shu-508 and Arthritis--Rheumatoid

Contrast-enhanced US (ultrasonography) can be used for the study of musculoskeletal diseases but this application still belongs to clinical research. Despite a theoretical value for the identification of microvascularity, the technical limitations of musculoskeletal US are challenging the use of contrast enhanced US. This can explain the slow development of this application and the reason why it remained limited to the assessment of Doppler signal intensity increase. However, the recent availability of real time contrast-enhanced US imaging and quantification data is very promising. The majority of published papers involves rheumatoid arthritis and demonstrates the value of this technique to improve diagnosis, stage the activity of the disease and follow the patients under therapy. These preliminary studies are extending to other disorders (inflammatory arthritides as well as degenerative disorders). Structures other than articular synovium are undergoing investigations (bone, enthesis). New applications are being developed such as contrast-enhanced US of muscular diseases. This new imaging technique appears to have great potentials for the assessment of musculoskeletal diseases.

Topics: Adult; Arthritis, Juvenile; Arthritis, Rheumatoid; Contrast Media; Dermatomyositis; Female; Fibromyalgia; Humans; Magnetic Resonance Imaging; Male; Microbubbles; Middle Aged; Musculoskeletal Diseases; Osteoarthritis, Knee; Phospholipids; Polysaccharides; Sensitivity and Specificity; Spondylarthropathies; Sulfur Hexafluoride; Ultrasonography; Ultrasonography, Doppler

The aim of this study was to examine, with dynamic contrast-enhanced MRI as the reference, if contrast-enhanced power Doppler ultrasonography (CE PDUS) of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints provides additional information for evaluation of synovial inflammation compared with PDUS. One MCP joint in each of 15 RA patients and 3 healthy control persons were examined with PDUS before and after intravenous bolus Levovist contrast injection. Corresponding rates of early synovial enhancement (RESE), previously shown to be closely related to histopathological synovitis, were calculated from dynamic contrast-enhanced MR images obtained the same day. Prior to ultrasonography, the joint was evaluated clinically. Levovist increased the flow signal in 7 of 9 joints with pre-contrast flow-signal and in 0 of 9 without pre-contrast signal. No healthy controls showed CE PDUS signal. The results of CE PDUS and dynamic MRI were closely related: RESE in joints with CE PDUS signal was significantly higher than in joints without CE PDUS signal (Mann-Whitney test, p<0.001). Among the patients with pre-contrast PDUS signal no statistically significant difference in RESE values was found between joints with and without post-contrast flow-signal increase. No correlation was found between clinical examination and CE PDUS. Based on comparisons with dynamic contrast-enhanced MRI, PDUS appears to be reliable for assessment of synovitis in RA MCP joints. Intravenous contrast injection may provide additional information in selected cases but did not in the present study increase the sensitivity of the method.

Topics: Adult; Aged; Arthritis, Rheumatoid; Contrast Media; Female; Humans; Injections, Intravenous; Magnetic Resonance Imaging; Male; Metacarpophalangeal Joint; Middle Aged; Polysaccharides; Synovial Membrane; Ultrasonography, Doppler

The therapeutic effects of histone deacetylase (HDAC) inhibitor combined with ultrasound (US) (1 MHz, 10% duty factor, 0.1 or 0.2 W/cm(2)) in RA synovial fibroblasts (RASFs) were examined.. RASFs were isolated from rheumatoid synovial tissues obtained from patients with RA during total knee arthroplasty. RASFs were treated with an HDAC inhibitor, trichostatin A (TSA), with or without US. Cell viability was estimated using the Trypan blue dye exclusion test and cell cycle was examined by flow cytometry using propidium iodide (PI) staining. Gene expression of cell cycle-related genes cyclin D, cyclin A, cyclin B and p21(WAF1/Cip1) was analysed by semi-quantitative RT-PCR. Detection of apoptosis was examined by flow cytometry using annexin V-FITC and PI staining. Microarray analysis was carried out to profile gene expression of inflammation-related genes.. Dose-dependent decreases in cell viability, cell cycle arrest and apoptosis in RASFs due to TSA were observed. US treatment in the presence of microbubbles increased cellular uptake, but did not induce cell cycle arrest or apoptosis. The combination of TSA and US modulated cell cycle-related gene expression and significantly decreased S phase cells and increased G(2)-M phase cells. US also further enhanced TSA-induced RASF apoptosis and regulated expression of inflammation-related genes.. HDAC inhibitor in combination with US effectively reduces cell viability and induces apoptosis in RASFs. The combination therapy could be useful to control synovial proliferation and inflammation, since US can be easily applied to targeted joints as local physiotherapy.

