OBJECTIVE: To compare in vivo the 3-dimensional (3-D) geometric architecture of the subtalar and midtarsal joints in normal and rheumatoid arthritic (RA) feet, using magnetic resonance imaging (MRI) analysis. METHODS: MRI was performed on 23 patients with RA, all of whom had disease activity in the subtalar and/or midtarsal joints. Image processing techniques were used to create 3-D reconstructions of the calcaneus (C), cuboid (c), navicular (N), and talus (T) bones. Twenty-four standard architectural parameters were measured from the reconstructions and were compared with data from 10 normal subjects. These parameters defined both 3-D distance and angular relationships among the 4 bones studied. Pattern classification techniques were used to establish a geometric architecture foot profile for the RA patients. The degree of individual patient fit to the new RA foot profile and to profiles for normal, pes planus, and pes cavus foot types was derived. Logistic regression was used to examine the relationship of foot architecture to inflammatory disease characteristics and physical examination variables. RESULTS: Subtalar or midtarsal pain was reported by all 23 patients, and 22 of the 23 patients presented with >/=1 clinical feature of pes planovalgus deformity. In 21 patients, ultrasonography revealed synovitis at >/=1 tarsal joint or surrounding tendon. In the RA group, the normalized distances between the geometric centroids were significantly closer for bone pairs Cc and cT and significantly distracted for bone pair CN compared with the distances in normal subjects. In RA patients (versus normal subjects), the angles subtended at the bone centroids were significantly decreased in 3 bone groups (CNc, TCN, and TNc) and significantly increased in 3 bone groups (CcN, CcT, NTc). The angles formed between the major principal axes of bone pairs CT and cT were significantly increased in RA patients compared with those in normal subjects. Pattern classification defined 11 RA feet as having normal structure and 12 as having abnormal structure. However, the abnormal feet did not fit consistently with structures defined for RA, pes planus, or pes cavus foot types. Logistic regression demonstrated that subtalar joint synovitis was the only predictive factor for abnormal subtalar and midtarsal architecture (odds ratio 19.2, 95% confidence interval 1.77-200.0). CONCLUSION: This unique 3-D MRI-based technique successfully quantified the effects of RA on the geometric architecture of the foot and the patient-specific nature of these changes. This technique can be used to provide logical therapy for correction. (+info)
(2/83) Smoking and osteoarthritis: is there an association? The Clearwater Osteoarthritis Study.
OBJECTIVE: To evaluate the association between cigarette smoking and the subsequent development of osteoarthritis (OA) at four separate sites: knee, hand, foot and cervical spine. METHODS: This cohort study examined 2505 men and women aged 40 years and older participating in the longitudinal Clearwater Osteoarthritis Study (1988-current). Biennial physical exams, including serial radiographs, as well as historical information, were collected. The Lawrence and Kellgren ordinal scale was used to determine radiological evidence of the study outcome, OA. Self-reported history of smoking behavior was used to determine the study exposure. Smoking was classified using four approaches: (1) ever/never, (2) former/never, (3) current/never, and (4) dose. RESULTS: Among the individuals at study entry, radiologically confirmed incident OA was detected during the follow-up period at four sites: knee (32%), hand (49%), foot (28%), and cervical spine (52%). Approximately 11% were self-reported current smokers. Unadjusted analyses indicated that individuals classified as current smokers demonstrated significant levels of protection from OA at all four sites investigated. However, adjusted point estimates ranging from 0.60-1.48 were suggestive of no association between smoking and the development of OA at any of the four sites investigated. CONCLUSION: Based upon the findings of this prospective study, smoking does not appear to convey a clinically significant level of protection against the development of radiologically-confirmed OA. While these findings corroborate previous studies indicating no association between smoking and OA, anecdotal evidence warrants investigation into the role that cigarette smoking may play in the symptomatology of OA. (+info)
(3/83) Mechanism of accumulation of 99mTc-sulesomab in inflammation.
