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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,... more
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.
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Purpose Inflammatory arthritis is not generally considered a risk factor for nephrolithiasis; however previous studies have found a higher point prevalence of nephrolithiasis in rheumatoid arthritis than the general population. A 1973... more
Purpose Inflammatory arthritis is not generally considered a risk factor for nephrolithiasis; however previous studies have found a higher point prevalence of nephrolithiasis in rheumatoid arthritis than the general population. A 1973 study reported an increased incidence of renal stones in patients with spondyloarthritis (SPA) as compared with rheumatoid arthritis (RA) controls (Mladenovic et al, Rheumatizm 1973;20:106-110). Our objective was to confirm this cross-sectional study with a cohort study comparing lifetime prevalence of nephrolithiasis in patients with (SPA) and (RA). Methods This study was designed as a VA retrospective cohort study. The study group was obtained from patients followed in the Minneapolis VA, with the diagnoses of SPA. Controls were rheumatoid factor positive, RA patients. The sample size was calculated by using an alpha of 0.05, a power of 0.80, an estimated prevalence of nephrolithiasis in the RA group of 5% and a 16% in the SPA patients. Controls are age and sex matched. The prevalence rate for the controls was estimated from the United States National Health and Nutritional Examination Survey II. Each patient was surveyed regarding their rheumatologic diagnosis, relevant coexistent conditions and history of kidney stones. Patient-reported history of kidney stones was confirmed whenever possible by chart review. All patients met ACR criteria for either RA or SPA. Results Forty-nine SPA patients and 27 RA patients have been enrolled. Our goal is to enroll 250 patients (84 SPA patients and 168 RA patients). These results will be discussed at the time of presentation. To date 16/49 (32.7%) SPA patients reported a history of renal stones compared with 4/27 (14.8%) RA patients. Chi square equals 3.95 (p=0.047). Four patients with kidney stones in the SPA group and 2/4 patients in the control group had other risk factors for stones. Conclusion These results show an increase in the prevalence of kidney stones in SPA compared to RA. This is similar to the findings of Mladenovic et al. These results suggest that other studies should be done to ascertain the cause of increased nephrolithiasis in SPA.
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A pulmonary vein varix is a localized dilatation of a pulmonary vein that usually is asymptomatic, presenting as a mass on a chest roentgenogram. Pulmonary angiography has been the mainstay of diagnosis. This case is the first in which... more
A pulmonary vein varix is a localized dilatation of a pulmonary vein that usually is asymptomatic, presenting as a mass on a chest roentgenogram. Pulmonary angiography has been the mainstay of diagnosis. This case is the first in which transesophageal echocardiography was used to diagnose pulmonary vein varix.
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Observing Industry trends over time increases our awareness about how economic changes can affect our life’s work in the future. Use this awareness to make plans to develop new skills through on-thejob learning, volunteer work, or by... more
Observing Industry trends over time increases our awareness about how economic changes can affect our life’s work in the future. Use this awareness to make plans to develop new skills through on-thejob learning, volunteer work, or by taking a class. In today’s economy, many people increase their job security by continually developing new skills to keep up with rapid changes in their current occupation or to be prepared for the possibility of a future job change.
Mounting evidence suggests that autoimmune mechanisms may underlie the chronic symptoms characteristic of Gulf War Illness (GWI). The presence of antiphospholipid antibodies including Lupus Anticoagulant (LA) are often associated with... more
Mounting evidence suggests that autoimmune mechanisms may underlie the chronic symptoms characteristic of Gulf War Illness (GWI). The presence of antiphospholipid antibodies including Lupus Anticoagulant (LA) are often associated with autoimmune disorders. Here we evaluated and compared blood samples from veterans with GWI and veterans with other autoimmune conditions including relapsing remitting multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, and lupus for the presence of LA using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. Positive LA was identified in onequarter of veterans with GWI; this proportion was not statistically different from the proportion of positive LA identified in patients diagnosed with the other autoimmune conditions. The present findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as a common contributing factor in GWI and other autoimm...
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Immunology, Occupational Therapy, Rheumatoid Arthritis, Medicine, Physical Therapy, and 14 moreActivities of Daily Living, Humans, Female, Male, Patient Satisfaction, Wrist joint, Clinical Sciences, Aged, Middle Aged, Adult, Public health systems and services research, Splints, Equipment Design, and Cross-Over Studies
To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function. Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study... more
To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function. 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. 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. 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.
