What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease.
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OBJECTIVES: To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period. METHODS: Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years. RESULTS: The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) > or =13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis. CONCLUSIONS: MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity. (+info)
Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis.
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OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n = 13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor tenosynovectomy. Synovial membrane cells were dissociated from connective tissue by enzyme digestion and cultured in vitro for 48 hours, and harvested supernatants were assayed for the cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by enzyme-linked immunosorbent assay. Gelatin zymography was performed to demonstrate enzyme activity. Statistical analysis was performed using Student's paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009) and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3 were similar in all synovial sample groups. Zymography demonstrated enzyme activity in all synovium samples from all 9 patients assessed. CONCLUSION: Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are important in the tissue degradation seen in RA. Increased production of the enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible explanation for the worse prognosis and increased rupture rate associated with invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that angiogenesis may have a role in tenosynovial proliferation and invasion of tendons. (+info)
Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symptoms.
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The pathophysiology of arm tremor in patients with cervical dystonia (CD) and its relationship to other types of tremor is unclear. In the present study, we have compared the tremor in these patients with that seen in patients with essential tremor (ET) using two neurophysiological techniques: the triphasic EMG pattern accompanying ballistic wrist flexion movements; and reciprocal inhibition between forearm muscles. During ballistic wrist flexion movements, the latency of the second agonist EMG burst was later in ET than CD patients. This suggests that the mechanism of the arm tremor in CD may differ from that in ET. There was no group difference between reciprocal inhibition in patients with ET or CD. However, there was much more variability in the data from patients with CD. Because of this, we subdivided the CD patients into two groups, group A with normal levels of presynaptic inhibition and group B with reduced or absent presynaptic inhibition. A posteriori, it turned out that the patients in these two subgroups had similar clinical symptoms, but different clinical histories. The arm tremor of patients in group A started simultaneously with torticollis (mean onset age of arm tremor 40 years +/- 20.7 SD, interval between onset of arm tremor and torticollis 0 +/- 2.9 years) whereas it began much earlier (mean onset age 14 years +/- 6 SD) and preceded onset of torticollis by a longer interval (21.6 +/- 17.5 years) in patients of group B. Patients in group A also had less co-contraction in their ballistic wrist movements between the first agonist and the antagonist burst than those patients in group B. We conclude that arm tremor in patients with CD may have a mechanism different from that seen in patients with ET. Moreover, the data imply that there are two subgroups of CD patients with arm tremor, one with a late and simultaneous onset of arm tremor and torticollis (group A), and another with an early onset of arm tremor and later development of torticollis (group B). These groups do not correspond to the currently proposed clinical subdivision of 'dystonic tremor' and 'tremor associated with dystonia'. (+info)
Directional tuning of human forearm muscle afferents during voluntary wrist movements.
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1. Single unit activity was recorded with the microneurography technique from sixteen spindle afferents and one Golgi tendon organ afferent originating from the forearm extensor muscles. Impulse rates were studied while subjects performed unobstructed aiming movements at the wrist in eight different directions 45 deg apart. In addition, similar imposed movements were performed while the subject was instructed to remain relaxed. Movement amplitudes were about 5 deg and the speed 10-30 deg x s(-1). Joint movements were translated to movements of a cursor on a monitor to provide visual feedback. 2. Individual spindle afferents modulated their activity over a number of targets, i.e. were broadly tuned, during these aiming movements. The preferred direction for a spindle afferent was the same during both passive and active movements, indicating that the fusimotor effects associated with active contractions had little or no effect on the direction of tuning. 3. The direction of tuning of individual spindle afferents could be predicted from the biomechanically inferred length changes of the parent muscle. Thus spindle afferents responded as stretch receptors, i.e. impulse rates increased with lengthening and decreased with shortening, in active as well as passive movements. 4. Spindles from muscles, which continuously counteracted gravity exhibited a stretch response and directional tuning during the phase of movement alone whereas their position sensitivity was poor. In contrast, spindle afferents from the muscles that had no or minimal antigravity role were directionally tuned during both the dynamic and the static phase of the aiming task and their position sensitivity was substantially higher. 5. In spite of the limited data base from three extensor muscles it could be demonstrated that wrist joint position was remarkably well encoded in the ensemble muscle spindle data. In some cases the ensemble muscle spindle data encoded the instantaneous trajectory of movement as well. (+info)
Changes in ulnar variance in relation to forearm rotation and grip.