99mTc-Sulesomab, the Fab fragment of anti-NCA-90, is used as an in vivo granulocyte labeling agent for imaging inflammation. It is not clear to what extent it targets cells that have already migrated into the interstitial space of an inflammatory lesion as opposed to circulating cells. The contribution to signal of radioprotein diffusion in the setting of increased vascular permeability is also poorly documented. METHODS: We compared the local kinetics of (99m)Tc-sulesomab and (99m)Tc-labeled human serum albumin (HSA), which have similar molecular sizes, in 7 patients with orthopedic infection proven by clearly positive (111)In-leukocyte scintigraphy. (99m)Tc-Sulesomab and (99m)Tc-HSA were administered in sequence separated by an interval of 2-6 d. Images were obtained 1, 3, 4, and 6 h after injection, and multiple venous blood samples were obtained for blood clearance measurement. Patlak-Rutland (P-R) analysis was performed to measure lesion and control tissue protein clearance. Target-to-background tissue (T/Bkg) ratios were calculated for each radioprotein and compared with the T/Bkg ratio for (111)In-leukocytes. (99m)Tc-Sulesomab binding to granulocytes was measured in vitro and ex vivo and to primed and activated granulocytes in vitro. RESULTS: After intravenous injection, <5% of the circulating radioactivity was cell bound with both radioproteins so that the P-R curves could therefore be assumed to represent extravascular uptake of free protein. The blood clearance (mean +/- SD) of sulesomab was 23.4 +/- 11.7 mL/min, approximately 5 times greater than that of HSA, for which it was 4.8 +/- 3.1 mL/min. Likewise, clearance into the lesion of sulesomab was consistently higher than that of HSA, on average about 3 times as high. Nevertheless, the T/Bkg ratios for sulesomab and HSA were similar, except at 6 h when that of HSA (2.14 +/- 0.6) was higher than that of sulesomab (1.93 +/- 0.5; P approximately 0.01). Both values were considerably less than the T/Bkg ratio on the (111)In-leukocyte images, which, at 22 h, was 12.3 +/- 5.3. Moderate clearance of sulesomab, but not HSA, was seen in the control tissue. Granulocytes bound significantly more (99m)Tc-sulesomab in vitro when primed or activated. CONCLUSION: (a) Sulesomab does not localize in inflammation as a result of binding to circulating granulocytes; (b) sulesomab is cleared into inflammation nonspecifically via increased vascular permeability; nevertheless, it may be cleared after local binding to primed granulocytes or bind to activated, migrated extravascular granulocytes; and (c) HSA produces a similar or higher T/Bkg ratio than sulesomab because sulesomab is cleared into normal tissues and because image positivity in inflammation is significantly dependent on local blood-pool expansion. (+info)
(4/83) Determinants of the clinical course of musculoskeletal complaints in general practice: design of a cohort study.
BACKGROUND: Musculoskeletal complaints are frequent and have large consequences for public health. Information about the prognosis after presentation in general practice is far from complete. Knowledge about determinants of the clinical course of musculoskeletal complaints is essential for management decisions and to inform patients about their prognosis. The purpose of this study is to provide information about the prognosis of musculoskeletal complaints other than low back pain by studying the course of these complaints in general practice and to identify determinants of this course. METHODS: Patients of 18 years and older, who present in general practice with a new episode of a musculoskeletal complaint of the neck, shoulder, elbow, wrist, hand, arm, hip, knee, ankle or foot, are recruited by their general practitioner (GP). Participants will receive complaint-specific questionnaires by mail at baseline and after 3, 6, 12 and 18 months. The following putative determinants of the course of the complaints will be investigated: sociodemographic characteristics, characteristics of the complaint, psychosocial job characteristics, physical workload, physical activity during leisure time, pain coping, mood, kinesiophobia, social support, optimism. The primary outcomes are perceived recovery, pain, functional status, sick leave and overall quality of life. (+info)
(5/83) Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis.
OBJECTIVE: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. PATIENTS AND METHODS: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0-5 and at year 10. Radiographs were evaluated according to Larsen (range 0-200). Predictive factors for progressive disease for years 0-5 and 5-10 were evaluated by logistic regression analyses. RESULTS: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. CONCLUSIONS: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years. (+info)
(6/83) The 5-yr HAQ-disability is related to the first year's changes in the narrowing, rather than erosion score in patients with recent-onset rheumatoid arthritis.
OBJECTIVE: To evaluate the predictive validity of radiological change on 5-yr disability in rheumatoid arthritis (RA). METHODS: The study was designed to be multicentre, prospective, longitudinal, with a 5-yr follow-up. Participants were RA patients (ACR criteria), with a disease duration of <1 yr at entry. Radiographs of the hands and feet in posteroanterior view at baseline and after 12 months of follow-up (van der Heijde's modification of Sharp method) were used for structural evaluation. Disability was evaluated with Health Assessment Questionnaire (HAQ) at yr 5. Analyses consisted of (i) correlation existing between the changes in the radiological scores during the first year and the HAQ value at yr 5 and (ii) determination of the optimal cut-off in the changes in the radiological scoring system, by ROC curve analysis, in which variable to be explained was disability status at yr 5, defined by HAQ value of at least 1. RESULTS: Due to missing data and/or lost to follow-up, 135 patients (out of the 191 recruited patients) were included in the analyses (mean change in the radiological score = 4.9 +/- 8.7 points, mean HAQ at yr 5 = 0.62 +/- 0.68). There was a statistically significant correlation between the HAQ-disability status at yr 5 and the changes observed in the radiological total damage and narrowing scores during the first year (r = 0.18, P = 0.046 and r = 0.25, P = 0.006, respectively). Conversely, the short-term changes in the erosion score were not correlated with subsequent HAQ-disability (r = 0.084, P = 0.36). A change of at least 2 points in the total X-ray score was considered as optimal (sensitivity, specificity, positive and negative predictive values of 66.7, 53.9, 32.8 and 82.8%, respectively). CONCLUSION: This work shows that early changes in joint damage in patients with recent-onset RA are related to subsequent HAQ-disability. This relationship is due to changes in narrowing, rather than in erosion score, suggesting that the joint narrowing score might be of great importance in the follow-up of RA patients and in the reports of scientific results. The weak performance of the thresholds established using predictive validity for subsequent HAQ-disability compromise their use at the individual level. (+info)
(7/83) Infliximab in active early rheumatoid arthritis.
OBJECTIVE: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA). METHODS: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group. RESULTS: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet. CONCLUSIONS: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity. (+info)
(8/83) Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal.
OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment. (+info)