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Immunology, Occupational Therapy, Rheumatoid Arthritis, Comparative Study, Medicine, and 14 moreActivities of Daily Living, Humans, Female, Male, Clinical Sciences, Middle Aged, Public health systems and services research, Hand, Splints, Cross-Over Studies, Wrist, Grip strength, Functional Laterality, and Learning Effect
To study the accuracy of diagnoses of spondylarthritides in computerized databases at the Minneapolis Veterans Affairs Medical Center. Medical records were available and reviewed for a random sample of 184 patients from a cohort of 737... more
To study the accuracy of diagnoses of spondylarthritides in computerized databases at the Minneapolis Veterans Affairs Medical Center. Medical records were available and reviewed for a random sample of 184 patients from a cohort of 737 patients seen at the rheumatology clinic between January 1, 2001 and July 31, 2002. We compared 4 database definitions with the medical record gold standard of rheumatologists' diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or reactive arthritis (ReA): presence of 1) > or =1 or 2) > or =2 International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for diagnoses of AS (720.0), PsA (696.0), and ReA (099.3, 711.11-711.19), and presence of 3) > or =1 or 4) > or =2 ICD-9 codes and prescription of a disease-modifying antirheumatic drug (DMARD). Accuracy was assessed by sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs), kappa statistic, and receiver operator characteristic (ROC) curve area. Of 184 patients, 11 (6%) had AS, 17 (9%) had PsA, and 7 (4%) had ReA as per the gold standard. ICD-9 codes for AS, PsA, and ReA were very specific (98-100%) with excellent NPV (99-100%) and PPV (83-100%), good to excellent sensitivity (57-100%), almost perfect kappa agreement (0.72-1), and high ROC curve area (0.79-1). Addition of presence of DMARD prescription to ICD-9 codes of AS and PsA decreased sensitivity to 27-65% without improving the specificity (which was already high at 99-100%). The ICD-9 codes for AS, PsA, and ReA in databases are accurate. ICD-9 codes may be used to identify cohorts of patients with spondylarthritides.
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Psychology, Immunology, Medicine, Humans, Male, and 15 moreAccuracy, Clinical Sciences, Minnesota, Medical Diagnosis, Aged, Middle Aged, Adult, Public health systems and services research, Bayes Theorem, Database, Area Under the Curve, Area Under Curve, Predictive value of tests, Department of Veterans Affairs, and Diagnostic errors
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. We conducted telephone interviews of persons... more
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. 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. 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. 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. 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.
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Rheumatology, Epidemiology, Immunology, Adolescent, Humans, and 15 moreChild, Female, Male, Population based study, Young Adult, Infant, Clinical Sciences, Minnesota, Adult, Public health systems and services research, Physical examination, Oregon, Arthritis Reactive, Acute Disease, and Child preschool
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Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release.... more
Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release. Paralytic toxicity is due to inhibition at the neuromuscular junction, and this effect has been utilized for treatments of painful dystonias. Pain relief following BoNT muscle injection has been noted to be more significant than muscle weakness and hypothesized to occur because of the inhibition of peripheral neuropeptide release and reduction of peripheral sensitization. Because of this observation, BoNT has been studied as an intra-articular (IA) analgesic for chronic joint pain. In clinical trials, BoNT appears to be effective for nociceptive joint pain. No toxicity has been reported. In preclinical models of joint pain, BoNT is similarly effective. Examination of the dorsal root ganglion (DRG) and the central nervous system has shown that catalyticall...
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Granulomatosis with polyangiitis (GPA) was diagnosed in a patient with a 16-month history of IgG4-related lung disease that spontaneously became asymptomatic. Cytoplasmic antineutrophil cytoplasmic antibody (ANCA) was positive at the time... more
Granulomatosis with polyangiitis (GPA) was diagnosed in a patient with a 16-month history of IgG4-related lung disease that spontaneously became asymptomatic. Cytoplasmic antineutrophil cytoplasmic antibody (ANCA) was positive at the time of diagnosis of IgG4-related disease (IgG4-RD), but there was no vasculitis or kidney disease. Sixteen months later he developed rapidly progressive glomerulonephritis that responded to cyclophosphamide treatment. While undergoing treatment for GPA, he was found to have a lung mass identified as small cell lung cancer. This mass was present at the time of the IgG4-RD diagnosis. GPA can be confused with IgG4-RD histologically and they rarely coexist. ANCA antibodies are primarily IgG4 subclass. IgG4-RD has been associated with cancer and may improve prognosis. We speculate that this patient may have had small cell lung cancer that incited an IgG4 predominant immune response with coexistent ANCA antibodies that eventually resulted in GPA. Immunosuppr...
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Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by... more
Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by intra-articular (IA) injection. To determine whether these vanilloid receptor agonists have benefit in Complete Freund's Adjuvant (CFA) induced chronic inflammatory arthritis pain, we measured changes in ADWB and EPS in arthritic mice with and without treatment with IA CAP and RTX. Chronic inflammatory arthritis was produced by IA injection of 30 µl of Complete Freund's Adjuvant (CFA) into the left knee of C57BL6 male mice 3 weeks prior to pain behavior testing. Mice were injected with either low or high dose IA RTX (10µl of 0.001 or 0.003%), or IA CAP (10 µL of 0.01%) 7 days prior to pain behavior testing. Chronic Inflammatory arthritis pain produced increased EPS and reduced ADWB measures for weight bearing in the affected limb of arthritic mice compare...
