Scoring magnetic resonance imaging (MRI) inflammation and structural lesions in sacroiliac joints of patients with axial spondyloarthritis: assessment of all MRI slices of the cartilaginous compartment versus standardized six or five slices.

Objectives: The Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint (SIJ) scoring system assesses six or five (6/5) semicoronal magnetic resonance imaging (MRI) slices for inflammation/structural lesions in patients with axial spondyloarthritis (axSpA). However, the cartilaginous SIJ compartment may be visible in a few additional slices. The objective was to investigate interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types using an 'all slices' approach versus standard SPARCC scoring of 6/5 slices.Method: Fifty-three axSpA patients were treated with the tumour necrosis factor inhibitor golimumab and followed with serial MRI scans at weeks 0, 4, 16, and 52. The most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. Scores for inflammation, fat metaplasia, erosion, backfill, and ankylosis in the cartilaginous SIJ compartment were calculated for the 'all slices' approach and the 6/5 slices standard.Results: By the 'all slices' approach, three readers scored mean 7.2, 7.7, and 7.0 slices per MRI scan. Baseline and change scores for the various lesion types closely correlated between the two approaches (Pearson's rho ≥ 0.95). Inflammation score was median 13 (interquartile range 6-21, range 0-49) for 6/5 slices versus 14 (interquartile range 6-23, range 0-69) for all slices at baseline. Interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types were similar.Conclusion: The standardized 6/5 slices approach showed no relevant differences from the 'all slices' approach and, therefore, is equally suited for monitoring purposes.

Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis.

OBJECTIVE: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated. RESULTS: The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions. CONCLUSIONS: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.

Intrauterine growth-restricted piglets have similar gastric emptying rates but lower rectal temperatures and altered blood values when compared with normal-weight piglets at birth.

Intrauterine growth-restricted (IUGR) piglets have lower survival rates and are more likely to have empty stomachs 24 h after birth than normal piglets. Although hypoglycemia may result from low colostrum intake per se, it is not known if slow gastric emptying may be an additional risk factor for poor immunization and glucose absorption in IUGR piglets. It is estimated that IUGR piglets consume less colostrum per kilogram BW than normal-weight piglets within the first 24 h, which could be due to a slower gastric emptying rate and a compromised energy metabolism. Therefore, we hypothesized that the gastric emptying rate and blood glucose would be lower in IUGR piglets. We investigated gastric emptying rates in normal and IUGR piglets and blood glucose and rectal temperatures at birth and after 15, 30, 60, and 120 min. In addition, blood parameters relevant for metabolism were studied. Forty-eight piglets (24 normal and 24 IUGR) were classified at birth as either normal or IUGR on the basis of head morphology. Piglets were removed from the sow at birth before suckling, and birth weight was recorded. Pooled porcine colostrum was tube-fed to all piglets at 12 mL/kg BW as soon as possible after birth (t = 0 min). The piglets were randomly allocated to be euthanized at 15, 30, 60, and 120 min (all groups, = 6) after bolus feeding, and the weights of the stomach and its residuals were recorded. There was no difference in gastric emptying rates between normal and IUGR piglets ( = 0.129); however, gastric DM residuals tended to by greater in IUGR piglets than normal piglets ( = 0.085). Overall, IUGR piglets had lower rectal temperatures (36.2°C ± 0.2°C vs. 37.5°C ± 0.2°C; < 0.001) and plasma glucose levels (2.8 ± 0.2 vs. 4.1 ± 0.2 mmol; < 0.001) than normal piglets. Interactions between piglet classification and time were observed in plasma values for NEFA, -3-hydroxybutyrate, albumin, aspartate, and alanine amino transferase, with greater levels in normal piglets at 15 min ( < 0.05) and 30 min for bile acid ( < 0.05) compared to IUGR piglets. In conclusion, the gastric emptying rates between normal and IUGR piglets were similar, but gastric DM residuals tended to be greater in IUGR piglets. Differences were observed in blood values and rectal temperatures, with lower values in IUGR piglets. Therefore, it is likely that factors like hypothermia and possibly reduced metabolic function are more important during the first hours after birth than gastric retention per se.

Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome.

OBJECTIVE: To compare changes in regional bone mineral density (BMD) of the metacarpal joints measured by dual x ray absorptiometry (DXA) and digital x ray radiogrammetry (DXR) in relation to disease activity and radiographic outcome in a two year follow up study of patients with early RA and unclassified polyarthritis. PATIENTS AND METHODS: 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least four weeks and less than two years were included. 51 patients fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis. The patients with RA were divided into groups according to mean disease activity, average glucocorticoid dose, and MRI and x ray detected bone erosions in the hands. Clinical and biochemical measurements were made every month and an x ray examination of the hands and BMD of the metacarpal joints every six months. RESULTS: DXR BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease. No changes in BMD measured by DXA were seen in any patient group. CONCLUSION: DXR is a useful measure of the destructive disease activity in patients with RA and unclassified polyarthritis, providing valuable information about bone changes associated with disease activity and erosive disease in early RA. DXR is better than DXA for detecting and monitoring periarticular osteoporosis of the metacarpal bone.

Differences in understanding and application of 1987 ACR criteria for rheumatoid arthritis and 1991 ESSG criteria for spondylarthropathy. A pilot survey.

OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.

Power Doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison with dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the effectiveness of power Doppler ultrasonography (PDUS) for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging (MRI) as a reference method. METHODS: PDUS and dynamic MRI were performed on 54 MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A series of 24 coronal T1-weighted images of the second through the fifth MCP joints was obtained, with intravenous injection of gadolinium diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the MR images, the rate of early synovial enhancement (RESE; defined as the relative enhancement per second during the first 55 seconds postinjection) was calculated and compared with the flow signal on PDUS, which was scored as present or absent. RESULTS: In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of 54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or = 1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8% and a specificity of 97.9%. CONCLUSION: PDUS was reliable for assessing inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the standard. PDUS and clinical assessment of joint swelling/tenderness were only weakly correlated.

Importance of timing of post-contrast MRI in rheumatoid arthritis: what happens during the first 60 minutes after IV gadolinium-DTPA?

BACKGROUND: Volumes of inflamed synovial membrane determined by magnetic resonance imaging (MRI) are closely related to histopathological synovitis and may predict erosive progression in rheumatoid arthritis (RA). However, after IV injection, leakage of MRI contrast from the synovium gradually compromises the differentiation of synovium from joint fluid. OBJECTIVE: To determine the time period after IV MRI contrast (gadolinium-DTPA (Gd)) injection in which synovial membrane volume determination is reliable. METHODS: MRI of five RA knees with clinical synovitis was carried out, with axial, T(1) weighted, spin echo images before IV Gd injection and every 1.75 minutes for 60 minutes post-Gd. By a semiautomated "signal enhancement threshold" method, including voxels with >35% or >45% relative post-Gd enhancement, synovial membrane volumes were estimated at each time point. At 4.25 minutes post-Gd, volumes were also determined by a more accurate but time consuming "manual method". RESULTS: The initially observed synovium-effusion borderline remained clearly visible, and on the same location, within at least the initial 11 minutes post-Gd (that is, within the normal time frame of post-Gd imaging in RA) but started blurring and moving centripetally thereafter. Compared with volumes at all other time points, synovial membrane volumes at 0.75 and 2.50 minutes post-Gd were significantly lower (Wilcoxon-Pratt), suggesting that some synovial membrane areas had not yet exceeded the enhancement threshold. Thereafter, the measured volumes remained practically unchanged. CONCLUSION: This study suggests that MR image acquisition in arthritic knee joints should be performed within the initial approximately 10 minutes after gadolinium contrast injection to achieve the most accurate distinction between synovium and joint fluid but that small time variations are not of major importance to the measured synovial membrane volumes.

Interreader agreement in the assessment of magnetic resonance images of rheumatoid arthritis wrist and finger joints--an international multicenter study.

Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Magnetic resonance imaging in rheumatoid arthritis: summary of OMERACT activities, current status, and plans.

Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. TIRA Group.

