTS: Frequencies of the wild-type CCR5 alleles (0.929, 0.907, and 0.942, respectively) and delta32CCR5 alleles (0.071, 0.093, and 0.058, respectively) in controls, SLE patients, and RA patients did not differ significantly. However, none of the RA patients had the homozygous delta32CCR5 genotype, compared with a frequency of 0.009 in controls (P = 0.014 by Fisher's exact test; chi2 = 4.12 with Yates' correction, P = 0.042) and 0.027 in SLE patients (P = 0.003 by Fisher's exact test; chi2 = 11.63 with Yates' correction, P = 0.0006). CONCLUSION: The results suggest that the CCR5 receptor plays an important role in RA and may be a suitable target for therapy.
9101508 Direct medical costs unique to people with arthritis. 1997 Apr OBJECTIVE: We report the results of a population based analysis of all health services used and charges incurred over a one-year period among a community based cohort of persons with a diagnosis of arthritis [including both osteoarthritis (OA) and rheumatoid arthritis (RA)] compared to a similar cohort of individuals from the same community who have never had a diagnosis of arthritis (NA), to examine the attributable costs of this chronic condition. METHODS: The unique resources of the Rochester Epidemiology Project were used to assemble the arthritis prevalence cohorts and the population based control cohort. The Olmsted County Health Care Utilization and Expenditures Database was used to collect information on health services utilization and charges. RESULTS: The average direct medical charges for the RA, OA, and NA cohorts were $3,802.05, $2,654.51, and $1,387.83, respectively (age and sex adjusted, p < 0.0001 for both the RA vs NA and OA vs NA comparisons). The median charges for these 3 groups were $1,050.00, $663.55, and $232.04 for the RA, OA, and NA groups, respectively (age and sex adjusted p < 0.0001 for both the RA vs NA and OA vs NA comparisons). These analyses indicated that, compared to the NA cohort both the OA and the RA prevalence cohorts incurred statistically significantly more charges, not only for the musculoskeletal disease care, but also for the care of numerous other conditions including respiratory, cardiovascular, gastrointestinal, neurological, and psychiatric conditions; and for general medical care. Individuals with arthritis (both OA and RA) also incurred statistically significantly more charges for diagnostic and therapeutic procedures, in-hospital care, imaging studies, physician services, equipment, and laboratory studies. Use of prescription medications was statistically significantly more common in the RA and OA groups compared to NA (96.3, 96, and 83%, respectively; age and sex adjusted p = 0.006 for the OA vs NA comparison and p = 0.015 for RA vs NA). CONCLUSION: These results emphasize the importance of considering all health services utilization (rather than only disease specific use) when estimating the economic effect of a chronic illness such as arthritis.
9811058 Pristane-induced arthritis in mice. V. Susceptibility to pristane-induced arthritis is det 1998 Nov OBJECTIVE: Pristane-induced arthritis (PIA) is an experimental seropositive arthritis that is characterized by serologic and cellular immune abnormalities and is dependent on the presence of a competent CD4+ T cell population. We examined the regulation of PIA by genes of the major histocompatibility complex (MHC) and the Mls-1 loci to determine whether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility. METHODS: Genetic regulation of PIA was investigated using F1 hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor Vbeta phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcription-polymerase chain reaction techniques. RESULTS: F1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-1 loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1a mice, where T cells expressing the Vbeta8.1 and Vbeta6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed toward Vbeta8.1 and Vbeta6 compared with the population observed in lymph nodes from either PIA or normal control DBA/1 mice. CONCLUSION: The data support the hypothesis that PIA is a T cell-mediated disease. While pristane causes a polyclonal T cell expansion that gives rise to lymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with the capacity to infiltrate synovial joints.