Reactive arthritis following culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon: a population-based study.

OBJECTIVE: To describe the epidemiology and clinical spectrum of reactive arthritis (ReA) following culture-confirmed infection with bacterial enteric pathogens in a population-based study in the USA. METHODS: We conducted telephone interviews of persons age>1 year with culture confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella and Yersinia infections reported to FoodNet (http://www.cdc.gov/FoodNet/) in Minnesota, USA and Oregon, USA between 2002 and 2004. SUBJECTS: with new onset joint pain, joint swelling, back pain, heel pain and morning stiffness lasting >or=3 days within 8 weeks of culture (possible ReA) were invited to complete a detailed questionnaire and physical examination. RESULTS: A total of 6379 culture-confirmed infections were reported; 70% completed screening interviews. Of these, 575 (13%) developed possible ReA; incidence was highest following Campylobacter (2.1/100,000) and Salmonella (1.4/100,000) infections. Risk was greater for females (relative risk (RR) 1.5, 95% CI, 1.3 to 1.7), adults (RR 2.5, 95% CI, 2.0 to 3.1) and subjects with severe acute illness (eg, fever, chills, headache, persistent diarrhoea). Risk was not associated with antibiotic use or human leukocyte antigen (HLA)-B27. A total of 54 (66%) of 82 subjects examined had confirmed ReA. Enthesitis was the most frequent finding; arthritis was less common. The estimated incidence of ReA following culture-confirmed Campylobacter, E coli O157, Salmonella, Shigella and Yersinia infections in Oregon was 0.6-3.1 cases/100,000. CONCLUSIONS: This is the first population-based study of ReA following infections due to bacterial enteric pathogens in the USA. These data will help determine the burden of illness due to these pathogens and inform clinicians about potential sequelae of these infections.

HLA-B27 has no effect on the phenotypic expression of progressive ankylosis in ank/ank mice.

OBJECTIVE: To investigate whether HLA-B27 influences the expression of murine progressive ankylosis (MPA), a single-gene autosomal recessive mouse model of ankylosing spondylitis that arises in mice homozygous for the ank gene. METHODS: Mice transgenic for HLA-B27 were bred with ank/ank mice, and the phenotypes of the F1 and F2 progeny were observed. RESULTS: ank/+ mice showed no abnormalities, and ank/ank mice showed the typical phenotype of MPA, irrespective of B27 status. CONCLUSION: HLA-B27 and the ank/ank genotype both predispose to diseases involving progressive bony ankylosis. These findings suggest that these disease processes are distinct and noninteractive, and they provide no support for the hypothesis that the human homolog of the ank locus participates in the pathogenesis of ankylosing spondylitis.

Fibroblasts from mice with progessive ankylosis proliferate excessively in response to transforming growth factor-beta 1.

BACKGROUND: Murine progressive ankylosis (MPA) is a spontaneous arthropathy that produces ankylosis of peripheral and spinal joints in mice homozygous for the gene ank. This animal model bears a striking resemblance clinically, radiographically, and histologically to ankylosing spondylitis. Phosphocitrate (PC) is the only treatment known to significantly delay disease progression in MPA. Transforming growth factor-beta (TGF-beta) is important for both developmental bone formation and fracture healing, and has been detected in biopsy specimens from sacroiliac joints of patient with ankylosing spondylitis. We hypothesized that TGF-beta might be involved in the pathogenesis of MPA. METHODS: We compared the proliferative response of resting fibroblasts from normal and MPA mice to TGF-beta 1 as measured by 3H-thymidine incorporation and the effect of PC on that response. Cells were cultured with 10% serum as a positive control. The mouse fibroblast cell line, BALB/3T3, controlled for culture conditions. RESULTS: MPA and normal fibroblasts responded similarly to serum. MPA fibroblasts proliferated significantly better in TGF-beta 1 than the poorly responsive normal mouse fibroblasts. PC, at 10(-3) mol/L, inhibited the TGF-beta 1-induced proliferation of MPA and 3T3 cells, but had no effect on normal fibroblasts. CONCLUSIONS: MPA fibroblasts proliferate excessively to TGF beta 1 in vitro. This effect could be caused by altered TGF receptors, changes in signal transduction, or impaired inhibition of the TGF-beta signal. This excessive response is blocked by PC. These results give further clues as to how PC inhibits the progression of ankylosis in MPA.