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Arthritis is the most common cause of disability in the US, and the primary manifestation of arthritis is joint pain that leads to progressive physical limitation, disability, morbidity, and increased health care utilization. Capsaicin... more
Arthritis is the most common cause of disability in the US, and the primary manifestation of arthritis is joint pain that leads to progressive physical limitation, disability, morbidity, and increased health care utilization. Capsaicin (CAP) is a vanilloid agonist that causes substance P depletion by interacting with vanilloid receptor transient receptor potential V1 on small unmyelinated C fibers. It has been used topically for analgesia in osteoarthritis with variable success. Resiniferatoxin (RTX) is an ultra potent CAP analog. The aim of this study was to measure the analgesic effects of intra-articular (IA) administration of CAP and RTX in experimental acute inflammatory arthritis in mice. Evoked pain score (EPS) and a dynamic weight bearing (DWB) device were used to measure nociceptive behaviors in a murine model of acute inflammatory monoarthritis. A total of 56 C57B16 male mice underwent EPS and DWB testing - 24 nonarthritic controls and 32 mice with carrageenan-induced arth...
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ABSTRACT
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Background: The incidence of reactive arthritis (ReA) following Campylobacter and Salmonella infections in the US is unknown; no population-based data are available. Methods: Between 2002-2004, we attempted interviews of all persons age... more
Background: The incidence of reactive arthritis (ReA) following Campylobacter and Salmonella infections in the US is unknown; no population-based data are available. Methods: Between 2002-2004, we attempted interviews of all persons age > 1 year with Campylobacter, Salmonella infections reported to the state health departments in MN and OR (population ~8 million). We defined a possible ReA (P-ReA) case as new musculoskeletal pain, stiffness or swelling lasting >3 days. P-ReA cases were invited for rheumatology evaluation; those with enthesitis, inflammatory back pain, or oligoarthritis were defined as definite ReA. A follow-up questionnaire was mailed at 6 months. Results: A total of 3,315 Campylobacter and 1,952 Salmonella cases were reported; 3,769 (72%) persons completed screening interviews. Among Salmonella cases screened, 63 % cases had one the following serotypes: Typhimurium (24%); Enteritidis (19%); Newport (8%); Heidelberg (8%); 4% Saintpaul. All speciated Campylobac...
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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. Mice transgenic for... more
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. Mice transgenic for HLA-B27 were bred with ank/ank mice, and the phenotypes of the F1 and F2 progeny were observed. ank/+ mice showed no abnormalities, and ank/ank mice showed the typical phenotype of MPA, irrespective of B27 status. 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.
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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... more
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. 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. Disease was neither ameliorated nor induced by these immune system manipulations. 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.
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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... more
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.
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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... more
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 ...
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To determine its similarity to human spondylarthropathies, we studied murine progressive ankylosis, a spontaneously occurring disorder of joints in mice. Clinically, peripheral joints were inflamed initially, then became ankylosed in a... more
To determine its similarity to human spondylarthropathies, we studied murine progressive ankylosis, a spontaneously occurring disorder of joints in mice. Clinically, peripheral joints were inflamed initially, then became ankylosed in a predictable sequence from distal to proximal. Forefeet were involved before hindfeet. Axial joint involvement produced severe spinal ankylosis. Extraarticular manifestations included balanitis and crusting skin lesions. Radiographically, bony erosions and calcification of articular and periarticular tissues were extensive, and vertebral syndesmophytes produced a "bamboo" spine. We conclude that progressive ankylosis is a systemic disease with many clinical and radiographic similarities to human spondylarthropathies, and it may represent a useful animal model for the study of the human diseases.
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Murine progressive ankylosis was studied by light and electron microscopy (EM). By light microscopy, the earliest synovial lesion was inflammatory followed by synovial proliferation and cartilage erosions. Later changes included... more
Murine progressive ankylosis was studied by light and electron microscopy (EM). By light microscopy, the earliest synovial lesion was inflammatory followed by synovial proliferation and cartilage erosions. Later changes included progressive joint ankylosis by fibrosis and ossification of articular and periarticular tissues and new bone proliferation. By EM, synovial cell proliferation and hypertrophy with collagen deposition was seen before the appearance of intracellular and extracellular hydroxyapatite crystals. These pathologic changes are the same as those found in the human spondyloarthropathies. Our EM findings demonstrate that hydroxyapatite crystals appear in the joints of ank/ank mice after the initial inflammatory phase.