OBJECTIVE: To determine whether variant alleles of the mannose binding lectin (MBL) gene causing low serum concentrations of MBL are associated with increased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 68 Danish patients with incident early polyarthritis observed for one year. The associations between MBL and specific HLA-DRB1 genotypes and disease outcomes were analyzed. RESULTS: Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 34.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% (21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) and 35.3% (6/16), respectively (p = 0.004). Patients with early polyarthritis homozygous for MBL variant alleles had an increased risk of having erosive RA at inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6 (p = 0.04). MBL deficiency was associated with increased levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (p < 0.05). HLA-DRB1 alleles were not found to be associated with disease outcome. CONCLUSION: MBL variant alleles appear to be weak susceptibility markers for RA, and patients with early polyarthritis and homozygous for MBL structural variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant alleles and the increased serum levels of IgM RF and CRP, point at the MBL gene as a relevant locus in the pathophysiology of RA.

Lessons from an international survey of paper cases of 10 real patients from an early arthritis clinic. CRI (Club Rhumatismes et Inflammation) Group.

OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early disease.

[Magnetic resonance imaging as a marker of inflammation, destruction and prognosis in rheumatoid arthritis wrists]. / Magnetisk resonans-billeddannelse som markør for inflammation, destruktion og prognose ved reumatoid artrit i håndleddet.

To evaluate MRI for assessment of inflammation, destruction and prognosis in rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti-rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone, were followed for one year with contrast-enhanced MRI of the dominant wrist (months zero, three, six and 12), conventional radiography and clinical and biochemical examinations. Significant synovial membrane volume reductions were observed in both groups, earliest in the DMARD + prednisolone group. The rate of erosive progression on MRI was highly correlated with baseline and area-under-curve (AUC)-values of synovial membrane volume, but not with baseline or AUC-values of local or global clinical or biochemical parameters, nor with +/- prednisolone. MRI was more sensitive than radiography as regards detection of progressive bone destruction (22 versus 12 new bone erosions). MRI may prove valuable as marker of joint disease activity and destruction and, perhaps, prognosis in RA.

Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis. The TIRA Group.

OBJECTIVES: To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one year. Additionally, to compare the results with radiography, bone scintigraphy, and clinical findings. PATIENTS AND METHODS: Fifty five patients were examined at baseline, of whom 34 were followed up for one year. Twenty one patients already fulfilled the American College of Rheumatology (ACR) criteria for RA at baseline, five fulfilled the criteria only after one year's follow up, whereas eight maintained the original diagnosis of early unclassified polyarthritis. The following MRI variables were assessed at baseline and one year: synovial membrane hypertrophy score, number of erosions, and tenosynovitis score. RESULTS: MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p<0.05). CONCLUSIONS: MRI detected more erosions than radiography. MR synovial membrane hypertrophy and scintigraphy scores did not parallel the changes seen over time in clinically assessed swollen and tender joint counts. Although joint disease activity may be assessed as quiescent by conventional clinical methods, a more detailed evaluation by MRI may show that a pathological condition is still present within the synovium.

Dynamic magnetic resonance imaging of the metacarpophalangeal joints in rheumatoid arthritis, early unclassified polyarthritis, and healthy controls.

OBJECTIVE: To introduce dynamic magnetic resonance imaging (MRI) as an indicator of inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) or early unclassified polyarthritis, and to compare the results with a healthy control group. MATERIALS AND METHODS: We examined 42 RA and 23 early unclassified polyarthritis patients, and 12 healthy controls in a cross-sectional study. Dynamic MRI (repeated FLASH-MR images after injection of a contrast agent) was performed through the 2nd to the 5th MCP joint. Two methods for identification of the enhancing synovial membrane were compared: 1) outlining of enhancing synovial membrane on subtraction images and 2) automated recognition by principal component analysis (PCA). The early enhancement (EE) rate was calculated on the basis of the first method. RESULTS: Method 1) and 2) were closely associated (P<0.00001). From the healthy control group, an upper limit (mean+2SD) of normal enhancement was established for the 2nd to 5th MCP joints, which served to identify abnormal EE rates in the corresponding joints of patients. The patients had higher EE rates in the 2nd to 5th MCP joints than had the healthy controls (P<0.01). There were no significant differences between the two patient groups (P>0.09). CONCLUSION: PCA seems to be a promising method for automated identification of enhancing tissue. EE rates of the finger joints may be useful in the assessment of the inflammatory activity in the joints of patients with RA and early unclassified polyarthritis and may reflect other aspects of disease activity than clinical evaluation.