Commercial wrist extensor orthoses: a descriptive study of use and preference in patients with rheumatoid arthritis.

OBJECTIVE: To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively. METHODS: Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods. RESULTS: Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support. CONCLUSIONS: No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.

Murine progressive ankylosis is not immunologically mediated.

OBJECTIVE: Murine progressive ankylosis is an autosomal recessive disorder in mice similar to the human spondyloarthropathies. The gene responsible for progressive ankylosis, ank, has not been identified and its product is unknown. We investigated whether the immune system plays a role in the pathogenesis of progressive ankylosis. METHODS: Reciprocal transfers of spleen or bone marrow cells or serum between ank/ank and normal mice were performed. CD4 T cells were depleted in vivo by injection with monoclonal antibody. Ank/ank; nu/nu mice were bred from double heterozygote offspring of homozygote parents. RESULTS: Disease was neither ameliorated nor induced by these immune system manipulations. CONCLUSION: We conclude that progressive ankylosis is not immune mediated. The similarities between ankylosing spondylitis and murine progressive ankylosis may be due to mechanisms producing osteogenesis in nonosseous tissues.

The importance of identifying depression in patients with rheumatoid arthritis: evaluation of the beck depression inventory.

Depression is common in patients with chronic illness including rheumatoid arthritis (RA). Identifying depression accurately and treating it appropriately are important for helping to maintain function in patients with RA. Several self-administered screening tools are available that are sensitive for the detection of depression in medical outpatients and are easy to use in a clinic setting. There has been debate regarding the validity of some of these tools for detecting depression in RA patients because of "arthritis-biased" questions. In this study, we evaluated 77 patients with RA and measured their responses to one of these screening tools, the Beck Depression Inventory (BDI). We compared disease activity and severity measures and measures of functional status between patients who were designated as depressed by BDI score and patients without depressive symptoms.We were unable to demonstrate differences in specific objective measures of disease activity, severity, or objective functional measures between nondepressed and depressed RA patients. However, depressed patients reported greater disease activity and poorer physical function, and observer global assessment of depressed patients was poorer. We conclude that the "arthritis-biased" questions in the BDI did not interfere with the detection of depression in patients with RA and should not be a deterrent for its use. We found that the BDI can be used effectively in a clinic setting as a screening tool for depression in patients with RA.

Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA). METHODS: Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor). RESULTS: Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time. CONCLUSIONS: The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.

Immediate and short-term effects of three commercial wrist extensor orthoses on grip strength and function in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function. METHODS: Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study of 3 commercial wrist extensor orthoses. Dominant-hand dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted. Functional impact was assessed using a written questionnaire. RESULTS: All 3 commercial orthoses reduced grip strength when first donned. After a 1-week adjustment period, one orthosis, the Smith and Nephew Roylan D-Ring (Roylan), afforded splinted grip strength equal to that of the nonsplinted grip strength. The other 2 orthoses continued to reduce grip strength, and afforded splinted grip strength significantly below that of the Roylan. The Roylan was deemed comfortable by more subjects than the other orthoses. CONCLUSIONS: The belief that commercial orthotic use increases grip strength, either immediately or after 1 week, is not supported by this study's data. Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength.

Exercise for arthritis.

The data available indicate that ROM, strengthening and aerobic conditioning exercises are safe for patients with OA, RA or AS, despite earlier concerns that exercise might exacerbate joint symptoms or accelerate disease. Less clear are the therapeutic benefits of exercise. In patients with OA, stretching, strengthening, and aerobic conditioning programmes can improve the deficits observed in these patients. The improvements observed generally have been small, and the evidence that these individual improvements result in improved overall function is minimal. None the less, it is likely that exercise will reduce pain, improve endurance for physical activities and improve cardiovascular fitness. Study of the long-term effects of exercise in the geriatric population, for sustaining independent living and functioning, is critically important for future health care and social expenditures. In RA, strengthening and aerobic conditioning exercise programmes can increase muscle strength and cardiovascular fitness and probably improve physical function as well. Improvements demonstrated in patients with RA seem more convincing than those in patients with OA and AS; this probably represents their poorer physical status prior to exercising. For patients with AS, intensive physiotherapy brings statistically significant short-term improvements in spinal and hip ROM which are only modestly clinically significant. It is possible that spinal mobility exercises decelerate loss of mobility over the long term, but controlled studies are needed to confirm this. Improvement in respiratory function with exercise appears to be related to cardiopulmonary fitness and perhaps to improvements in diaphragmatic respiration rather than to changes in thoracic cage mobility. Given the overall safety and likely benefits of the described forms of exercise, exercise should be included in the overall treatment of patients with OA, RA or AS. Careful patient evaluation and education about exercise should be a part of the exercise programme.