Topics: Apoptosis; Arthritis, Rheumatoid; Cell Cycle; Cell Survival; Cells, Cultured; Combined Modality Therapy; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Genes, cdc; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Microbubbles; Oligonucleotide Array Sequence Analysis; Polysaccharides; Reverse Transcriptase Polymerase Chain Reaction; Synovial Membrane; Ultrasonic Therapy

The aim of this study was to evaluate the ability of power Doppler sonography (PDS) with ultrasound contrast agent to assess the synovial perfusion changes induced by intra-articular steroid injection therapy in the knee joints of patients with rheumatoid arthritis (RA). Eighteen RA patients (16 women, 2 men) with a history and signs of active knee synovitis were studied. Tenderness was evaluated using Thompson's modified index of synovitis activity. All patients underwent joint aspiration followed by intra-articular injection of 40 mg of triamcinolone hexacetonide. Gray-scale ultrasonography and PDS with an intravenous ultrasound contrast agent (Levovist) examinations were carried out before and 3 weeks after the intra-articular steroid injection. The calculation of the time--intensity curves provided a quantitative estimation of the synovial perfusion. The median values of the index of synovitis activity decreased significantly from 7.0 (95% confidence interval (CI) 6.0-8.0) to 3.0 (95% CI 2.0-4.0) ( p<0.01) 3 weeks after the intra-articular steroid injection. All patients showed a reduction of PDS signal after intra-articular steroid therapy and the baseline and follow up median values of the area underlying time-intensity curves were 7.48 (95% CI 5.79-8.73) and 2.45 (95% CI 1.92-3.61), respectively. The comparison between baseline and follow-up median values of the area under the curves showed a statistically significant reduction of PDS findings ( p<0.01). At follow-up examinations the changes in the index score of the synovitis activity were significantly correlated to the changes in the values of the area underlying time-intensity curves ( r=0.785; p<0.01). A significant correlation was also observed between baseline values of the area underlying time-intensity curves and C-reactive protein (CRP) ( r=0.548; p=0.023). In conclusion, PDS with an intravenous ultrasound contrast agent has been shown to be able to detect changes in synovial perfusion after intra-articular steroid injection and may be an additional useful method in the evaluation of synovial inflammation and in the assessment of the therapeutic response.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Contrast Media; Female; Humans; Image Enhancement; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Polysaccharides; Regional Blood Flow; Synovial Membrane; Synovitis; Treatment Outcome; Triamcinolone Acetonide; Ultrasonography, Doppler

To evaluate patients with clinically active rheumatoid arthritis (RA) of the shoulder for joint effusion and synovitis using conventional sonography, power Doppler (PD) sonography with and without echo-enhancing contrast agent, and contrast-enhanced MRI.. Twenty-four patients (mean age 64 years) with known RA had one symptomatic shoulder evaluated by conventional gray-scale sonography and PD sonography before and after intravenous administration of the echo-enhancing contrast agent Levovist (300 mg/ml, 2.5 g). The degree and extent of the altered echo pattern in the subacromial bursa, axillary recess and glenohumeral joint seen by conventional gray-scale sonography and the intensity of vascular signals of PD sonography were compared with the findings of MRI obtained with T2-weighted turbo spin-echo sequences and contrast-enhanced T1-weighted fat-saturated spin-echo sequences. MRI was evaluated by two readers in consensus without knowledge of the sonographic findings.. MRI, which was used as the reference examination, detected joint effusion in 71% (17/24) and synovitis in 92% (22/24) of the patients. Conventional sonography revealed an abnormal articular echo pattern in 96% (23/24) of the patients, especially in the axillary recess and subacromial bursa, but failed to attribute the altered echo pattern to either fluid or specific synovitis. PD sonography allowed a specific diagnosis of synovitis in 33% (8 patients), which increased to 50% (12 patients) after administration of an echo-enhancing contrast agent. In 42% (10/24) of the patients, the findings of synovitis demonstrated by MRI corresponded to an altered echo pattern by conventional sonography, but vascular signals were absent by PD sonography with or without echo-enhancing contrast agent.. Using MRI as the "gold standard," PD sonography with and without echo-enhancing contrast agent cannot reliably identify synovitis or distinguish synovial inflammation from effusion in the shoulder joint.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Contrast Media; Diagnosis, Differential; Exudates and Transudates; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Polysaccharides; Reproducibility of Results; Sensitivity and Specificity; Shoulder Joint; Synovitis; Ultrasonography, Doppler, Pulsed

To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity.. Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health-visual analogue scale, disability index-Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves.. The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables.. PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.

Topics: Adult; Aged; Area Under Curve; Arthritis, Rheumatoid; Contrast Media; Cross-Sectional Studies; Female; Humans; Knee Joint; Male; Middle Aged; Polysaccharides; Regional Blood Flow; Severity of Illness Index; Synovial Membrane; Synovitis; Ultrasonography, Doppler; Ultrasonography, Doppler, Color