Wrist and finger joint MR imaging in rheumatoid arthritis.

PURPOSE: To elaborate the best MR imaging protocol for studies in rheumatoid arthritis (RA) and to evaluate the sensitivity and interobserver agreement with respect to detection of bone erosions (MR and radiography) and grading of synovial membrane hypertrophy (MR imaging only). MATERIAL AND METHODS: MR imaging and conventional radiography of wrist and metacarpophalangeal (MCP) joints were performed in 41 RA patients and 3 healthy controls. The following pulse sequences were applied: T1-weighted spin-echo (T1-SE) with and without contrast enhancement, T2-SE, T2-turbo-SE, T1-2D-FLASH, T1-3D-FLASH, fat-saturated-T1-SE, STIR and 3D-DESS. RESULTS: Bone erosions were found by MR compared to radiography in 261 versus 85 bones of the wrist (ratio 3.1) and 59 versus 21 MCP joint quadrants (ratio 2.81). MR and radiography interobserver agreements were both approximately 90%. Likewise, MR scored synovial membrane hypertrophy in wrist and MCP joints with a high interobserver agreement. The most informative MR sequence appeared to be contrast-enhanced T1-SE MR, preferably with fat saturation. A STIR sequence or T2-weighted fat saturation sequence was useful in screening for joint disease. CONCLUSION: The sensitivity of MR is superior to conventional radiography with respect to detection of bone erosions in wrist and MCP joints. The interobserver agreement for MR and radiography was similar. Thus, MR of wrist and finger joints may become a useful supplement to conventional radiography in the evaluation of RA patients in clinical trials and clinical practice.

Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions). CONCLUSION: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.

Finger joint synovitis in rheumatoid arthritis: quantitative assessment by magnetic resonance imaging.

OBJECTIVE: To assess quantitatively, by magnetic resonance imaging (MRI), the synovial membrane volume in second to fifth metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis and healthy controls, and to compare the synovial membrane volumes with a more easily obtained semi-quantitative score for hypertrophic synovial membrane. PATIENTS AND METHODS: MCP joints of the dominant hand of 37 patients and five controls were examined clinically and by MRI. Laboratory assessments were performed. RESULTS: Median synovial membrane volumes were considerably larger in clinically active rheumatoid arthritis (RA) joints (e.g. 0.97 ml in the second MCP joint) than in clinically inactive joints (0.54 ml) and control joints (0.04 ml). Nevertheless, group distributions overlapped and marked volume differences were found within clinically uniform groups. The semi-quantitative score was highly correlated with the synovial volumes (Spearman rho = 0.79; P < 0.00001). Synovial membrane volumes were poorly related to the presence of rheumatoid factor and to laboratory markers of inflammation. CONCLUSION: These findings suggest that synovial membrane volumes, as determined by MRI, in finger joints are related to clinical signs of synovitis, but also that the volumes may vary more than what can be accounted for by the clinical appearances. A semi-quantitative score may be sufficient for more routine purposes.

Randomized controlled smoking cessation study: transient increase in plasma high density lipoprotein but no change in lipoprotein oxidation resistance.

Low plasma levels of high density lipoprotein (HDL) and high levels of low density lipoprotein (LDL) as well as smoking are known risk factors in coronary heart disease. It has been suggested that oxidative modification renders LDL atherogenic. We investigated the influence of smoking cessation on plasma lipid and lipoprotein levels and on the ability of lipoproteins to resist oxidation in vitro (lag time). A total of 182 healthy smokers who smoked more than 15 cigarettes per day were randomized to stop smoking (smoking cessation group, n = 100) or to continue smoking for 4 weeks (control group, n = 82). The smoking cessation group was followed up after 26 weeks. After 4 weeks, the HDL level had increased from mean +/- SD 1.36 +/- 0.34 to 1.48 +/- 0.40 mmol l-1 (p < 0.001) in 62 successful quitters, while levels were unchanged in the control group (72 subjects in per-protocol analysis). However, after 26 weeks there was no change in HDL (1.34 +/- 0.36 vs. 1.36 +/- 0.35 mmol l-1) in 29 subjects from the smoking cessation group who fulfilled the study. Plasma levels of very low density lipoprotein (VLDL), LDL, total cholesterol, triglycerides and oxidation resistance of VLDL + LDL did not show significant changes any time during the study for either group. Thus, plasma levels of lipids and lipoproteins as well as oxidation resistance of lipoproteins seem unaffected by smoking cessation for 26 weeks.