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We studied radiographs of the wrists of 120 healthy volunteers in order to determine the normal range of ulnar variance. They had been taken in various positions under both unloaded (static) and loaded (dynamic) conditions. Pronation posteroanterior, supination anteroposterior and neutral posteroanterior views were taken of each wrist before and during a maximum grip under identical conditions. The mean normal ulnar variance in neutral rotation was +0.74+/-1.46 mm, a value which was significantly lower in males than in females. We found negative variance in 26% of cases. We measured maximum ulnar variance (UVmax +1.52+/-1.56 mm) when gripping in pronation and minimum ulnar variance (UVmin +0.19+/-1.43 mm) when relaxed in supination. We subtracted UVmin from UVmax to calculate a mean maximum dynamic change in ulnar variance of 1.34+/-0.53 mm. We consider this database of normal values to be useful for both the diagnosis and treatment of conditions related to discrepancy in radio-ulnar length and for clinical research. (+info)
Peripheral tears of triangular fibrocartilage complex: results of primary repair.
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In 16 patients with ulnar wrist pain, we performed primary arthroscopic or open repair of the peripheral rim tears of the triangular fibrocartilage complex (TFCC) (14 ulnar, 4 volar, and 3 radial tears). The wrist function was assessed before and 1 year after the repair using the Mayo-modified wrist score. The average pain score improved from 9.1+/-8.0 to 21.2+/-6.5, the average functional score from 5.0+/-8.1 to 20.6+/-6.3, the average motion score from 4.7+/-2.8 to 15.6+/-7.3, and the average grip point from 4.4+/-3.5 to 15.6+/-7.7, all with significant differences (P<0.01). Ten of the 17 cases had instability of the distal radioulnar joint and five had recurrent instability after repair. (+info)
Normal anteroposterior laxity of the radiocarpal and midcarpal joints.
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The patterns of laxity of normal wrists subjected to dorsal and volar stresses were analysed. Dorsal and volar displacement tests were carried out on both wrists of 50 subjects under image-intensifier control. Lateral projections in neutral, and dorsal and volar stress positions were taken to analyse the behaviour of the carpal bones. Varying degrees of capitolunate subluxation under dorsal and volar stress were noted. Dorsal displacement of the capitate appeared to be more prominent than volar displacement. The lunate either extended or subluxed dorsally in response to a dorsal stress, suggesting a different pattern of laxity for the radiolunate joint. These observations provide a baseline for the interpretation of dorsal and volar stress views in the symptomatic wrist. (+info)
Morphology-based systematics (MBS) and problems with fossil hominoid and hominid systematics.
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The generalized/primitive nature of the hominoid dentition and often fragmentary nature of fossils, coupled with enthusiastic optimism for making revolutionary finds, has wreaked havoc with recognition of early human ancestors and reconstruction of fossil hominoid phylogeny. As such, the history of paleoanthropology is one of repeated misidentification of fossil ancestors and of occasional fraud. Although this history has led many workers to lose confidence in morphology based systematics (MBS), past and present misidentifications are actually due to a disregard of systematic methodology. Systematics depends on the continuity of life and gains its objectivity largely from the order alpha taxonomy imposes on morphologic discontinuities in closely related taxa (i.e., species and genera). Transformation of characters fixed in species into character complexes, as manifested in taxa nested at different levels of relationship, form the foundation for higher-level taxonomy and for phylogeny. Because in most cases, hominoid fossils are unable to provide the data needed to resolve alpha taxonomy, classification and phylogeny of fossil taxa must be guided by analogies to living taxa. Hominid and hominoid fossil taxonomy and phylogeny, however, has been based largely on preevolutionary notions and on misinterpretations of the polarity of assumed diagnostic characters. More often than not, fossils lack resolution for the taxonomic level or rank they are assigned to and taxa are erected without appropriate analogies to living forms. As such, phylogenies based on these classifications are unlikely to be correct. More in-depth anatomical studies that are in accordance with systematic methodology are likely to hold the key to correctly classifying fossils and unraveling hominoid and hominid phylogeny. (+info)