Phosphocitrate prevents disease progression in murine progressive ankylosis.

OBJECTIVE: Mice with progressive ankylosis, a spontaneous arthropathy, were treated with phosphocitrate (PC) in vivo to determine the effect of PC on disease progression. METHODS: Two groups of mice with progressive ankylosis (matched for age, weight, and sex) were treated parenterally for 6 weeks with either PC or saline vehicle. RESULTS: Clinically, histologically, and microradiographically, there were significant differences in disease progression and severity in the PC-treated and the saline-treated mice. CONCLUSION: PC appears to inhibit disease progression in murine progressive ankylosis.

Validity and reliability of the timed-stands test for patients with rheumatoid arthritis and other chronic diseases.

The timed-stands test (TST) is a simple measure of lower extremity strength which correlates with age in healthy people. We validated the TST as a functional assessment tool against other measurements of functional capacity and comorbidity in 147 patients with rheumatoid arthritis (RA) or other chronic diseases. The TST was significantly impacted by RA disease activity and by comorbidity. Age affected TST only in patients without arthritis or life threatening disease. TST is a simple, reproducible measure of lower extremity function that was valid in this patient population.

Transient inhibition of murine progressive ankylosis by indomethacin.

Murine progressive ankylosis (MPA) is an heritable disorder which produces acute arthritis and ankylosis of peripheral and axial joints similar to ankylosing spondylitis. Because indomethacin inhibits heterotopic bone formation in vivo, we studied its effects on MPA. Indomethacin was administered for 6 weeks beginning at weaning to litters from heterozygote breeder pairs. Progression curves for peripheral, spinal and thoracic joint ankylosis in treated and untreated ank/ank animals wer compared. There was no delay in ankylosis of peripheral or spinal joint ankylosis in MPA animals treated with indomethacin. interestingly, transient delay of thoracic ankylosis occurred in indomethacin treated MPA animals.

Calcergy in murine progressive ankylosis.

Murine progressive ankylosis (MPA) is characterized by periarticular ossification and joint ankylosis. We studied calcergy and calciphylaxis in MPA. Calcergy represents a chemical attraction between heavy metal salts and apatite followed by hydroxyapatite deposition around collagen. Mice were injected subcutaneously with FeCl2, PbAcetate, and saline, and sacrificed at intervals between 5 minutes and 14 days. Section of skin and subcutaneous tissues were stained with Von Kossa's stain. No mice developed calcifylaxis. PbAcetate produced calcergy in all mice. MPA mice exhibited calcergy qualitatively and quantitatively the same as normal mice suggesting abnormal calcergy is not responsible for joint ankylosis in MPA.

Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. III. Proliferative spleen cell response to T cell mitogens.

Murine progressive ankylosis is a spontaneous disorder of mice resulting from a homozygous recessive genetic defect (ank/ank) which produces an inflammatory arthritis of peripheral and axial joints eventually resulting in ankylosis of these joints. This disorder resembles the human spondyloarthropathies clinically, radiographically and histologically. Various studies in humans with spondyloarthropathies have described defects of cellular immunity but these results are conflicting. We measured the spleen cell response to mitogen in ank/ank mice and in normal littermates. The spleen cell response to the T cell mitogens phytohaemagglutinin and concanavalin A was decreased in ank/ank mice compared with their normal littermates. The response to the B cell mitogen lypopolysaccharide was normal in both ank/ank mice and normal littermates. Serum from ank/ank mice did not inhibit spleen cell responses to mitogen. Ank/ank spleen cells were not inhibitory of normal spleen cell responses to mitogens. Addition of irradiated normal spleen cells to ank/ank spleen cells did not restore the mitogen responses to normal. It is possible that the ank/ank gene results in the phenotypic expression of an abnormal or decreased cell product involved in T cell proliferation. Several recently described cytokines could be potential candidates for this product.