Effect of smoking cessation on oxidative DNA modification estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion.

BACKGROUND: Reactive oxygen species from, e.g. tobacco smoke are suggested to be involved in carcinogenesis by oxidative modification of DNA. The urinary excretion rate of the oxidized nucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) has been validated as a biomarker of the rate of oxidative DNA modification with mechanistic relation to carcinogenesis. In cross-sectional studies, the urinary excretion rate of 8-oxodG has been shown to be elevated in smokers compared with non-smokers. PURPOSE: In this randomised, controlled smoking cessation study, we investigated whether cigarette smoking per se causes oxidative DNA modification. METHODS: Of the 182 healthy smokers included, 100 were randomized to quit smoking after baseline samples had been taken, and 82 were randomized to continue usual smoking. Before the start of the study and after 4 weeks, the subjects collected 24-h urine samples that were analysed for 8-oxodG content by high-pressure liquid chromatography with electrochemical detection. The subjects randomized to smoking cessation were followed up after 26 weeks. RESULTS: Four weeks of smoking cessation resulted in a 21% decrease in 8-oxodG excretion rate (from mean +/- SD, 30.5 +/- 13.9 to 24.1 +/- 10.5 nmol/24 h, P < 0.001) in 58 quitters included in per-protocol data analysis. Sixty-five continued smokers included in per-protocol analysis showed a 9% decrease in 8-oxodG excretion rate (from 31.6 +/- 13.2 to 28.7 +/- 12.6 nmol/24 h, P = 0.026). After 4 weeks, the 8-oxodG excretion rate was 16% (95% confidence interval 4 to 28%) higher in the continued smokers than in the quitters (P = 0.0085, ANCOVA), demonstrating the effect of smoking per se. A 23% (P < 0.005) decrease in 8-oxodG excretion rate was sustained for 26 weeks in 27 quitters who completed the study. CONCLUSION: Smoking cessation significantly reduces the urinary excretion rate of 8-oxodG, giving direct and controlled evidence that cigarette smoking causes an increased rate of oxidative DNA modification. This could represent a mechanism by which tobacco smoke is carcinogenic.

Smoking cessation does not change urinary albumin excretion in normal subjects.

The aim of the study was to examine the effect of smoking cessation on urinary albumin excretion (UAE) in normal subjects. The study consisted of two parts. The first was a randomized 4-week study, in which 182 heavy smokers were asked to quit smoking immediately (n = 69, available for analysis) or to continue smoking for another 4 weeks (n = 70, available for analysis). After 4 weeks, the latter group was also asked to stop smoking. The second part was a non-randomized follow-up study comparing UAE in 33 unsuccessful and 57 successful quitters followed for 26 weeks. Measurements of UAE (ELISA) were taken from 24-h urine samples before smoking cessation, after 4 weeks, and after 26 weeks. After 4 weeks, no statistically significant change in UAE was found within each group or between quitters and smokers. The 95% confidence intervals of the change in log UAE were -7.4 to 9.9% of the initial value in the smoker group and -4.9 to 11.3% in the quitter group. In the second part of the study, after 26 weeks, a 16% increase (95% confidence interval 5.5 to 26.5%) in mean log UAE was found in the group that had stopped smoking (p < 0.003), but no statistically significant difference in UAE between continued smokers and quitters was found after adjusting for the baseline level (ANCOVA). In conclusion, smoking cessation seems to have no effect on UAE within the physiological range in normal subjects over an observation period of 4 weeks, and no sign of a decrease in UAE was seen after 26 weeks of smoking cessation.